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Year : 2017  |  Volume : 21  |  Issue : 8  |  Page : 4-79

ESICON 2017 Abstracts

Date of Web Publication6-Oct-2017

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How to cite this article:
. ESICON 2017 Abstracts. Indian J Endocr Metab 2017;21, Suppl S2:4-79

How to cite this URL:
. ESICON 2017 Abstracts. Indian J Endocr Metab [serial online] 2017 [cited 2021 May 8];21, Suppl S2:4-79. Available from: https://www.ijem.in/text.asp?2017/21/8/4/216074

   Pituitary: A study on clinical and hormonal evaluation of anterior pituitary dysfunction after traumatic brain injury and subarachnoid haemorrhage Top

Manoj Mengade, Babul Reddy1, Prasun Deb2

DNB Endocrinology Resident, Krishna Institute of Medical Sciences, Secunderabad, 1DM Endocrinology, Senior Cosultant, Krishna Institute of Medical Sciences, Kondapur, 2DM Endocrinology, H.O.D. Department of Endocrinology, Krishna Institute of Medical Sciences, Secunderabad, Telangana, India.

E-mail: [email protected]

Objectives: Incidence of anterior pituitary hormonal dysfunction at 0-10 days of TBI and at 6th month of TBI. Materials and Methods: It's Prospective observational study with sample size 10 patients having moderate to severe traumatic head injury (GCS <12) and subarachnoid haemorrhage, admitted in neurosurgical ICU. Hormonal evaluation for serum Cortisol, Growth Hormone, IGF-1, LH, FSH, Testosterone, Estradiol (E2), TSH, free T4 and prolactin was done on 0-10 days of traumatic brain injury (TBI) at 8am and labelled as baseline tests. Subsequent hormonal work up was done around 6th month of TBI with same panel of tests at 8 am and data was compared with the baseline. Data was presented as mean and standard deviation (SD) and comparison between the groups was done by ANOVA test. Results: At baseline 40% patients had one hormonal axes dysfunction and 30% patients had 2 axes involvement and 30% had >2 axes dysfunction. At 6th month 30% patients had >2 axes involvement and 20% had single axis involvement. Hypocortisolism at baseline was 40% and 20% at 6th month. Serum growth hormone was normal in all patients at baseline and 6th month. Serum IGF-1 was low in 40% patients at baseline and 20% at 6th month. Serum prolactin was high in 30% cases at baseline and 10% at 6th month. Serum LH was low in 30% cases at baseline and at 6th month. Serum FSH was low in 40% cases at baseline and at 30% at 6th month. Serum testosterone was low in 20% cases at baseline and at 6th month. Serum TSH was low in 30% cases at baseline and 10% at 6th month. Conclusion: Recovery of HPA axis and GH-IGF-1 axis were observed in 50% patients at 6th month of TBI, so it's recommended that regular check of HPA axis at 6th of TBI. Sick euthyroid syndrome incidence was 30% at acute phase only. Clinically non significant hyperprolactinemia incidence was 30% in acute phase which was recovered in 70% cases over 6 months. So regular screening of anterior pituitary hormones is required to detect new onset dysfunction and to avoid unnecessary treatment.

   Adult hypopituitarism: A single centre experience Top

Jubin Kurian, Rajeev Philip, Cherian Jacob1, C. S. Abdul Kadar1, Keshavan Charamelsankaran1, R. N. Sharma1

Departments of Endocrinology and 1Medicine, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: The incidence of hypopituitarism in general population in 4 in 1,00,000 population, but remains a under diagnosed disease, and there is paucity of data on hypopituitarism. There are only two studies published from India on clinical features of panhypopitutarism. Objectives: To study the of hypopituitarism from a tertiary center in Kerala. Materials and Methods: This study was carried out in patients attending medicine and endocrinology OPDs in Pushpagiri Medical College Hospital Tiruvalla, Kerala between December 2013 and November 2016. All new patients were studied prospectively and those diagnosed before September 2013 were studied retrospectively. Patients diagnosed after the age of 15 years were included in the study. Relevant clinical, hormonal, and imaging data were collected. Dynamic testing for pituitary functions was carried out as necessary. Hypopituitarism was defined as deficiency of one or more pituitary hormone and panhypopituitarism was defined as deficiency of three or more pituitary hormones. Results: This study included 69 subjects. The mean age was 48.6 years. There were 39 (56%) males and 30 females (44%). The commonest presentation included altered sensorium (55%), hypogonadism and menstrual irregularity (45%). 17% patients presented with pituitary apolplexy. 14% patients were diagnosed following evaluation of pituitary masses. As for the etiology of hypopituitarism, tumors comprised of 47.7% of cases. Empty sella was found in 22% of patients, with post snake bite in 13%, Sheehans syndrome in 9%, and hypophysitis in 9% causing hypopituitarism in the rest. Hypogonadism (94%) was the most common abnormality seen followed by hypothyroidism (81%) and growth hormone deficiency (81%). Hypoadrenalism was seen in 65% of patients. Panhypopituitarism was seen in 82% of patients. Conclusion: The most common cause of hypopituitarism at tertiary care center is pituitary tumors and the commonest presenting complaint is altered sensorium. Panhypopituitarism is present in majority 85 cases. As compared to previous studies, the incidence of Sheehans syndrome is less, but we have a high incidence of hypophysitis and post snake bite hypopituitarism.

   Study of bone mineral density and prevalence of vertebral fractures in acromegaly patients Top

Kishan Delampady, Sushil Gupta

Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

E-mail: [email protected]

Objective: To assess the bone mineral density, incidence and risk factors of vertebral fractures in patients with acromegaly. Materials and Methods: Cross sectional, case control study where 68 acromegaly patients (45.6% male and mean age of 38 years) and 69 age and sex matched controls were included. Patients and controls were assessed for bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) at lumbar spine and femoral neck. Also the prevalence of vertebral fractures in 51 acromegalic patients was evaluated by Instant/Lateral Vertebral Analysis using DXA scanners. Fractures were graded according to Genant semiquantitative method. Results: BMD was normal (58.8%), osteopenic (16%), osteoporotic (11.8%) and osteosclerotic (13.2%) in acromegalic patients. When compared to controls, mean BMD of acromegalic patients were higher at hip (0.981 vs 0.863g/cm2, P value- 0.00) and lumbar spine (0.982 vs 0.929g/cm2, P value- 0.02). Vertebral fractures were seen in 23.5% of acromegaly patients (male 41.6%). Fractured and non fractured patients showed no significant difference in age, duration of illness, disease activity and BMD. Conclusions: This is a first study from India to report that BMD of acromegalic patients are higher than controls. Also vertebral fractures are frequent in acromegalic patients and affect the quality of life and survival. In screening for acromegalic complications, it is necessary to look for vertebral fractures.

   A rare cause of growth hormone deficiency: Septo optic dysplasia Top

Chaitanya Konda, Vijay Sheker Reddy Danda, P. Sreedevi, Srinivas Rao, Madhavi Verpula, P. Shalini

Department of Endocrinology, Gandhi Medical College and Hospital, Secunderabad, Telangana, India.

E-mail: [email protected]

Background: Septo optic dysplasia, described first by de morsier, manifests as a triad of midline defects, growth hormone deficiency and optic nerve hypoplasia. Clinical diagnosis requires the presence of at least two characters. Only about 30% patients have all the three features. We present a case of an 11 year old girl fulfilling all three criteria for the clinical diagnosis of Septo Optic Dysplasia (SOD). Number of mutations implicated in the pathogenesis of SOD including HESX1, SOX2, SOX3, and OTX2. Case History: An 11 year old girl presented with short stature, with very small height gain over past three years compared to her peers. Child was born of non-consanguineous marriage, first in birth order with birth weight of 3 kgs. Her mother was 18 years old and father 28 years old at her birth. She was diagnosed with a seizure disorder at 8 months of age and she is on regular antiepileptic drugs since then. Her height was 114cm, with -4SDS for IAP charts. Her bone age was 8 yrs and delayed. On clinical examination, she had grade 3 nystagmus. Upon detailed ophthalmological examination, she was found to have compound hypermetropic astigmatism with optic atrophy. MRI brain showed partial carpus callosum agenesis with pituitary hypoplasia. Her IGF level was 25 ng/ml (less than -3SDS). A clonidine stimulation test was suggestive of growth hormone deficiency. Conclusion: SOD is one of the important considerations in the differential diagnosis of growth hormone deficiency and should be considered. A complete diagnosis in the childhood allows for appropriate and adequate management of these children, as they require multi-disciplinary team approach.

   Prevalence and severity of obstructive sleep apnoea in acromegaly and its correlation with morphology of the upper airways Top

M. Sreejith, Mohd Ashraf Ganie, Ravinder Goswami, Tandon N, Devasenathipathy Kandasamy1, Randeep Guleria2

Departments of Endocrinology and Metabolism, 1Radiodiagnosis and 2Pulmonary Medicine, AIIMS, New Delhi, India.

E-mail: [email protected]

Objectives: To find out the prevalence and severity of obstructive sleep apnoea (OSA) among acromegaly patients and to correlate it with disease activity, metabolic parameters and morphology of the upper airway. Materials and Methods: Thirty patients with acromegaly admitted in endocrinology ward/attending the endocrinology OPD were recruited after informed consent. Patients with contraindication for MRI, those with untreated hypothyroidism, critically ill patients and age <18 years and >70 years were excluded. Diagnosis of acromegaly was confirmed by a nadir GH >1ng/ml following oral glucose challenge with 75 gm of anhydrous glucose. Detailed physical examination including anthropometric parameters (neck circumference, waist circumference and hip circumference) was done in all patients. Metabolic workup included fasting blood glucose, HbA1C, fasting lipid profile. Serum levels of IGF1, GH, T4, Prolactin, Cortisol were measured by electrochemiluminescenceassay. All patients underwent overnight polysomnography by ALICE 5 sleep diagnostic system. Cephalometric parameters (nasopharynx diameter, oropharynx diameter, hypopharynx diameter, tongue length, uvula length and uvula thickness) were measured by MRI Pharynx. Results: A total of 30 patients were studied (19 males and 11 females). 28/30 (93.3%) patients had macroadenomas. 19/30 (63.3%) were treatment naïve at the time of assessment. Only 3 out of 30 patients had controlled disease. 28/30 patients (93.4%) had OSA. 20% (6/30) patients had mild OSA. The frequency of both moderate and severe OSA was 36.6%. Among the cephalometric parameters, tongue length strongly correlated with severity of OSA while there was a weak correlation of severity of OSA with uvula length and uvula thickness. There was no correlation of IGF1 levels with severity of OSA. We could not find any correlation between severity of OSA and HbA1C levels and blood pressure. Conclusion: There is a high prevalence of obstructive sleep apnoea in acromegaly patients. The pathogenesis could be due to tongue and uvular hypertrophy. Appropriate treatment of this complication could help in improving the metabolic parameters and cardiovascular mortality in this group of patients although more studies are required in this regard.

   Hyperprolactinemia with infertility in a lady with porencehaly: Causal or casual association Top

V. Madhavi1, Vijay Sheker Reddy Danda1,2, Sreedevi Patnala1,2, Srinivas Rao Paidipelly1,2, Sarath Aleti1,2, Chaitanya Konda1,2

1Department of Endocrinology, Gandhi Medical College and Hospital, Secunderabad, 2Kaloji Narayana Rao University of Health Sciences, Warangal, Telangana, India.

E-mail: [email protected]

Introduction: Porencephaly is a rare, major congenital malformation of the brain characterized by cysts or the formation of cavities within the brain. Porencephalic cysts were originally described by R Heschl in 1859. Patients with porencephalic cysts range from asymptomatic, to profoundly impaired. Often signs and symptoms become evident in the first year of life, with spasticity and seizures being common early manifestations. Language impairment, mental retardation, and motor deficits are also frequently encountered. Porencephaly in association with hyperprolactinemia has not been widely reported. We report a case of a young lady with porencephaly, otherwise asymptomatic, presenting with infertility, secondary to associated hyperprolactinemia. Case Report: A 30-year-oldlady, married for six years, presented with primary infertility. She had attained menarche at 14 years of age. She had irregular cycles from the onset. She does not have any other complaints like headache, visual disturbance or seizures. She had not been on any medication. Antenatal, natal and postnatal period was uneventful. Early development was normal, with normal intelligence. General and systemic examination was unremarkable. Investigation revealed a serum prolactin level of 88.9 ng/ml. She was euthyroid. Pelvis imaging was normal. MRI brain and sella revealed a normal anterior pituitary gland with preserved posterior pituitary bright spot and porencephaly with adjacent gliosis in left posterior temporal and occipital lobes. EEG awake record was normal. She was initiated on 0.5 mg/week cabergoline and advised barrier contraception. After 3 months, her prolactin normalized. She is in follow up. Conclusion: It is unclear if porencephaly and hyperprolactinemia concur by chance or are causally related. This case highlights the need for further research.

   Wilson's disease presenting with Hypopituitarim Top

Ganesh Namani, Rakesh Sahay, Neelaveni Kudugunti

Department of Endocrinology, Osmania Medical College, Osmania General Hospital, Hyderabad, Telangana, India.

E-mail: [email protected]

Wilson's disease is an autosomal recessive disease of copper metabolism predominantly affecting liver and brain. Endocrine changes in Wilson's disease are growth retardation and delayed puberty secondary to the presence of a long standing chronic illness. Hyopothyroidism, hypoparathyroidism and metabolic bone disease also can occur with Wilson's disease. However hypopituitarism is a rare association seen in Wilson's disease. Very few cases have been reported having hypopituitarism with Wilson's disease, where the pituitary was either normal or showing an empty sella. It is not known whether the hypopituitarism is a consequence or a co-occurrence with Wilson's disease. Case Report: A 16 year female presented with failure to gain height and delayed puberty. On examination, she had severe proportionate short stature with height 112 cm (SDS -7.5) and SMR was prepubertal. She had rigidity and gait abnormality with short steps with difficulty in turning around. She also had a KF ring detected on slit lamp. Investigations revealed Growth Hormone Deficiency (peak stimulated Growth hormone was 0.05 ng/ml after clonidine stimulation) and hypogonadotropic hypogonadism (FSH-0.6 and LH 0.17) with normal thyroid and cortisol axis, and MRI was showing small hypoplastic pituitary with hyperintense lesions in basal ganglia. 24 hour Urine copper was elevated (163 μg/day). She was diagnosed as having Hypopituitarism with Wilson's disease. As the child has severe short stature, she was advised growth hormone therapy along with copper chelation therapy for Wilson's disease and the child is under followup.

   A study of diabetes mellitus: Its prevalence and predictors in acromegaly Top

Suhas Shantaram Khaire, Nikhil Bhagwat, Chaitanya Yerawar, Manoj Chaddha, Gayatri Ghanekar, P. K. Varthakavi

Department of Endocrinology, Topiwala National Medical College, B. Y. L. Nair Ch. Hospital, Mumbai, Maharashtra, India.

E-mail: [email protected]

Objectives: Carbohydrate intolerance and diabetes mellitus (DM) are frequently associated with Acromegaly. The aim of this study was to evaluate the prevalence of DM or Prediabetes and to study the factors which predicts its development in patients with Acromegaly. We also studied the impact of surgery on hyperglycemia. Materials and Methods: 32 patients (18 male and 14 females) with Acromegaly who were primarily evaluated at our centre from 2010 to 2017 and were followed up post operatively were included in the study. The study cohort was divided based on ADA criteria for DM diagnosis into two groups: diabetics (n-12) and Non-diabetics (n-20). The following variables were studied for association with diabetes: age, sex, Waist Circumference (WC), body mass index (BMI), duration of Acromegaly, GH levels, IGF1levels (% of upper limit of normal for age), pituitary tumour size, hypertension, and family history of diabetes. Results: The prevalence of DM in Acromegaly in our cohort was 37.5% while combined prevalence of IGT with DM was 43.75%. Patients with diabetes were older (Mean 47.25 + SD 15.25; P = 0.027), and higher WC (Mean 91.92 + SD 10.01; P = 0.033) than non-diabetics. The levels of GH and IGF1 were not significantly different between the two groups. Family history of diabetes was not found risk factor in our study. Only hypertension (P = 0.014) was significantly more frequent in patients with diabetes. After pituitary surgery 75% patients became normoglycemic and requirement of medication reduced in those that remained hyperglycemic. Conclusions: In our population, the prevalence of diabetes in acromegalics was estimated to be 37.5%, while prevalence of (IGT + DM) was 43.75%. Age, WC and hypertension-, but not GH and IGF1 levels, family history of diabetes -were significant risk factors for development of DM. After pituitory adenectomy 75% of patients with DM became normoglycemic.

   Clinical, hormonal and imaging profile of Sheehan's syndrome in a tertiary care centre in South India Top

Kalyani Sridharan, Rajan Palui, Harsh Durgia, Nandhini Laxmana Perumal, Jayaprakash Sahoo, Sadish Kumar Kamalanathan

Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

E-mail: [email protected]

Objective: The study presents clinical, hormonal and imaging characteristics of patients with Sheehan's syndrome from a tertiary care centre in South India. Materials and Methods: Hospital records of patients with a diagnosis of Sheehan's syndrome were retrospectively screened and the clinical, hormonal and imaging data were analysed. Results: Twenty patients with Sheehan's syndrome were studied. The mean age at presentation was 36.4 ± 2.44 years (range 22-65 years). The mean duration from the post partum event to the first clinical presentation was 6.7 ± 6.39 years (range 0.027 – 23 years). All the patients had secondary amenorrhea at first clinical presentation. Sixteen (80%) patients had lactational failure. Thirteen (65%) patients had symptoms of hypothyroidism. Eleven (55%) patients had symptoms of hypoadrenalism of whom four presented in adrenal crisis. Two (10%) patients had diabetes insipidus (DI). Mean free T4 was 0.58 ± 0.10ng/dl (range 0.06-1.90ng/dl), mean TSH was 1.87 ± 0.39μIU/ml (range 0.00-5.68μIU/ml). Mean basal cortisol was 3.80 ± 1.14μg/dl (range 0.20-11.6μg/dl). Mean prolactin was 3.88 ± 1.21pg/ml (range 0.05-17.73pg/ml). Mean FSH was 3.24 ± 0.57μIU/ml (range 0.14-9.09μIU/ml) and mean LH was 1.51 ± 0.40μIU/ml (range 0.0-6.4μIU/ml). GH-IGF-1 axis was not evaluated. MRI pituitary imaging was available for thirteen patients. Seven (53%) patients had complete empty sella, four (30.7%) had partial empty sella, one patient had absent posterior pituitary bright spot with relatively small anterior pituitary and one patient had normal imaging. Conclusions: In the absence of evaluation of growth axis, hypogonadism is the most common clinical presentation followed by lactational failure. Thyroid and cortisol axes may be spared in some patients and DI is uncommon. MRI imaging most commonly shows complete empty sella. Early diagnosis and treatment is important to prevent presentation with adrenal crisis.

   An unusual case of drug induced hyperprolactinemia Top

Amitabh Sur, Ashok Kumar, Subhankar Chowdhury, Pradip Mukhopadhyay, Sujoy Ghosh, Rana Bhattacharya, Dibakar Biswas, Arijit Singha, Satinath Mukhopadhyay

Department of Endocrinology and Metabolism, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: We report a 32 year old lady, with drug induced hyperprolactinemia in which her prolactin level increased to 362.2 ng/ml. Materials and Methods: Serum Prolactin and TSH assay using CLIA. Case Report: 38 year old patient presented to our OPD which chief complaint of galactorrhea for 3 months. She did not report any headache or visual disturbance. She was on combined OCPs (Ethinyl Estradiol 35 ug + Levonorgestrel 150 ug) for 5 years, Levosulpride 75 mg for 3 months and Dothiepin 75 mg daily for 6 months. Her (initial) serum prolactin came out to be 362.2 ng/ml and TSH 2.5 uIU/ml, FT4 1.9 ng/dl. and creatinine 0.8 mg/dl. Repeat serum Prolactin on stopping all 3 drugs for 6 weeks came out to be 5.5 ug/dl. It did not increase significantly on 1:10 dilution. Discussion and Conclusion: Drug induced hyperprolactinemia, usually do not cross 100 ng/ml but influence of multiple medications causing hyperprolactinemia used simultaneously, has to be kept in mind before interpreting prolactin levels even when they are reasonably high. Drug induced hyperprolactinemia is common and it's important to differentiate it from prolactinoma.

   Post snake bite panhypopituitarism: Delay in diagnosis or delayed presentation? Top

Toniya John, Rajeev Philip, Cherian Jacob1, C. S. Abdul Kadar1, Keshavan Charamelsankaran1, R. N. Sharma1

Departments of Endocrinology and 1Medicine, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: Post snake bite panhypopituitarism is a described entity. Most of the cases are diagnosed long after the snake bite, and this delay has been attributed to clinical inertia and lack of awareness. But on careful analysis of the case reports, it is found that at least a few of them started having symptoms after a latent period, which can be up to 5 years. We present 9 cases of post snakebite hypopituitarism, which were diagnosed late, but also had a delayed onset of symptoms. Aims: To study the clinical profile of post snake bite panhypopituitarism. To study the duration and sequence of onset of symptoms, and presentation. Materials and Methods: 9 patients, who were diagnosed to have post snake bite hypopituitarism between May 2014 and April 2017 were studied. All patients were male. The type of snake, the complications and treatment initially given were studied, and then the time of onset of symptoms of hormonal deficiencies was collected. All patients underwent relevant hormonal tests, including dynamic tests and imaging for pituitary. Results: All patients were male, all were bitten by Russels viper, all had hypotension after the bite and required blood transfusions and hemodialysis. The mean duration from the snake bite to the diagnosis was 7.75 years. The onset of symptoms were also delayed, with symptoms occurring an average 4.25 years after the snake bite. All patients had symptoms of hypogonadism, which was the first symptom to occur in 7 out of 9 patients. Lethargy, tiredness, weakness were present in all and appeared next, a mean of 6 months later. Adrenal crisis occurred in 4 patients, a mean of 13 months later. On hormonal evaluation all patients had panhypopituitarism, (low FSH/LH Testosterone, Cortisol, IGF1, and FT4). MRI done showed empty sella in 8 patients and small anterior pituitary in 1 patient. Conclusions: Contrary to our earlier understanding of post snake bite hypopituitarism, the pituitary damage is not a single time event, but a gradual loss of pituitary function initiated by the snake bite, which results in a delayed appearance of symptoms. The sequence of loss of pituitary hormone functions- Gonadotropin- GH-Thyrotropin-ACTH also points to the same fact. The late presentation may be due to an autoimmune destruction of pituitary, initiated by the snake bite.

   Macroprolactinemia: Prevalence and etiopathologic associations Top

Amanpreet Kaur Kalsi, Manish Jain, J. B. Sharma1, Amita Srivastava2, M. Mathew, Pradeep Kumar Chaturvedi, Ashutosh Halder

Departments of Reproductive Biology, 1Obstetrics and Gynecology and 2Pharmacology, AIIMS, New Delhi, India.

E-mail: [email protected]

Objectives: To find prevalence and etiopathologic associations with autoimmune, heavy metal and genetic factors in macroprolactinemia. Materials and Methods: A total of 102 women with pathological hyperprolactinemia having prolactin level of more than 100 ng/ml along with 24 control women and 185 physiological hyperprolactinemia (50 pregnant and 85 lactating) cases were recruited for the study. After taking detailed medical history 5 ml blood was collected in plain vial for serum separation and EDTA vial for DNA extraction. The pathological hyperprolactinemia cases were classified according to the cause of hyperprolactinemia as pituitary adenoma (n = 18), idiopathic/likely idiopathic (n = 31), drug induced (n = 38) and secondary to hypothyroidism and chronic disease like kidney and liver (n = 15). Polyethylene glycol precipitation was done in all cases and controls to segregate macroprolactinemia from true hyperprolactinemia. In order to analyze autoimmune basis various screening tests like VDRL, APTT, anti-TPO, anti-tg, anti-CCP were analyzed besides IL-2, IL-4, IL-5 and IFN-γ serum levels. Implicated (in hyperprolactinemia) heavy metals like chromium, cadmium, manganese and lead were also analyzed in serum using ICP-AE spectrometry. Genomic screening for copy number variation was studied using Illumina 300 K bead array in pituitary adenoma (n = 18) and idiopathic (n = 9) hyperprolactinemia cases (macroprolactinemia in 2 and 3 cases, respectively). Results: Prevalence of macroprolactinemia was detected as 20.6% (21/102 cases). We did not find macroprolactinemia in normal control or physiological hyperprolactinemia cases. All macroprolactinemia cases presented with reproductive dysfunction (menstrual abnormality and infertility). IL-4 level was significantly higher in patients (P value < 0.05), although there was no significant difference between macroprolactinemia (n = 21) and true hyperprolactinemia (n = 42) groups. Chromium and Manganese levels were significantly low in patients (P < 0.05) however there was no significant difference between macroprolactinemia (n = 21) and true hyperprolactinemia (n = 81) groups. DNA microarray analysis revealed 22 CNVs (10 gains and 12 losses) but only two were found to be likely pathogenic and contains genes like OLFML1 (11p15.4 loss) in a case of pituitary microadenoma (with macroprolactinemia) and HCCS (Xp22.2 gain) in a case of idiopathic hyperprolactinemia (without macroprolactinemia). Conclusion: Prevalence of macroprolactinemia in hyperprolactinemia was found to be as high as 20.6% and often symptomatic. IL-4, a marker of Th2 cell activity, seems to be produced in excess in hyperprolactinemia (with/without macroprolactinemia). Chromium and manganese were deficient in hyperprolactinemia (with/without macroprolactinemia). Gain of HCCS gene (role in inhibition of cell death pathway in brain) and loss of OLFML1 gene (role in cell proliferation) may likely play role in hyperprolactinemia (with/without macroprolactinemia).

   Spontaneous remission of Cushing's disease due to pituitary apoplexy following varicella infection Top

Harsh Durgia, Henith Raj, Rajan Palui, Kalyani Sridharan, Jayaprakash Sahoo, Sadishkumar Kamalanathan

Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

E-mail: [email protected]

Objectives: Cushing's disease is caused by hypersecretion of adrenocorticotropic hormone (ACTH) by pituitary corticotroph tumour. Spontaneous remission of Cushing's disease following pituitary apoplexy is a rare entity. We here report a case of 17 years old male who had spontaneous remission of Cushing's disease following pituitary haemorrhage during varicella infection. Materials and Methods: Our patient presented with complaints of increasing weight gain, diffuse hyperpigmentation, headache and striae over the abdomen. His clinical and hormonal evaluation was diagnostic of Cushing's disease. Magnetic Resonance Imaging (MRI) of pituitary gland showed two hypo-enhancing lesions – 4 * 3 mm on right side and 8 * 4 mm on left side. Inferior petrosal sinus sampling confirmed pituitary origin of hyper-cortisolism. While waiting for surgery, he developed fever with skin eruptions. Results: On clinical examination, he had vesicles over face, chest, abdomen and proximal limbs. Tzanck smear showed multinucleated giant cells suggestive of Varicella and he was started on intravenous acyclovir. He further developed respiratory distress and his chest x-ray showed bilateral lung infiltrates. He was treated with intravenous antibiotics for suspected secondary bacterial pneumonia. Following recovery from pneumonia, he developed recurrent vomiting. His repeat hormonal evaluation was suggestive of central adrenal insufficiency and repeat MRI pituitary showed hemorrhage into left sided microadenoma. Conclusion: Spontaneous remission of Cushing's disease is an infrequent event which can be explained principally by pituitary apoplexy occurring due to infarction and/or haemorrhage. remission of Cushing's disease due to an ACTH secreting pituitary microadenoma caused by apoplexy following varicella infection.

   Ectopic ACTH Syndrome associated with myxoid liposarcoma in an adult Top

Karthik Prabhakar, Deepika Loganathan

Department of Diabetes and Endocrinology, Manipal Hospital, Bengaluru, Karnataka, India.

E-mail: [email protected]

A 66-yr-old lady attended Endocrinology Clinic with 10-day history of generalised swelling/weight-gain, breathlessness, easy bruising, profound fatigue, difficulty in walking, and depression. Past Illnesses: Diabetes/Hypertension, on Insulin/Metoprolol/Telmisartan. She was Cushingoid, with BP 160/90 mmHg, peripheral oedema and severe proximal-myopathy. Relevant blood tests: RBS 328 mg/dL, Potassium 2.5 mmol/L (3.5-5.2), Bicarbonate 37 mmol/L (21-31), Creatinine 0.6 mg/dL normal, Albumin 3.4 g/dL (3.5-5.2), Normal Serum-Calcium, CPK, TSH, blood-counts except Haemoglobin 11.5 g%; Urine-Glycosuria; ECHO – ejection fraction >50%. Intravenous Insulin and Potassium infusions started. Cushing's syndrome suspected – Serum Cortisol levels: Random (5 PM) 3083 nmol/L, Midnight 3347, and 9 AM 3127 (138-635) with ACTH 89.17 pg/mL (7-60). 24-hour Urinary-Cortisol was 1489 (N <213). Following Overnight-Dexamethasone-Suppression-Test, 9 AM-serum Cortisol 3695 revealed a paradoxical rise. Contrast-MRI confirmed normal Pituitary-fossa; PET-CT revealed FDG-avid large heterogeneous mass with central necrosis in right Iliacus, multiple bilateral lung-nodules and bilateral adrenal hyperplasia. CT-guided multiple biopsies: 'Myxoid Liposarcoma of Iliacus', and 'Acute Lung Injury with no evidence of malignancy'. Oral Ketoconazole 300 mg/day initiated, increased to 600 mg/day, and Spironolactone added. Serum-Cortisol reduced to 1645 after 3-days, Potassium level normalised, LFTs stable but patient deteriorated with Pancytopenia and severe bilateral broncho-pneumonia. Despite supportive treatment, the patient expired before definitive treatment was possible. Ectopic ACTH syndrome (EAS) occurs in about 5–10% of all patients with ACTH-dependent Hypercortisolism, mostly caused by intrathoracic-neoplasms. The most common cause of ectopic ACTH production is the expression of pro-opiomelanocortin (POMC) by a tumour. POMC is cleaved to produce big Melanocyte-Stimulating Hormone and ACTH, leading to Cushing's syndrome. While small-cell lung cancer, pulmonary-carcinoid, MTC, islet-cell malignancy, neural-tumours, thymoma, etc., are recognised causes of EAS, Sarcomas (Ewing's, Clear-cell Sarcoma of the kidney) in children are reported in relation with EAS. Liposarcomas are known to cause paraneoplastic syndromes, and Myxoid Liposarcoma is associated with anti-Hu paraneoplastic manifestations. We report a case of EAS associated with Myxoid Liposarcoma.

   Diverse presentations of Sheehan's syndrome at diagnosis: A Tertiary Care Centre experience from East India Top

Sreenath Ravindranath, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami

Department of Endocrinology, NRS Medical College and Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: Ischemic pituitary necrosis resulting from severe post partum haemorrhage leads to Sheehan's syndrome. The aim of the present study was to review the diverse presenting features of Sheehan's syndrome at diagnosis. Materials and Methods: Retrospectively 14 cases of Sheehan's syndrome at diagnosis were studied. Presenting clinical features, laboratory data, pituitary hormone deficiencies, and magnetic resonance imaging of the sella were analysed. Results: Mean age of patients was 51.1 ± 9.4 years. Mean time to diagnosis of Sheehan's syndrome from last child birth was 13.6 ± 7.4 years. Two (14.28%) patients were referred for recurrent hyponatremia, two (14.28%) for hypotension and hypoglycemia. Five (35.71%) patients presented with weakness and weight loss, one (7.14%) with raised thyroid secreting hormone. Only four (28.57%) presented with complaints of amenorrhea. Nine (64.28%) patients had lactational failure. Gonadotroph failure were present in all at diagnosis but corticotroph preservation was documented in five (35.71%) and thyrotroph in three (21.42%) patients. Eight (57.14%) patients had empty sella while six (42.85%) had partial empty sella on MRI. Conclusion: Sheehan's syndrome patients end up in different specialities with variable features. They present with subtle clinical features of hypopituitarism, resulting in delayed diagnosis. H/o post partum haemorrhage, lactational failure and amenorrhea are important clues.

   Three siblings with kallmann syndrome Top

Nunna Shashank, Kalra Pramila

Department of Endocrinology, Ramaiah Medical College, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Kallmann syndrome the most common cause of isolated hypogonadotrophic hypogonadism has a prevalence of 1 in 10000 to 1 in 60000 with a male to female ratio of 5:1. Here we present a case series of 3 brothers. Case Report: Three brothers aged 26, 22 and 18 years, presented to our department with complaints of absence of secondary sexual characters and smaller size of penis. One out of 3 was operated for right undescended testis at the age of 15 years. They were born out of second degree consanguineous marriage. On examination, all 3 had pre-pubertal voice, genitalia with eunuchoid proportions along with anosmia and bimanual synkinesia. The hormonal assays were consistent with isolated hypogonadotrophic hypogonadism with low FSH, LH and testosterone. Ultrasound abdomen showed non visualized right kidney and hypoplastic prostrate. MRI pituitary gland showed non visualized olfactory bulb and sulci bilaterally. All of them were started on testosterone depot preparations, after which they developed secondary sexual characteristics. Discussion: The basic defect in Kallmann syndrome is in the hypothalamus due to defect in migration of GnRH secreting neurons from neuroepithelium of nasal placode. They also have anosmia/hyposmia. Synkinesia is a unique feature present in upto 80% of X-linked cases. Unilateral renal aplasia or dysplasia is another feature present in around 30% patients. In our cases, all 3 had bimanual synkinesia, one patient had unilateral renal aplasia. Conclusion: This case report shows that it is prudent to study genotype phenotype association in Kallmann syndrome. Thus analysis of family history and pedigree should be done in all suspected cases of Kallmann syndrome.

   Optimizing the clonidine stimulation test Top

Darshana Sudip Thakur, Nikhil Bhagwat, Milind Bhide, Chaitanya Yerawar, Manoj Chaddha, Gayatri Ghanekar, Prema K. Varthakavi

Department of Endocrinology, Topiwala National Medical College, BYL Nair Ch. Hospital, Mumbai, Maharashtra, India.

E-mail: [email protected]

Objectives: Clonidine stimulation test (CST), the most commonly used provocative test to rule out Growth Hormone Deficiency; involves frequent sampling and is cumbersome and expensive. We undertook this study is to determine whether focused sampling during CST could be convenient yet efficacious. Materials and Methods: We administered tablet clonidine (150 μg/m2) and estimated GH (CLIA on Siemens Immulite System) basally and at 30, 45, 60 and 90 minutes thereafter. Priming was done with ethinyl estradiol or testosterone in prepubertal children with chronological age >8 years. We reviewed retrospective data of CST performed at our center on 79 patients presenting with unexplainedshort stature (SDS<-2.5) after Institutional Ethics Committee approval. Using GH values >10 ng/ml to definitively rule out GHD, the specificity and false positives at each timing were calculated. Results: The most frequent time to peak GH was 60 min (Table 1). The specificity of test increased from 79.5% to 92.3% (Table 1) by estimating GH at 60 minutes and 90 minutes. Conclusions: Assaying a single sample at 60 minutes after clonidine resulted in 5 (10.2%) false positive tests with specificity of 79.5%. Addition of 90 min sample increased specificity to 92.3%. Combined sampling at 60 min + 90 min is economical, less cumbersome without compromising on the specificity.
Table 1: Diagnostic value of CST at various time points

Click here to view

   Bilateral inferior petrosal sinus sampling: The IPGMER, Kolkata experience Top

Kaushik Sen, Suvrendu Sankar Kar, Ashok Kumar, Sujoy Ghosh, Pradip Mukhopadhyay, Rana Bhattacharya, Arijit Singha, Subhankar Chowdhury

Department of Endocrinology and Metabolism, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Cushing's disease is the most common cause (85%) of ACTH dependent Cushing's syndrome although anatomic localisation remains a challenge. Bilateral inferior petrosal sinus sampling (BIPSS) is still the 'gold standard' for localisation, but is only infrequently performed in most of the centers. We present last couple of years' data on BIPSS in our institute. Objective: To differentiate between eutopic and ectopic lesions in patients with ACTH dependent Cushing's syndrome. (1) To assess the efficacy and safety of using injection Vasopressin for stimulation in BIPSS. Materials and Methods: Consecutive patients of ACTH dependent Cushing's syndrome were selected for BIPSS. After drawing the basal samples, Injection Vasopressin (Pitressin) was used at a dosage of 3 – 5 mg intravenously depending on the patient's BP response. All the samples were immediately transferred and tested in endocrinology lab. Conclusion: BIPSS is the 'gold standard' investigation for localisation of sources of ACTH dependent Cushing's Syndrome. However, experienced interventional radiologists and good logistic support are two most important pillars of success. In our series of ten patients with cushing's disease, the importance of having experienced interventional radiologist (s) were reconfirmed. The role of injection ADH for stimulation needs further evaluation.

   Neonatal diabetes insipidus secondary to ventriculitis treated with thiazide diuretics Top

Y. P. Ganavi, S. Chitra, Justin Easow Sam, Sandeep Donagaon

Department of Endocrinology, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Central Diabetes Insipidus (CDI) in neonates is associated with midline malformations with polyuria (urine volume >150 ml/kg/24 h) and elevated serum sodium and osmolality (>300 mOsm/kg) in combination with low urine osmolality (<300 mOsm/kg). Desmopressin in neonates has a risk of hyponatremia due to its fixed anti-diuresis action and the obligate high fluid intake with milk feeds. Thiazide diuretics reduces the risk of hyponatremia and polyuria. Case Report: A pretem infant with bilateral frontal periventricular leucomalacia and gross hydrocephalous underwent ventriculo-subgaleal shunt and developed hypernatraemia (170 mEq/L) together with polyuria (75 ml/m2/hour) postoperatively DI was suspected. Fluid replacement of up 1 litre/m2/day with vasopressin infusion at 1.25 units/hour was titrated to maintain a serum sodium of 145 to 156 mmol/L with urine output of 61 ml/m2/hour and subsequently put on thiazide diuretic 1.5 mg/kg/day in two divided doses. Central DI persisted and the infant remained on thiazides with urine output of 68 ml//m2/hour and serum sodium ranging between 134 mEq/L-142 mEq/L. Discussion: Vasopressin for CDI at 0.5 mU/kg/hr is titrated to maintain a urine output of <2 ml/kg/hr but has a risk of hyponatremia. Thiazides at the distal convoluted tubule (DCT) inhibit Na-Cl cotransport inducing natriuresis. Prolonged administration causes extracellular fluid depletion with water and sodium reabsorption at the proximal tubules with reduced water and sodium delivery to DCT and reduction in urine output. Low renal solute (LRS) feed in breast milk and commercial formula is used with thiazides. Since the baby now at 10 months has still not developed neck holding, LRS diet is being administered as transition to solid food was not possible. Transition to desmopressin should occur when solid nutrition is initiated to facilitate growth which might be hampered with chronic diuretic use. Conclusion: We report a neonate with acquired CDI secondary to ventriculitis treated successfully with thiazide diuretics.

   Screening for MEN1, AIP and GNAS1 gene variations in anterior pituitary adenoma cases without family history Top

Ekta Malik, Viveka P. Jyotsna1, Arundhati Sharma

Departments of Anatomy and 1Endocrinology and Metabolism, AIIMS, New Delhi, India.

E-mail: [email protected]

Objective: To screen the MEN1, AIP and GNAS1 genes in sporadic Anterior Pituitary Adenoma (APA) patients. Materials and Methods: 90 clinically diagnosed APA patients from the outpatient department of Endocrinology and Metabolism and 40 healthy individuals from the general population were recruited. Detailed clinical and family history was noted and 5ml blood collected after taking informed consent. Genomic DNA was subjected to PCR amplification of all the exons of MEN1 and AIP and exons 8, 9 of GNAS1, followed by direct sequencing. Results were compared with reference sequences in the public databases and prediction of functional effects of the variations was done using bioinformatics tools Mutation [email protected] and Human Splicing Finder (HSF). Results: Out of 90 patients (37 corticotropinoma, 25 somatotropinoma, 15 prolactinoma, 12 silent adenoma and 1 thyrotropinoma), 60 were females and 30 males. Genetic screening revealed 3 intronic and 1 exonic variations in MEN1 and 2 intronic changes in AIP gene. MEN1 changes identified were synonymous variation L404L (1 patient), reported intronic variations c.913-79T >A (2 patients), c.784-129T>A (1 patient) and c.913-42G>C (2 patients) and SNP rs669976 in 21 patients. These changes were not identified in the controls. SNPs rs654440 (50% cases; 70% controls) and rs2071313 (56% cases; 70% controls) were also found. AIP screening revealed reported intronic splice site variations c.100-6C>A and c.100-18C>T in 1 patient each, SNPs rs2276020 (12 patients), rs641081 (20 patients) and rs4084113 in 25 patients. Variations c.913-42G>C (MEN1) and c.100-6C>A (AIP) were predicted to be damaging by mutation [email protected] and MEN1 variations c.913-79T>A, c.784-129T>A, c.913-42G>C and variation c.100-6C>A of AIP were found to alter the splice site as predicted by HSF. No variations were found in the GNAS1 exons. Conclusion: This study suggests that intronic MEN1 and AIP variations may affect splicing resulting in altered protein and thereby leading to disease causation in sporadic cases of APA.

   Diabetes And Insulin Resistance Visceral adipose tissue in chronic pancreatitis: comparison between dual energy X-ray absorptiometry and bioelectric impedance analysis Top

K. V. S Hari Kumar, Rahul Sharma, Manish Manrai1, A. K. Sood1

Departments of Endocrinology and 1Gastroenterology, Army Hospital (Research and Referral), New Delhi, India.

E-mail: [email protected]

Objective: Visceral adipose tissue (VAT) is a risk factor for the diabetes and we investigated the amount of VAT in patients with chronic pancreatitis (CP). Methods: Serial patients with CP seen between January 2015 and June 2016 were included in this cross-sectional, observational study. The study population is divided into alcoholic CP (Group 1; N = 67) and tropical CP (Group 2; N = 35). VAT was estimated using the bioelectric impedance analysis (BIA) and dual energy x-ray absorptiometry (DEXA) method. The results were analyzed by appropriate statistical methods. Results: The study participants (85M, 17F) had a mean age 40.8 (12.6) yr, CP duration 3.7 (4.7) yr and body mass index 22.5 (3.2) kg/m2. Pancreatogenic diabetes was seen in 54 patients and the total body fat percentage was lower in the alcoholic CP. VAT mass was similar in both the groups (P = 0.8749). CP patients with diabetes had a higher VAT mass (436 vs. 341 gm) than without diabetes (P = 0.0132). DEXA and BIA correlated with total body fat (P < 0.0001) but not in the estimation of VAT (P = 0. 0922). Conclusion: VAT is a determinant in the development of diabetes, even in patients with CP. DEXA is a better modality for VAT estimation in comparison to BIA.

   Efficacy and Safety of Liraglutide versus Insulin for Glycemic Control in Intensive Care Unit: A Randomized, Open-label, Clinical Study Top

Vishesh Verma, Narendra Kotwal, Vimal Upreti, Yashpal Singh, Amit Nachankar, K. V. S. Hari Kumar

Department of Endocrinology, Army Hospital (R&R), New Delhi, India

Background: Intravenous insulin is the cornerstone in the management of hyperglycemia in the Intensive Care Unit (ICU). We studied the efficacy of liraglutide compared with insulin in the ICU. Methods: In this prospective, open-labeled, randomized study, we included 120 patients (15–65 years, either sex) admitted to ICU with capillary blood glucose (CBG) between 181-300 mg/dl. We excluded patients with secondary diabetes and APACHE score >24. The patients were divided into two groups (n = 60) based on the CBG: Group 1 (181–240) and Group 2 (241–300). They were randomized further into four subgroups (n = 30) to receive insulin (Groups 1A and 2A), liraglutide (Group 1B) and insulin with liraglutide (Group 2B). The primary outcome was the ability to achieve CBG below 180 mg/dL at the end of 24 hours. The secondary outcomes include mortality at one month and hospital stay. Data and results were analyzed using appropriate statistical methods. Results: The mean age of the patients (93 males and 27 females) was 57.1 ± 13.9 years, hospital stay (16.9 ± 7.5 days) and CBG was 240.5 ± 36.2 mg/dl. The primary outcome was reached in 26, 27, 25, 28 patients of Groups 1A, 2A, 1B and 2B respectively. 30 days mortality and hospital stay were similar across all the four groups. Hypoglycemia was common with insulin, and gastrointestinal side effects were more common with liraglutide (P < 0.001). Conclusion: Liraglutide is a viable alternative to insulin for glycemic control in the ICU. Further studies with large number of patients are required to confirm our findings.

   Incidence of chronic pancreatitis in adult male population: A 25 year follow up study Top

K. V. S. Hari Kumar, S. K. Patnaik1

Departments of Endocrinology and 1Pediatrics, Army Hospital (Research and Referral), New Delhi, India.

E-mail: [email protected]

Objective: The data on the epidemiology of chronic pancreatitis (CP) is scarce from India. We studied the incidence of CP in a cohort of young military personnel followed for a long duration. Methods: The data for this descriptive study was derived from the electronic medical records (EMR) of the military personnel enrolled between 1990 and 2015. All subjects were recruited before 18 years of age in good health. The data pertaining to the CP was derived from the EMR using the International Classification of Diseases (ICD) codes. We calculated the incidence rates as per person years using appropriate statistical methods. Results: Our study population includes 51,217 participants (median age 33 years, range 17 – 54) with a mean follow up of 12.5 years, giving a cumulative follow up duration of 613,925 person-years (py). A total of 46 patients developed CP giving an incidence rate of 7.5 per 100,000 py. Eight patients (17.4%) out of the 46 had an additional diagnosis of the alcohol dependence syndrome in the EMR. Conclusion: Our cohort had high incidence rates of CP when compared with other studies from abroad. Alcohol consumption in the military service is the major contributing factor for the excess incidence rate.

   Normative values for electrochemical skin conductance measurements for quantitative assessment of sudomotor function in healthy Indian adults Top

Amit Goel, C. Shivaprasad

Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India.

E-mail: [email protected]

Context: Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, an earliest-detected neurophysiologic abnormality in diabetic patients with distal symmetric polyneuropathy. Aims: This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex and BMI on ESC measurements. Methods and Materials: A sample of 217 healthy participants, 18-75 years old was recruited, and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet. Results: The mean age of the participants was 43.3 ± 13.2 years, and BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet were 68.9 ± 13.1 μS and 71 ± 12.9 μS, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.001). ESC values of both hands and feet declined with age. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis. Conclusions: Normative values for Indians are lower than that reported for Caucasians.

   Glycometabolic profile in type 2 diabetic patients with erectile dysfunction Top

Tuhin Dubey, Subhash Kumar Wangnoo1, Satish Kumar Agarwal2, Mohammad Asim Siddiqui1, Radhika Jindal1, Sajad Sumji3, Monika Sharma1

Department of Endocrinology, Medipulse Hospital, Jodhpur, Rajasthan, 1Apollo Centre for Obesity, Diabetes and Endocrinology, Indraprastha Apollo Hospital, 2Department of Internal Medicine, Indraprastha Apollo Hospital, New Delhi, 3Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

E-mail: [email protected]

Objectives: To study the glycometabolic and hormonal profile of type 2 diabetic patients suffering from erectile dysfunction (ED) and to determine the risk factors of ED in these for early intervention. Materials and Methods: The study was a cross sectional (analytical) study and included 100 type 2 diabetic males attending the Endocrine OPD between 1st June 2013 to 31st December 2014 at Apollo Hospital, Delhi after written informed consent. After applying exclusion criteria, patients were screened for presence of ED (IIEF criteria). Patients without ED were also studied for comparison and to serve as control group. Patients were subjected to detailed history, physical examination, anthropometric measurements and laboratory investigations. Microsoft Word and Excel were used to generate graphs and tables and descriptive statistical analysis was carried out. Statistical significance (P value < 0.05) of variables was determined among two groups. Results: The overall prevalence of ED was 62%. The mean age of the patients was higher in ED group (49.23 years) compared to non ED group (40.76 years). Patients with ED have a higher mean duration of diabetes (9.57 years) compared to patients without ED (4.67 years). The presenting symptoms, use of drugs and smoking habit was comparable in the two groups. Absent ankle reflex was significantly more common in patients with ED. No association was found with any sign of autonomic dysfunction. ED was significantly associated with obesity (higher BMI), central adiposity (higher waist/hip ratio), insulin resistance (HOMA-IR) and high hsCRP levels. ED was significantly associated with poor glycemic control (higher HbA1c%) and low HDL cholesterol levels. No significant association was found with testosterone levels and SHBG levels. Conclusion: The management of ED in diabetes should focus on weight reduction, strict glycemic control and maintaining a healthy lifestyle rather than focusing on exogenous testosterone therapy.

   Prevalence of maturity onset diabetes of young associated mutations in patients with young onset diabetes and significant family history Top

Geethalakshmi Sampathkumar, Praveen V. Pavithran, Nisha Bhavani, Vasantha Nair, Harish Kumar, Arun S. Menon, Usha V. Menon, Nithya Abraham, Annie Pullikkal

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Objectives: To estimate the prevalence of MODY mutations in patients with young age of onset of diabetes mellitus and a positive family history of diabetes mellitus. Materials and Methods: 51 Subjects with onset of Diabetes at > 1 year and < 30 years of age and positive parental history of Diabetes (onset < 30yr of age) attending Endocrinology OPD from November 2015 to October 2016 were chosen. Patients who had radiological evidence of pancreatic disease, BMI > 27, History of DKA and positive GAD 65 antibodies were excluded. Detailed pedigree chart and clinical data were recorded. Biochemical tests including HbA1C, stimulated C peptide, ALT and fasting lipids were done. MODY genetic testing was performed by targeted next generation sequencing. Non parametric tests were used to compare patients with and without positive genetic testing. Results: Median age of onset of Diabetes was 21 years (range 3 to 27) and median duration of disease was 4 years (1 to 47yrs). Median BMI was 22.3 kg/m2. Out of the 51 subjects, 43.1% of individuals had genetically proven MODY (63.6% males). 27.2% had microvascular complications. Distribution among subtypes were as follows- (a) MODY 4(PD × 1)- 31.8%, (b) MODY 1 (HNF 4A), 3 (HNF1A), 12 (ABCC8) -13.6% each respectively, (c) MODY 8 (CEL)- 9.1%, and (d) MODY 5(HNF 1B), 6 (NEUROD1), 7 (KLF 11), 9 (PAX4) - 4.5% each respectively. Out of the genetically proven MODY subjects, 6 had novel mutations. There was no difference in the age of onset, BMI, C peptide levels lipid profile parameters or prevalence of microvascular complications between patients with and without MODY mutations. Conclusion: The patterns of MODY mutations is distinct with MODY 4 (PD × 1- 31.8%) being the most common type. The mutation prevalence in this study group consisting of patients from a single geographical region is higher than previously reported from a major South Indian tertiary care centre. Clinical similarity between the MODY positive and negative patients probably points towards as yet undiscovered genes contributing to the MODY phenotype (MODY X).

   Detemir reduced efficacy Top

Arunkumar R. Pande1,2, Santosh Kumar Chaubey1

1Consultant Endocrinologist, Sahara Hospital, 2Lucknow Endocrine Diabetes and Thyoid Clinic, Lucknow, Uttar Pradesh, India.

E-mail: [email protected]

Introduction: Glycemic control is very important during pregnancy. NPH insulin and Detemir are 2 basal insulin approved in pregnancy. Case Report: We report a case of 35 years old housewife who had pre-existing diabetes with pregnancy. She was on aspart and protaminated aspart (30/70) 30 and 15 Units bid at presentation. She was switched to once a day inj. detemir subcutaneous and premeal aspart subcutaneous tid for better glycemic control. Surprisingly, her glycemic control was difficult to achieve in spite of uptitration of detemir dose to 0.8 IU/Kg/day (48 IU) and total insulin dose to 2 IU/Kg/day as her fasting blood glucose remained between 108 to 131 mg/dl. Detemir was used for almost 3 weeks. As glycemic control is very important during pregnancy, she was shifted to NPH insulin at lesser dose than detemir i.e., 0.68 IU/kg (40 IU) with which she responded well and achieved normalization of fasting blood glucose (FBS) and her FBS was 89 very next day. She did reasonably well glycemic control on NPH and had preterm ceaserean delivery due to fetal bradycardia. Discussion: Detemir is one of the 2 basal insulins approved in pregnancy and are frequently used in diabetes with pregnancy. The reduced efficacy of detemir is an important aspect of treatment in diabetes with pregnancy. As against previously shown that detemir reduced efficacy was shown in individuals with NAFLD and hypertriglycerdemia. In our case she had transaminitis but there was no evidence of hypertriglyceredemia and her USG liver was normal.

   Study of glycemic status in patients of liver cirrhosis Top

Akanxa Yadav, Mukul P. Agarwal, S. V. Madhu1

Departments of Medicine and 1Endocrinology, UCMS, GTB Hospital, Delhi University, New Delhi, India.

E-mail: [email protected]

Objectives: To assess the glycemic status in patients with liver cirrhosis. Materials and Methods: 60 patients of liver cirrhosis of any etiology ≥18 years of age were studied. Patients of chronic pancreatitis, known malignancy, those receiving corticosteroids, or with complications like advanced encephalopathy, gastrointestinal bleeding within past two weeks were excluded. Demographic and clinical parameters were recorded for all patients. All subjects were assessed by FBS and those having FBS ≥126 mg/dl were classified as diabetic. The remaining patients were subjected to OGTT. Data was analysed using SPSS software v 20.0. Prevalence was calculated as percentage. Unpaired t test was used to see association with quantitative factors, and chi square test for qualitative factors. P < 0.05 was considered significant. Results: The subjects included 49 male and 11 females; age range 19 to 72 years. 42 patients had history of significant alcohol intake, 5 were HbsAg reactive and 3 anti-HCV reactive. On FBS, 55 had normal FBS, 3 had IFG and 2 had DM (known diabetics). On OGTT, 19 patients had abnormal values - 16 had IGT and 3 had diabetes. 5 patients had increased HbA1c - 4 had HbA1c between 5.7-6.4% and only 1 had >6.4%. Child Pugh class A, B and C was seen in 14, 41 and 5 patients respectively. The mean MELD score was 11.9 ± 5.17. 18 patients had increased insulin resistance. Thus out of 60 subjects, 2 were known diabetics, 41 were normoglycemic, 14 had IGT and 3 had IFG; (of these 3, 2 also had IGT and 1 DM by OGTT). Conclusion: OGTT is required for detecting IGT and diabetes in patients of liver cirrhosis as it can be missed on routine FBS and HbA1c estimation. Increasing severity of liver disease as assessed by Child Pugh and MELD scores was associated with higher risk of IGT and DM, though the association was not statistically significant.

   Effect of parental history of diabetes on markers of inflammation, insulin resistance and atherosclerosis in first degree relatives of patients with type 2 diabetes mellitus Top

Deepak Kumar Dash, Arun Kumar Choudhury, Anoj Kumar Baliarsinha

Department of Endocrinology, S.C.B Medical College, Cuttack, Odisha, India.

E-mail: [email protected]

Aim and objective: To study the effect of parental history of diabetes on markers of inflammation, insulin resistance, adiposity indices and carotid intima media thickness (cIMT) in first degree relatives of patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This cross sectional study was carried out in department of Endocrinology, S.C.B Medical College, Cuttack between January 2016 to June 2016. Normal glucose tolerant (NGT) first degree relatives of T2DM patients of age group 20-40 years (FHP) were enrolled in the study meeting inclusion and exclusion criteria. Depending on the parental history of diabetes they were divided into three groups: family history positive in father (FHF), family history positive in mother (FHM) and family history positive in both (FHB). Age, sex and BMI matched controls without any history of diabetes in their parents (FHN) were also taken for comparison. All subjects underwent detailed clinical evaluation and biochemical investigation. These included fasting plasma glucose, 2 hour post glucose plasma glucose, HbA1C, fasting insulin, lipid profile and highly sensitive C reactive protein (hsCRP). cIMT and adiposity indices like visceral adipose tissue thickness (VAT) and subcutaneous adipose tissue thickness (SAT) were assessed using ultrasonography. Necessary statistical analysis was done to derive the result. Results: A total no. of 64 cases (FHP) were taken out of which 21 subjects were in FHF group, 29 subjects in FHM group and 14 subjects in FHB group. 42 subjects were taken as controls (FHN). Total cholesterol (P = 0.003), LDL (P = 0.005), hsCRP (P = 0.039) and cIMT (P = 0.003) were significantly higher in FHP group than controls. FHB group subjects had significantly higher hsCRP, fasting insulin, HOMA IR, VAT, SAT and cIMT than either FHF or FHM group. However no significant difference existed in between FHF and FHM groups for these parameters. Conclusions: hsCRP and cIMT are significantly higher in the first degree relatives of type 2 diabetes mellitus patients than controls. However, only paternal or only maternal history of T2DM does not lead to significant differences in hsCRP, HOMA IR, VAT, SAT and cIMT among their first degree relatives.

   Prevalence of chronic periodontitis among diabetic patients of out patients' medical clinic at Teaching Hospital Kurunegala, Sri Lanka Top

Suranga Ravinda Manilgama, R. M. S. D. K. Ranathunga, Wathsala Premarathne, W. M. S. S Wijayasundara

Teaching Hospital, Kurunegala, Sri Lanka.

E-mail: [email protected]

Introduction: Chronic periodontitis is a common chronic inflammatory disease characterized by destruction of the supporting structures of the teeth. Diabetes is a major risk factor for periodontitis. Increased risk includes the prevalence, severity and progression of the periodontal disease. Objectives: The study was aimed to assess the prevalence, the severity of the Chronic Periodontitis Disease (CPD) among diabetic patients, and identify its association with hyperglycemia. Methodology: A descriptive cross sectional study was carried out among all diabetic patients, aged 30 to 60 years who attended to the OPD Medical Clinic Teaching Hospital Kurunegala (THK), during May 2016 to May 2017. They were assessed for CPD in restorative dental clinic at THK. Results: Eligible population was 390. Out of them, 62.6% were females. The prevalence of CPD was 40.5% (n = 158) and the occurrence among males was 37% and females was 42%. Disease severity was categorized as mild, moderate, and severe. There were 10.3% (n = 40) mild, 12.3% (n = 48) moderate and 17.7% (n = 69) severe patients among the study population. There was a statistically significant association (P <.05) between increased severities of the CPD with advanced age. Associations of CPD severity and hyperglycemia were calculated; mild, moderate, severe disease had mean FBS of 152, 180, 187 mg/dl and mean HbA1c of 8.28, 8.68, 9.25 respectively. There was 71.6% (n = 245) patients with HbA1C >7 and among them, 66.5% was female. There was a statistically significant association (P <.05) with high HbA1c and female sex. Conclusion: The prevalence of CPD among the study population was comparable to previous studies and the disease severity was associated with advanced age and mean glycemic status.

   Effect of canagliflozin on liver function tests in patients with type 2 diabetes mellitus and presumed liver fibrosis suggestive of non-alcoholic steatohepatitis Top

T. S. Deepak, Gary Meininger1, David Polidori2

CVM Metabolics, Janssen Medical Affairs, Mumbai, India, 1CVM Metabolics, Janssen Research & Development, LLC, Raritan, NJ, 2Translational Biomarkers, LJ CVM, Janssen Research & Development, LLC, San Diego, CA, USA.

E-mail: [email protected]

Background and Objectives: Type 2 diabetes mellitus (T2DM) and obesity are risk factors for non-alcoholic fatty liver disease (NAFLD), including its more severe form, non-alcoholic steatohepatitis (NASH). Non-invasive liver fibrosis risk scores, such as Fibrosis (FIB)-4, have been used in lieu of liver biopsy to identify patients with presumed liver fibrosis suggestive of NASH. Canagliflozin (CANA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been previously shown to improve glycaemic control, body weight (BW), and liver function tests (LFTs; e.g., alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma glutamyl transferase [GGT]) across a broad array of T2DM patients in Phase 3 studies. Whether CANA improves LFTs in patients with T2DM and presumed liver fibrosis suggestive of NASH is unknown. Materials and Methods: This post hoc analysis used pooled data from the 4 placebo (PBO)-controlled, Phase 3 studies in a general population of patients with T2DM with an elevated FIB-4 score (≥1.3) consistent with liver fibrosis (~20% of the total population, N = 501; mean (SD) baseline BW = 89 (21) kg, HbA1C = 7.9 (0.9) %, ALT = 31 (20) U/L, AST = 30 (18) U/L, GGT = 49 (63) U/L, total bilirubin = 10 (5) μmol/L). Results: At 26 weeks, both ALT and GGT were reduced with CANA 100 and 300 mg compared with PBO (Table 1). Conclusion: In summary, in patients with T2DM and presumed liver fibrosis suggestive of NASH, both CANA 100 and 300 mg reduced liver enzymes compared with PBO.
Table 1: Change in liver function tests with canagliflozin at week 26

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   Study conducted to evaluate association of serum vitamin D level with diabetic polyneuropathy in rural population of central India Top

Sushil Kumar, Anand Kumar Singh, Santosh Kumar, Vivek Kumar Verma, Ranjit Kumar Nim

Department of Medicine, Uttar Pradesh University of Medical Sciences, Saifai, Uttar Pradesh, India.

E-mail: [email protected]

Objective: To evaluate association of serum Vitamin D level and development of polyneuropathy. Methods: This was a case -control study and the study was conducted on an out patient basis. Fifty five subjects were recruited from the Medicine OPD of UPUMS Saifai. All subjects had type-2 diabetes (male and female, 40-60 years old). The Michigan Neuropathy Screening Instrument (15 point questionnaire) was used to identify patients with neuropathy (score >7/15). 20 patients did not have neuropathy and were designated the control group. 35 patients did have neuropathy (“study group”) and these patients underwent a detailed quantitative neuropathy evaluation by a neurologist using the 46-point Michigan Diabetic Neuropathy Scale (MDNS) and nerve conduction studies. We measured the serum 25-hydroxyvitamin D concentrations with liquid chromatography-tandem mass spectrometry (LC/MS) chromatography in all patients. These values were compared between the control and study group, and were correlated with the detailed neuropathy score in the study group. Result: Patients with diabetic polyneuropathy had a lower mean serum 25- hydroxyvitamin D level (16. 41 ng/ml with the SD of: 2.026) in comparison to the controls (38.76 ng/ml with the SD of 5.483). Conclusion: However, there was no correlation between the vitamin D level and the detailed quantitative neuropathy score in the study group. There is an association between serum 25- hydroxyl vitamin D level and diabetic polyneuropathy.

   Changes in lipid profile in pregnancy and its impact on the incidence of gestational diabetes mellitus and neonatal birth weight Top

M. Senthil Raja, S. Catherine1, Elsy Thomas1, Annie Regi1, Nihal Thomas, Thomas Vizhalil Paul

Departments of Endocrinology, Diabetes and Metabolism and 1Obstetrics and Gynaecology, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objective: To assess the longitudinal changes in lipid profile during the three trimesters of pregnancy and to determine if alterations in lipid profile are associated with adverse pregnancy outcomes like occurrence of gestational diabetes mellitus (GDM) and changes in birth weight of neonates. Materials and Methods: One hundred thirty pregnant women with singleton pregnancy were recruited in the first trimester from antenatal OPD. Fasting lipid profile in each trimester, blood pressure, fasting sugars, oral glucose tolerance test, incidence of adverse outcome such as GDM were observed. Results: Out of one hundred thirty women recruited, lipid profile for all three trimesters was available for seventy six women. There was a significant increase in the total cholesterol (36%), triglyceride (120%), LDL (49%) and HDL cholesterol (7%) between the three trimesters of pregnancy. There was no significant positive correlation between maternal lipid profile in each trimester and the birth weight of the baby. Thirty three percent of the women enrolled were diagnosed to have GDM. There was no significant association between components of lipid profile changes over three trimesters and occurrence of GDM. Conclusion: Although there was an increment in components of lipid profile across the three trimesters, it did not have a significant impact on the birth weight of the baby. There was no difference seen between mothers with or without GDM with regards to lipid profile.

   To study the distribution of glucose tolerance among women with previous history of gestational diabetes mellitus by IADPSG criteria and their spouses Top

Alpesh Goyal, Yashdeep Gupta, Nikhil Tandon

Department of Endocrinology and Metabolism, AIIMS, New Delhi, India.

E-mail: [email protected]

Objectives of the Study: To estimate the percentage post partum conversion of GDM into prediabetes or diabetes (dysglycemia). To study the glycemic and metabolic parameters in spouses of these women. Materials and Methods: Using hospital medical records, women with GDM by IADPSG criteria diagnosed between 2012-16 and their spouses were invited in a fasting state. Socio-demographic, anthropometric and medical data were collected and 75 gm OGTT with serum insulin estimation, HbA1c and fasting lipid profile done at the hospital visit. Results: Of the 824 women with GDM eligible for inclusion, 502 (61%) were contactable, of whom 243 (48%) agreed to participate. 185/243 women participated along with their spouses. At a median post partum interval of 17 months following the index pregnancy, 138 (57%) women had dysglycemia, including 111 (46%) with prediabetes and 27 (11%) with diabetes. Age, post partum interval, total number of pregnancies, current BMI, insulin use during index pregnancy, prior history of GDM, presence of metabolic syndrome and fasting insulin were found to be positively correlated with risk of dysglycemia. Among 185 spouses tested, 95 (52%) had dysglycemia, including, 75 (41%) with prediabetes and 20 (11%) with diabetes. Conclusion: Patients diagnosed with GDM by IADPSG criteria remain at high risk for dysglycemia in the post partum period. Post partum screening with a 75 gm OGTT at 6 weeks should therefore be targeted in this high risk group for early diagnosis and implementation of effective health strategies. A high prevalence of dysglycemia in spouses of these women may indicate social clustering of disease in biologically predisposed individuals.

   Microarchitecture of foot bones of diabetic patients with chronic Charcot arthropathy gives insight into pathogenesis Top

Salini Dharmadas1, Harish Kumar2, Minnie Pillay1, Annie Jojo3, Tessy PJ4

Departments of 1Anatomy and 2Endocrinology, Amrita Institute of Medical Sciences, Amrita University, 3Department of Pathology, Amrita Institute of Medical Sciences, Amrita University, Kochi, 4Department of Pathology, Government Medical College, Kalamassery, Ernakulam, Kerala, India.

E-mail: [email protected]

Introduction: Degenerated and malaligned bones and joints of foot are the hallmark features of Charcot arthropathy (CA). Knowledge on the changes caused by CA on bones of the foot in diabetic patients is limited. Objective: Analyze the microscopic structure of foot bones in diabetic patients with chronic CA. Materials and Methods: Samples of bone were collected from six diabetic patients with chronic CA who underwent foot amputation as a part of corrective foot surgery in the podiatry department of a tertiary care hospital. Bone specimens were fixed in formalin, decalcified in 10% nitric acid, embedded in paraffin wax, sectioned and stained by haematoxylin and eosin. Histology and histomorphometry of sections were detailed by two different pathologists. Result: Chronic CA foot bones displayed a lamellar architecture with fibrous tissue. Thin trabeculae was seen. Osteocytes were present but reduced in number. Large number of empty lacunae were observed. Marrow cavity was filled with fatty marrow and had thick walled blood vessels in it. Discussion: Unlike the results obtained in the present study on chronic CA foot bones, the only published study on microstructure of acute CA foot bones describes a woven bone architecture with an increasingly large number of Howship lacunae, indicative of increased osteoclast activity. Conclusion: This is the first study on the structure of chronic CA foot bones in diabetic patients. Our study will help better understanding of the pathogenesis of Charcot foot.

   Non alcoholic fatty liver disease, insulin resistance and proatherogenic lipid profile in paediatric patients on antiepileptic treatment Top

Kingini Bhadran, Nisha Bhavani, K. P. Vinayan, Praveen V. Pavithran, Vasantha Nair, Harish Kumar, Arun S. Menon, Usha V. Menon, Nithya Abraham, Annie Pullikkal

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Objectives: To compare the prevalence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in paediatric patients on various antiepileptic drug monotherapy and polytherapy. Materials and Methods: Children diagnosed with epilepsy as per International League Against Epilepsy definition aged 5-15 years on antiepileptic monotherapy or polytherapy for at least 1 year were recruited into the study from the Pediatric Epilepsy Clinic of a tertiary centre. After clinical and anthropometric evaluation (including body mass index [BMI] and waist circumference), the blood samples were analyzed for fasting blood glucose, fasting lipid profile, Insulin and LFT. USG abdomen was done to look for fatty liver. The results were compared between various individual drugs as well as monotherapy and polytherapy. Results: Total of 50 patients (25 monotherapy and 25 polytherapy) were recruited into the study. The baseline characteristics were comparable. Though blood glucose, insulin resistance and lipid profile did not vary between 2 groups, 3 patients on polytherapy group were found to have fatty liver (P = 0.037). Among individual drugs, oxcarbamazepine and sodium valproate were shown to have a significantly higher blood glucose values and insulin resistance. Conclusion: The study showed patients on long term antiepileptics did not vary in their metabolic profile depending on monotherapy or polytherapy except for the incidence of fatty liver. However, some of the antiepileptic drugs like sodium valproate and oxcarbamazepine have been found to have poor metabolic profile compared to other drugs on paediatric patients, which needs further larger studies to confirm the effect.

   Does insulin resistance precede the onset of diabetesin euglycemic subjects with tropical calcific pancreatitis? A “pancreatic-clamp” study from India Top

Praveen Gangadhara, Riddhi Das Gupta, S. Shajith Anoop, Roshna Ramachandran, Anneka Wikramanayake1, Eric Frenzy1, Roshan Livingstone2, Joe Fleming3, Meredith Hawkins1, Nihal Thomas

Departments of Endocrinology, Diabetes and Metabolism, 2Radiology and 3Biochemistry, Christian Medical College, Vellore, Tamil Nadu, India, 1Einstein Diabetes Institute, Albert Einstein College of Medicine, New York, USA.

E-mail: [email protected]

Background and Hypothesis: Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non-alcoholic pancreatitis, seen in the developing countries of the tropical world. Though insulin secretion defects are well-known in Fibrocalculous pancreatic diabetes (FCPD) - a late stage of TCP, the metabolic milieu of TCP remains unexplored.Our study aimed to detect any changes in insulin sensitivity, insulin secretion and body fat composition that presage the onset of diabetes in TCP. Methodology: In this cross-sectional study over a period of 2 years (2015-2017), a total of 35 age and bmi matched males including 20 TCP subjects (Mean age: 31.4 ± 7.5 years, Mean BMI: 20.5 ± 3.1 kg/m2), 15 non-diabetics (Mean-age: 30. ± 8.2 years, BMI: 19.1 ± 2.2 kg/m2) were included. Insulin secretion was assessed by C-peptide deconvolution techniques after a mixed meal challenge test. Peripheral and hepatic insulin sensitivity was analyzed through “Euglycemic-Hyperinsulinemic pancreatic clamp” procedures. Body composition analyses were measured using DEXA. SPINK1 gene mutations were screened using Next generation sequencing. Resting energy expenditure was measured using Indirect Calorimetry. 1H-Nuclear-magnetic-resonance-spectroscopy was performed to assess hepatic, intra-and extra-myocellular lipid distribution. Results: The insulin and glucagon secretion rate was higher in the TCP group (1186 ± 448 pmol/kg) and (11853 ± 4002 pmol/kg) as compared to non-diabetic (984 ± 245 pmol/kg) and (8222 ± 2037 pmol/kg) respectively.In the TCP group hepatic insulin resistance was significantly higher (P < 0.001) than non-diabetics while peripheral insulin sensitivity showed no significant difference between the groups (P = 0.1). Resting Energy expenditure was significantly higher (P = 0.03) in TCP subjects as compared to non-diabetic. Significantly increased total and truncal fat percentage (P < 0.001) were also seen in the TCP group. Hepatic, intra myocellular fat was higher in TCP group when compared to the non-diabetic group. 5 out of 15 TCP patients positive for SPINK1 gene mutations. Conclusion: Our study, using the first of its' kind “pancreatic clamp techniques” in the world, suggests that increased hepatic insulin resistance, increased adiposity and altered energy expenditure precedes the onset of diabetes mellitus in TCP. Given the subsequent complexities in managing pancreatic diabetes, our findings can have significant therapeutic implications.

   Effect of high dose Vitamin D supplementation on beta cell function in obese asian-indian children and adolescents, aged 11-17 years: A randomized, double blind, active controlled study Top

Shweta Varshney, Rajesh Khadgawat, Monita Gahlot1, Ashok Jaryal2, Nandita Gupta, V. Sreenivas3

Departments of Endocrinology and Metabolism, 1Dietetics, 2Physiology and 3Biostatistics, All India Institute of Medical Sciences, New Delhi, India.

E-mail: [email protected]

Background: Vitamin D deficiency has been found to be associated with insulin resistance. Objective: Study was planned to investigate the effects of high dose vitamin D supplementation on beta cell function and cardiovascular risk factors in Asian-Indian obese children and adolescents. Methods: A randomized, double blind, active-controlled study, was carried out to investigate the effects of high dose (120,000 IU) vitamin D supplementation in comparison to daily requirement dose (12000 IU) for 12 months, given orally as once a month single. Beta cell functions were assessed by disposition index which was measured at baseline and after 12 months of intervention. As secondary outcomes, inflammatory cytokines (serum IL-6, TNF-α and hsCRP) and cardiovascular risk factors (lipid profile, aortic pulse wave velocity and radial pulse augmentation index) were also assessed before and after supplementation. Results: A total of 189 obese children and adolescents were recruited. The mean serum 25 hydroxy vitamin D evel (S.25OHD) of the study population was 8.68 ± 5.51 ng/ml. At baseline, 94.7% subjects were vitamin D deficient (<20 ng/mL). After 12 months of supplementation, S.25OHD level in intervention group was 26.89 ± 12.23 ng/mL while in control group, it was 14 ± 4.67 ng/mL (P < 0.001). No significant difference in disposition index as well as other parameters of insulin resistance and sensitivity was seen after supplementation. Similarly, no significant difference in BMI, HbA1c, fasting blood glucose, lipid profile, inflammatory cytokines and pulse wave velocity were observed between the two groups after supplementation. Conclusion: Supplementation with vitamin D in doses of 120,000 IU per month for 12 months in obese Asian-Indian children and adolescents did not affect beta cell function as well as cardiovascular risk factors.


Study was funded by Indian Council of Medical Research (ICMR).

   Performance of novel surrogate index of insulin resistance [20/(FCP × FPG)] in low and normal birth weight cohorts: A hyperinsulinemic euglycemic clamp data from South India Top

Shivendra Verma, Riddhi Das Gupta, Nihal Thomas

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Background: Asian Indians with low birth weight (LBW) have increased predisposition to insulin resistance (IR), Type 2DM and cardiovascular diseases. As Hyperinsulinaemic-Euglycaemic clamp (HEC) studies are highly technical, surrogate measures of insulin resistance are widely used. However, data lacks on such indices of IR in birth weight based cohorts of healthy Asian Indians. Aims: The study aimed to evaluate predictive accuracy of established surrogate measures of insulin resistance like Homeostasis model assessment for insulin resistance (HOMA–IR), Fasting glucose/insulin ratio (FG-IR), Quantitative insulin sensitivity check index (QUICKI) and the novel 20/fasting C-peptide X fasting plasma glucose [20/(FCP × FPG)] index in comparison to M value derived from HEC studies in two birth weight based cohorts of healthy Asian Indian males. Methods: 122 unrelated men aged between 18-22 years, born of LBW (n = 60, birth weight <2.5 kgs) or normal birth weight (n = 62, birth weight >2.5 kgs) were recruited and HEC studies were performed. Surrogate measures of IR were derived and data were analysed by Spearman's correlation test and Random calibration model (RMSE) analysis. Results: In LBW cohort, the 20/(FCP × FPG) index and FGIR, showed a significant correlation with HEC derived M-values, while RMSE analysis showed better predictive accuracy for QUICKI and 20/(FCP × FPG) index. Contrastingly, in normal birth weight cohort, HOMA-IR and FGIR showed better predictive accuracy on RMSE analysis when compared with other surrogate indices of insulin resistance. Conclusion: Our study highlights for the first time, the difference in performance of established surrogate indices of IR when compared to HEC studies, in LBW and normal birth weight cohorts of Asian Indian males. The better performance of the novel 20/(FCP × FPG) index in LBW cohort could probably due to hepatic insulin resistance in these individuals. This underscores the need to develop novel surrogate indices based on the birth weight in Asian Indians.

   Clinical profile of rheumatological manifestations in type 2 diabetes mellitus Top

Gaurang Sudhir Deshpande, Girish Muthhadotti

Department of General Medicine, KMC, Mangalore, Karnataka, India.

E-mail: [email protected]

Objectives: (1) To estimate the proportion of rheumatological manifestations in DM type 2 patients. (2) To correlate the occurrenceof various rheumatological manifestations in DM type 2 patients in relation to age, sex, disease, duration of disease, glycemic control (HbA1c), and type of treatment. Materials and Methods: This is a Cross sectional study conducted among Type 2 diabetes mellitus patients attending the constituent hospitals attached to Kasturba medical college, Mangalore from September 2015 to July 2017. After informed consent, 333 diabetics were examined and patient characteristics like age, sex, duration of diabetes, glycemic control, BMI, smoking history and type of treatment were recorded. Patients with known musculoskeletal disorders, renal osteodystrophy, collagen vascular disorders, joint diseases and pregnant women were excluded. The occurrence of the rheumatological conditions like Dupuytren's contracture, frozen shoulder, carpal tunnel syndrome, flexor tenosynovitis, cheiroarthropathy were identified with help of clinical examination and relevant imaging. The correlation between rheumatological manifestations and these variables were analysed using logistic regression. Results: 142 (42.6%) out of 333 patients found to have the rheumatological manifestations. Prevalence of complications observed: Dupuytrens contracture (5.1%), Frozen Shoulder (13.5%), Cheiroarthropathy (10.2%), Carpal tunnel syndrome (9.6%), Flexor tenosynovitis (4.2%). Among the variables BMI (odds ratio 6.56), Duration of diabetes (odds ratio 4.12) are common risk factors. Poor glycemic control also associated with increased risk of occurrence of rheumatological complications. Conclusion: Occurrence of Rheumatologic manifestations is very common in diabetes mellitus Type 2 and these manifestations have significant correlation with poor glycemic control, BMI, duration of diabetes. This suggests that routine careful examination of musculoskeletal system in diabetic patients is very important.

   Prevalence and severity of periodontal disease in type 2 diabetes mellitus (noninsulin dependent diabetes mellitus) patients in Coimbatore city: An epidermiological study Top

P. Asha, Suresh Damodharan1

Department of Periodontics, Sri Ramakrishna Dental College and Hospital, 1Department of Diabetology, Sri Ramakrishna Hospital, Coimbatore, Tamil Nadu, India.

E-mail: [email protected]

Aim: The purpose of the study was to assess the prevalence and severity of periodontal disease in type 2 diabetes mellitus (DM) patients in Coimbatore city and to compare the findings with non-diabetic patients and to compare the periodontal status among well-controlled, moderately-controlled, poorly-controlled diabetic patients with the possible influence of other factors such as age, sex, oral hygiene habits, personal habits, duration of diabetes, and Glycated hemoglobin as contributory risk elements for periodontal disease. Materials and Method: The study involved 400 type 2 diabetic patients (Study Group) and 100 non diabetic patients (Control Group) among the age group of 35-75 years were included in the study. The study group was divided based on Glycated hemoglobin levels into well, moderately and poorly controlled. Relevant information regarding age, oral hygiene habits and personal habits was obtained from the patients. Oral examination was done using Community Periodontal Index (CPI) and Plaque Index (PlI).The statistical analysis was calculated by using multivariate logistic regression analysis for multiple comparisons. Results: The mean CPI score and the number of missing teeth was higher in diabetics compared with non diabetics, and was statistically significant (P < 0.05), indicating that prevalence and extent of periodontal disease was more frequent and more severe in diabetic patients. The risk factors like Glycated hemoglobin, duration of diabetes showed a positive correlation with periodontal destruction, according to the multiple regression analysis. The association between duration of diabetes with prevalence of periodontal disease according to CPI was 55.6% (CPI code3) which showed a significant value (P < 0.05) as duration of diabetes increases (i.e., >10 years). There was a positive correlation between age and prevalence of periodontal disease in diabetic patients with a significant rise in p- value (P < 0.05). The prevalence and severity of periodontal disease was higher (61%) in diabetic patients compared with non diabetics The odds ratio of a diabetic showing periodontal destruction in comparison with a non diabetic was 0.259, 3.283 and 2.329 (95% CI) in well, moderately and poorly controlled diabetics, respectively. Conclusion: The present study made an attempt to determine the association between type 2 DM and periodontal disease in Coimbatore city. It was found that type 2 diabetes mellitus subjects manifested relatively higher prevalence and severity of periodontal disease as compared with non diabetics.

   Supplemental DHA on a n-6 PUFA diet lowers oxidative stress but cannot protect against cell death in STZ-diabetic rat hearts Top

Sanjoy Ghosh, Jiayu Ye, Deanna Gibson

Department of Biology, IKBSAS, University of British Columbia, Okanagan, Canada.

E-mail: [email protected]

Objective: The recent surge in diabetes and cardiovascular diseases worldwide including India correlates with a dietary shift from a traditional fats towards more n-6 polyunsaturated fatty acid (n-6 PUFA) -based vegetable oils, leading to the current, high dietary n-6: n-3 PUFA ratio. Here, we evaluated the cardiac effects of high n-6 PUFA in diabetic rats and hypothesized a protective role of supplemental docosahexaenoic acid (DHA), a n-3 PUFA by normalizing the n-6: n-3 PUFA ratio. Materials and Methods: 2 month-old, male Sprague-Dawley rats were fed one of three isocaloric, diets (16.5% of energy from fats) made from canola (C, balanced n-6/n-3 PUFA), safflower (S, high n-6 PUFA) and safflower oil supplemented with DHA for 4 weeks, following which a subset of these rats were made diabetic with streptozotocin for a week and then sacrificed. Hearts were isolated for various genetic, biochemical and histological analyses. Results: Cardiac muscle in S-fed rats showed augmented cell death, superoxide generation and increased immunopositivity for 8-hydroxyguanine and 4-hydroxynonenal (DNA-oxidation and lipid peroxidation product respectively), with a lowering of GSH/GSSG ratio compared to C-fed rats. Feeding DHA promoted mitochondrial biogenesis and attenuated the above mentioned oxidative stress biomarkers. However, cell death as measured by TUNEL was unaffected and the mechanism shifted from a caspase-dependent to a endonuclease G-dependent, caspase-independent pathway. Conclusion: Our novel results show the cardiac lipotoxic potential of dietary n-6 PUFA, in the context of diabetes and supports the role of DHA in reducing oxidative damage in diabetic hearts. However supplemented DHA cannot protect from a pro-apoptotic fate, stimulated by n-6 PUFA diet and diabetes. Thus, although a high n-6 PUFA diet is detrimental, a curative approach with supplementary DHA in a high n-6 PUFA diet may be an incomplete preventative strategy and instead lowering of dietary n-6 PUFA itself is warranted.

   Bone mineral density in diabetes mellitus patients with and without chronic charcot foot: A cross sectional study Top

Preyander S. Thakur, Sandip Chindhi, K. Felix JebaSingh, Riddhi Das Gupta, Nihal Thomas, Thomas V. Paul

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: Osteoporosis has been long suggested to be associated with in the development of Charcot arthropathy. However, there is no definitive evidence to confirm the above mechanism. Hence our study was proposed to compare the bone mineral density (BMD) and bone turn over markers (BTMs) in those patients with type 2 diabetes mellitus with and without charcot foot. Materials and Methods: This was a cross sectional study done over 1 year. A total of 65 subjects were evaluated, 20 had Charcot arthropathy (Group-1), 18 had diabetes mellitus with distal peripheral neuropathy (Group-2) and 27 had diabetes without peripheral neuropathy (Group-3). Twenty eight healthy controls (Group-4) were also included. BMD at femoral neck (FN) and lumbar spine (LS) was measured using DXA scan and BTMs (P1NP and CTX) were done and compared among four groups. Results: The mean age (years) of the patients was 55.4 ± 6.9, 58.5 ± 9.2, 56.5 ± 9.3 and 57.9 ± 8.8 respectively. The mean BMI (kg/m2) was 28.4 ± 3.0, 25.7 ± 3.9, 28.2 ± 9.1, and 26.2 ± 7.6 for the study groups respectively. The mean BMD (gm/cm2) at LS (1.01 ± 0.14, 1.05 ± 0.18, 0.93 ± 0.15, 0.97 ± 0.20) and the mean BMD (gm/cm2) at FN (0.786 ± 0.12, 0.848 ± 0.13, 0.762 ± 0.13, 0.751 ± 0.16). The mean CTX (pg/ml) levels were 374.10 ± 315.03, 322.19 ± 1.02, 355.77 ± 156.35 and 514.57 ± 271.38. The mean P1NP (ng/ml) levels were 75.36 ± 48.30, 65.90 ± 23.20, 61.05 ± 21.08, 67.46 ± 31.05. The difference between these bone parameters among 4 study groups was not statistically significant. Conclusion: There was no significant difference between four groups with regards to BMD and BTMs. However, it has to be further validated in a large cohort of subjects with Charcot arthropathy.

   Hypoglycemia: A case series Top

Sunetra Mondal, Debarati Bhar, Neha Agrawal, Rana Bhattacharya, Sujoy Ghosh, Pradip Mukherjee, Satinath Mukhopadhyay, Subhankar Chowdhury

Department of Endocrinology and Metabolism, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Background: Hypoglycemia in non-diabetic adults arises from underlying causes that are often difficult to identify or localise. The following series of cases of hypoglycemia emphasizes on the need for extensive work-up in many cases since, once identified, most causes are amenable to cure. All the depicted cases satisfied Whipple's hypoglycemia triad. Hypocortisolism, renal/liver failure, sepsis, autoimmune hypoglycemia, family h/o DM; psychiatric ailment and possibility of AHA intake were excluded. For cases 1 to 3; endogenous hyperinsulinism was proven during supervised prolonged fasting. Histopathological examination in all cases confirmed benign pancreatic neuro-endocrine tumor (NET)/insulinoma. Case 1: 51 y/M obese; EUS and Triphasic-CT revealed a lesion in pancreatic head-neck junction. FNAC revealed rosettes of monomorphic cells s/o NET. The tumor was enucleated easily with resolution of hypoglycemia. Case 2: 58y/M, BMI 18. 5; Trans-abdominal sonography (TAS) and CECT abdomen-normal. EUS revealed an ill- defined hetero-echoic foci in pancreatic tail. Whole body 68Ga-DOTANOC-PET-CT failed to localize any NET. Diffusion-weighted (DW-MRI) pancreas identified a T2-hyperintense discrete SOL in pancreatic body. Intra-operatively, the tumor was well-visualised and enucleated. Case 3: 38y/M; TAS and Triphasic-CT showed no pancreatic lesion. EUS- echogenic SOL in uncinate process; FNAC s/o NET. MRI (with DWI pancreas) confirmed the lesion. However, intraoperatively, tumor couldn't be identified separately so, Whipple's pancreaticoduodenectomy was done. Case 4: 60y/M, admitted with left adrenal pheochromocytoma, h/o recurrent fasting hypoglycemia without evidence of hyperinsulinism on prolonged fasting and no insulinoma localised with Triphasic-CT/Tc99m-hynic-TOC scintigraphy. IGF-1 was low. Following resection of pheochromocytoma however, there was no further hypoglycemic episode. Conclusion: Pre-operative localization of insulinoma is known to be challenging; but the imaging modalities have varying sensitivity from case-to-case. There seems to be little correlation between pre-operative and intra-operative identification of the tumor and success of resection. Case reports of hypoglycemia due to pheochromocytoma are extremely rare but reversible following resection.

   Real-world persistence and HbA1c goal attainment in type 2 diabetes mellitus patients initiated on canagliflozin or a glucagon-like peptide-1 Top

Anil Rajani1, Michael Pfeifer2, Patrick Lefebvre3, Dominic Pilon3, Mike Ingham2, Marie-Hélène Lafeuille3, Bruno Emond3, Rhiannon Kamstra3, Carol H. Wysham4

1Janssen Medical Affairs, Mumbai, India, 2Janssen Scientific Affairs, LLC, Raritan, NJ, USA, 3Groupe d'analyse, Ltée, Montreal, QC, Canada, 4Rockwood Clinic, Spokane, WA, USA.

E-mail: [email protected]

Objectives: This study compared real-world persistence and HbA1c goal attainment in patients with type 2 diabetes mellitus (T2DM) initiated on oral canagliflozin 300 mg (CANA) versus injectable glucagon-like peptide 1 (GLP-1). Materials and Methods: Adults with T2DM newly initiated on CANA 300 mg or a GLP-1 were identified from the QuintilesIMS electronic medical records (EMRs) – US database (03/29/2012-04/30/2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. Outcomes were compared using weighted Cox models (hazard ratios [HRs] and confidence intervals [CIs]) and Kaplan Meier curves and included time to: HbA1c <8%, discontinuation (gap >90 days), add/switch to a new antihyperglycaemic agent (AHA), and the composite of failure to maintain HbA1c <8% or add/switch to a new AHA. Attaining an HbA1c goal of <8% was evaluated among patients with baseline HbA1c ≥8%. Failure to maintain HbA1c <8% was evaluated among patients starting at HbA1c <8% (from index) or reaching HbA1c <8% (from first day below). Results: 11,435 CANA and 11,582 GLP-1 patients (62.6% liraglutide) formed the weighted study cohorts, with well-balanced baseline characteristics and HbA1c. Time to HbA1c <8% was comparable (HR [95% CI]: 0.98 [0.91, 1.06]; P = 0.642) as was failure to maintain HbA1c <8% (HR: 1.00 [0.90, 1.11]; P = 0.988). CANA patients were 30% less likely to discontinue than GLP-1 patients (HR [95% CI]: 0.70 [0.66, 0.74]; P < 0.001; median time to discontinuation 12.4 vs. 8.6 months) and were 28% less likely to add/switch to a new AHA (HR: 0.72 [0.68, 0.77]; P < 0.001; median 21.3 vs. 15.1 months). CANA patients were 17% less likely to either fail to maintain HbA1c <8% or add/switch to a new AHA (HR [95% CI]: 0.83 [0.77, 0.90]; P < 0.001; median 15.4 vs. 12.6 months). Conclusion: Reaching and maintaining HbA1c below 8% was comparable between CANA and GLP-1 patients; however, fewer CANA patients required the addition/switch to a new AHA vs. GLP-1 patients.


This study was supported by Janssen Scientific Affairs, LLC. Technical editorial support was provided by Shannon O'Sullivan, ELS, of MedErgy, and was funded by Janssen Scientific Affairs, LLC.

Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation.

Conflicts of interest

This study was funded by Janssen Scientific Affairs, LLC. BE, MHL, DP, PL, and RK are employees of Analysis Group, Inc., a consulting company that has received research grants from Janssen Scientific Affairs, LLC to conduct this study. AR is an employee of Janssen Medical Affairs, Mumbai, India. MP and MI are employees and stockholders of Janssen Scientific Affairs, LLC. CW is a paid consultant for Astra Zeneca, Boehringer Ingelheim, Janssen Scientific Affairs, LLC, Novo Nordisk, and Sanofi, and is on the speaker's bureau for Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Insulet, Janssen Scientific Affairs, LLC, Novo Nordisk, Sanofi.

   Patient empowerment through family centered structured education improves metabolic outcomes in type 1 diabetes mellitus Top

Hesarghatta Shyamasunder Asha, D. M. Mahesh, Riddhi Das Gupta, Jambugulam Mohan1, Felix Jebasingh, Mercy Inbakumari, Flory Christina, A. Vijayalakshmi, G. Jayalakshmi, Dukhabandhu Naik, Thomas Vizhalil Paul, Nihal Thomas

Departments of Endocrinology, Diabetes and Metabolism and 1Medicine, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objective: The management of type 1 diabetes mellitus (TIDM) is challenging, and significantly different from type 2 diabetes. We assessed the impact of a structured diabetes self management education (DSME) program on metabolic outcomes in people with T1DM. Methods: A multidisciplinary team approach was adapted to deliver structured diabetes education (once in 4-8 weeks) to subjects with T1DM from June 2012 to December 2014. This involved didactic lectures and group education (12 sessions) incorporating strategies to address the diabetes AADE7 (American Association of Diabetes Educators) self-care behavior measures (viz., being active, healthy eating, regular monitoring, taking medication, healthy coping, problem solving and reducing risks). Family centered support group meetings were conducted to address their social, psychological, and practical support needs. We assessed clinical improvement in terms of serial HbA1C measurements, episodes of hypoglycemia and diabetic ketoacidosis (DKA). SPSS version 16 was used for statistical analysis. Results: In this study period of two and half years, 117 subjects with T1DM received structured education. The mean age was 24.9 (±6.9) years with 67 male and 50 female subjects. The mean duration of diabetes was 10.3 (±7) years. The average HbA1c of these subjects declined from 9.4% (±2.4%) before the DSME to 8.3% (±2.1%) in 2014 (P = 0.001), and further to 7.9 (±1.3%) in 2016 (P = 0.001). The episodes of diabetic ketoacidosis decreased from 22 to 8 episodes after implementation of structured education; with no significant difference in the number of hypoglycemic episodes. Conclusion: Patient empowerment through structured education to individuals with T1DM and their family improved self-care behaviors, resulting in improvement of the metabolic parameters.

   Evaluation of hypogonadism and effect of clomiphene citrate treatment in male patients with type 2 diabetes mellitus Top

Jitendra Chouhan, Surya Kumar Singh

Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: The association of Type 2 Diabetes Mellitus (T2DM) and hypogonadism is highly prevalent. To study the hypogonadism in male patients with T2DM and evaluate the effect of Clomiphene citrate (CC) treatment based on both symptoms (ADAM) and biochemical measures (serum total testosterone and Luteinizing hormone level). Materials and Methods: The study included 25 T2DM patients with symptomatic hypogonadism (screening by ADAM questionnaire) and low and low normal serum testosterone level attending University hospital. The subjects with serum testosterone ranges 8-12 nmol/l (200-350 ng/dl) and with serum LH level range ≤6 IU/ml were treated with CC 25 mg/day. The post treatment hormone estimation along with ADAM questionnaire value was evaluated 3 month after commencing treatment. Serum testosterone and LH level of all the patients were measured by chemiluminescence immunoassay (Beckman Coultor, USA). Data were expressed as mean ± SD and student t-test was used to compare the pre and post mean values of biochemical parameters. Results: The mean age of all the study subjects was 47.9 ± 6.64 which ranged from 40-70 years. The significant difference was observed in term of symptom score (ADAM) at baseline and during follow up from 7.52 ± 1.35 to 2.68 ± 0.90 (P < 001). There was also significant difference in the mean values of total testosterone 270.48 ± 45.23 ng/dl to 550.16 ± 85.05 ng/dl with P value <0.001 and LH levels 4.49 ± 1.17 mIU/ml to 7.49 ± 1.60 mIU/ml with P value <0.001. No adverse event was reported in any of the study subjects. Conclusion: In this study we found that treatment with clomiphene citrate in appropriate patients with hypogonadism and T2DM shows improvement in both clinical (ADAM) and biochemical measures. Clomiphene citrate might be considered as an alternative treatment strategies in secondary hypogonadism.

   Does dapsone therapy influence HbA1C levels: The first identified single centre cohort in patients with Hansen's disease and type 2 diabetes mellitus Top

S. Basavaraj, Bhavesh N. Patel, Dincy Peter1, Anu Anna George1, Riddhi Das Gupta, Thomas Vizhalil Paul, Nihal Thomas

Departments of Endocrinology, Diabetes and Metabolism and 1Dermatology, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: To assess the prevalence of Dapsone associated inappropriate lowering of HbA1C and evaluate the clinical and biochemical characteristics of this cohort. Materials and Methods: A retrospective data review of outpatient and inpatient charts of consecutive patients with Hansen's disease and Diabetes Mellitus following up with Department of Endocrinology and Department of Dermatology, at Christian Medical College Vellore, was done over a period of two years from January 2014 to January 2016. Results: Out of the total 245 diabetic patients screened with a confirmed diagnosis of Hansen's disease, on Dapsone (100 mg/day), 49 were eligible for the study as per inclusion criteria. Among these, 35 (71%) patients had a low HbA1C discordant with corresponding plasma glucose and estimated average glucose values (eAG) while the remaining14 (29%) had HbA1C concordant with the plasma glucose and eAG. On comparison, those in the discordant group had a significantly higher number of males and higher RBC Mean corpuscular volume (MCV), the latter finding pointing towards a possible hemolytic mechanism. Further, influence of Dapsone on HbA1C was most pronounced in the initial 3 months of therapy, which is traditionally the period of maximal hemolytic effect of Dapsone. G6PD levels were negative in all subjects. Conclusions: We report the first and largest cohort describing a significant prevalence and possible hemolytic mechanism leading to Dapsone induced inappropriate HbA1C lowering in diabetic patients with Hansen's disease.

   Descriptive study in diabetic patients attending diabetic clinic at District General Hospital Ampara Sri Lanka Top

Nirosha Madhuwanthi Hettiarachchi, Nikujani Widisinghe1

Teaching Hospital, Peradeniya, 1General Hospital, Negambo, Sri Lanka.

E-mail: [email protected]

Introduction: Diabetes mellitus, has reached epidemic proportions globally. The rise in the prevalence in rural communities leads to an increase in number of patients seeking treatment in hospitals. Objectives: To assess the social demographic data, associated risk factors, patient characteristics, complications of the disease, and hospital admissions in patients attending a Diabetes Clinic in General Hospital Ampara. Materials and Methods: Data was collected using a questionnaire filled by an investigator through direct questioning in 100 randomly selected patients from the (VP/OPD) Diabetic Clinic held on 4/10/2013. Results: Mean age of the sample was 55.3 (SD 11.3) Out of 100 patients 77% were females. Males were 23%. 59% were housewives, while farmers and manual labourers were 15% and 4% respectively. 72% lead a sedentary lifestyle. Only 24% was educated up to O/Ls. Mean BMI was 23.8 (SD-3), but 31% were overweigh or obese. Age at diagnosis in a majority was 41-50 yrs (36%) Mean age was 49.2 years. Mean years of follow up was 4. Majority (91%) commenced treatment as soon as the diagnosis was made. 41% had been followed up for more than 5 years. At the diagnosis 46% had no other co-morbidities, 10% had hypertension (HT), 14% had dyslipidaemia and 4% had IHD, HT and dyslipidaemia. First degree relatives with diabetes were 49%, 46% had no family history. 36% were on oral monotherapy while 51% were on oral drug combination. Insulin was used by 6% while 7% were on insulin and oral medication. Compliance was good in 85%. Medical nutrition therapy was followed by 64%. 5% was hospitalized for hypoglycemia and 19% were admitted for hyperglycemia. 4% had developed retinopathy as well as nephropathy. 22% had neuropathy. Conclusion: Diabetes was common in females with sedentary life style. 1/3rd of patients had a BMI of >25. Most were diagnosed during their forties. Majority had no family history. Initiation of treatment was excellent. Disease complications and hospital admissions due to complications of drug treatment were few.

   Large, multicentre, prospective, observational study to understand usage and effect of saxagliptin as first add-on after metformin in indiAn T2DM patients Top

Sanjay Kalra, Sarita Bajaj1, A G Unnikrishnan2, Manash P Baruah3, Rakesh Sahay4, Hardik V5, Amit Kumar5

Department of Endocrinology, Bharti Research Institute of Diabetes and Endocrinology, Karnal, Haryana, 1Moti Lal Nehru Medical College, Allahabad, Uttar Pradesh, 2Chellaram Diabetes Institute, Pune, Maharashtra, 3Excel Center, Guwahati, Assam, 4Osmania General Hospital, Hyderabad, Telangana, 5AstraZeneca Pharma India Ltd., Bengaluru, Karnataka, India.

E-mail: [email protected]

Aims and Objective: The aim of this multicentre observational study was to understand the usage and effect of saxagliptin on HbA1c reduction as first add on after metformin in Indian patients. The study also assessed effect side effects, hypoglycaemia and changes in quality of life scores. Methodology: A total of 1109 participants were enrolled from 50 centres and each participant was followed up for 3 months. Participants with T2DM not controlled on metformin monotherapy and prescribed with saxagliptin as add on therapy in past 15 days were enrolled in this study. Results and Conclusions: A total of 1109 participants (658 men and 451 women) with mean age of 51.17 ± 11.85 years were enrolled from 50 centres throughout India. Mean change of -0.86% was observed in HbA1c from baseline to end of study (P < 0.0001). The quality of life assessed by WHOQOL-BREF questionnaire was reported to be “good” (44.5% to 49.8%) or “neither good nor bad” (39.7% to 39.2%) by majority of the participants at baseline and after 3 months of treatment, respectively. A total of 15 AEs and no SAEs occurred during the study. All AEs were of mild intensity and did not require intervention. Overall, saxagliptin addition to ongoing metformin therapy significantly reduced the HbA1c levels and is effective for better glycaemic control with lesser side-effects of hypoglycaemia and weight gain. This combination was generally well-tolerated in Indian T2DM patients, with no new or unexpected safety events identified.

   A prospective study on clinical characteristics, beta-cell dysfunction and treatment outcomes in the first identified Indian cohort Top

Riddhi Das Gupta, Roshna Ramachandran, Praveen Gangadhara, Shajith Anoop, Surjitkumar H. Singh, Anil Satyaraddi, Samantha Sathyakumar, Hesarghatta Shyamasunder Asha, Nihal Thomas

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: Ketosis-prone diabetes (KPD), an atypical form of diabetes, has emerged as a heterogeneous syndrome in multiple ethnic groups. The A−β+ subset of KPD has been alternatively referred to as 'Flatbush Diabetes'. The objectives of this study were to look into the clinical characteristics of adult Asian Indian patients with recently diagnosed, antibody negative diabetes presenting with unprovoked ketoacidosis (A−β+ KPD) and to determine the natural course of recovery of beta-cell functions on serial follow-up over one year. Materials and Methods: Newly diagnosed adult diabetes patients (n = 11) with suspected KPD (A−β+) were prospectively studied over a period of 1-year with serial evaluations of clinical, biochemical and beta-cell secretion characteristics. These were compared with a control group (n = 23) of Type 1A diabetes (KPD A+β−) with similar presentation. Beta-cell secretion was assessed by fasting and stimulated 90-minute C-peptide values after a standard mixed meal challenge at baseline and then at 3, 6 and 12 months follow-up. Glycemic control and treatment outcomes were also documented. Results: In comparison to the A+β− KPD controls, the A−β+ KPD patients had a significantly older age (P = 0.001), higher BMI (P = 0.01), stronger family history of type 2 diabetes (P = 0.02), more severe ketoacidosis (P = 0.01) and higher fasting and stimulated C-peptide level at presentation (P < 0.01). On serial follow-up, the patients with KPD achieved complete recovery of their beta-cell function with remission from insulin-dependence within 93 ± 4.5 days without further recurrences of DKA. Conclusions: This is the first reported series of Flatbush Diabetes (A−β+ KPD) from India. The phenotype of Indian A−β+ KPD patients differs from their Western counterparts in that they are relatively younger and leaner, though the male preponderance and natural history of recovery of beta-cell dysfunction bears similarity. Does Aβ+ketosis-prone diabetes (flatbush diabetes) exist in India?

   Psychological evaluation with diabetes distress scale in Indians with type 2 diabetes Top

Madhukar Mittal, Pratishtha Mishra, Deepa Kulkarni, Nikha Sharma, Babita Bharti, Aparna Shukla

Department of Endocrinology, King George's Medical University, Lucknow, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: The world's second largest population of diabetics is in India. Psychological issues like depression and diabetes-related distress have not been systematically investigated in Indians with type 2 diabetes (T2D). We sought to evaluate the amount of diabetes-related distress in T2D patients. Materials and Methods: We included 364 patients with T2D attending Diabetes OPD. Diabetes Distress Scale was used to assess total diabetes distress and subscales (emotional distress, interpersonal distress, regimen-related distress, physician distress). This scale is well validated and has been used in South Asians in Canada. Initially 2-item screener and then full 17-point DDS questionnaire was administered. Results: 135 of 364 T2D patients had a score of 3 or more in initial screener who were then administered the full DDS17. Of the 135 patients included, 53 (39%) were females. The rate of emotional burden and regimen related distress was seen in 81 (60.0%) and 34 (25.2%) patients respectively. 14 (10.4%) patients had physician related distress and 22 (16.3%) patients had interpersonal distress. Overall 50 (37.0%) patients had no distress. On grading, moderate distress was seen in 58 (43.0%) patients and high distress in 27 (20.0%). 31 (37.8%) males and 27 (50.9%) females had moderate distress while high distress was seen in 16 (20.7%) males and 11 (19.7%) females. Emotional burden was seen in 45 (54.8%) males and in 36 (67.9%) females. Regimen related distress was similar in both males and females 19 (23.1%) and 15 (28.3%) respectively. Physician related distress was seen in 7 (8.5%) males and in 7 (13.2%) females. Interpersonal distress was present in 11 (13.4%) males and in 11 (20.7%) females. Conclusion: Our data shows that diabetes-related distress is a serious concern for Indians with T2D. Emotional burden and Regimen-related burden were predominant. Females had greater moderate distress and Emotional burden. Studies recruiting a larger sample from diverse regions of India should be conducted for better understanding the psychological issues that may impact diabetes management.

   A descriptive study on causes of hypoglycemia, knowledge and awareness of hypoglycemia in a diabetic population admitted to a tertiary care hospital with a hypoglycemic episode Top

Dayakshi Abeyaratne1, B. G. A Rathnamali2, Chathuranga Lakmal Fonseka3,4, Chathuri Liyanapathirana2, Maathuri Sivapalan2, Piumi Hettiarachchi1, Sanjeewa Wijekoon2,5

1Diabetes and Endocrinology Unit, National Hospital of Sri Lanka, Colombo, 2University Medical Unit, Colombo South Teaching Hospital, Dehiwala-Mount Lavinia, 3University Medical Unit, Teaching Hospital Karapitiya, Galle, 4Department of Medicine, University of Ruhuna, Matara, 5Department of Medicine, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.

E-mail: [email protected]

Introduction: Hypoglycemia had become an important complication globally, especially when meeting current diabetic goals with multiple drugs. Finding out gaps in patient's knowledge about hypoglycemia is important to plan a strategy to prevent this serious complication. Objectives: To assess the common causes of hypoglycemia in diabetic patients and to assess knowledge, awareness and practices about hypoglycemia in patients admitted with a hypoglycemic episode. Methodology: Patients admitted with documented or severe hypoglycemia to medical wards of a Tertiary care Hospital in Sri Lanka over 6 months period were recruited. Data was collected using an interviewer based questionnaire. Results: 60 patients were admitted with hypoglycemia during the study period. 57% were Males. 85% were older than 50 years. 65% had diabetes for >5 years with Macro-vascular (76%) and micro-vascular (92%) complications. 21% had at least one previous attack. 42% were on insulin. Blood glucose level on admission was <50 g/dl in majority (71%). Commonest symptoms of current episode were loss of consciousness (82%), confusion (18%) while most had associated other symptoms such as sweating (43%) and oral numbness (5%). 77% were previously educated thoroughly on hypoglycemia. some patients correctly identified altered consciousness (70%), confusion (40%), sweating (61%) and palpitations (22%) as symptoms of hypoglycemia. 88% knew how to manage a minor hypoglycemic episode. The common causes for hypoglycemia were missing a meal while on insulin (75%), renal impairment (20%), and alteration of drugs (5%). only 32% owned a glucometer. Conclusions: Patients on insulin as well as oral drugs, should be educated on common hypoglycemic symptoms to enable early identification and treatment to prevent neuroglycopenia. Importance of taking regular meals should be emphasized.

   Autoimmunity and endocrine dysfunction in type 1 dm Top

Rajeev Philip, Sarojiniyamma Cheradiyil Sivaramannair1, Cherian Jacob1, C. S. Abdul Kadar1, Keshavan Charamelsankaran1, R. N. Sharma1

Departments of Endocrinology and 1Medicine, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Background: Type 1 diabetes is divided into antibody positive 1a diabetes and antibody negative 1b diabetes. As per literature, majority of the Indian type 1 diabetic patients are 1b, as compared to the western population. The Commonest autoimmune disorders associated with Type 1DM are Autoimmune thyroid disease and celiac disease. Aims and Objectives: (1) To study the autoimmune antibody profile of type 1 diabetic patients. (2) To study the prevalence of other autoimmune disorders in type 1 diabetics. Materials and Methods: All the patients with the clinical diagnosis of Type 1 diabetes who attended the OPD or got admitted in the wards of Pushpagiri Medical College, Kerala were included in the study. A total of 120 patients were studied. The period of the study was from January 2014 to July 2017. All patients underwent screening for auto antibodies- GAD 65 and IA2 as well as thyroid dysfunction and thyroid auto antibodies,(TSH and Anti TPO antibodies), and Anti TTG antibody estimation was done in all patients to screen for celiac disease. In clinically indicated patients, a ACTH stimulated cortisol levels, FSH, LH and testosterone or estrogen levels were done to diagnose other autoimmune endocrine disorders. Results: Majority of the patients were antibody positive Type 1 A diabetes 71.6% (86/120), out of which GAD positivity was seen in 81.3% of the positive cases (70/86) IA2 was positive in 45.3% cases (39/86). Both were positive in 31.3% (27/86). The average age of presentation was 12.2 ± 2.8 years. On screening for other autoimmune disorders associated, Anti TPO Positivity was found in 45/120 (37.5%), Elevated S.TSH in 14/120 (11.6%), Anti TTG positivity in 2/120 (1.6%) and 1 patient (1%) had primary ovarian failure. No patients had clinical features or investigations suggestive of adrenal failure. Conclusions: Our study population is predominantly autoantibodies positive (1A), which is similar to the Caucasian population.This is contrary to what literature states, that majority of the Indian type 1diabetic patients are antibody negative (1b), as compared to the western population. Early screening for autoantibodies in work up of Type 1DM can aid in its diagnosis as well as associated disorders and predict future risk of development of other autoimmune disorders. Thyroid disease still remains the most common autoimmune disorder in Type 1 DM. The incidence of celiac disease in the population studied is lesser than what is described in literature.

   Correlation between acanthosis nigricans neck severity scoring with insulin resistance and parameters of metabolic syndrome Top

M. S. Gokul, Philip Rajeev1, Cherian Jacob, C. S. Abdul Kadar, R. N. Keshavan Charamelsankaran Sharma

Departments of Medicine and 1Endocrinology, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: Acanthosis nigricans, the velvety pigmentation of neck, axilla, knuckles and other surfaces is seen in obesity, diabetes, malignancies, drugs, pineal tumors, and other endocrine disorders. It is considered a cutaneous marker of tissue insulin resistance. Aims and Objectives: To determine the prevalence of acanthosis nigricans in type 2 diabetes mellitus and its correlation of acanthosis neck grading with various anthropometric measurements BMI, waist circumference, waist hip ratio and insulin resistance by HOMA-IR and other metabolic parameters. Materials and Methods: One hundred consecutive subjects (50 males and 50 females) with newly diagnosed type 2 DM, attending the endocrinology/medicine OPD of Pushpagiri medical college were studied. Acanthosis was graded based on standard scale of 0-4 (0: Not visible, grade 1 Present: clearly present on close visual inspection, not visible to the casual observer, extent not measurable. grade 2, Mild: limited to the base of the skull, does not extend to the lateral margin of the neck, grade 3: extending to the lateral margins, not visible from the front, and grade 4: extending anteriorly). Anthropometric data were obtained and insulin resistance calculated as HOMA-IR from fasting insulin and fasting blood sugar values. Other parameters of metabolic syndrome and obesity- HDL, Triglycerides, Uric acid levels were estimated. Results: The average age of the study population was 42.5 years, with male to female ratio of 0.81 The prevalence of acanthosis in males was 53.2% and in females was 76.6%. The acanthosis neck severity grading had a statistically significant correlation with fasting glucose levels, fasting insulin levels, and insulin resistance values calculated by HOMA-IR (P < 0.05). Acanthosis severity scoring had statistically significant correlation with triglyceride values, and uric acid levels. The correlation showed a trend towards significance with waist circumference, but not with BMI. Conclusion: Acanthosis nigricans neck severity grading correlates well with insulin resistance and can be used as a clinical surrogate for assessment of severity of insulin resistance.

   Association of ALR gene polymorphism with increased activity of aldose reductase enzyme and subsequent inhibition by AR inhibitor in patients with diabetic neuropathy Top

Balram Gupta, Surya Kumar Singh

Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: Aldose reductase (ALR) is a first and rate limiting enzyme of the polyol pathway, catalyzes reduction of glucose to sorbitol. Our previous study suggested the role of ALR gene polymorphism (-106C>T) in association of peripheral neuropathy in type 2 diabetes mellitus. The aim of this study was to detect ALR activity and sorbitol level at baseline and 6 months of follow up after treatment of aldose reductase inhibitor (ARI) (Epalrestat 150 mg once daily) in patients with type 2 diabetes mellitus with peripheral neuropathy proved to be C-106T polymorphism of ALR gene. Materials and Methods: The study subjects were divided in to two groups. Group I included 356 patients with Diabetes having peripheral neuropathy and Group II included 294 patients with Diabetes without neuropathy. ALR activity, sorbitol levels and hemoglobin levels were determined by spectrophotometrically, ELISA and high-performance liquid chromatography (HPLC) respectively. The data were expressed as mean ± standard deviation and compared by one-way ANOVA. A P value <0.05 were considered to be significant. Results: The mean age of Group I and Group II was 51.63 ± 10.03 and 55.0 ± 8.74 years respectively with no statistical difference (P = 0.316). A significantly increased ALR activity was observed in group I as compared to group II at baseline (6.54 ± 4.38 Unit/g-Hb vs 3.98 ± 2.36 Unit/g-Hb respectively). The base line erythrocyte sorbitol level was also significantly increased in group I than group II (6.16 ± 3.56 μg/mL vs 3.72 ± 2.01 μg/mL respectively). The ARI treatment significantly reduces the ALR activity and sorbitol level in group I patients which has wild type alleles for C-106T polymorphism of ALR gene. Conclusion: The study suggested pivotal roles of ALR in the pathogenesis of diabetic peripheral neuropathy, and the potential use of AR inhibitors may serve as an effective adjunct therapeutic strategy for prevention of diabetic complications. This would be example of personalized pharmacotherapy.

   Prevalence of NAFLD by fibroscan among newly detected type 2 DM patients Top

Y. P. Ganavi, Mala Dharmalingam

Department of Endocrinology, Ramaiah Medical College, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Type 2 Diabetes Mellitus (T2DM) is a risk factor for NAFLD and it has been regarded as a manifestation of the metabolic syndrome. Non-invasive assessment and staging of disease are based on clinical parameters such as age, sex, LFT, platelet count, lipid profile and BMI and imaging modalities such as ultrasound, transient elastography (TE) and MRI mass spectroscopy. Such clinical scoring systems and TE are useful in the detection of NAFLD and predicting fibrosis. Objective: To study the prevalence of NAFLD in newly detected T2DM and to look at predictive value of different indices for NAFLD [AR ratio (AST/ALT ratio), FIB4 (AST, ALT, Platelet count, Age), NAFLD Fibrosis score (Age, BMI, Presence of Diabetes/Impaired Fasting Glucose, AST, ALT, Platelets, Albmin) and BARD score (AST, ALT, BMI, Diabetes/Impaired Fasting Glucose)]. Materials and Methods: We conducted a cross sectional study to include 32 patients with Newly detected T2DM attending OPD from January 2017 to July 2017. Exclusion criteria were pregnancy, alcohol consumption >/=20 g/d in the last year and all other secondary causes of NAFLD. The following parametes were calculated: Fibroscore based on TE, AR ratio, FIB4, NAFLD Fibrosis score, BARD score. Results: A total of 32 patients were included, with a mean age ± SD of 48 ± 12.76 yrs, 53.125% were males. The prevalence of fibroscan by TE was 82.125% (n = 26, >/=F2). The sensitivity and specificity of AR ratio for predicting NAFLD was 88.46% (CI 69.85%-97.55%) and 16.67% (CI 0.42-64.12%). The sensitivity and specificity of BARD score for predicting NAFLD was 96.15% (CI 80.36%-99.9%) and 0% (CI 0-45.3%). The sensitivity and specificity of Fibrosis score for predicting NAFLD was 34.62% (CI 17.21-55.6%) and 66.67% (22.28%-95.6%). The sensitivity and specificity of FIB4 score for predicting NAFLD was 0% (CI 0-33.63%) and 100% (CI 85.18-100%). Conclusion: The prevalence of NAFLD by TE was 82.125%. The most sensitive indicator for predicting NAFLD was BARD score and specific indicator was FIB4 score.

   Clinical profile of type 1 diabetic children from Kerala Top

Nisha Bhavani, Annie A. Pulikkal, Praveen V. Pavithran, Vasantha Nair, Harish Kumar, Arun S. Menon, Usha V. Menon, Nithya Abraham

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Objectives: Type 1 Diabetes Mellitus incidence has been on the rise in recent years. There is no literature available on the clinical profile of Type 1 Diabetes mellitus from Kerala. This study aims to describe the clinical features of Type 1 Diabetic children who attended a tertiary care referral centre in central Kerala from 2006 till date. Methods: Clinical details of Type 1 Diabetic children were collected from chart analysis or EMR entries. Details of 182 children with Type 1 Diabetes who were diagnosed before 20 years of age were analyzed. (Final presentation will include close to 400 children). Results: There were 102 females and 80 males. Mean age at presentation was 9.6 ± 5 years (1-20 range). Majority 37% presented between 5 and 10 years with 31% presenting between 10 and 15 years. Only 41% had DKA at presentation and 12 had DKA on follow up. Documented severe hypoglycemias were noted only in 8 patients. 62% were on basal bolus, 19% on two premixed and 11% on split mix regimen. 62% used conventional insulin, 29% used analogues and 9% used a mixed regimen. 28/179 had thyroid disease out of which 57% had hypothyroidism 7% had subclinical hypothyroidism and 32% had positive thyroid antibodies alone. Autoantibody IA2 alone was positive in 8% GAD 65 alone in 35% and both auto antibodies were positive in 56%. Conclusion: This is the clinico-epidemiologic data of Type 1 Diabetes children from Central Kerala and is probably the first of its kind from this population.

   Detailed description of myocardial infarctions and the various subtypes in the LEADER trial Top

Anil Bhansali, Michael A. Nauck1, John B. Buse2, Tea Monk-Hansen3, Søren Rasmussen3, Marianne Bach Treppendahl3, Steven P. Marso4

Department of Endocrinology, PGIMER, Chandigarh, India, 1Division of Diabetology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany, 2Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA, 3Medical and Scientific Affairs, Novo Nordisk A/S, Søborg, Denmark, 4Research Medical Center, Kansas City, MO, USA.

E-mail: [email protected]

Objective: Type 2 diabetes (T2D) is associated with increased risk of myocardial infarction (MI). In the LEADER trial (NCT01179048), liraglutide reduced the risk of a composite cardiovascular (CV) outcome (CV death, non-fatal MI, non-fatal stroke) vs. placebo. This post hoc analysis characterises MIs in the LEADER trial, and within each treatment arm. Materials and Methods: 9340 subjects, with T2D and established CV disease or high CV risk, were randomised 1:1 to liraglutide or placebo and followed for 3.5–5 years. Subjects experiencing MI were included in this analysis. Results: 780 MIs were observed in total: 359 with liraglutide and 421 with placebo (P = 0.02). 17.8% of MIs were silent. More liraglutide- vs. placebo-treated subjects with MI had a history of coronary artery bypass graft (30.8 vs. 21.5%; P = 0.008) and percutaneous coronary intervention (47.6 vs. 40.4%; P = 0.070), while fewer had a history of diastolic dysfunction (13.4 vs. 18.9%; P = 0.061), peripheral arterial disease (9.9 vs. 17.7%; P = 0.005) and >50% stenosis of coronary, carotid or other arteries (33.2 vs. 41.0%; P = 0.044) at baseline. 641 symptomatic MIs (555 non-ST-elevation MI [non-STEMI; 86.6%]) were observed: 297 with liraglutide and 344 with placebo. Numerically fewer fatal MIs and a trend toward less troponin release were observed in the liraglutide arm [Table]. Conclusions: Fewer MIs were observed in liraglutide-treated subjects. MIs in both arms were mainly non-STEMI, with a trend toward smaller infarct severity and size in liraglutide-treated subjects, which could impact the clinical prognosis of subjects experiencing MI.
Table: Symptomatic MI according to MI subtypes

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   Day-to-day variability of fasting self-measured plasma glucose correlates with risk of hypoglycemia in adults with type 1 and type 2 diabetes Top

Ganapathi Bantwal, Timothy S. Bailey1, Anuj Bhargava2, J. Hans De Vries3, Gregg Gerety4, Janusz Gumprecht5, Wendy S. Lane6, Carol H. Wysham7, Britta Anker Bak8, Elise Hachmann-Nielsen8, Athena Philis-Tsimikas9

Prof of Endocrinology, Department of Endocrinology, St.John's Medical College & Hospital, Bangalore, Karnataka, India, 1Internal Medicine, AMCR Institute, San Diego, CA, 2Endocrinology, Diabetes and Metabolism, Iowa Diabetes and Endocrinology Research Center, Des Moines, IA, USA, 3Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands, 4Department of Internal Medicine, Albany Medical Center, Albany, NY, USA, 5Department of Internal Medicine, Medical University of Silesia, Zabrze, Poland, 6Endocrinology, Diabetes and Metabolism, Mountain Diabetes and Endocrine Center, Ashville, NC, USA, 7Diabetes and Endocrinology, Rockwood Clinic, Spokane, WA, USA, 8Medical and Scientific affairs, Novo Nordisk, Søborg, Denmark, 9Chief medical director and Executive Vice President, Scripps Whittier Diabetes Institute, La Jolla, CA, USA.

E-mail: [email protected]

Objective: The relationship between hypoglycemia and day-to-day variability of glycemic control has not been well established. A post hoc analysis was performed correlating day-to-day variability of fasting SMPG with hypoglycemia. Materials and Methods: Two double-blind, treat-to-target, crossover trials that compared insulin degludec once daily (OD) with insulin glargine U100 OD in adults with T1D (SWITCH 1, n = 501) or insulin experienced adults with T2D (SWITCH 2, n = 721). Available SMPG measurements were used to determine a weekly variance for each patient, using the log SMPG values to allow for relative comparisons. For each patient and treatment, the geometric mean of the weekly variance was calculated and these values were categorized into low, medium and high tertiles as a measure for day-to-day variability. The effect of having low or high variability compared with medium variability was analyzed in relation to overall symptomatic (severe or blood glucose [<56 mg/dL] confirmed), nocturnal symptomatic (00:01–05:59), and severe (requiring third-party assistance and confirmed by a blinded adjudication committee) hypoglycemia. Results: Day-to-day SMPG variability was a significant predictor for the risk of overall and nocturnal hypoglycemia in T1D and T2D, and severe hypoglycemia in T1D [Table]. Conclusion: Day-to-day glycemic variability relates to hypoglycemia risk.
Table: Effect of Fasting SMPG Variability on Hypoglycemia in SWITCH 1 and 2: Low and High Tertiles Compared with Medium Tertile

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   Severe hypoglycemia, cardiovascular outcomes and death: The LEADER experience Top

Sunil M. Jain, Bernard Zinman1, Steven P. Marso2, Erik Christiansen3, Salvatore Calanna3, Søren Rasmussen3, John B. Buse4

Department of Diabetes, TOTALL Diabetes Hormone Institute, Indore, Madhya Pradesh, India, 1Department of Medicine, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada, 2Research Medical Center, Kansas City, MO, 3Medical and Scientific affairs, Novo Nordisk, Søborg, Denmark, 4Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

E-mail: [email protected]

Objective: In the LEADER cardiovascular (CV) outcomes trial (N = 9340; NCT01179048), the risk of CV and hypoglycemia events was reduced with liraglutide treatment vs. placebo, when added to standard of care, in patients with type 2 diabetes and high risk for CV events. This post-hoc analysis examines the potential associations between severe hypoglycemia and time to first MACE (CV death, non-fatal myocardial infarction or non-fatal stroke), CV death and all-cause death. Materials and Methods: This posthoc analysis compared patients with/without severe hypoglycemia, and adjusted for different periods of follow-up and randomized treatment. Results: During the trial, 267 patients experienced severe hypoglycemia (liraglutide n = 114, placebo n = 153; rate ratio, 0.69; 95% CI: 0.51; 0.93). These patients were more likely than those without severe hypoglycemia to experience MACE, CV death and all-cause death, with a considerably higher risk up to 60 days after the hypoglycemic episode, irrespective of treatment group. The protective effect of liraglutide on risk of MACE was unchanged when patients with severe hypoglycemia were excluded from the analysis (patients with severe hypoglycemia accounted for 5% of all MACE in the trial). Conclusion: Patients experiencing severe hypoglycemia were at greater risk of CV events and death, particularly early after the hypoglycemic episode. Reducing severe hypoglycemia remains a cornerstone of diabetes management.

   Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes Top

Rajesh Rajput, Tadej Battelino1, Larry Deeb2, Panagiota Diamantopoulou Reiter3, Tina Maria Greve4, Georgeanna Klingensmith5, Miriana Kocova6, Margarita Kovarenko7, Naim Shehadeh8

Department of Endocrinology, PGIMS, Rohtak, India, 2Pediatric Endocrinology, Children's Clinic, Tallahassee, FL, 5Department of Pediatrics, Barbara Davis Center, University of Colorado School of Medicine, Aurora, CO, USA, 6Department of Pediatrics, University Pediatric Clinic, Skopje, Macedonia, 1Department of Paediatric Endocrinology, UMC Ljubljana, University Children's Hospital, Ljubljana, Slovenia, Balkans, 3Medical and Scientific Affairs, Novo Nordisk A/S, Søborg, 4Medical and Scientific affairs, Novo Nordisk A/S, Bagsvaerd, Denmark, Europe, 7Novosibirsk Medical University, Novosibirsk, Russia, 8Endocrinology, Diabetes and Metabolism, Rambam Medical Centre, Haifa, Israel.

E-mail: [email protected]

Objective: To assess the efficacy and safety of Insulin degludec/insulin aspart (IDegAsp) administered once-daily (OD) plus meal-time IAsp for remaining meals in controlling glycaemia as assessed by change in HbA1c from baseline in a paediatric population. Materials and Methods: A 16-week, 1:1, open-label, parallel group, randomised, treat-to- target trial. Results: Children aged 1–5 years (n = 82), 6–11 years (n = 122), 12–17 years (n = 158) with a diabetes duration of 1.6–6.0 years, HbA1c of 7.9–8.3% and fasting plasma glucose (FPG) of 8.1–8.6 mmol/l (all range of means at baseline) were randomised to receive either IDegAsp OD + meal-time IAsp for remaining meals (n = 182) or insulin detemir (IDet) + meal-time IAsp (n = 180). IDegAsp was non-inferior (limit 0.4%) to IDet for change in HbA1c (estimated treatment difference (ETD) -0.04 (-0.23; 0.15) 95%CI), which was accomplished with a numerically lower basal insulin dose: IDegAsp + IAsp: 0.36 vs IDet + IAsp; 0.5 U/kg. ETD for FPG at Week 16 was 0.31 (-0.70; 1.33) 95%CI. Rates of confirmed hypoglycaemia were 46.2 (IDegAsp + IAsp) vs 49.6 (IDet + IAsp) events/patient-years of exposure (PYE) (estimated ratio (ER) 0.95 (0.76; 1.17) 95%CI). Rates of nocturnal hypoglycaemia were 5.77 (IDegAsp + IAsp) vs 5.40 (IDet + IAsp) events/PYE (ER 1.09 (0.81; 1.48) 95%CI). Rates of severe hypoglycaemia were 0.26 (IDegAsp + IAsp) vs 0.07 (IDet + IAsp) events/PYE (ER 3.20 (0.88; 11.66) 95%CI; P = ns). Rates of hyperglycaemic episodes with ketosis were 0.11 (IDegAsp + IAsp) vs 0.22 events/PYE (IDegAsp + IAsp) (ER 0.44 (0.11; 1.74) 95%CI) and ETD for body weight SD scores was 0.07 (0.02; 0.12) 95%CI. Adverse event profiles were similar. Conclusion: IDegAsp+IAsp was non-inferior to IDet+IAsp for change in HbA1c, at a numerically lower basal insulin dose. There were no significant differences in rates of confirmed or severe hypoglycaemia between IDegAsp+IAsp and IDet+IAsp. IDegAsp+IAsp offers an alternative to basal–bolus treatment with one injection of combination insulin per day.

   Effect of short term yoga practice on ambulatory glucose profile in type 2 diabetes mellitus: Report of pilot outcomes Top

Venugopal Vijayakumar, Aditi Raju1, Ramesh Mavathur, Subramanian Kannan2

S-VYASA University, 1The International School of Bangalore, 2Department of Endocrinology, Narayana Health City, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Yoga is a moderate intensity physical activity, which is considered to be beneficial for patients with type 2 diabetes. The lower intensity makes it a safer practice with reduced risk of hypoglycemia and reduction in glycaemic variability. We performed a small pilot study using a 14-day continuous glucose monitoring (CGM) device, to see the effect of short term yoga practice on ambulatory glucose profile. Aim: To analyse the effects of yoga on glucose excursions and glycemic variability in patients with type 2 diabetes. Methodology: This is an ongoing unblinded randomised control trial where adult patients with Type 2 diabetes, were recruited. Patients who are actively practicing Yoga or patients on insulin and/or with advanced diabetes related complications were excluded. Ambulatory glucose monitoring was done using Freestyle Libre© sensor. It was a 2 week study with a pre-Yoga phase (week-1) where patients continued with their medications and usual activities and Intervention Yoga phase (week-2). A traditional validated yoga module including asanas, pranayamas and meditation was delivered by a certified yoga professional. Glycemic variability parameters were calculated during both the phases and compared using standard statistical tests. Results: Nine participants with type 2 diabetes have been recruited so far. The mean reduction in average glucose level of 12 mg/dl (0.68 mmol/L) (P = 0.01) was observed after the one week yoga practise. A significant reduction in the glycemic variability (CONGA: 7.38 ± 2.29 vs 6.744 ± 1.99 (P = 0.03); MODD: 1.97 ± 0.71 vs 1.67 ± 0.56; SD: 2.30 ± 0.86 vs 1.99 ± 0.66 (P = 0.04)) and higher percentage of time within the target (GRADE: 6.21 ± 5.85 vs 4.79 ± 4.92 (P = 0.04); ADRR: 19.73 ± 12.25 vs 15.33 ± 9.25 (P = 0.02); J Index: 39.44 ± 23.18 vs 32.23 ± 18.07 (P = 0.04)) was also observed. Conclusion: Pilot results of the ongoing study suggests even a short term yoga practice has a statistically significant reduction in the glycaemic variability parameters.

   Mitogen inducible gene (Mig-6) as a biomarker for type 2 diabetes: A pilot study Top

Bidisha Mukherjee, Chinmay Saha, Samim Ali Mondal, Subhodip Pramanik, Satinath Mukhopadhyay

Department of Endocrinology and Metabolism, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

Objectives: Insulin resistance in Type 2 diabetes is associated with low grade inflammation. Mig-6 is an adaptor protein containing the epidermal growth factor (EGF) receptor. Mig-6 is a negative regulator of EGF signaling and an immediate early response gene that is rapidly induced by heterologous arrays of mitogenic and stressful stimuli. Mig-6 is induced by insulin but the regulation of insulin induced Mig-6 expression is seems to be different from cell to cell. In this study our objective is to evaluate the association of serum levels of Mig-6 with glycemic status and to find out possible correlation with insulin resistance. Materials and Methods: In this observational cross-sectional study, 20 euglycemic, 30 prediabetic and 20 diabetic individuals were taken as per ADA criteria. Blood samples were taken for measurement of FBS, OGTT, HbA1c, lipid profile, serum insulin and HOMA IR was calculated. Venous blood serum were stored at -80°C for Mig-6 measurement by standard ELISA method. We excluded pregnant women, steroid use, Severe renal and liver disease. Results: The waist circumference, hip circumference, triglyceride and LDL were significantly higher and HDL was significantly lower in diabetics than prediabetic (P < 0.05) and in prediabetic than controls (P < 0.05). The mean ± SD of Mig-6 (pg/ml) in 3 groups were as follows: Controls 91.75 ± 23.03, Prediabetic 376.92 ± 164.39 and Diabetics 890.04 ± 275.21 (P < 0.05 for Mig-6 among the groups). HOMA-IR was positively correlated with Mig-6 (r = 0.85, P < 0.05). Conclusion: Our study results suggest that concentration of Mig-6 significantly varies with the glycemic traits in diabetes and may have a potential role as a predictive marker of insulin resistance. This finding indicates the potential of Mig-6 as a novel therapeutic target of diabetes.

   Association between interleukin-1 beta (+3953) polymorphism with foot ulcer in patients with type-2 diabetes mellitus Top

Prem Narayanan, Neeraj Kumar Agrawal

Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

E-mail: [email protected]

Background: Interleukin-1b is one of the major pro-inflammatory cytokine involved in the pathogenesis of type 2 diabetes mellitus and its complications. IL-1 b (+3953) exon 5 C/T polymorphism may result in decreased levels of IL-1 beta. After a thorough literature search we could not find any studies that demonstrate the association between IL-1b (+3953) polymorphism with foot ulcer in Type-2 diabetes mellitus. Objective: To study the association between IL-1 b (+3953) C/T polymorphism with foot ulcer in patients with Type 2 diabetes mellitus. Materials and Methods: This is a case-control study, patients with foot ulcer and T2DM as cases and those with T2DM alone as controls. The inclusion criteria was all patients with T2DM and foot ulcer (DFU) more than 4 weeks duration. Exclusion criteria was hypothyroidism and other chronic inflammatory disorders. DNA was extracted from the blood sample and PCR-RFLP done. Results: 50 cases (DFU) and 39 controls (T2DM) were enrolled in this study. CC is the wild genotype and its frequency was 54% cases v/s 31% controls. The heterozygous CT genotype frequency was 36% cases v/s 49% controls (odds ratio = 0.431,95% CI = 0.173-1.070, P = 0.11). The homozygous TT mutant genotype frequency was 10% cases v/s 20% controls (odds ratio = 0.279, 95% CI = 0.077-1.002, P = 0.09). The C allele frequency in the cases and controls were 72% and 55% respectively. The T allele frequency was 28% in cases v/s 44% in controls (OR = 0.48, 95% CI = 0.258-0.890, P = 0.029), which is statistically significant. Conclusions: The findings from our study showed a decreased frequency of T allele in cases compared to controls. This may represent an increased level of IL-1β in patients with DFU as compared to patients without DFU. Hence our study reveals a significant protective association of IL-1β (+3953) T allele with DFU cases.

   Prevalence and risk factors of peripheral arterial disease in subjects with diabetic foot ulcer in Eastern India Top

Hariballav Mahapatra1,2, Monalisa Khuntia1, Abhay Kumar Sahoo2, J. B. Kanwar2, Susant Mishra3, Apurba Ranjan Jena1

1Sevayan Diabetes Centre, Puri, 2Departments of Endocrinology and 3Plastic Surgery, IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India.

E-mail: [email protected]

Background: Diabetes and peripheral arterial disease (PAD) are two independent risk factors for lower limb amputation. Our aim was to determine the prevalence of PAD in subjects with diabetic foot ulcer in Eastern India. Methodology: Type 2 diabetic subjects diagnosed within 5 years and presenting to Sevayan Diabetes Centre, Puri between 01.04.2015 to 31.03.2016 with foot ulcer were selected. Seriously ill or those who had unilateral/bilateral AK/BK amputations were excluded. All subjects (Total 358; M/F: 255/103) underwent BP check, HbA1c measurement and lower limb Doppler analysis. ABI <0.9 was used to defined PAD. Results: Mean age of the sample was 55.7 (95% CI: 56.7-58.7) years and HbA1c was 10.5 ± 2.6 (95% CI 10.3-10.7). Mean ABI was 1.06 (95% CI 1.01-1.12). The overall prevalence of PAD was 19.6% in diabetic foot syndrome. There was no significant difference in PAD across the genders (19.2% in males Vs 20.4% in females). ABI was significantly lower for the elderly subjects. Sixty percent of the participants were on statins, whereas 44% reported tobacco use. Tobacco abuse and elevated HbA1c levels were factors directly linked to higher rates of PAD. Subjects with longer duration of diabetes (>2 years) had higher PAD prevalence than those diagnosed recently (26.4% Vs 16.6%; P = 0.01). Conclusion: Among Eastern Indian subjects with diabetic foot ulcer, PAD was significantly associated with older age, long diabetes duration, high HbA1c and tobacco consumption. There was no impact of gender on PAD.

   Management of diabetic peripheral neuropathy using low frequency pulsed electromagnetic field Top

Satish Chander Wasoori, Chetan Bhardwaj

Paras Hospital, Gurugram, Haryana, India.

E-mail: [email protected]

Objective: To evaluate and compare effectiveness of LF-PEMF with pregabalin, in the management of DPN symptoms. Methods: A comparative observational study of 40 patients, male and female (1:1) aged 55 to 80 years. Enrolment criteria - known diabetics, HbA1c 7 to 10 and DPN of 1-4 years, randomized into 2 treatment groups, G1-20 patients were treated with LF-PEMF therapy and G2-20 patients were treated with pregabalin. Study period - 60 days, results assessed at baseline and monthly follow-ups using diabetic neuropathy symptom (DNS) score. Results: In G1, application of LF - PEMF therapy significantly facilitated the regression of the main clinical symptoms of DPN. Out of 20 patients we achieved the following DNS scores at week 8-0 in 3 patients, 1 in 5 patients, 2 in 6 patients, 3 in 4 patients and 4 in 2 patients. Overall 14 patients had significant relief (with a DNS score of 0 – 2). In G2, there was a mild regression of the main clinical symptoms of DPN. Out of 20 patients we achieved the following DNS scores at week 8-0 in 1 patient, 1 in 2 patients, 2 in 5 patients, 3 in 3 patients and 4 in 9 patients. Overall 8 patients had a relief of main clinical symptoms (with a DNS score of 0-2). Conclusion: The present study provides convincing data regarding the effectiveness of LF - PEMF therapy on patients with DPN symptoms. The usage of pregabalin is limited due to the high frequency of adverse events and dependence. Considering the benefits and safety, LF - PEMF can be used as an adjacent in the management of DPN cases. Limitations of this study include small sample size, short duration of treatment and non-availability of follow-up data.

   Clinical features, radiological characteristics and offloading modalities in stage 0 acute charcot neuroarthropathy: A single centre experience from South India Top

Anjely Pulparampil Sebastian, Riddhi Dasgupta1, Felix Jebasingh1, Bharathi Saravanan1, Bobeena Chandy2, Koyeli Mary Mahata3, Dukhabandhu Naik1, Thomas Paul1, Nihal Thomas1

Departments of General Medicine, 1Endocrinology, 2Physical Medicine and Rehabilitation and 3Radiology, CMC, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: Acute Charcot Neuroarthropathy (ACN) is one of the most challenging complications of diabetes mellitus. While traditionally foot X-Rays have been relied upon to detect ACN, lack of radiological changes in the incipient (stage 0) ACN can lead to delayed treatment initiation. Early identification of the stage 0 can (clinical and scintigraphic signs without X-ray abnormalities) can significantly reduce morbidity. The aim of our study was to assess the clinical and radiological characteristics, offloading modalities and outcomes in patients presenting with stage 0 disease. Methods: A retrospective chart audit of patients attending the Integrated Diabetes Foot Clinic, CMC Vellore over a period of 3 years (2014-2017) was done. Results: A total of 10 diabetic patients with stage 0 ACN were identified. There was a male preponderance (n = 7) with a mean age of 58.9 (±19) years, mean duration of diabetes of 14 (±5.2) years and mean BMI of 28.3 (±4.2) kg/m2. The mean HbA1c was 9.1 (±1.8) % while acute inflammatory markers were negative. Pain was present in only 50% (n = 5) patients, while skin temperature difference of >40C on infrared thermometer was the most consistent finding (n = 10). X-ray foot was normal, while stage 0 ACN was detected by MRI of the affected foot and ankle in n = 7, bone scan in n = 2 and FDG-PET-CT in n = 1 patient. Amongst those with MRI, 5 patients had active, high severity (grade 1) and 2 patients had active, low severity (grade 0) neuroarthropathy according to Chantelau's classification. Offloading included total contact cast (n = 6), walker (n = 2) or wheelchair (n = 2) initially followed by modified footwear using pneumatic boot (n = 4), AFO (n = 4) or moulded insole (n = 2). Use of oral alendronate (n = 3) was not associated with earlier disease stabilization (P = 0.15), though resulted in faster resolution of pain and erythema (P = 0.04). The mean duration to disease stabilization was 6.2 (±1.5) weeks. Progression to chronic destructive disease was seen in 60% (3/5) of grade 1 but none in grade 0 disease. Conclusion: Normal X ray of foot can lead to missed diagnosis of stage 0 ACN. Differences in skin temperature and specific MRI changes can help in early detection and effective stabilization in stage 0 disease.

   Pattern of pulse pressure distribution and it's determinants in various stages of diabetic nephropathy Top

Hariballav Mahapatra1,2, Monalisa Khuntia1, Rajesh Kumar Padhi3, Biswaranjan Jena4, Soumitra Ranjan Barik5, Basanta Kumar Rout1

1Sevayan Diabetes Centre, Puri, Departments of 2Endocrinology and 3Nephrology, IMS and SUM Hospital, 4Department of Cardiology, Apollo Hospitals, Bhubaneswar, Odisha, 5 Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.

E-mail: [email protected]

Background and Aim: Pulse pressure (PP) is an indicator of vascular stiffness and is a CV risk determinant. Diabetes is a coronary equivalent. It also multiplies the risk of CKD. With this background, we investigated the distribution and determinants of pulse pressure among diabetic subjects with nephropathy. Methods: After obtaining consent from consecutive diabetic subjects visiting Sevayan Diabetes Centre, eGFR was calculated by Cackroft-Gault formula using serum creatinine. A total of 350 (M/F: 192/158) subjects with eGFR <90 ml/min were selected. BP was recorded 3 times and PP was calculated from the mean values. Based on PP, subjects were divided into 3groups (PP ≤40, 41-60 and >60 mm Hg). Results: Seventy percent of the participants were hypertensive. Mean values for age, duration of diabetes and PP were 52.5 (95% CI: 51.5-53.5) years, 7.3 (6.7-7.9) years and 52 (50.5-53.5) mm Hg respectively. Nearly 80% of adults aged >50 years had PP more than >40 mm Hg compared to 57% in the younger age group (P = 0.01). Male gender directly influenced PP, which was statistically significant. In subgroup analysis, among CKD stages-4 and 5 subjects 50% documented PP >60 mm Hg, whereas less than one fourth subjects (23.4%) in stages-2 and 3 had similar PP measurements (P = 0.01). Progressively increased PP was observed with declining eGFR. Compared to those with diabetes <10 years, subjects with longer diabetes duration had wider PP. Conclusion: Declining eGFR, male gender, advanced age and longer diabetes duration were independent risk factors for wide pulse pressure in subjects with diabetic nephropathy.

   Are sleep disorders common in diabetes? Top

Hariballav Mahapatra1,2, Monalisa Khuntia1, Abhay Kumar Sahoo2, J. B. Kanwar2, Biswaranjan Jena3, Soumitra Ranjan Barik4

1Sevayan Diabetes Centre, Puri, 2Department of Endocrinology, IMS and SUM Hospital, 3Department of Cardiology, Apollo Hospitals, Bhubaneswar, Odisha, 4Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.

E-mail: [email protected]

Background: Abnormal sleep patterns in the form of insomnia, excessive daytime sleepiness, obstructive sleep apnoea and snoring are risk factors for diabetes, metabolic syndrome, hypertension, stroke and CAD. Diabetes increases the likelihood of sleep disorders (SD). Aim: This single centre study aimed to look for the prevalence and predictors of sleep disorders in diabetes in Eastern India. Methods: Consecutive new patients attending Sevayan Diabetes Centre, Puri, Odisha between May to July 2015 were enrolled in this cross sectional study. Those without diabetes or diabetes other than type 2 diabetes were excluded. Demographic and anthropometric data were recorded. FBS, PPBS and HbA1c values were measured. Sleep quality was elicited using Epworth Sleepiness Scale (ESS), with of a set of 8 questions (score range 0 to 24). A score of <6 implied good sleep and scores ≥9 defied significant SD. Results: A total of 300 subjects consented to participate. Mean age of the participants was 57.8 ± 12.8 years and mean duration of diabetes was 5.3 ± 4.8 years. The average ES score was 8.2. Only one third (31%) of the participants had good quality sleep, while 40% were poor sleepers. SD was significantly common in males (42% Vs 34% in females: P < 0.05%). SD had a liner correlation with the duration of diabetes and higher plasma glucose values. Majority (67%) of the elderly males aged ≥50 years, encountered sleep derangement, which could be due to nocturia secondary to BPH. More than half (55%) of the females younger than 50 years, had sleep problems. Conclusion: Though sleep disorders are under addressed issues in diabetes, they are very much prevalent in the community. Identification of the cases, routine evaluation and management of abnormal sleep patterns may improve the quality of life as well as glucose control in these subjects.

   Insulin secretion, Insulin sensitivity and Adipose tissue characteristics in Asian Indians with 'lean' (<19 kg/m2) diabetes: Insights from 'metabolomic' and pancreatic clamp studies from South India Top

Riddhi Das Gupta, Anneka Wikramanayake1, Shajith Anoop, Roshna Ramachandran, V. Padmanaban, Flory Christina, Roshan Livingstone2, Meredith Hawkins1, Nihal Thomas

Departments of Endocrinology, Diabetes and Metabolism and 2Radiology, Christian Medical College, Vellore, Tamil Nadu, India,

1Department of Endocrinology, Einstein Diabetes Institute, Albert Einstein College of Medicine, New York, USA.

E-mail: [email protected]

Objectives: Dysregulation of glucose and lipid metabolism in “Lean diabetes” in India remains sparsely researched. This study was performed to decipher the role of insulin secretion and sensitivity defects and adiposity in this unique form of diabetes. Methodology: In this prospective study over a period of 4 years (2012-2016), a total of 50 age matched males including 10 lean diabetes (BMI18.3 ± 0.1 kg/m2), 10 Type 2 DM (BMI: 25.8 ± 1.1kg/m2), 15 Type 1 DM (BMI: 20.5 ± 1.6 kg/m2) and 15 non-diabetics (BMI 19.5 ± 2.3 kg/m2) were included. 'Lean-Diabetes' subjects were negative for auto-antibodies, pancreatic calculi, exocrine insufficiency and MODY mutations. Insulin secretion was assessed by C-peptide deconvolution following a mixed-meal test (MMT).Peripheral and hepatic insulin sensitivity were analyzed through hyperinsulinemic-euglycaemic pancreatic clamp procedures. 1H-Nuclear-magnetic-resonance-spectroscopy was performed to assess hepatic, intra and extra myocellular lipid distribution. Biocrates-derived metabolomics and adipose tissue gene expression were also performed. Results: In the lean-diabetes group, Insulin secretion rate was lowest (15 ± 3.0 pmol/kg/min) compared to non-diabetics (794 ± 3 21.3 pmol/kg/min), T2DM (231.0 ± 166 pmol/kg/min) and T1DM (27.5 ± 61 pmol/kg/min) groups (P < 0.001), Hepatic insulin resistance was significantly higher (P < 0.001) than non-diabetics and T1DM groups while peripheral insulin sensitivity showed no significant difference (P = 0.1). Hepatic and myocellular lipid content in lean DM was significantly less than the T2DM (P = 0.001) group. Metabolomics revealed Insulin resistance to be associated with increases in the concentrations of several phosphatidylcholines that are potential markers of inflammation, while Targeted RNA sequencing using Ampliseq technology revealed Toll-like-receptor 4 expression to be 22-fold higher in adipose tissue of Lean-diabetes compared to T1D and 5.8-fold higher than in T2D. Conclusion: These findings show that 'lean' Diabetes in Asian Indian males is an unique disorder characterized by reduced insulin secretion, increased hepatic insulin resistance and a pro-inflammatory adipose tissue profile despite reduced lipid distribution. These findings can have significant implications for devising therapeutic interventions for this intriguing form of diabetes.

   The correlation of Indian diabetes risk score (IDRS) to identify nondiabetic individuals at high risk of nonalcoholic fatty liver disease (NAFLD) Top

Swapnil Sidram Kanire, Dinesha Bantval

Department of General Medicine, Kasturba Medical College, Mangalore, Karnataka, India.

E-mail: [email protected]

Objectives: (1) To determine whether a simple Indian diabetes risk score (IDRS) is associated with individuals with non-alcoholic fatty liver disease (NAFLD) among nondiabetic South Indians. (2) To detect proportion of Non alcoholic fatty liver disease with 'high risk'of IDRS. (3) To detect indirect parameters and abnormal biochemical profile (LFT and Lipid Profile) of the NAFLD. Materials and Methods: The study was conducted in GOVERNMENT WENLOCK HOSPITAL and KMC Hospitals in Mangalore. Nondiabetic and nonalcoholic participants (n = 150) were selected from southern part of India, Mean age was 48.45 ± 12.60 year, mean BMI was 25.8 ± 3.49 kg/m2 and 111 (74%) were men. The IDRS was classified as high (≥60), medium (30–50), and low (<30) risk. Non-alcoholic fatty liver disease was assessed by high-resolution β mode ultrasonography. To determine the factors associated with NAFLD, a univariate analysis was first done and a stepwise logistic regression analysis was done based on the factors associated with NAFLD. Biochemical and anthropometric measurements were obtained using standardized procedures. Results: The overall prevalence of NAFLD was 44% (66/150 participants), and it was significantly higher among those with a high (66%) and medium IDRS (42.82%) compared with the low IDRS group (11.11%); (trend chi square; P =0.003). In stepwise logistic regression, IDRS was associated with NAFLD with an adjusted odds ratio of 0.357 (95% confidence interval 0.142–0.899), even after adjusting for potential confounders. Conclusions: A simple diabetes risk score could be used as an initial screening tool to identify individuals at high risk of NAFLD.

   Descriptive study to evaluate the risk of Metabolic Syndrome among health staff members at District General Hospital Ampara, Sri Lanka Top

Nirosha Madhuwanthi Hettiarachchi, G. L. Ravindra Sampath1

Teaching Hospital, Peradeniya, 1General Hospital, Kalutara, Sri Lanka.

E-mail: [email protected]

Introduction: Metabolic Syndrome (MS) is common among Sri Lankan adults affecting nearly one-fourth of the adults in Sri Lanka. It is a cluster of risk factors including obesity, dysglycemia, dyslipidemia and hypertension that occur together, increasing the risk of cardiovascular diseases, stroke and diabetes. If more than one of these conditions occur in combination, the risk is even greater. Insulin resistance plays a central role in the pathophysiology of Metabolic Syndrome. Very few studies were done to identify the risk of MS in health staff members. Objective: To identify the risk of Metabolic Syndrome among health staff members at DGH Ampara. Materials and Methods: 100 staff members were chosen by simple random sampling. In each individual Fasting Blood Sugar (FBS), Total Serum Cholesterol (TC)/Lipid Profile (LP) and Electrocardiograph (ECG) were performed, and their BMI (body mass index), abdominal circumference (AC), Blood Pressure (BP) were measured. Structured self-administered questionnaire was given. The data was categorized and analyzed using EXCEL with the aid of WHO, JNC 8 and ATP3 guidelines. Results: Majority were females (63%) and the mean-age of the sample is 37.56 years (female 39.46, SD-7.6 and male 34.75, SD-9.5). 96% had normal FBS, 4% had impaired blood glucose. 55% of the population had TC >200 mg/dl and the mean TC is 203 mg/dl. (males SD-30.6, females-32.3) Majority had normal BP and 37% of them were in pre-hypertension category. 2.77% of the males have abdominal circumference >102 cm and 62.5% of the females have abdominal circumference >88 cm. The mean female abdominal circumference is 90.74 cm (SD-11.25 and male is 86.70 cm (SD-11.21). Overall 37% are at risk of developing metabolic syndrome. In which 8% are male and 29% are female. Conclusions: A significant proportion is at risk of developing metabolic syndrome and majority were females. Mean serum cholesterol was significantly high and female had higher abdominal circumference. Strict lifestyle modifications are needed in health staff members.

   Short term metabolic outcome following bariatric surgery: A single center experience in Sri Lanka Top

Thejana Wijeratna1, Sonali Gunatilake2, Uditha Bulugahapitiya2, Abeysinghe P2, Maneesha Weerakkody3, Piyumi Nishadi4, Chandrika Subasinghe2, Nayananjani Karunasena5, Samanthi Cooray6, Asela Gunawardena7

1Department of Surgery, Faculty of Medicine, University of Sri Jayawardenapura, Nugegoda, 2Endocrinology and Diabetes Unit, Colombo South Teaching Hospital, Dehiwala-Mount Lavinia, Sri Lanka, 3University of Pittsburgh, Pennsylvania, USA, 4Endocrinology and Diabetes Unit, National Hospital of Sri Lanka, Colombo, 5Endocrinology and Diabetes Unit, District Hospital, Negombo, 6Endocrinology and Diabetes Unit, General Hospital, Kurunegala, 7Medical Administration Department, Colombo South Teaching Hospital, Dehiwala-Mount Lavinia, Sri Lanka.

E-mail: [email protected]

Background: Obesity and related co-morbidities have become an emerging major health concern in South Asian region. In addition to the efficacy in weight control, bariatric surgery improves metabolic disorders, thus is a recognized mode of treatment for obesity. Objectives: To review the outcome of metabolic disorders in a group of obese patients in Sri Lanka following bariatric surgery. Methods: Patients who underwent bariatric surgery at Professorial Surgical Unit, Colombo South Teaching Hospital, Sri Lanka from January 2013 to October 2016 were identified from a prospective database. Patients who had completed 12 months of post-operative period were included. Changes in the metabolic parameters at 1-year post-operative were statistically analyzed using paired t test. Results: A total of 31 Sri Lankan patients were analyzed. Mean age was 37.7 years (range: 22-53). 28 (90.3%) were females. All patients had undergone sleeve gastrectomy. Initial mean weight 103.4 kg has reduced to 74.08 kg (P < 0.001). Mean percentage expected weight loss was 60.28%. Mean BMI shows significant reduction from 42.7 kgm-2 to 30.8 kgm-2 (P < 0.001). 13 (42%) had type II diabetes mellitus; all showing improved HbA1c 12 months post operatively (P < 0.001) with complete resolution of diabetes in 61.5%. Among the initial pre-diabetics (7), 71.4% showed normoglycemia. Mean systolic blood pressure was 131 mmHg (range: 110-156), with a significant drop post-operatively (P = 0.001). 7 (22.5%) were initially hypertensive, of which all became normotenstive requiring no medication. Total cholesterol (P = 0.183), LDL (P = 0.198), HDL (P = 0.442) and Cholesterol/HDL (P = 0.856) showed no significant improvement 12 months post-operatively. In contrast, triglycerides levels showed an improvement (P < 0.001). Pre-operative fatty liver (9/31; 29%) showed an improvement in 88% of patients at 12-months post-bariatric surgery. Conclusion: Metabolic parameters at 12 months post-operatively following bariatric surgery for obese Sri Lankan patients show significant improvement, comparable to similar studies in other parts of the world.

   Correlation of postprandial hypertriglyceridemia with carotid intima media thickness in patients with type 2 diabetes mellitus Top

Smit Rajput

Department of Endocrinology, PGIMER and RML Hospital, New Delhi, India.

E-mail: [email protected]

Introduction: Several studies indicate that post-prandial metabolic derangements, most notably hyperglycemia and hypertriglyceridemia are important cardiovascular risk factors since they induce oxidative stress and endothelial dysfunction. Measurement of Carotid Intima Media Thickness (CIMT) by ultrasonography is a non-invasive and quantitative method of evaluating early atherosclerotic changes in the vasculature. It has been shown that an increase in CIMT is associated with an increased risk of IHD or CVD. Aim: Estimation of fasting and postprandial triglyceride levels, carotid intima media thickness (CIMT) and to find out the correlation between postprandial triglyceride levels (4 hours after standard meal) and carotid intima media thickness. Materials and Methods: Fifty patients having Diabetes for more than one year, and without any known cardiovascular disease were incorporated into the study. There fasting LDL, HDL, TGs and postprandial TGs were estimated using standard laboratory methods. CIMT was measured using B mode ultrasonography. Pearson's correlation co-efficient was used to find out the correlation between different parameters. Results: Both PPTG and FTG showed a strong correlation with CIMT, the correlation coefficients being 0.879 and 0.764 respectively. If the subjects with normal FTG were taken to calculate correlation between PPTG and CIMT, correlation coefficient was 0.848 and if only the subjects with raised FTG were taken then the correlation coefficient was 0.735; suggesting a stronger correlation of PPTG with CIMT at normal fasting triglyceride levels. Conclusion: Both, increased postprandial triglyceride levels and fasting triglyceride levels are risk factors for increasing carotid intima media thickness in patients with Type II Diabetes Mellitus. However the correlation between increased PPTG and CIMT is even stronger and thus can be an independent risk factor of atherosclerosis.

   Peripartum cardiomyopathy in type 2 diabetes Top

Suresh Damodharan, Elisabeth Saji Cherian1, Harikrishnan S, Jibin John Cherian2

Sri Ramakrishna Hospital, 1Royal Care Super Speciality Hospital, 2College of Pharmacy, Sri Ramakrishna Institute of Paramedical Science, Coimbatore, Tamil Nadu, India.

E-mail: [email protected]

Introduction: Peripartum cardiomyopathy is an idiopathic cardiomyopathy that presents with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the initial months after delivery, in the absence of any other cause of heart failure. Although the left ventricle may not be dilated, the ejection fraction is always reduced. Case Study: A 24 year old female, Gravida 4 parity 1 Live birth 1 Abortions 2 (POG: 36th week) was admitted in the obstetrics and gynecology department with complaints of palpitation on and off -1month, chest pain, and difficulty in breathing. She was a known case of type 2 diabetes for the past 3 yrs and was on metformin. Her HbA1C was 7.6%. Further investigations were mainly focused on her symptoms. Results: The patient was promptly evaluated. Her ECG showed sinus tachycardia with left axis deviation and her ECHO confirmed peripartum cardiomyopathy with an ejection fraction of 46%. 27 days post admission she gave birth to baby who presented with hypoglycemia. Conclusion: Peripartum cardiomyopathy is a relatively rare disease, which can lead to devasting consequences with overall morbidity and mortality rates. Diagnosis of peripartum cardiomyopathy is challenging, as most women in the last month of normal pregnancy or soon after delivery experiences its symptoms. Therefore, close attention should be paid for signs and symptoms. Here the patient had a strong evidence for peripartum cardiomyopathy, but does her diabetes and metabolic abnormalities have any contribution for cardiomyopathy?

   An elevated glycemic gap is associated with adverse outcomes in critically ill patients with diabetes Top

Sandeep Donagaon1, Mala Dharmalingam2, Y. P. Ganavi1, Easow Sam Justin1

1Senior Resident, Department of Endocrinology, 2Prof. and HOD, Department of Endocrinology, Ramaiah Medical College, Bengaluru, Karnataka, India.

E-mail: [email protected]

Objectives: Currently HbA1c is used as a marker of glycemic control. However, it has its own shortcomings in predicting glycemic variability and adverse outcomes. Glycemic gap is a marker of glycemic excursions in patients with diabetes. It can be used to predict adverse outcomes in patients with diabetes admitted to the ICU. It is calculated by subtracting ADAG (A1C derived average glucose= [(28.7×HbA1c)-46.7] from plasma glucose at admission. Objective of this study was to correlate glycemic gap and adverse outcomes in patients with diabetes admitted to the ICU. Materials and Methods: We conducted an ambispective study to include patients with type 2 diabetes mellitus admitted to the ICUs from July 2015 to June 2016. The following adverse outcomes were recorded: multi-organ dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), shock, UGI bleed, acute kidney injury (AKI), acute respiratory failure (ARF). Results: A total of 200 patients were enrolled, with a mean age ± SD of 62 ± 11.24 years, 64.5% were males. The duration of hospital stay and ICU stay were 10.69 ± 8.05 days and 5.64 ± 5.02 days, respectively. The most common primary diagnosis was cardiovascular (39.5%) followed by neurological (16.5%), infection at diagnosis (16.5%), respiratory (14%), gastrointestinal (7.5%), others (6%). A higher glycemic gap was associated with occurrence of MODS (P < 0.01), ARDS (P = 0.026), shock (p0.043), UGI bleed (P = 0.013), AKI (P = 0.01) and ARF (P < 0.01). Glycemic gap cut-offs of 43.31, 45.26 and 39.12 were found to be discriminatory for predicting ICU mortality (AUROC = 0.631, P = 0.05), MODS (AUROC = 0.725, P < 0.001) and ARF (AUROC = 0.714, P < 0.001). Conclusion: Our study showed that higher glycemic gap levels were significantly associated with an increased risk of MODS, ARDS, shock, UGI bleed, AKI and acute respiratory failure. Glycemic gap is a simple tool that can be used to determine prognosis in patients with diabetes admitted to the ICU.

   Type 1 diabetes mellitus and disturbed eating behaviours Top

Sree Divya B1, Sachan A1, Suresh V1, Harini Devi N2, Sivanandh B3, Ashok V1

Departments of 1Endocrinology, 2Biochemistry and 3Psychiatry, SVIMS, Tirupati, Andhra Pradesh, India.

E-mail: [email protected]

Objective: To identify the patients with type 1 diabetes mellitus who are at risk for developing eating disorders. Materials and Methods: This was a cross sectional study. Fifty patients (24 males and 26 females) were consecutively recruited. All patients were administered Eating Attitude Test-26 questionnaire (EAT-26) and diabetes distress score (DDS) questionnaire. Clinical data were collected and HbA1c was measured. Data are presented as mean ± SD and analysed with student's t-test and Chi-square test as appropriate. Results: Age of study population was 20.1 ± 5 years. 64% of the subjects scored above the EAT-26 cutoff which indicates that they are at risk for eating disorder. Males and females scored similarly on EAT-26 questionnaire (P = 0.42). Mean HbA1c was higher among those at risk of developing eating disorder (10.9 ± 2.1) than those without the risk (9.4 ± 1.9) (P < 0.05). Age (P = 0.3) and duration of diabetes (P = 0.4) did not affect the risk of developing eating disorder. Mean BMI SDS was -1 ± 0.96 and it was not different among patients with and without disturbed eating behaviour (p- 0.7). DDS was similar among those with and without risk of developing eating disorder (p-0.6). Conclusion: Our study reports a higher risk of disturbed eating behaviours in unselected patients with type 1 diabetesmellitus. Disturbed eating behaviour was associated with poor glycemic control.

   Are changes in basal and thermogenic energy expenditure in gestational diabetes mellitus evident during early pregnancy: Preliminary findings from a longitudinal single centre Indian study Top

Geethu Antony, Riddhi Das Gupta, Roshna Ramachandran, Shajith Anoop, Annie Regi1, Jiji Elizabeth Mathew1, Hesarghatta Shyamasunder Asha, Thomas Paul, Nihal Thomas

Departments of Endocrinology and 1Obstetrics and Gynaecology, CMC, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: Gestational diabetes mellitus (GDM) is associated with significant alterations in energy and fat metabolism. But there is paucity of longitudinal data in pregnancy. Our study aimed at assessing the longitudinal changes in resting energy expenditure (REE), body composition and postmeal thermogenesis (PTE) in a population of women with GDM and normoglycemia during pregnancy and postpartum. Here we report the preliminary findings in early pregnancy. Materials and Methods: 26 GDM and 16 normoglycemic pregnant women were included in the study. REE was estimated using indirect calorimetry. Subsequently PTE was calculated by energy expenditure over 3 hours following a mixed meal challenge test. Body composition was assessed using bio impedance analysis, diet by 24 hour recall and activity energy expenditure (AEE) using PPAQ questionnaire. Results: At baseline GDM group had higher BMI, fat mass content and fat mass percentage, P < 0.05).Skin fold thickness at triceps and neck, mid arm and neck circumference were significantly higher in GDM group (p -<0.05). REE; in absolute terms and adjusted to fat free mass, were lower in GDM group (2427.03 + 89.3 versus 2505 + 14150 kcal/day and 60.96 + 2.49 versus 67.81 + 3.99 kcal/kg/day). Physical activity was significantly lower in GDM (82.76 + 41.2 versus 115 + 70.63), while dietary intake was similar in both groups. Fasting insulin and HOMA-IR was higher in GDM. Although overall PTE were similar in both groups, BMI adjusted PTE showed reduced thermogenesis in GDM patients, further HOMA –IR showed significant correlation with PTE (R -0.68, p-005). Conclusion: Our study is the first of its kind in Indian mothers showing significant alterations in basal, thermogenic and activity induced energy expenditure in early pregnancy, probably associated with insulin sensitivity. Follow up data from the study will help in understanding the metabolic alterations better.

   Simultaneous pancreas kidney transplant: A single centre experience Top

Nithya Abraham, S. Nisha Bhavani, Arun S. Menon, Praveen V. Pavithran, Usha V. Menon, Annie Pullikkal, Vasantha Nair, Harish Kumar

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Introduction: Simultaneous pancreas kidney transplant (SPK) has revolutionized the management of type 1 diabetic patients with end stage renal disease. It provides more physiological glucose metabolism with improved quality of life free from injections and dialysis. We share our experience of 6 patients who underwent SPK in the last 3 years done in a single centre. Materials: This is a retrospective analysis of 6 patients who underwent SPK from August 2014 to June 2017. The baseline characteristics are as shown below (Table 1). Median age of our study population was 35 years. Patient survival was 100%, however graft survival was 83.3%. Case 1 had a stormy course with varicella and tuberculous infections later going into renal rejection subsequently requiring a second renal transplant. His latest C peptide following renal transplant is 1.74ng/ml requiring small dose insulin. The average time to normalization of blood sugars after anastomosis post transplant was 2-2.5 hrs. Further details post transplant are given in (Table 2). Conclusion: SPK is the most effective treatment for patients with type 1 DM and ESRD. In our study, patient survival was 100% and graft survival was 83.3%.Although it involves major surgery and is not without risks, it improves the quality of life. However long term follow up is needed as there is a trend towards decline in C peptide.
Table 1

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Table 2: Posttransplant data

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   Analysis of noninvasive central aortic systolic pressure measurement in type 2 diabetic patients Top

Kirtikumar D. Modi, Vaibhavi Modi, Harsh Parekh, Ashutosh Kumar1

Department of Endocrinology and 1Cardiology, CARE Hospital, Hyderabad, Telangana, India.

E-mail: [email protected]

Objectives: To compare noninvasive central aortic systolic blood pressure (CSBP) with standard manual peripheral systolic blood pressure (PSBP) measurement in type 2 diabetic patients and normal healthy individuals. Materials and Methods: “Pulscor - BP+” device was used to assess non invasive CSBP while mercury based sphygmomanometers was used to assess manual PSBP measurement (Type 2 DM: n = 508, Normal healthy individuals: n = 510). Patients with secondary hypertension and with pregnancy were excluded. Cut off values to define normal central and peripheral blood pressure measurements were taken as less than 125 and 140 mm of Hg respectively. Results: For 508 Type 2 diabetic patients (M/F: 200/308), mean age was 50.72 + 11.66 years, mean body mass index (BMI) was 30.50 + 12.626 kg/meter2, mean duration of diabetes was 8 + 4.2 years and mean HbA1C was 8.03 + 5.8%. Among them 356/508 (70%) were known hypertensive, while 152 (30%) patients were non-hypertensive. Of these 152 patients, 107 (70%) had high CSBP, while 87/152 (57%) had high PSBP (newly detected hypertensive). Among 356/508 known hypertensive patients, 138/508 (27%) had normal CSBP, while 199/508 (39%) had normal PSBP. Normal CSBP was seen in 59/157 (37.5%) patients on RAS blockade antihypertensive group and 14/60 (23.3%) patients on beta blockers group. Among 510 healthy individuals, mean PSBP and mean CSBP in healthy individuals were 120.6 + 15.29 and 110.17 + 15.96 mm of Hg respectively. Number of newly detected hypertensive patients in healthy individuals was significantly lower (16.6%) than those in non hypertensive type 2 diabetes group (57%). Conclusion: CSBP was significantly higher than PSBP in type 2 diabetic patients and healthy individuals. Newly detected hypertensive patients were more in non hypertensive diabetic patients than healthy individuals. Among hypertensive type 2 diabetic patients RAS blockade group had relatively better CSBP control than beta blocker group.

   Pharmacokinetics and pharmacodynamics of canagliflozin in pediatric patients with type 2 diabetes mellitus Top

Mayuresh Fegade, William Tamborlane1, David Polidori2, Nicholas Di Prospero3

Medical Affairs, Janssen India, Mumbai, Maharashtra, India, 1Professor of Pediatrics (Endocrinology), Chief, Pediatric Endocrinology, Yale University School of Medicine, New Haven, CT, 2Janssen Research and Development, LLC, San Diego, CA, 3Janssen Research and Development, LLC, Raritan, NJ, USA.

E-mail: [email protected]

Background: CANA, an SGLT2 inhibitor approved for the treatment of adults with T2DM, increases urinary glucose excretion (UGE) and lowers plasma glucose (PG) levels by reducing the renal threshold for glucose (RTG). Objective: This open-label study assessed the PK and PD of CANA in pediatric patients aged 10 to <18 y with T2DM on a stable metformin dose (mean age = 14.6 y; HbA1c = 6.9%; BMI = 38 kg/m2, eGFR = 149 mL/min/1.73 m2). Materials and Methods: Patients received CANA 100 mg (n = 8) or 300 mg (n = 9) QD for 14 days and underwent assessments of PK and PD parameters, tablet acceptability, safety, and tolerability. Results: Drug exposures tended to be similar to or slightly lower than corresponding PK parameters measured in adults. CANA dose-dependently reduced mean (SD) 24-h RTG to 85 (14) mg/dL with CANA 100 mg and 69 (10) mg/dL with CANA 300 mg at Day 14, consistent with the reductions in RTG seen in adults. Mean 24-h UGE increased from 5 (11) g at baseline to 74 (37) g at Day 14 with CANA 100 mg and from 0.1 (0.04) g to 69 (27) g with CANA 300 mg. Both CANA doses were safe (no serious adverse events) and well tolerated; the tablet had acceptable qualities with respect to taste, smell, and ability to swallow. Conclusion: In pediatric T2DM patients, both doses of CANA lowered RTG, increased UGE, and lowered PG concentrations in a manner that is consistent with the relationship defined by adults with T2DM and clinical studies are planned in a T2DM pediatric population.

   Clinical and electrophysiological correlation of peripheral neuropathy in newly diagnosed type 2 diabetes mellitus Top

Sonali Appaiah, Dipti Sarma, Ashok Krishna Bhuyan, Uma kaimal Saikia, Bipul Kumar Choudhury

Department of Endocrinology, Gauhati Medical College and Hospital, Guwahati, Assam, India.

E-mail: [email protected]

Objectives: To compare the prevalence of peripheral neuropathy in newly diagnosed type 2 Diabetes mellitus (DM) by clinical examination and nerve conduction study (NCS), and to correlate them with risk factors. Materials and Methods: Fifty newly detected cases of type 2DM diagnosed during last 6months of age >18 years attending Endocrinology Department of Gauhati Medical College and Hospital from Dec 2016-June 2017 were evaluated. Detailed medical history, clinical examination, followed by grading of symptoms and signs were done using the Neuropathy Symptoms Score (NSS) and Neuropathy Disability Score (NDS) respectively, and NCS was done in all patients. Neuropathy was diagnosed based on either positive NSS, NDS or NCS. Confounding causes of neuropathy were excluded. Results: The mean age at diagnosis of type 2 DM was 47.04 (SD ± 11.05) years and mean HbA1c was 10.4 (SD ± 2.56) %. Prevalence of peripheral neuropathy was 62%. The most common presenting symptom was tingling and numbness of feet (70.96%) followed by motor weakness in lower limbs (16.12%). The most common sign was impairment of perception of vibration (74.06%), followed by absence of ankle reflex (61.8%). Severity of neuropathy by NSS was of mild grade in 9.52%, moderate in 52.32% and severe in 38.08%. Grading by NDS was mild in 10.52%, moderate in 78.9% and severe in 10.52%. Positive NCS finding was seen in 80.5% of patients with neuropathy. Of all the patients with neuropathy, only 8% had subclinical neuropathy, that is positive NCS finding in absence of sign and symptoms. In rest 92% of the patients, clinical examination was sufficient for diagnosis of neuropathy. Neuropathy was demyelinating in 20%, axonal in 28% and mixed in 52%; whereas 4% had motor, 12% sensory and 84% had mixed sensorimotor neuropathy. Peripheral neuropathy diagnosed by NSS/NDS/NCS had significant association by linear regression with age at diagnosis, duration of neuropathy symptoms, NSS and NDS (P < 0.01). No significant association was seen with HbA1c, lipid profile, eGFR, Creatinine. However, in subgroup analysis of mild, moderate and severe neuropathy, 'one way between group ANOVA' showed statistically significant difference in HbA1c, FBS, PPBS and Creatinine between the groups (P < 0.05). NCS had a significant association by linear regression with age at diagnosis, duration of neuropathy symptoms, NSS, NDS, HbA1c, FBS, Creatinine and eGFR (P < 0.01). No association was seen between NCS and lipid profile. Conclusion: Patients with type 2DM have a high prevalence of peripheral neuropathy at diagnosis and very few of them harbour subclinical neuropathy. This study has shown that clinical examination still remains the main tool for detection of neuropathy.

   Results of a mobile diabetes clinic based screening program in rural India Top

Anjali Bhatt, Ambika Gopalakrishnan Unnikrishnan, Prasanna Dhore1, G. Mehmood Sayyad2, D. D. Pratyush3, Shailesh Deshpande4, Vedavati Purandare, Rajesh Javherani, M. K. Mandal1

Department of Clinical Diabetology and Endocrinology, 1Department of Medical Administration, 2Consultant Bio-Statistician, 3Department of Research and 4Department of Education, Chellaram Diabetes Institute, Pune, Maharashtra, India.

E-mail: [email protected]

Background: A large proportion of Indian population lives in rural area which lack affordability and accessibility for diagnosis and treatment of chronic diseases. Methods: We designed a hub and spoke model of screening the rural population where door to door screening by Accredited Social Health Activist (ASHA) is followed by an assessment at Mobile Diabetes Clinic. Results: A house to house survey was conducted (n ~ 120,460) to administer a questionnaire to identify high risk subjects. Out of which 24,092 subjects were screened at Mobile Diabetes Clinic. Diabetes was detected in 3751 (15.6%) subjects and prediabetes was detected in 2902 (12%) subjects. Subjects with diabetes were also screened for complications related to diabetes. Conclusion: The Mobile Diabetes Clinic supported by ASHA using a pre-determined questionnaire for house to house visits to identify high risk individuals to be screened at Mobile Diabetes Clinic is an effective method of screening for diabetes and its complications. This results in a good case finding rate as one out of every 3-4 pre-categorised subjects is detected with diabetes or prediabetes.

   An audit to evaluate the quality of care for diabetic patients at VP/OPD diabetic clinic District General Hospital Ampara Srilanka Top

Nirosha Madhuwanthi Hettiarachchi, Nikujani Widisinghe1

Teaching Hospital, Peradeniya, 1General Hospital, Negambo, Sri Lanka.

E-mail: [email protected]

Introduction: Prevalence of diabetes in adults over 20 years of age in Sri Lanka is 10.3% and is expected to rise to 13.9% in the year 2030 (Katulanda et al. 2008). Only few audits are available to assess the diabetic care given to these patients in Sri Lanka. Objectives: To evaluate and asses the delivery of services and achievement of treatment targets in a Diabetic Clinic at District General Hospital Ampara. Materials and Methods: Data from 100 randomly selected patients in (VP/OPD) Diabetic Clinic held on 4/10/2013. Audit tools were an interviewer administered questionnaire and clinic notes. Standard of treatment evaluated according to the guidelines issued in 2007 from Ministry of Healthcare and Nutrition of SriLanka and the 2013 guidelines for diabetes care standards of American Diabetes Association (ADA). Results: Mean age was 55.2 y (SD-11.2y), Mean duration of follow up was 4 years. FBS and blood pressure regularly monitored in 99% and 97% of patients respectively. 78% achieved the blood pressure target. Only 29% had achieved target fasting blood sugar values (FBS). Lipids were checked 6monthly in 48%. Only 36.17% have achieved LDL cholesterol level <100 mg/dl. 87% was on statins and 55% was on ACEI. Annual Microalbumin levels were done only in 17% while 7% had checked HBA1C. 80% couldn't afford the two investigations. 61% had done annual retinopathy assessment. Foot care and Diabetic centre referral was done in 83%. 21% has got annual foot care assessment. 6 month renal functions were done in 51%. Cardiovascular risk prediction score was >10% in 26 patients, out of that only 15 (57.7%) of them were given Aspirin. Only 2% had had cardiovascular events. Conclusion: Achievement of treatment targets as defined by ADA needs further improvement mainly on lipid management, screening for retinopathy and nephropathy, foot assessment and aspirin therapy. Blood glucose and blood pressure were monitored closely but targets were not achieved in a significant number of patients. Re auditing in 6 months is planned once further education of health care workers is implemented.

   Knowledge and awareness of mellitus in South Asian diabetic patients Top

Aashish Reddy Bande, Mala Dharmalingam

Department of Endocrinology, Ramaiah Medical College, Bengaluru, Karnataka India.

E-mail: [email protected]

Objectives: To assess the awareness about type, cause, complications, comorbidities and medications among patients with type 2 diabetes mellitus (DM). Materials and Methods: The study was done at a tertiary care hospital in Bangalore after taking an informed consent. It is a cross sectional prospective study of 200 patients of type 2 DM as defined by ADA criteria. They were divided based on duration of diabetes into Group 1: 0-5 years, Group 2: 6-10 years and Group 3: >10 years. A validated questionnaire in their language of preference was given. Results: 200 consecutive patients were recruited. 93 (46.5%) were women and 107 (53.5%) were men. Mean age was 52.31 years in women and 56.20 years in men. 7% knew about their type of diabetes, 37.5% said that diabetes was hereditary. Knowledge about vascular complications was nephropathy (20%), retinopathy (22.5%), neuropathy (38%), IHD (16%), Cerebrovascular disease (9.5%) respectively. 35% knew about their anti hypertensive drugs and 27% knew their anti lipid drugs. Group 1 had 64 (32%), Group 2 had 59 (29.5%) and Group 3 had 77 (38.5%) patients. Awareness of nephropathy was there in 4.6%, 20.3% and 43% respectively. Awareness of retinopathy was there in 1.6%, 18.6% and 42% respectively. Awareness of neuropathy was there in 4.7%, 42.4%, 62.3% respectively. Around 50% in each group knew their diabetic medication. The knowledge about its composition and side effects was very less. Acute complication like hypoglycemia was known by around 50% in each group. Conclusion: Patients with type 2 DM have less awareness about the type of DM, the medication they are taking, irrespective of duration of diabetes. With increase in duration of diabetes, patients had better knowledge of diabetes complications. Patients with higher level of education had a significant better knowledge about their medication.

   Diabetes mellitus below one year of age: Two different stories Top

Suvrendu Sankar Kar, Rana Bhattacharjee, Sujoy Ghosh, Padip Mukhopadhyay, Subhankar Chowdhury, Kaushik Sen, Ashok Kumar

Department of Endocrinology and Metabolism, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

Background: The common forms of diabetes are type 1 and type 2. Neonatal diabetes mellitus (NDM) is a rare disease and occurs in the first 12 months of life. It occurs in only one in 100,000 to 400,000 live births. It may be permanent (PNDM) or transient (TNDM). Specific genes that can cause NDM have been identified. As a rule autoimmune diabetes is very rare below 12 months. Here we are presenting two cases of NDM with different etiologies. Both of them were born out of non consanguineous marriage and none had any family history of diabetes. Case No 1: 16 weeks girl presented with hyperglycemia without ketonemia. She was initially managed with subcutaneous insulin and investigated for genetic analysis. she was found to have positive KCNJ11 mutation (heterozygous for KCNJ11 missense variant, p.Glu227Lys) who was successfully shifted to oral sulfonylurea. Case No 2: 33 weeks male child presented with hyperglycemia along with diarrhoea and dehydration without ketoacidosis. This child was also initially treated with subcutaneous insulin till the genetic analysis report was available. But Sequence analysis of KCNJ11 and INS genes did not detect a disease-causing mutation. Interestingly this patient was found to have anti GAD antibody positive in very high titre, >2000 IU/mL (ref 0-10.9); the result is consistent with type 1 diabetes. He had no IA2 or Zinc transporter antibody. He was discharged with insulin therapy and follow up. Here the first case was a case of monogenic diabetes due to heterozygous KCNJ11 missense mutation, p.Glu227Lys, a cause of PNDM responsive to sulfonylurea treatment. Second one was an autoimmune/T1 DM which is also very very rare below 6 months of life.

   Diabetic eye disease: Sri Lankan experience Top

E. M. S. B. Ekanayake, G. P. Samarasinghe, D. Beminiwaththe

Ophthalmology, Diabetes and Endocrinology Unit, Teaching Hospital, Kandy, Sri Lanka.

E-mail: [email protected]

Introduction: The ocular manifestations of diabetes mellitus have significantly negative impact on the quality of life as well as awfully high economic burden.[1] Eventhough diabetic retinopathy being the most well-known microvascular complication, there are several other important ocular manifestations of diabetes such as include cataract, glaucoma, cranial nerve palsies and recurrent corneal erosion with dry eye syndrome. Objective: To identify the types and characteristics of ocular manifestations as well as to explore the causes of visual loss in a cohort of type 2 diabetic patients with the aim of designing a relevant educational intervention programme in order to prevent correctable causes of diabetes. Methods: A descriptive cross sectional study was conducted at eye unit, Teaching Hospital, Kandy, Sri Lanka over a period of one and half year from November 2015 recruiting a cohort of diabetic patient who are attending eye unit, as clinic and inward patients. Results: A total of 417 patients were included. Their mean age was 57.7 years (range 19-90y) and majority was males (54.2%). The visual impairment was manifested as sudden (15%) or gradual (85%) loss of vision. The associated complaints were floaters (22%), flashes (14%), dryness (23%) and ocular pain (6%). Mean duration of diabetes was 7.25 years (range: 1month to 36y). The main causes for sudden loss of vision were diabetic retinopathy (58%), vitreous haemorrhage (19%) and retinal detachment (14%). The causes of gradual visual impairment were cataract (36%), diabetic retinopathy (50%), glaucoma (6%) and retinal vein occlusion (5%). Of them 11.7% had clinically significant macular edema. Conclusion: Several modifiable risk factors are associated with visual impairment in type 2 Diabetes Mellitus specially cataract and diabetic retinopathy. Patient awareness on diabetic ocular manifestations and attending the recommended eye examination as well as good practices with regard to controlling diabetes are crucial.


  1. Fong DS, Sharza M, Chen W, Paschal JF, Ariyasu RG, Lee PP. Vision loss among diabetics in a group model Health Maintenance Organization (HMO). Am J Ophthalmol 2002;133:236-41.

   Pesticide exposure and risk of diabetes Top

Shipra Tyagi, Brijesh Mishra1, A. J. Urfi, B. D. Banerjee2, S. V. Madhu1

Department of Environmental Studies, University of Delhi, 1Department of Endocrinology and Metabolism, UCMS, 2Department of Biochemistry, Environmental Biochemistry and Molecular Biology Laboratory, UCMS, New Delhi, India.

E-mail: [email protected]

Objective: Diabetes mellitus is a metabolic disorder that is characterized by hyperglycemia caused due to endocrine disruption. Environmental pollutants such as Organochlorine pesticide (OCP) which is an important class of xenobiotic compounds. OCPs may act as endocrine disruptor which may lead to Diabetes. Hence, the present study was planned to find out association of OCPs with risk of diabetes. Materials and Methods: In this case-control pilot study, data were obtained based on Pre-diabetic cases (n = 15) and Normal glucose tolerance (NGT) subjects controls (n = 21) from North India. The study was conducted during January 2016 to July 2017 as samples were obtained from Department of Endocrinology, GTB hospital, Delhi. We examined the whole blood for pesticide levels in normal and Pre-Diabetic patients using Gas chromatography with ECD detector. Results: The β HCH (95% CI= -3.111 – 0.32, Mean diff.= -1.712) level was found to be significantly higher (P = 0.018) in Pre-Diabetic cases as compared to term controls. Conclusions: The preliminary study suggests that the OCP levels are higher in Pre-Diabetic patients and it could be a possible cause among various promoting factors towards Diabetes.

   Psychosocial assessment in type 1 diabetes mellitus in South India Top

Justin Easow Sam, Mala Dharmalingam

Department of Endocrinology, Ramaiah Medical College, Bengaluru, Karnataka, India.

E-mail: [email protected]

Objective: To evaluate the prevalence and pattern of psychosocial illness in patients with Type 1 DM. Materials and Methods: Conducted as a cross-sectional study in a tertiary care centre, it included 56 patients having T1DM. “DSM-5 parent/guardian- Rated (Child age 6-17), self rated (child age 11-17), self rated (adult) 'Level 1 Cross-Cutting Symptom Measure” was used to assess pattern and prevalence of psychosocial illness. The sample was divided into 3 groups as per age: Group I (10 yrs), Group II (10-17 yrs) and Group III (≥18 yrs) for the purpose of evaluation. Results: The most common abnormality found in 10- 17 age group was anger and irritability (31%) followed by mania (25%) and psychosis (21.8%). In the age group above 18 yrs, somatic symptoms (45%) and mania (45%) followed by depression (40%), anxiety (40%) and psychosis (44%) were the most common psychosocial abnormalities. Below 10 yrs of age, inattention, anger and irritability were found to be most common. Conclusion: This study shows the high prevalence of psychosocial illness in individuals with T1DM. Adequate psychosocial evaluation of T1 DM patients and interventions should be stressed as a treatment modality to improve outcomes.

   Incidence of posttransplant diabetes and long term metabolic outcome in patients undergoing liver transplant Top

Nithya Abraham, Arun S Menon, Nisha Bhavani, Praveen V Pavithran, Usha V Menon, Annie Pullikkal, Vasantha Nair, Harish Kumar

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Background: Liver transplantation has been accepted as a therapeutic option for patients with end stage liver disease. With improved survival more attention is given to the complications that occur long term, that are related to the immunosuppressive therapy. A number of studies have reported the prevalence of new onset diabetes, dyslipidemia, hypertension, bone related complications among patients who have undergone liver transplantation. Objectives: To study the incidence of PTDM, long term treatment profile and rate of remission of diabetes in liver transplant recipients. Materials and Methods: We retrospectively analysed data records of 175 recipients who underwent liver transplant from October 2006 to september 2013 and have followed them up till date. Results: Out of 175 recipients, 62 had preexisting diabetes. Out of the remaining 113, 45 (39.8%) developed post transplant diabetes over 6.88+- 2.2 years of follow up. The mean age of recipients with PTDM was 43.8+-9.2 yrs as compared to those without diabetes 35.4+-15.5yrs (P = 0.002). 1Yr, 5yr, 10 yr survival rates of those with PTDM were 95.5%, 88.8%, 86.6% respectively. The mean HBA1C post transplant in PTDM was 6.2+-1.3% as compared to 7.5+-1.1% in those with preexisting diabetes (P = 0.00). Among the 45 with PTDM, 37 developed diabetes within the first 3 months, 2 within 1-2 yrs and 6 within 3-5 yrs of follow up. Diabetes in 21/45 (46.6%) went into remission. Remission occurred in 6 within 3 months, 8 within 3-6 months, 2 within 6months – 1 yr and 5 within 3-5 yrs. Of the remitters, 11 (52.4%) were found to have IFG on follow up. In the PTDM group who continued to have diabetes, 11 were on insulin, 7 on OAD and 5 on a combination of OAD + insulin. The preferred OADs were metformin and sulfonylureas and the preferred insulin regimen was biphasic isophane insulin (82%). Recipients with PTDM were older and had higher prevalence of hypertension and dyslipidemia as compared to those without diabetes (P < 0.05). 18/45 (40%) in the PTDM group had dyslipidemia as compared to 10/68 (14%) in the non diabetic group. No significant difference was observed in survival rate, MELD score, rejection episodes in those who developed PTDM. The donor type (cadaver vs live) did not have an influence on the survival rate or incidence of PTDM. Conclusion: Our study shows that the incidence of PTDM following liver transplant is higher (39.8%) in South Indian population when compared to the available western data (10-36%) with a higher prevalence of dyslipidemia and hypertension. Although 46.6% achieved remission with a significant proportion in the first 6 months, nearly half of them continued to have IFG on follow up. This highlights the importance of closely following up all patients who develop PTDM including those who remit since the chance of progression to Type 2 diabetes in future as well as vascular complications remain high.

   Efficacy and safety of insulin degludec/liraglutide versus basal–bolus therapy in patients with type 2 diabetes: DUAL VII trial Top

Ambika Gopalakrishnan Unnikrishnan, Liana K. Billings1, Didier Gouet2, Alejandra Oviedo3, Helena W. Rodbard4, Nikolaos Tentolouris5, Randi Grøn6, Natalie Halladin6, Esteban Jodar7

Department of Endocrinology and Diabetes, Chellaram Diabetes Institute, Pune, Maharashtra, India, 1Endocrinology, Diabetes & Metabolism, NorthShore University Health System Evanston, IL/University of Chicago Pritzker School of Medicine, Chicago, IL, 2Department of Endocrinology, La Rochelle Hospital, La Rochelle, France, 3Santojanni Hospital and Cenudiab, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 4Endocrine and Metabolic Consultants, Rockville, MD, USA, 5Department of Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece, 6Medical and Scientific Affairs, Novo Nordisk, Søborg, Denmark, 7Department of Endocrinology, University Hospital Quiron Salud, Madrid, Spain.

E-mail: [email protected]

Objective: To assess the efficacy and safety of once daily IDegLira compared to BB insulin therapy. Materials and Methods: In a 26-week open-label trial, 506 patients (pts) with T2D uncontrolled on metformin and 20–50 units (U) insulin glargine U100 (IGlar) were randomized 1:1 to IDegLira or BB therapy (IGlar + insulin aspart up to 4 times a day). Results: Mean HbA1c decreased from 8.2% at baseline to 6.7% at end of trial in both arms; non-inferiority (by <0.3%) for IDegLira was confirmed (P < 0.0001; Table). A similar proportion of pts achieved HbA1c targets with IDegLira versus BB (66.0% vs. 67.0% for <7%/49.6% vs. 44.6% for ≤6.5% respectively). Total daily insulin dose was lower for IDegLira (40.4 U) vs. BB (84.1 U) (P < 0.0001). Body weight decreased with IDegLira and increased with BB (P < 0.0001); the rate of hypoglycemic episodes (HEs) was lower with IDegLira versus BB (P < 0.0001). More pts achieved a triple composite endpoint (HbA1c <7% with no HE in the last 12 wks and no weight gain) with IDegLira versus BB (34.9% vs. 4.7%; odds ratio 12.56 [6.46; 24.45] P < 0.0001). Mean pre- to postprandial plasma glucose increment decreased more with BB versus IDegLira (P = 0.0032). SF-36 (mental component summary) and TRIM-D (total scores) improved more with IDegLira versus BB (P = 0.0074 and P < 0.0001 respectively). Adverse event rates were similar. Conclusion: In patients with HbA1c >7% on metformin and IGlar, IDegLira versus BB resulted in similar HbA1c reductions, lower insulin dose, weight loss and lower risk of HEs.

   Insulin degludec/liraglutide is efficacious and safe in patients with type 2 diabetes with normal, mild, or moderate renal impairment: Analyses from phase 3 trials Top

Binayak Sinha, Vanita R. Aroda1, Bruce W. Bode2, Helena W. Rodbard3, Andreas Andersen4, Anne Kaas4, Tina Vilsbøll5

Department of Diabetes and Endocrinology, AMRI Hospital, Kolkata, India, 1Endocrinology, Diabetes, and Metabolism, MedStar Health Research Institute, Hyattsville, MD, 2Department of Medicine, Emory University School of Medicine, Atlanta, GA, 3Endocrine and Metabolic Consultants, Rockville, MD, USA, 4Medical and Scientific Affairs, Novo Nordisk, Søborg, Denmark, 5Steno Diabetes Center Copenhagen, University of Copenhagen, Denmark.

E-mail: encoregroup [email protected]

Objective: The DUAL I-V clinical trials investigated the efficacy and safety of IDegLira vs. different comparators; basal insulin, glucagon-like peptide-1 receptor agonist (GLP-1 RA) and placebo. This post-hoc analysis aimed to evaluate the effects of IDegLira vs. comparators in patients with T2D as a function of baseline renal function. Materials and Methods: Patients were grouped by their baseline renal function (normal, mild or moderate impairment, with estimated glomerular filtration rates [eGFR] of ≥90, ≥60-<90 and ≥30-<60 mL/min/1.73m2, respectively. Results: A1C reductions from baseline to end of trial were significantly greater with IDegLira vs. comparators in all baseline renal function groups. Across renal function groups, hypoglycemia rates were lower with IDegLira vs. basal insulin but higher vs. GLP-1 RA and placebo, and eGFR was unchanged at the end of trial for all treatments. Adverse event rates (per patient-year exposure) were similar for patients with normal, mild and moderate renal impairment (IDegLira [4.1, 3.8 and 4.6]; basal insulin [3.6, 3.6 and 3.5]; GLP-1 RA [4.8, 4.9 and 4.5]; placebo [3.0, 4.1 and 4.6]).Conclusion: IDegLira is safe and more efficacious than comparators in patients with mild or moderate renal impairment. The results resemble those observed in patients with normal renal function.

   Effect of metformin on hepatic antioxidant enzymes status: A study in streptozotocin hyperglycaemia induced Wistar albino rats Top

T. P. Seena, P. G. Sreejesh1, Ahamed Shahal1, Sreekumaran E1

Department of Endocrinology, Government Medical College, Thiruvananthapuram, 1Department of Life Sciences, University of Calicut, Malappuram, Kerala, India.

E-mail: [email protected]

Background: Diabetes mellitus is a non - communicable disease which develops due to derangement in metabolism. Oxidative stress is one of the consequences of phenotypic hyperglycaemia and is a risk of further complications in diabetes mellitus. This study examines whether the metformin treatment is a risk factor for increase in the oxidative stress response in hyperglycaemia induced rats. Objective: To evaluate the oxidative stress response on the basis of hepatic antioxidant enzymes in metformin treated and untreated hyperglycaemia induced rats. Materials and Methods: Total 18 adult Wistar albino male rats were used for this study. Rats (weighing about 150 – 220 g) were housed in a certified animal house with food and water ad libitum. Duration of the experiment was 30 days. All the experiments were conducted as per the approval of Institutional Animal Ethical Committee. On the 1st day of the experiment, twelve of the animals were injected with streptozotocin (IP) at a dosage of 40 mg/kg body weight after overnight fasting, and 6 animals were vehicle injected with citrate buffer alone. The blood glucose level ≥200 mg/dL was considered to be hyperglycaemic. Then the animals were grouped into group I – normal, group – II diabetic control and group III – diabetic test. On the 10th day of the experiment, animals were orally treated with metformin (100 mg/kg body weight) for group – III and drinking water (1.0 ml/kg body weight) for group I and group II respectively. After a 10 days' consecutive treatment, the blood glucose level was reduced in diabetic test group and the treatment was stopped for a few days. After a 5 days' interval, blood glucose level was found to be increased in metformin treated group. Then the treatment was continued for a further 5 days and blood glucose level was checked. On the 30th day, the experimental animals were sacrificed under deep anaesthesia and the organ liver was isolated for further investigation of hepatic antioxidant enzymes SOD, CAT and GST. A portion of the liver tissue homogenized with phosphate buffer (10% w/v) and supernatant was obtained for the enzyme analysis. Results: The results were expressed as mean ± SEM. Metformin treated groups showed better response and their blood glucose level reached 135.00 ± 12.61 mg/dL when compared with that of the diabetic untreated control groups (374.50 ± 28.60 mg/dL). The antioxidant enzyme status in liver tissue in diabetic condition, there was a statistical significant difference (P < 0.01**) between diabetic control and diabetic test (metformin treated) group. Conclusion: Metformin treatment significantly reduced blood glucose level and maintained the hepatic antioxidant enzymes SOD and GST and CAT to a normal level. Further oxidative stress biomarkers are to be done in this area for a better management of diabetes mellitus.

   Association of nonalcoholic fatty liver disease and metabolic syndrome with cardiovascular risk factors and atherosclerosis Top

S. Bajaj, Sandeep Kumar Prajapati, P. Saxena, R. K. Yadav, V. Misra, B. Nath

Motilal Nehru Medical College, Motilal Nehru Medical College, Allahabad, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a well known contributor for the development of cardiovascular disease. NAFLD is considered the liver component of metabolic syndrome. This study is aimed to assess the influence of NAFLD and metabolic syndrome on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), ankle-brachial pressure index (ABI). We also investigated the diastolic and systolic functional parameters of patients with NAFLD and the impact of metabolic syndrome on these parameters. Design: A cross sectional observational study. Patients and Measurements: The study was conducted on 48 non alcoholic subjects in the age range of 18-65 yrs. Metabolic syndrome was assessed by using IDF criteria (2005). Anthropometric factors- height, weight, waist circumference, BMI and blood pressure were measured. Liver ultrasonographic scanning was used for assessing fatty liver. Carotid atherosclerosis was assessed by B-mode ultrasonography of common carotid artery and internal carotid artery. Results: The prevalence of non-alcoholic fatty liver disease was 79.16% in non alcoholic populations and 73.68% of NAFLD pts had metabolic syndrome. After adjusting for potential confounding factors, NAFLD or MeTS was not associated with CIMT. However, individuals with both NAFLD and MeTS had a significantly higher risk of CIMT (P = 0.004). MeTS was significantly associated with ABI (P = 0.002) while NAFLD alone was not associated with ABI. Individuals with both NAFLD and MeTS had a significantly higher risk for ABI (P = 0.001). LVEF and LVDD were independent of NAFLD and Metabolic syndrome when considered as separate entity, however both were significantly associated with NAFLD and Metabolic Syndrome when they appeared together (P = 0.0003 and 0.002 respectively). ABI and CIMT could be significantly correlated with only S. Cholesterol among all the parameters of lipid profile (P = 0.029 and 0.0004 respectively). Conclusion: The results show that NAFLD and metabolic syndrome have a synergistic impact on the atherosclerosis and cardiovascular risk factors, which suggests that individuals with both NAFLD and metabolic syndrome should be strongly advised to engage in cardiovascular disease prevention strategies.

   Metabolic Bone: Disease Parathyroid carcinoma: Atypical presentation, diagnosed on ultrasound: A case report Top

Alka Ashmita Singhal, Sanjay Saran Baijal, Deepak Sarin1, Sowrabh Kumar Arora1, Ambrish Mithal2, Shafi Khuchay2, Parjeet Kaur2, Beena Bansal2

Medanta Division of Radiology and Nuclear Medicine, 1Medanta Head and Neck Onco Surgery, 2Medanta Division of Endocrinology and Diabetes, Medanta, The Medicity Hospital, Gurugram, Delhi NCR, India.

E-mail: [email protected]

We report here an atypical case of Parathyroid carcinoma in the neck which was diagnosed primarily on high resolution colour Doppler ultrasound imaging, followed by Surgery[1] (Parathyroidectomy and hemi thyroidectomy) and Histopathology. Clinical Details: A 66 year male, presented in Medical oncology with complaints of weight loss, back pain. CECT Spine showing multiple lytic lesions in D10, D12, and L4. Bone Marrow biopsy to exclude metastasis or multiple myeloma was negative. Patient was referred to endocrinology for elevated serum calcium levels. Biochemical Investigations: Serum Calcium to be 10.8 mg/dL. Serum PTH was 947.0 pg/mL and 25– OH Vitamin D 16.3 g/mL. SESTAMIBI scan showed left inferior parathyroid adenoma (below the lower pole of left thyroid gland) and ultrasound was advised as a routine preoperative localization before planned left inferior parathyroidectomy. ULTRASOUND showed a heterogeneous hypoechoic solid cystic lobulated mass lesion, measuring 38 × 21 × 29 mm, volume 11.2 cc below the lower pole of left thyroid gland. The margins of the lesion appeared to be in close proximity to the thyroid and adjoining structures. It showed amorphous calcifications and heterogenous increased vascularity, suggestive of parathyroid carcinoma.[2] Findings were discussed with the surgeon, and despite not so elevated serum calcium and PTH levels, parathyroid carcinoma was the likely diagnosis. Patient was counselled and a Left Hemithyroidectomy was done along with Left Inferior Parathyroidectomy. Histopathology showed Parathyroid Carcinoma.


  1. Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer 1973;31:600-5.
  2. Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. Am J Surg 1985;149:522-7.

   Better preoperative localization of hyperfunctioning parathyroid glands in primary hyperparathyroidism with four dimensional computed tomography Top

Ashish Sehgal, Gh. Mohammad Wani1, Shariq Rashid Masoodi, Raiz Ahmad Misgar, Khurshid Alam Wani2, Munir Ahmad Wani2, Romana Hamid3

Departments of Endocrinology, 1Radiodiagnosis, 2General and Minimal Invasive Surgery and 3Pathology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

E-mail: [email protected]

Introduction: In Primary Hyperparathyroidism (PHPT), accurate pre-operative localization of parathyroid adenoma (PA) is essential to facilitate a Directed Parathyroidectomy (DP).[1] Four dimensional computed tomography (4DCT) provides a way of detailed structural and functional imaging of abnormal parathyroid glands.[2] Objective: To evaluate role of Ultrasonography (USG), 99mTc Sestamibi scan (MIBI) and 4DCT for preoperative localization of abnormal parathyroid glands in patients with PHPT and compare with 'gold standard' surgical findings. Materials and Methods: 37 patients with PHPT planned for excision of hyperfunctioning parathyroid glands underwent USG of neck, MIBI and 4DCT preoperatively. Results of imaging were compared to intraoperative and histopathologic findings. Sensitivity and positive predictive value (PPV) of each imaging modality was calculated for lateralization of PA to correct side (Right or Left); and localization to correct quadrant of neck (Right Superior, Right Inferior, Left Superior or Left Inferior).[3] Results: Out of 37 patients with PHPT, 33 underwent surgery. 28 had single PA, 4 had ≥2 abnormal glands, 1 had ectopic (thymic) PA, while 4 patients refused surgery and hence not included in final analysis. For lateralization to correct side of neck, 4DCT exhibited better sensitivity (89.3%) compared to USG (63%) and MIBI (67.9%). Similarly, it localized PA to correct quadrant with sensitivity of 88.9%, which was more than that of USG (60%) and MIBI (64%). When both USG and MIBI were taken together, sensitivity of the combination for localization of PA (82%) was still inferior to 4DCT (88.9%). In patients with multigland disease, 4DCT missed 5/9 (55.6%) of abnormal glands, while USG and MIBI missed 4/9 (44.4%) and 3/9 (33.3) respectively. Both MIBI and 4DCT localized the ectopic (thymic) PA. Conclusion: 4DCT is more sensitive than combined USG and MIBI for preoperative localization of single PA in patients with PHPT.
Table 1: Accuracy of ultrasonography, MIBI and four-dimensional computed tomography for localizing parathyroid adenoma in patients with single gland disease

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  1. Bilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F, et al. Primary hyperparathyroidism. Nat Rev Dis Primers 2016;2:16033.
  2. Hoang JK, Sung WK, Bahl M, Phillips CD. How to perform parathyroid 4D CT: Tips and traps for technique and interpretation. Radiology 2014;270:15-24.
  3. Bhansali A, Masoodi SR, Bhadada S, Mittal BR, Behra A, Singh P, et al. Ultrasonography in detection of single and multiple abnormal parathyroid glands in primary hyperparathyroidism: Comparison with radionuclide scintigraphy and surgery. Clin Endocrinol (Oxf) 2006;65:340-5.

   Association of Vitamin D and parathyroid hormone with insulin sensitivity, beta cell function and gestational diabetes mellitus in pregnancy Top

A. Nachankar, N. Kotwal, V. Upreti, K. V. S. Hari Kumar

Department of Endocrinology, Army Hospital (Research and Referral), New Delhi, India.

E-mail: [email protected]

Objective: To evaluate the association of 25-hydroxy vitamin D (25OHD) and parathyroid hormone (PTH) with insulin sensitivity, beta cell function and gestational diabetes mellitus (GDM) in pregnancy. Materials and Methods: A cross-sectional observational study involving 75 pregnant women assessed for GDM at 24-28 weeks of pregnancy by 75 g OGTT (IADPSG criteria). A fasting venous sample was collected for plasma glucose (FPG), HbA1c, insulin, iPTH and 25OHD. After 75 gm glucose, samples for glucose and insulin were collected at one and two hours. Beta cell function by Matsuda index (MI) and insulin sensitivity using Insulin secretion sensitivity inde × 2 (ISSI-2) were calculated. We stratified the subjects into three groups as per the 25OHD level (1 >30; 2:20 – 30 and 3 <20 ng/mL) and PTH tertiles (1 <25; 2: 26 – 45 and 3 >46 pg/mL) to compare the MI, ISSI-2 and incidence of GDM. Results: The mean 25OHD level in groups 1, 2 and 3 were 17.2 ± 2.7, 25 ± 2.6 and 36.7 ± 3.5 ng/mL respectively. There were 40 women in the first tertile of PTH [15.7 ± 5.4 pg/mL], 15 in second tertile [28.9 ± 3.4 pg/mL] and 20 in the third tertile [47.2 ± 10.2 pg/mL]. Out of 14 women with GDM, 2 were 25OHD deficient, 7 insufficient and 5 sufficient. Three women with GDM were in first PTH tertile, 1 in second while the remaining 10 were in third tertile. MI and ISSI-2, though did not correlate with the 25OHD or GDM incidence, have reduced from first to third PTH tertile (P < 0.001). HbA1c, FPG, AUCgluc and GDM incidence were not statistically different with 25OHD status but increased from first to third PTH tertile with statistically significant differences (P < 0.001). Conclusion: Increased PTH and not 25OHD status was associated with insulin sensitivity, beta cell dysfunction and dysglycemia in pregnancy.

   Vitamin D toxicity: A prospective study from an area with endemic hypovitaminosis D Top

Raiz Ahmad Misgar, Arshad Iqbal Wani, Ashish Sehgal, Shariq Rashid Masoodi, Sajad Ahmad Malik, Mir Iftikhar Bashir

Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India.

E-mail: [email protected]

Objective: The literature about vitamin D toxicity (VDT), a rare but potentially serious condition is limited to case reports and animal experiments. We sought to assess the clinical characteristics and time taken for resolution of VDT. Materials and Methods: We studied 22 consecutive patients admitted with VDT. Toxicity was defined as hypercalcemia and serum 25-hydroxy Vitamin D (25-OHD >100 ng/ml), with hypercalciuria and suppressed intact parathyroid hormone (iPTH). All patients underwent clinical and biochemical evaluation as per a proforma. The treatments included saline hydration with diuresis (all patients), zoledronic acid (14 patients) and glucocorticoids (11 patients). After discharge the patients were followed monthly. Results: The age of patients (11 males and 11 females) was 59.00 ± 17.20 years (range 16–70 years). All had received multiple intramuscular injections of vitamin D3 in doses ranging from 2 to 30 million units. The mean serum calcium was 14.00 ± 1.44 with a range 11.20 to 17.20 mg/dl; 14 patients had severe hypercalcemia (serum calcium ≥14 mg/dl). The mean serum 25-OHD was 526.73 ± 595.11 ng/ml with a range of 105- 2800 ng/ml. The mean serum iPTH was 8.91 ± 6.68 pg/ml. Hypercalciuria was seen in all and azotemia in 17 patients. Gastrointestinal symptoms occurred in 21 patients, altered sensorium in 10 and 4 patients presented with pancreatitis; 6 patients had nephrocalcinosis. One patient died, 21 patients were discharged in stable condition, and 6 paients were lost to follow up. Out of 15 patients on follow up, hypercalcemia resolved in 14 and persisted in one patient. The mean time to resolution of hypercalcemia was 7.60 ± 1.55 months (range 4 -10 months). Conclusions: We conclude that VDT is not an uncommon cause of hypocalcaemia in our setting. Hypercalcemia can last months, be severe and present with life threatening manifestations like pancreatitis.

   Postmenopausal osteoporosis - Age stratified prevalence and optimal age for screening: A study from rural South India Top

Kripa Elizabeth Cherian, Nitin Kapoor, Nihal Thomas, Thomas V. Paul

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: Postmenopausal osteoporosis is the most common metabolic bone disease; its incidence continues to rise, as the population ages. Our objectives were to study the age stratified prevalence of osteoporosis in ambulant postmenopausal women, and to determine an optimal age to initiate screening in this population. Materials and Methods: It was a cross-sectional study conducted in 1565 ambulatory South Indian rural postmenopausal women. Bone mineral density (BMD) was estimated by Dual-energy Xray Absorptiometry (DXA) scan at femoral neck and lumbar spine. Age specific prevalence of osteoporosis was calculated among six groups that were stratified by five years each. Receiver Operating Characteristic (ROC) curve was constructed and area under curve (AUC) was calculated with various sensitivities and specificities to determine the optimal age for screening of osteoporosis (T score ≤ -2.5) in this population. Results: The mean (SD) age and body mass index (BMI) of this population were 60.7 (7.2) years and 26.2 (4.8) kg/m2 respectively. The prevalence of osteoporosis was 22% at femoral neck and 39% at lumbar spine. There was a significant increase in the prevalence of osteoporosis at both sites, in each successive age category (P < 0.001). The AUC for femoral neck and lumbar spine were 0.73 (95% CI 0.71-0.76) and 0.63 (95% CI 0.60 -0.66) respectively. Screening at the age of 65 years had good sensitivity and acceptable specificity of 84% and 44% respectively to diagnose osteoporosis at femoral neck. Conclusion: A significant proportion of this large cohort of south Indian healthy rural postmenopausal women had osteoporosis at either site with advancing age. Screening at the age of 65 years and beyond would appropriately identify a large number of these asymptomatic women.

   Bone mineral density in morbidly obese postmenopausal women: A paradox Top

Nitin Kapoor, Sahana Shetty, Kripa Elizabeth Cherian, Nihal Thomas, Thomas V. Paul

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objective: Obesity has long been considered to have a protective effect on bone, but specific complications in the morbidly obese are known to have a detrimental impact on bone architecture. We aimed to study the bone mineral density (BMD) in morbidly obese post-menopausal women and also to determine the prevalence of osteoporosis and osteopenia in morbidly obese postmenopausal women. Materials and Methods: Eighty five consecutive morbidly obese (BMI ≥35kg/m2) postmenopausal women, attending the bariatric clinic in a tertiary care centre in southern India, were enrolled. BMD was assessed at femoral neck (FN) and lumbar spine (LS) in all subjects using a dual-energy Xray absorptiometry (DXA) scanner. The data obtained was compared to age matched obese and non-obese postmenopausal controls. Results: The mean (sd) BMI of morbidly obese (n = 85), obese (n = 80) and non-obese (n = 85) subjects was 38.5 (3.2), 27.2 (3.9) and 21.1 (2.3) kg/m2, respectively. The mean (sd) age of these individuals was similar (P = 0.9) in the 3 groups [morbidly obese -58.1 (6.3), obese 57.6 (5.1) and non obese- 58.1 (4.4) years]. The mean BMD (gm/cm2) at the FN in morbidly obese individuals was found to be significantly lower as compared to the age matched postmenopausal obese controls (0.723 versus 0.762, P value = 0.03). The mean BMD (gm/cm2) at lumbar spine and hip was not significantly different. The mean BMD (gm/cm2) of non obese women, at FN (0.756), spine (0.625) and hip (0.733) was significantly lower than the other 2 groups (P < 0.001). The prevalence of osteoporosis and osteopenia in morbidly obese postmenopausal women at lumbar spine was 17% and 41% and that at femoral neck was 10% and 43%, respectively. Conclusion: Obesity may not be associated with an increased BMD and it may have a differential impact at various sites, especially in morbidly obese postmenopausal women. Further studies are needed to ascertain the driving factors that explain this paradox.

   Primary hyperparathyroidism in Kerala – Do we resemble the west? Top

Athulaya Ashokan, Rajeev Philip1, Cherian Jacob, C. S. Abdul Kadar, Keshavan Charamelsankaran, R. N. Sharma

Departments of Medicine and 1Endocrinology, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: The clinical spectrum in primary hyperparathyroidism (PHPT) though varied, has undergone a striking change in developed countries, with the predominant form being asymptomatic PHPT, detected on routine biochemical screening for other causes. Recent data from India showed that PHPT still presents with classic skeletal and renal manifestations. In this study, we analyzed clinical presentation, investigations, management, operative findings and immediate postoperative course of patients with histologically proven PHPT at our center. Aims: To study the clinical and biochemical presentation of HPT. Materials and Methods: Patients diagnosed to have newly diagnosed Primary hyperparathyroidism were studied. All patients underwent biochemical investigations including Calcium, Phosporus, Alkaline phosphatase, albumin, 25 OH vitamin D, PTH, creatinine, skeletal survey, urine calcium/creatinine, BMD and Parathyroid scan. The period of study was from September 2013 to June 2017. Results: Out of the 31 patients studied, 19 patients were female and 12 were male. 14 patients were incidentally detected during screening, (12 during checkups, 2 during screening of family members) and out of the rest 17, the presentation involved renal failure in 4 patients, altered sensorium in 4 patients, evaluation of renal calculi in 8 patients and fracture in 1 patient. The mean age was 42.7 ± 12.4 years. The mean calcium levels were 11.5 ± 1.8 mg/dl, phosphate was 2.8 ± 0.87 mg/dl. Mean PTH value was 206.4 ± 74.2 pg/ml. 2 patients had brown tumour on Skeletal survey. The Mean BMD was -3.6 ± 0.8 (femur neck), -3.9 ± 0.86 (spine) -3.9 ± 0.7 (forearm) The cause of hyperparathyroidism included single parathyroid adenoma in 18 patients, double adenoma in 6 patients, triple adenoma in one patient, ectopic adenoma (mediastinal) in 1 patient, hyperplasia in 5. 3 patients had MEN 1 syndrome. 5 patients had familial HPT (3 MEN1 associated). Conclusions: Hyperparathyroidsm in Kerala resembles the disease trend seen in the developed countries, than the rest of India, with more cases being picked up incidentally in the asymptomatic stage. Renal calculi is a very common presentation of hyperparathyroidism in our study. Fracture of bones and brown tumours were rare in our study, probably due to the early diagnosis.

   Effect of alendronate in postmenopausal osteoporosis Top

Palaparthi Sai Krishna Chaitanya, Vaikkakara Suresh, Alok Sachan, K. M. Sateesh, P. V. L. N. Srinivasa Rao1

Departments of Endocrinology and Metabolism and 1Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.

E-mail: [email protected]

Objective: To study the effect of alendronate on Bone mineral density (BMD) of lumbar spine, femoral neck and distal forearm in Post menopausal osteoporosis. Materials and Methods: Study Design: This study was a retrospective before after inteventional study. Study Population: Postmenopausal women on regular follow-up at endocrinology OPD, SVIMS who satisfied the following inclusion and exclusion criteria were included. Inclusion Criteria: (1) A T-score below –2.5 in the lumbar spine, femoral neck or total hip was taken as a diagnosis of osteoporosis (WHO) in post-menopausal women. (2) They should have BMD assessed atleast 2 years apart on Alendronate. Exclusion Criteria: (1) Patients suffering with other systemic diseases known to affect bone health (chronic kidney disease, chronic liver disease, malabsorption syndromes, connective tissue disorders). (2) Endogenous or exogenous cushings syndrome. (3) Hyperparathyroidism. (4) Hyperthyroidism. 35 women who satisfied the above criteria were included in the study. Baseline serum calcium, phosphorous, albumin, 25 hydroxy vitamin D and Paratharmone (PTH) were obtained from patient records. Bone mineral density (BMD) at 4 sites (lumbar AP, lumbar lateral, femoral neck, distal forearm) was recorded before and after treatment using DXA scanner (HOLOGIC Europe, Discovery QDR series, Belgium). Continuous variables were expressed as Mean ± SD. Comparison of means between baseline variables and post treatment variables was performed by paired t test. Results: Thirty five patients were included in the study. Mean age at entry was 56.6 ± 5.9 years. Baseline serum calcium, phosphorus, albumin, alkaline phosphatase, 25 hydroxy vitamin D, PTH were 9.8 ± 0.4 mg/dL, 3.8 ± 0.59 mg/dL, 4.07 ± 0.17 g/dL, 78 ± 14.2 U/L, 25 ± 8.6 ng/mL, 42.9 ± 17.6pg/mL respectively. Effect of Alendronate on BMD: Mean BMD at lumbar spine (AP) increased from 0.70 ± 0.08 to 0.74 ± 0.09 which was clinically significant (P = 0.002). T-score decreased from -3.04 ± 0.62 to -2.76 ± 0.85. BMD at femoral neck and forearm was maintained without any deterioration. Conclusion: Alendronate causes a significant increase in lumbar spine BMD and reduces the incidence of vertebral fractures. It also prevents the age related decline in BMD at femoral neck and distal forearm.

   Refractory seizures in a case of hypoparathyroidism Top

Harsh Parekh, Vaibhav Dukle, Srinivas Kandula, K. D. Modi

Department of Endocrinology, Care Hospital, Hyderabad, Telangana, India.

E-mail: [email protected]

A 28 year old male, product of consanguineous marriage was being treated for hypoparathyroidism since the age of 10 years with calcitriol and calcium preparations. He had previous reports of low calcium, high phosphorus, low PTH (2pg/ml) and CT scan brain showing basal ganglia calcification along with some subcortical and cerebellar calcification. For last 4 years he was also receiving anti-epileptic drugs (phenytoin sodium and phenobarbitone) for seizure disorders. Frequency of seizures had increased for last 6 months to almost every week. During present admission, biochemistry reports of hypoglycemia (blood glucose 46 mg/dl), hyponatremia (serum sodium: 117 meq/l) and hyperkalemia (serum potassium 5.6 meq/l) with normal renal function, made us to think of associated adrenal insufficiency. His serum cortisol was 0.2 mcg/dl with simultaneous ACTH 522 pg/ml. Subsequent clinical examination also revealed evidence of mucocutaneous candidiasis with nail and dental fungal infection. His nail scrapping was positive for dermatophytes. His general condition and seizures improved after correction of hypoglycemia, cortisol deficiency and electrolyte imbalance. Chronology of Type 1 Poly Glandular Failure is mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency, which manifest in same order in early childhood and almost all 3 components manifest by the age of 20 years. Two out of 3 manifestations are a must to label this condition of Type 1 PGF. Sometimes a masked component of this syndrome complex can create major hurdles in overall clinical management of the patient. We report one such case of Type 1 PGF whose adrenal insufficiency was diagnosed late and we feel it might be contributing to his recurrent and refractory seizures, a major clinical problem in his management. In conclusion, associated adrenal insufficiency and possibility of Type 1 PGF should be kept in mind in case of refractory seizures with primary hypoparathyroidism.

   A rare case of ectopic mediastinal parathyroid carcinoma Top

Aashish Reddy Bande1, Pramila Kalra1, P Venkatesh Rao2, Ravi Shankar Shetty3

1Department of Endocrinology, M.S. Ramaiah Medical College, 2Consultant Endocrine Surgeon, 3Consultant Cardiothoracic Surgeon, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Parathyroid carcinoma is a rare malignancy, accounting for 0.005% of all cancers, and ectopic parathyroid carcinoma is particularly very rare. Here we present a case of a 36 year old lady with mediastinal parathyroid carcinoma. Case Report: A 36 year old female presented with complaints of multiple fractures secondary to trivial trauma for past seven years. On examination she was conscious, oriented, bedridden with normal vitals. Initial evaluation showed hypercalcemia (corrected serum calcium of 12.1 mg/dl) with 25 hydroxy vitamin D level of 14.37 ng/ml and increased parathyroid hormone levels (2291 pg/ml). Her renal and liver parameters were normal. TC-99M Sestamibi scan showed an ectopic parathyroid adenoma in the mediastinum. Ga68 – Dotanoc PETCT showed a 10 × 6 mm nodule in the anterior mediastinum, abutting ascending aorta, with expansile somatostatin receptors expressing osteolytic lesions in the left iliac wing, left pubis, bilateral ribs suggestive of brown tumours of hyperparathyroidism. She underwent mediastinal exploration and an ectopic parathyroid adenoma was found between the tracheal carina and pulmonary trunk and was removed. Post operative PTH levels on day 1 and day 2 were 604.4 pg/ml and 11.30 pg/ml respectively. Histopathology report was suggestive of well differentiated parathyroid carcinoma. Discussion: Ectopic mediastinal parathyroid carcinoma is a very rare entity. The biochemical evaluation revealed hypercalcemia with primary hyperparathyroidism. Sestamibi and Dotonoc scan were suggestive of ectopic parathyroid in the anterior mediastinum with brown tumours. Histopathology report confirmed the diagnosis of parathyroid carcinoma. Post surgery her calcium and PTH levels became normal. On follow up patient was able to ambulate and started walking without support after eight months of surgery. Conclusion: Ectopic mediastinal parathyroid carcinoma even though is a rare disease, but a well identified entity and a treatable condition. Prognosis following successful surgery is very good especially in reducing the morbidity.

   Correlation of Vitamin D levels with immunological and virological parameters in HIV-infected adults Top

Ellareddy Chinthala, Neelaveni Kudugunti, Rakesh Kumar Sahay

Department of Endocrinology, Osmania Medical College Hyderabad, Telangana, India.

E-mail: [email protected]

Background: Vitamin D is an immune-modulatory agent and benefits patients with HIV/AIDS. It reduces the risk of bone mineral loss and osteoporosis, improves the immune system by producing proteins cathelicidin and defensins that help fight bacteria and viruses. Objectives: This study observes Vitamin D levels in HIV infected adult patients to correlate Vitamin D levels with clinical presentation, CD4 counts and HIV viral load and to observe the effect of various HAART regimens on Vitamin D levels. Materials and Methods: A cross-sectional, observational study was done at a tertiary care referral centre for HIV patients in Osmania General Hospital, Hyderabad from June 2016 to January 2017 with 100 HIV-infected adults above 18 years, with and without antiretroviral treatment, recruited by systematic random sampling (every 10th patient). Patients with renal insufficiency (GFR < 30 mL/min), liver disease and patients on vitamin D replacement were excluded. The variables are plasma levels of 25(OH) D, CD4 count and viral load. The Statistical software R v. 3.2.3 was used for data analysis. Results: The prevalence of subnormal vitamin D levels (<30 ng/ml) in study population was 93%. The mean vitamin D levels in, asymptomatic patients was 23.31 ± 6.95 ng/ml, with category B symptoms was 16.5 ± 5.78 ng/ml and in patients with category C symptoms was 13.3 ± 5.18 ng/ml (P value <0.001). Of the total 72 patients in non ADI group, 39 (54.2%) had vitamin D deficiency, 26 (36.1%) had vitamin D insufficiency, and 7 (9.7%) had normal vitamin D levels. In ADI group, 26 (92.9%) had vitamin D deficiency, 2 (7.1%) had vitamin D insufficiency and none had normal vitamin D levels. The mean ± SD in non ADI and ADI groups (20.49 ± 7.33 Vs 13.01 ± 4.47) was statistically significant (P value = 0.0012). Vitamin D levels in the study population positively correlated with the CD4 counts, with a P value of <0.001 and negatively correlated with the HIV viral load, with a P value of <0.001. The prevalence of Vitamin D deficiency in patients with EFV based regimens was 26 (89.7%), and TDF based regimens was 27 (87.1%). Conclusions: Lower vitamin D levels correlated with greater clinical severity, higher viral load and statistically significant positive correlation of vitamin D levels with CD4 count. In patients on HAART, EFV based and TDF based regimens, higher was frequency of subnormal vitamin D levels. It can be concluded that vitamin D may be a good index of disease progression in HIV patients.

   Hypocalcemic cardiomyopathy: A rare case report Top

Sunetra Mondal, Debmalya Sanyal1

Department of Endocrinology and Metabolism, IPGME&R, 1Department of Endocrinology and Metabolism, KPC Medical College and Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

Introduction: Cardiomyopathy can occasionally be reversible if the underlying etiology can be corrected. Hypocalcemia can predispose to cardiac failure by reducing sodium excretion, prolonging the phase 2 of Action Potential and predisposing to arrhythmias or by reduced contractility of cardiac myocytes. Case: 43 y/M presented with acute LV failure following an episode of severe gastroenteritis. He was non-diabetic, non-alcoholic without any prior history of cardiac symptoms or known cardiac illness. Two years back, he underwent a total thyroidectomy for papillary thyroid carcinoma followed by radioiodine ablation. Immediate post-operative period was uneventful and he was discharged with LT4 and calcium supplements and had been asymptomatic over past 2 years. Clinical examination revealed a positive Chvostek's sign in addition to features of overt CCF. Investigations revealed normal Hb, renal function and T4, TSH levels. ECG- QTc was 480 ms; no evidence of ischemia. ECHO: global hypokinesia with EF 25% and dilated LV cavity. NT-pro BNP was very high. Serum corrected calcium was 5.7 mg/dl, PO43- was 9.4 mg/dl and iPTH 3.7 pg/ml. CT brain showed dense B/L basal ganglia calcification. He was managed with adequate diuretics, ACEi and beta blockers with some clinical response. Correction of hypocalcemia with parenteral calcium followed by oral calcium and calcitriol led to further clinical improvement and he reached NYHA class 1 by ten days. He was discharged with oral calcium, calcitriol and LT4. At two months follow up, he was asymptomatic without the need for diuretics. Corrected Calcium had improved to 8.9 mg/dl by four months. QTc was normalized. ECHO at 2 months and 4 months showed an increase in EF of 49% and 67% respectively with normalization of LV dimensions. Conclusion: Chronic hypoparathyroidism presenting with hypocalcemic cardiomyopathy is rare but calcium levels should be monitored in cardiomyopathy patients with a plausible clinical background.

   Relation of bone mineral density with homocysteine and cathepsin K levels in postmenopausal women Top

Pratishtha Mishra, Madhukar Mittal, Rajeev Verma1, Arvind Mishra1, Ajai Singh2, Vivek Kumar1, K. K. Sawlani, M. Kaleem Ahmed3, Rishika Gaur1

Departments of Endocrinology, 1Medicine, 2Orthopedics and 3Biochemistry, KGMU, Lucknow, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: Homocysteine (HCY) interferes with collagen cross-linking in bone and stimulates osteoclast activity. The activated osteoclasts secrete cathepsin-K (CathK), a cysteine protease, in eminent quantity during bone resorption. Hyperhomocystinemia may affect bone mineral density (BMD) through CathK. We therefore examined the relationship between HCY and BMD along with cathepsin-K, 25-hdyroxyvitamin D [25(OH) D], intact parathyroid hormone (iPTH) and vitB12. Methods: We recruited a total of 93 postmenopausal women between ages 40–65 years, attending the Endocrine OPD at King George's Medical University. BMD was done by DXA scan using Hologic QDR1000 system. Based on WHO criteria, patients were segregated into three groups: normal bone mass, osteopenia and osteoporosis. All women underwent routine biochemical laboratory parameters, HCY, vitamin B12 and CathK levels. Results: Of the 93 postmenopausal women, 56% (52) had osteoporosis. 18 (19%) had normal BMD (mean age 53.2 ± 8.5 years) and 23 (25%) had osteopenia (mean age 52.8 ± 6.7 years). The mean age of females in the osteoporotic group was 56.2 ± 6.9 years. The median (IQR) levels of HCY in the three groups were 14.5 μmol/L (12.2-24.7), 15.05 μmol/L (12.1-19.9) and 13.2 μmol/L (10.3-17.0) respectively. CathK levels were similar in the three groups 7.6 ng/ml (7.0-80.5), 8.3 ng/ml (7.3-8.5), 8.6 ng/ml (7.2-8.9). Both HCY and CathK were found positively associated with serum phosphorus (r = 0.584, P < 0.01 and r = 0.249, P < 0.05 respectively). Levels of homocysteine positively correlated with PTH (r = 0.303, P < 0.01) and inversely with vitamin B12 (r = -0.248, P < 0.05). No significant association was seen between CathK level and 25(OH) D, iPTH, serum calcium. Conclusions: More than half of the postmenopausal females had osteoporosis. Less than one-fourth of the postmenopausal females had normal BMD. There was no significant difference found in HCY and cathK levels between the three groups. BMD neither correlated with HCY nor with cathK. Hence our data suggest that HCY and cathK do not reliably correlate with bone loss in postmenopausal women. Phosphorus levels correlating with HCY and CathK could be an area of further research in bone loss pathophysiology.

   Reversible dilated cardiomyopathy as presenting feature of primary hypoparathyroidism Top

Ch. Sree Harsha Varma, T. V. S. Pradeep, K. Dileep kumar, P. Amaresh Reddy

Department of Endocrinology, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India.

E-mail: [email protected]

Introduction: Hypoparathyroidism is associated with chronic hypocalcaemia which can have a variety of manifestations including cardiovascular changes. Hypocalcemic cardiomyopathy is a rare but potentially reversible cause of heart failure. We describe here a case of primary hypoparathyroidism presenting as a dilated cardiomyopathy in addition to other manifestations. Case Report: A 40 year old female presented to cardiac emergency with complaints of acute dyspnoea and pedal oedema. On evaluation she has severe LV dysfunction with ejection fraction (EF) of 24% and dilatation of all chambers with global hypokinesia. Her ECG showed prolonged QTc interval of 520 msec following which serum calcium was ordered, which showed hypocalcemia (4.5 mg/dl). She had a history of bilateral premature cataract and recurrent generalized tonic clonic seizures since 4 years for which she is on sodium valproate. She also has history of carpopedal spasms of both hands. On examination she has short stature with height of 147 cm, Chvostek's and Trousseau's signs were positive, pitting of nails, subcutaneous calcifications over the dorsum of hands, easily pliable hair, enamel hypoplasia and premature loss of teeth. AHO phenotype was not present. Her biochemical investigations showed serum Calcium - 4.5 mg/dl, serum Albumin - 3.26 g/dl, serum Phosphorus - 8.8 mg/dl and iPTH - 4.8 pg/ml based on this the diagnosis of primary hypoparathyroidism was made and she was started on calcium supplementation, calcitriol and phosphate binders. Her EF improved from 24% to 40% as the calcium returned to baseline in 6 days. Her symptom improved and was discharged. Two weeks later in follow up she was completely asymptomatic and EF improved to 50%. Conclusion: Hypocalcemia is a rare but treatable cause of DCMP and therefore should be looked for in all unexplained cases of severe LV systolic dysfunction.

   Six-year retrospective study on emerging pattern of asymptomatic hyperparathyroidism in South India Top

Ganesh Viswanathan, Vivek Mathew, V. J. Mallikarjuna, Vageesh Ayyar, Ganapathy Bantwal, Belinda George, G. N. Hemanth1, John Michael2

Departments of Endocrinology and 1Surgical Oncology, St. Johns Hospital and Medical College, 2Department of Biostatistics, St. Johns Research Institute, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Primary hyperparathyroidism (PHPT) is a common endocrine disease with a variable clinical presentation. PHPT is usually symptomatic at presentation in majority of the patients, especially in developing countries. As the accessibility to investigations, advanced imaging methods and surgical procedures are improving the clinical profile of the patients with PHPT has undergone a palpable change compared to the earlier description. There is a recent increase in number of asymptomatic cases due to the use of multichannel automated analysers. Hence we decided to look for a change in clinical, imaging and surgical outcomes of PHPT patients from South India. Methods: We collected the data on clinical presentation, biochemical findings, radiological features and operative findings of patients with PHPT treated in our hospital from 2011-2017. Cases of PHPT were identified from the laboratory values using the biochemical criteria, after the exclusion of secondary and tertiary hyperparathyroidism cases. Results: Our study identified 80 patients with age ranging from 16 to 76 years. Significant proportions (40%; n = 32) of the patients were asymptomatic. Number of females in the study were 47 and males were 33. We compared the presentations between symptomatic and asymptomatic groups. We found that with increase in Preoperative PTH, the adenoma gland weight increased (0.0005291 gms per unit increase in PTH); but there was no significant difference between the two groups. We found no significant difference in the mean age at presentation between the groups. No significant differences between mean values of calcium, ALP, gland weight and PTH was found between the two groups. We found no significant between group differences in the incidence of post-operative hypocalcemia. Conclusion: Asymptomatic hyperparathyroidism constitutes a significant proportion of hyperparathyroidism cases in South India. The differences between symptomatic and asymptomatic hyperparathyroidism is getting blunt with early detection of cases and high index of suspicion in patients with non-specific symptoms unexplained by other routine work up.

   A Randomized Double Blind Controlled Trial to Investigate the Effects of Vitamin D supplementation on maternal and new-born baby's vitamin D status in Asian-Indian Subjects Top

Tarang Gupta, Garima Kachhawa, Harshna Sharma, Jaya Bajpai, Vidushi Kulshreshtha, Rajesh Khadgawat, Nandita Gupta, V. Sreenivas, Arul Selvi

Department of Endocrinology, Obstetrics and Gynecology, Biostatistics, Pediatrics, and Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India.

E-mail: [email protected]

Introduction: High prevalence of vitamin D deficiency (VDD) has been well documented during pregnancy. Maternal vitamin D status has been linked to maternal and fetal outcomes. It is hypothesized that supplementation of vitamin D during pregnancy may improve these outcomes. We planned a study to investigate the efficacy of vitamin D supplementation, given in early stage of pregnancy, on maternal, fetal and newborn parameters. Materials and Methods: This randomized double blind active controlled clinical trial was carried out in pregnant subjects attending antenatal clinic, AIIMS. The inclusion criteria were age between 18-40 years, singleton pregnancy with gestational age between 12-16 weeks. Any subject who had high risk pregnancy, or any systemic disease, or received vitamin D supplementation in doses exceeding 600 IU in last three months, on any medication known to affect metabolism of vitamin D were excluded. Similarly, after screening, any subject with serum vitamin D level (S.VitD) >100 ng/ml or serum calcium more than upper limit of normal were also excluded. Sample size for this study was calculated based on primary outcome of improvement of vitamin D status of mother at the time of delivery. Subjects randomized into four groups in ratio of 1:1:1:1 (Group 1 - active control group received 600 units of vitamin D per day; Group 2 – 1000 units/day; Group 3 – 2000 units/day; Group 4 - 4000 units per day). All groups received 1000 mg of elemental calcium (in two divided doses), and similar nutritional and lifestyle advice for standard management of pregnancy. Doses of vitamin D were calculated on daily basis but given orally, once a month, supervised in hospital. The primary outcome of the study was changes in vitamin D status of mother and newborn. Secondary outcomes of the study were weight gain during pregnancy, blood pressure, preterm labor, pre-eclampsia, fetal growth, newborn's anthropometry, and insulin resistance in mother as well as in cord blood. Safety of intervention was assessed by regular monitoring of urinary calcium creatinine ration and serum calcium levels. Results: Total 243 subjects completed the study and were analyzed. High prevalence of vitamin D deficiency was seen in study population. Of total 243 subjects, 93.6% of subjects had VDD (S.VitD <20 ng/ml) while 97.5% subjects had S.VitD level <30 ng/ml. No significant difference was seen in S.VitD level among all four groups. Improvement in S.VitD level after supplementation is shown in (Table 1). Among cord S.VitD status, 77.8% babies in group 1, 47.1% in group 2, 17.8% in group 3 and 6.2% in group 4 were VDD. Apart from S.VitD level, no significant difference was observed among all four groups in any other maternal, fetal and newborn parameters (maternal wt gain, pre-eclampsia, fetal growth, newborn's anthropometry, and insulin resistance in mother as well as in cord blood). Conclusion: Our study shows that supplementation of vitamin D in mother improves vitamin D status of newborn. However, vitamin D supplementation during pregnancy did not shown any effect on any other maternal, fetal and newborn parameter.
Table 1

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   Changes in bone mineral density and bone markers over a year in liver transplant recipients: A prospective study Top

Neha Singhal, Arun. S. Menon, V. P. Praveen, Nisha Bhavani, Nithya Abraham, Vasantha Nair, Harish Kumar, S. Sudhindran

Department of Endocrinology, Amrita Institute of Medical sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

E-mail: [email protected]

Objectives: Hepatic Osteodystrophy is common is common in patients with chronic liver disease with worsening in the first 3-6 months after liver transplantation. Data on Indian patients regarding post liver transplant changes in bone health are scarce. We prospectively followed the changes in BMD and bone markers over a year in patients who underwent liver transplant in our centre. Methods: 60 adult patients with liver cirrhosis who underwent liver transplantation from Jan 2014 to September 2015 were prospectively followed up. BMD at lumbar spine and femoral neck, bone markers like serum osteocalcin (OC) and urine DPD (deoxypyridinoline) and other biochemical parameters were measured at baseline, at 4 months and at 1 year (11 patients) post-transplant. Results: Baseline characteristics showed BMD at lumbar spine to be lower compared to femur. Lower BMD at spine was found to positively correlate with duration of liver cirrhosis. Osteoporosis prevalence was 25.9% and 33.3% for patients >50 years and <50 years respectively. Pre transplant patients had a lower vitamin D status (median-14.30 ng/ml). They showed lower levels of bone formation marker (serum OC mean 10.05 ng/ml) and a higher level of bone resorption marker (urine DPD mean 14.08 nmol/mmol creatinine). On follow up 14 patients (23.33 %) died before 4 months of follow up. 39 patients had complete data at 4 months of follow up and showed a statistically significant worsening of BMD at right and left femur at 4 months after liver transplant (P value 0.01 and <0.001 respectively). While BMD at lumbar spine improved at 4 months (P value 0.03) and continued to improve at 1 year after transplant with statistically significant P value 0.01. BMD at femur did not show any statistical significant change but showed a trend toward decline at 1 year. Serum osteocalcin improved to a mean of 37.45 ng/ml (P value < 0.001). No fractures were recorded for a minimum of 6 months follow up. Conclusions: A year follow-up of post liver transplant patients shows an ongoing improvement in spine BMD with a suggestion of decline in femoral BMD. While the former finding is reassuring, we need further long term follow-up of femoral BMD changes to confirm whether the decline would persists and turn out to be clinically significant in terms of hip fractures.

   Study of the correlation of fat mass and lean mass with measures of bone health in overweight and obese eastern Indian adults Top

Sayan Ghosh, Ghosh Soumitra, A. K. Basu, A. Maiti, A. Sinha

Department of Endocrinology, Medical College, Kolkata, West Bengal, India.

E-mail: [email protected]

Introduction: Increased in Fat mass and decrease in Lean mass in obesity have a deleterious effect on bone health. Interrelation between Obesity and Osteoporosis is a rising health problem in our community. Objective: The purpose of this study is to establish a correlation of Total Fat mass and Total Lean mass with Bone Mineral Density (BMD) and Bone Mineral Content (BMC) in Overweight and Obese adults. Methods: A cross-sectional study was conducted in 60 overweight and obese subjects aged 18-60 years in male and 18 – 45 in female. Total body, Lumbar spine and Femoral neck BMD, BMC along with Total Fat mass and Total Lean mass were measured by DEXA. To evaluate the correlation of Fat mass and Lean mass with BMD and BMC Pearson's correlation test or Spearmen correlation test were used in Simple Linear Regression model. Results: Among the study population, 38 (63.3%) were female and 22 (36.7%) were male, 20 (33.3%) were overweight and 40 (66.7%) were obese. After controlling age and sex, Total Fat mass was significantly negatively correlated with BMD of Spine (P = 0.049, r= -0.134) only and BMC (P = 0.0001, r= -0.47) but Total Lean mass was significantly positively correlated with BMD of Spine (P = 0.0002, r = 0.47), BMD of Femoral neck (p=<0.0001, r = 0.61), BMD of Total body (p=<0.0001, r = 0.69) and BMC (p= <0.0001, r = 0.74). BMI values were not significantly correlated with BMD and BMC. Conclusion: Lean mass had a significant beneficial effect on BMD and BMC in overweight and obese subjects irrespective of age and sex. The effect is more prominent than the deleterious effect of Fat mass on bone health. Lean mass can be considered as one of the determinants of Bone mass, even better than the Fat mass, where simple BMI is ineffective in predicting Bone mass.

   Thyroid: Papillary thyroid carcinoma with tall cell histology: Prevalence, clinico pathological characteristics, comparison with classic papillary thyroid carcinoma and short term outcome Top

Geethalakshmi Sampathkumar, Vasantha Nair, Usha V. Menon, Nisha Bhavani, Praveen V. Pavithran, Harish Kumar, Arun S. Menon, Annie Pullikkal

Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Objectives: Papillary Thyroid Cancer (PTC), usually has excellent prognosis except for certain aggressive subtypes such as Tall cell variant. Our aim is to study the clinicopathological characteristics of PTC with Tall Cell histology (PTC-TCH) and compare it with classical PTC (cPTC). The WHO and ATA have described Tall Cell Variant (TCV) as PTC with >50% tall cells. Materials and Methods: This is an analysis of PTC-TCH patients who are being followed up in Thyroid Cancer Clinic of our hospital. From our prospective database, we took 742 consecutive DTC patients from 2010-17 with complete data out of which 40 PTC-TCH patients were compared with 352 cPTC. In view of the small number, tumours with tall cell variant (tall cells >50%) and focal tall cell features (tall cells <50% were grouped together (PTC-TCH). Results: Prevalence of PTC-TCH was 5.3% (40/742 DTC) and 10.2% (40/392 PTC) with 52.5% females. Mean age was 42.9 years. Mean tumour size was 30.3 mm. When pathological features were compared, PTC-TCH had more (P < 0.05) extrathyroidal extension (55% vs 30.4%) and distant metastasis (20% vs 6.5%) (predominantly lung-17.5% vs 4.5%) than cPTC. Multivariate analysis showed that PTC-TCH was strongly associated with Lung metastasis. Out of those with follow up >6 months, 72% have incomplete/indeterminate response to therapy at last follow up. We grouped PTC-TCH into TCV (>50% tall cells) and focal tall cell (TCF) group (<50% tall cells). Surprisingly more patients in TCF group had incomplete/indeterminate response compared to TCV. Conclusion: Patients with PTC-TCH have aggressive clinicopathological features like extrathyroidal extension and distant metastasis. Also there was less vascular invasion and multifocality when compared with the various published data. We conclude that (1) percentage of tall cells did not affect the prognosis, (2) Early appearance of lung metastasis raises concern requiring close follow up (3) Tall cell histology is an important prognostic factor in patients with PTC influencing the survival.

   Changing spectrum of recent onset thyrotoxicosis and trends in thyroiditis: A three year study Top

Rajeev Philip, Sarojiniamma Cheradiyil Sivaramannair1, Varkey Kuruvilla2, C. S. Abdul Kadar1, Keshavan Charamelsankaran1, R. N. Sharma1

Departments of Endocrinology and 1Medicine, PIMS, Thiruvalla, 2Department of Nuclear Medicine, Bharath Hospital, Kottayam, Kerala, India.

E-mail: [email protected]

Introduction: Thyroiditis is considered as the least common cause of thyrotoxicosis as per classical literature. But our experience has been quite different, and we have found that thyroiditis is very common in Kerala. Added to that, there are definite seasonal trends and varying presentations. This study is intended to highlight these aspects. Aims: To evaluate the cause of thyrotoxicosis in patients presenting with symptoms and biochemical features of thyrotoxicosis. To look at the seasonal and year wise trends in thyroiditis. To study the natural course of thyroiditis. Materials and Methods: All patients with recent onset thyrotoxicosis (defined as symptoms less than 4 months) who presented to the medicine OPD from Jan 2013 to December 2016 were studied. Relevant clinical data was collected and thyroid function tests, ESR, CRP, Total and differential count was done for all patients. All patients underwent a thyroid ultrasound and technetium uptake scan. Results: A total of 387 patients were studied. The average age of the study population was 34.4 years, with male to female ratio of 0.48. 67% of the cases had thyroiditis as the cause of thyrotoxicosis. Graves was seen in 18%, toxic MNG in 7% and 3% had toxic adenoma. As for the seasonal trends, majority of the thyrotoxicosis occurred in the winter months (Oct, Nov, Dec, Jan) 58%, with very few case during summer months (Feb, March, April, May)- 12%, with a small increase during the rainy season (June, July August Sept) 30%. Thyroiditis has a define annual trend, with majority of the thyroiditis in 2013 being painless (69.5%). In 2014, majority was painful, (71%) and was presenting with prolonged fever (61%). 2016 was the year of pseudonodular thyroiditis, with thyroiditis mimickingthyroid nodules (58%) As for the follow up of thyroiditis, (6 months), 92% have become euthyroid. Conclusions: Thyroiditis is the most common cause of thyrotoxicosis in central Kerala, which is in stark contrast to the classic literature. The reason for this variation is not known, but thyroiditis should be ruled out in all patients with new onset thyrotoxicosis, before starting them on anti thyroid therapy. There is marked seasonal variation in the occurrence of thyroiditis, and thyroiditis can have varying presentations including painless, painful, pseudonodular and fever of prolonged duration. The clubbing of similar presentation may be due to seasonal viruses. Most of the thyroiditis cases recover.

   Serum ferritin levels in thyrotoxicosis Top

Aswathy Sasidharan, Rajeev Philip1, Cherian Jacob, C. S. Abdul Kadar, Keshavan Charamelsankaran, R. N. Sharma

Departments of Medicine and 1Endocrinology, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: Thyrotoxicosis is a common clinical problem and may be due to Graves disease, toxic multinodular goitre or subacute thyroiditis. The search for a blood test for differentiating Graves disease from thyroiditis would prove to be of immense value, as it will do away with the need of doing a uptake scan. Aims: To study ferritin levels in various types of thyrotoxicosis. To study the utility of ferritin in differentiating the various causes of thyrotoxicosis. Materials and Methods: Patients with the diagnosis of thyrotoxicosis based on signs, symptoms and biochemical parameters were included in the study. The study was done in the department of endocrinology PIMS, Thiruvalla, Kerala and the study period was from June 2016 to May 2017. All patients underwent a technetium scan for finding the etiology of thyrotoxicosis. A total of 46 patients were studied. Ferritin levels were done in all patients. Results: Out of the 46 patients studied, 26 patients has subacute thyroiditis, 16 had Graves, and 4 had toxic MNG. Ferritin levels were significantly high in the SAT group (398.3+/- 42.8 mcg/l) as compared to the Graves group (185.8+/- 32.3 mcg/L) and toxic MNG group (161.7+/- 48.1 mcg/L). A high ferritin level had a sensitivity of 90.91%, specificity of 70.00%, positive predictive value of 76.92% and negative predictive value of 87.50% in differentiating SAT from Graves disease. Conclusions: Serum ferritin levels is emerging as a useful laboratory investigation in differentiating thyroiditis from Graves disease. This simple lab test may replace the more expensive and laborious Technetium scan in differentiating thyroiditis from Graves disease.

   Impairment of health-related quality of life among Indian patients with hypothyroidism Top

Rakesh Boppana, C. Shivaprasad, Amit Goel, Anish Kolly

Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background and Objectives: Health-related quality of life (HRQL) is an important outcome measure for various diseases, although there are sparse data regarding HRQL among Indian patients with hypothyroidism. Therefore, this study aimed to assess HRQL among Indian patients with hypothyroidism using the SF-36 questionnaire. Methods: This cross-sectional study evaluated 244 consecutive patients with hypothyroidism who were treated at the Vydehi Institute of Medical Sciences and Research Centre in Bangalore. All patients were > 18 years old and visited the outpatient department for endocrine treatment. Perceived health status was evaluated using the SF-36 questionnaire. The patients' data were compared to data from 250 age- and sex-matched healthy controls. Results: Compared to the healthy controls, the patients with hypothyroidism had significantly lower scores for six of the eight SF-36 scales. No significant inter-group differences were observed in the “role emotional” and “social functioning” dimensions. Interpretation and Conclusions: Hypothyroidism was associated with reduced HRQL among Indian patients. These patients generally experienced greater reductions in physical dimensions, compared to social and emotional dimensions.

   Paediatric DTC – A single centre experience Top

Kingini Bhadran, Nisha Bhavani, Vasantha Nair, Praveen V. Pavithran, Harish Kumar, Arun S. Menon, Usha V. Menon, Nithya Abraham, Annie Pullikkal

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Objectives: To study the demographic characteristics of paediatric thyroid cancer, applying current ATA risk stratification system and to study the factors that would influence the outcome of treatment in an Indian cohort of patients. Methods: A retrospective study of patients less than or equal to 18 years of age with DTC being followed up in a single centre from 2008 onwards. Results: 43 patients were included in the study. Mean age at diagnosis was 14.1 years and 77% were female. Mean duration of follow up was 37.5 months. 28 (65%) of them underwent total thyroidectomy with lymph node dissection, whereas 12 of them underwent total thyroidectomy alone and 3 of them underwent an initial hemithyroidectomy followed by completion thryoidectomy. Most common histopathological type was classical papillary carcinoma thyroid (n = 27, 63%), followed by follicular variant of papillary carcinoma thyroid (FVPTC) (n = 11, 25.6%) and other high risk variants (25.6%). The high risk histopathological types seen in our cohort were diffuse sclerosing (n = 3), tall cell, follicular and cribriform-morular variant (n = 1 each). Classical papillary carcinoma showed greater remission rate compared to FVPTC and other high risk subtypes (P = 0.001). 81% (35) had lymph node metastasis at diagnosis. However the presence of lymph node metastasis didnot influence the outcome. All except 2 underwent high dose radioiodine ablation in view of residual thyroid tissue/elevated thyroglobulin levels. 2 of them had distant lung metastasis however they had non progressive disease at the end of follow up. The final outcome showed no evidence of disease (NED) in 17, persistant disease in 15, decreasing antitg antibody levels in 7 patients. None of them had progressive disease. Applying the current ATA risk stratification, 9 belonged to low risk, 25 to intermediate risk and 9 to high risk groups respectively. However this stratification didnot predict outcome. Conclusions: Paediatric DTC was found to have good outcome in the study cohort. Presence of lymph node metastasis at diagnosis was not found to determine their outcome whereas the histological subtype did influence the outcome. However the utility of ATA risk stratification to predict outcome needs larger studies.

   Neglected congenital hypothyroidism: A case report Top

Sanjay Saran, Balram Sharma, Hardevaram Nehara, Vijay Kumar Bhavi

Department of Endocrinology, SMS Medical College, Jaipur, Rajasthan, India.

E-mail: [email protected]

Congenital hypothyroidism, occurring in approximately 1:2000 to 1:4000 newborns, is the most common preventable cause of mental retardation and delay in physical growth. Geographic location and ethnicity have a great impact on its prevalence. The incidence of congenital hypothyroidism has risen mainly because of changes in newborn screening strategies. Sometimes it is diagnosed during childhood but we reported a case of congenital hypothyroidism who left untreated till age of 32 years. Case Report: A 32-year-old male was brought to the endocrinology OPD for evaluation of slurring of speech, difficulty in walking and frequent fall. He also had a history suggestive of mental retardation. On physical examination, he had a short stature with bone age of 13 years, large head, short neck, facial puffiness, coarse hair, dry and cold skin, pallor, macroglossia, and non-pitting edema. His tendon reflexes showed delayed relaxation. His sexual maturity score was A3 P5, Testicular volume 24 ml bilateral. The electrocardiogram showed sinus bradycardia with low voltage complexes, and no electrical alternance was observed. Chest X-ray showed enlarged cardiac silhouette and echocardiogram revealed mild pericardial effusion. On routine biochemical and hematological test he had megaloblastic anaemia and raised CPK and LDL. On thyroid function test TSH was 1664 μIU/ml and FT4 was 0.17 ng/dl. His EMG was done which showed myopathic affection. His MRI Pituitary showed pituitary macroadenoma with mild compression over optic chiasm. In neck ultrasonography no thyroid tissue was detected. On psychiatric evaluation his global IQ was 65.19. So based on the aforementioned findings diagnosis of congenital hypothyroidism was made and started on LT4. Discussion: Congenital hypothyroidism (CH) is one of the most common preventable cause of mental retardation. The best way to detect infants with CH are by screening large populations of newborns. If the diagnosis is made and treatment started within a few weeks of birth, neurodevelopmental outcome generally is normal.
Figure 1: Congenital Hypothyroidism

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Figure 2: Pituitary Enlargement with compression on optic chiasm

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

   Thyroid ophthalmopathy, dermopathy, and acropachy: A Case Report Top

Sanjay Saran, Balram Sharma, Vijay Kumar Bhavi, Hardevaram Nehara

Department of Endocrinology, SMS Medical College, Jaipur, Rajasthan, India.

E-mail: [email protected]

Graves' disease is an autoimmune condition with extrathyroidal immune-mediated manifestations. Traditionally described, severe Graves' acropachy and tibial myxoedema are now only encountered in certain severe forms of Graves' disease. The presence of high levels of thyrotropin receptor antibodies indicates a more severe autoimmune process. We reported a case of Graves' disease with ophthalmopathy and dermopathy. 20 years old man was referred for evaluation for weight loss and protrusion of eyes. Four years back he was diagnosed Graves' disease with thyroid-associated ophthalmopathy and dermopathy. He was advised antithyroid drugs but took irregularly. On clinical examination large goiter was present. Pretibial myxedema was present on both lower limbs which was functionally limiting and resembled elephantiasis. In addition, his hands were enlarged and coarsened, and his fingers had a clublike shape. Radiography of the hand showed periostitis of multiple phalangeal and metacarpal bones, with diffuse swelling of the soft tissue, changes that were consistent with thyroid acropachy, a rare manifestation of Graves' disease. Laboratory results showed that FT4 was >20 and TSH was suppressed, levels of thyrotropin-receptor antibodies were in excess of 48 IU per liter. Diagnosis of Gravse' disease with thyroid ophthalmopathy, dermopathy, and acropachy was made and patient was started on a treatment with intravenous immune globulin along with antithyroid drugs. Thyroid dermopathy that occurs in 4–13% of patients with Graves' ophthalmopathy is an extrathyroidal manifestation of Graves' disease. Thyroid acropachy commonly presents with clubbing of digits and occurs in 20% of patients with dermopathy. Basic pathogenesis of dermopathy is similar to ophthalmopathy. Presence of TSH receptor in the fibroblasts and its interaction with TSH receptor antibodies and stimulation of fibroblasts resulting in production of glycosaminoglycans is the most likely immune process. Localization of thyroid dermopathy to lower extremity is explained by mechanical factors such as dependency of the lower extremity (Figure 1),(Figure 2),(Figure 3).
Figure 1: Thyroid dermopathy

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Figure 2: Thyroid acropachy

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Figure 3: Thyroid associated ophthalmopathy

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

   Impact of thyrotoxicosis on bone health and body composition in south Indian women: A cross sectional study Top

Kripa Elizabeth Cherian, Nitin Kapoor, Nihal Thomas, Thomas V. Paul

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: Thyrotoxicosis may have an adverse impact on bone mineral density and body composition. The aim of this study was to evaluate bone mineral density (BMD), bone turnover markers and body composition in female subjects diagnosed to have Graves' disease, compared with age and body mass index (BMI) matched control subjects. Materials and Methods: This was a cross sectional study done over a period of six months. Study subjects included 41 consecutive south Indian female patients diagnosed with Graves' disease and 74 age and BMI matched controls. Analysis of body composition and BMD at femoral neck and lumbar spine was done using a DXA (Dual Energy Xray Absorptiometry) scan. Thyroid function tests and parameters of bone health including calcium, phosphorus, iPTH (parathormone), 25 (OH) vitamin D, CTX and P1NP were measured. Results: The mean (SD) age of our study subjects was 34.5 (9.0) years and BMI was 23.2 (4.8) kg/m2. The bone mineral density (g/cm2) in the study subjects, when compared with controls were significantly reduced at the femoral neck [0.737 (0.111) vs 0.791 (0.117)] and lumbar spine [0.909 (0.100) vs 0.975 (0.119) P < 0.01]. Bone turnover markers were significantly elevated in subjects with Graves' disease as compared to controls. [CTX (pg/mL): 813.6 (620.3) vs 383.5 (201.9); P < 0.01, P1NP (ng/mL) 122.1 (90.3) vs 54.4 (44.6); P < 0.01)]. The mean (SD) lean body mass (kg/m2) in the study subjects was significantly lower than in age and BMI matched controls [5.80 (0.91) vs 7.84s (7.73); P < 0.05)]. There was a significant inverse correlation seen between duration of symptoms prior to treatment and femoral neck BMD (r = -0.34; P < 0.05). Conclusion: Graves' disease was associated with a significant reduction in bone density at the femoral neck and lumbar spine, increased bone turnover markers and loss of lean body mass, when compared to healthy, age and BMI matched controls.

   Correlation of serum lipoprotein (a) levels in hypothyroidism: A case control study Top

Humera Naaz, K. N. Shivashankara, B. Vaideki1, Krishnananda Prabhu1

Departments of Medicine and 1Biochemistry, KMC, Manipal, Karnataka, India.

E-mail: [email protected]

Objectives of the Study: (1) Measure lipoprotein (a) [Lp (a)] levels in newly diagnosed hypothyroid patients. (2) To investigate the relationship between the levels of Lp (a) and FLP, including non-HDLC with TSH, in newly diagnosed hypothyroids. Materials and Methods: The study was a hospital based study conducted in Kasturba Hospital, Manipal over a period of 2 years. Study design: Prospective; Case-Control Study duration: September 2015 to May 2017; Sample size: 126, 63 cases, 63 controls. All the patients and controls were clinically examined and routine biochemical tests were analyzed for all subjects prior to selection. A pre-structured proforma was used to collect data. A written informed consent was taken from all the cases and controls after complete explanation of the study. Relevant investigations such as thyroid function tests, lipid profile, free t4, etc., were done. Based on the results of examination and investigations, cases and controls were then selected for the study. For all the subjects, lipoprotein (a) was measured. Results: Comparison of lp (a) between the two groups shows that lp (a) is higher among the overt hypothyroids with mean of 78.6 than controls with mean of 19.18 and is statistically significant with a P value of <0.001. Pearson correlation between TSH and lp (a) in overt Hypothyroids shows positive correlation with P value of <0.001, with moderate linear relationship with r square value of 0.587. Conclusions: Individuals with hypothyroids were found to have higher levels of lp (a) as compared to age and sex matched controls. The Pearson correlation between TSH and lp (a) was significant with positive correlation. Similarly, the Pearson correlation between TSH and Non HDL-C was fair and significant. Thus, lp (a) and non-HDL-C along with FLP may be used in assessing the cardiovascular risk in Hypothyroids.

   Normokalemic thyrotoxic periodic paralysis: A unique scenario Top

Subrata Chakrabarti, Satinath Mukhopadhyay, Subhankar Chowdhuri

Department of Endocrinology and Metabolism, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Introduction: Although serum potassium levels are usually subnormal in Thyrotoxic Periodic Paralysis (TPP), but in exceptionally rare circumstances, it may be normal leading to the entity called normokalemic TPP. Here, the authors describe the case of a 31-year old male with untreated Graves' disease and TPP who was normokalemic during the acute phase of paralysis. Hypokalemia was documented only after resolution of paralytic attack. Case Report: A 31-year old male was rushed to the emergency with acute onset and rapidly progressive bilaterally symmetrical lower limb muscle weakness followed by upper limb weakness which started 8 hours ago after waking up from sleep in the morning. He had suffered 3 attacks of similar muscle weakness in last one year with no similar family history. Each paralytic attack lasted 16 h to 24 hours and had their onset after meals or post-exercise rest and resolved spontaneously by 2-3 days. Occasional H/O palpitation was provided by the patient. Resting tachycardia (112/min), fine tremors; diffuse thyromegaly with bruit were noted. Symmetrical flaccid weakness in both upper and lower extremities with hyporeflexia were found. Routine biochemistry including serum electrolytes were normal. Serial potassium concentrations at the time of admission was 4.2 mEq/L (normal 3.5-5 mEq/L). It progressively diminished over the next few hours and days (3.1, 2.8, 2.3 at 18 hrs, 36 hrs and 4th day). However, progressive drop in potassium was not associated with significant increase in weakness or disappearance of reflexes. Thyroid profile showed frank hyperthyroidism (FT4 – 3.97 mcg/dl; TSH – 0.01 Miu/ml). Thyroid radioiodine uptake scan revealed a diffuse homogeneous uptake. Urine sodium and potassium, and serum aldosterone and renin levels, ECG, EMG, NCV findings, MRI spine were normal. A diagnosis of normokalemic TPP associated with Graves' disease was made based on clinical and laboratory findings. Treatment with propranolol and carbimazole was initiated. He was administered potassium chloride syrup during the hypokalemic phase and advised a low carbohydrate diet and a caution to avoid heavy or strenuous exercise, to be followed life-long. Discussion: Although serum potassium levels classically decrease in most cases, it is not universal. Isolated cases of TPP are found to have normal or even increased potassium levels even in the acute paralytic phase. Hypokalemia usually sets in after certain interval usually without further increase in weakness as seen this case. The mechanism is still elusive. Normokalemic TPP is usually confused with other neurologic diseases such as Guillain-Barré syndrome (GBS), multiple sclerosis or even psychiatric ailments like hysteria, malingering, etc., TPP should be kept in mind as a cause of acute muscle weakness to avoid missing a treatable and curable condition as unfamiliarity with the syndrome can result in respiratory failure, dysrhythmia and death. Conclusion: The importance of the case report is to highlight upon the fact that TPP should always be considered in an “previously asymptomatic” young Asian individual with acute paralysis with or without hypokalemia, and thyroid function and serial potassium values should be evaluated for diagnosing the usual hypokalemic type or the rarer variant normokalemic TPP.

   Differentiated thyroid carcinoma in adults: A single institution experience a study of clinicopathological characteristics, risk categories and response to therapy Top

Shiga Rappai Chirayath, Vasantha Nair, Usha V. Menon, V. P. Praveen, Harish Kumar, Nisha Bhavani, Nithya Abraham, Arun S. Menon

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India.

E-mail: [email protected]

Objective: As per the National Cancer Registry Programme, thyroid cancer is among the top 10 cancers among females in Kerala. This study aimed at evaluating clinicopathological characteristics, risk categories, response to therapy among our DTC cohort. Method: This study included 741 patients (>18 years) diagnosed with DTC being followed up at Thyroid Cancer Clinic, Endocrinology Department 2010-2017. The management of these patients was based on ATA guidelines 2006 and response to therapy assessment in accordance with ATA guidelines 2015. Results: Out of 741, 71.3% (528/741) females, 28.7% (213/741) males. Mean age: 44.11+/- 13.37. Mean follow-up: 41.9+/- 30 months). Median duration of neck swelling was 12 months. Most common procedure was total thyroidectomy 52.2% (385/741).Histopathological features: Papillary thyroid carcinoma (PTC) 91% (675/741), follicular thyroid carcinoma (FTC) 8.63% (64/741). Median tumor size 12 mm. Tumor multifocality- in 42% (227/536) cases. High risk histology in 21.8% (140/642)- commonest being tall cell, columnar variants. 53.4% (306/573) had lymphatic spread. 10.6% had extrathyroidal extension, commonest site- perithyroidal fat (76.1%). Vascular and capsular invasion in 24.5% (132/537) and 36.9% (203/550). Metastasis was diagnosed at presentation in 192/741 (25.9%), neck nodes 73.4%, bone 12%, lung 3.6%, mediastinal nodes 3.1%, liver 2.6%. ATA risk stratification at 6 months was possible in 598/741: 39.2% (235/598), 35.6% (213/598), 25% (150/598) low, intermediate, high risk respectively. Response to therapy at 2 yrs was assessed in 429/741 (57%): 47.5%, 16.5%, 13.5%, 3.4%, 18.8% excellent, acceptable, incomplete biochemical, incomplete structural and incomplete structural and biochemical response respectively. Conclusion: PTC was the commonest. 39.2% was in low risk category at 6 months. 57% had excellent response at 6 months.


We thank the Department of Pathology, Amrita Institute of medical Sciences.

   Knowledge, awareness and practice's study among hypothyroid individuals Top

Nilekya Naidu Anigundi, Prem Kumar Asokumar

Department of Endocrinology, SKS Hospital, Salem, Tamil Nadu, India.

E-mail: [email protected]

Introduction: Thyroid disorders are amongst the most prevalent of medical conditions. Very less data is available on the Knowledge, Awareness and Practices (KAP) among these patients. Aim: To study knowledge, awareness, compliance and practices in patients of hypothyroidism. Materials and Methods: It is an observational, cross sectional study conducted in Endocrinology OPD in SKS Hospital, Salem, Tamil Nadu. 700 patients of hypothyroidism aged >16 years on treatment were given a structured KAP questionnaire of which, 646 consented to participate in the study. Results: Out of total 646 participants in the study the mean age was 38.6 years, while the mean duration of hypothyroidism was 5 years. 38.63% of participants went to high school whereas 35.62% were graduates and post graduates. 47% of the patients answered weight gain as the initial manifestation of hypothyroidism, while 20.5% answered the first symptom of hypothyroidim as menstrual irregularity. 61% of the patients opined that hypothyroidism is treatable. 68.5% of participants felt endocrinologist as the right person to consult and 5.4% felt physicians are to be consulted in thyroid related problems. 65% of the participants marked thyroid as a hormone while 19.6% didn't know what does a thyroid mean. 31% of participants opined their thyroid problem is hereditary and can affect blood relatives. 52% of participants marked that medication should be taken till doctor advices whereas 21.2% responded that medication is taken lifelong. Regarding practices, 28.8% of participants missed the tablet once a week whereas 53.7% never missed the medications. 46% of the participants meet the doctor once in 3 months, 23% once in 6 months and 19% once in a year. 90.6% of participants considered that there is no role of alternate medications while 9.4% gave the history of consuming alternative medications before taking thyroxine. Conclusion: Majority of the patients attending tertiary care centres are well informed and knowledgeable with better knowledge, attitude and practices including the adherence of treatment compared to earlier published data.

   Patterns of thyroid uptake with technetium-99m scintigraphy in patients with Graves' disease Top

Vaibhav Vasudev Dukle, Harsh Yogesh Parekh, Jayant Vishwanath Kelwade, Srinivas Kandula, Tejonath Gadepalli1, Kirtikumar D. Modi, Bipin Kumar Sethi

Departments of Endocrinology and 1Nuclear Medicine, Care Hospitals, Hyderabad, Telangana, India.

E-mail: [email protected]

Objectives: To assess the patterns of radiotracer uptake with Technetium 99m thyroid scintigraphy in patients with Graves' disease. Materials and Methods: Data from thirty nine consecutive patients with Graves' disease was retrospectively analyzed in this study. Graves' disease was established on the basis of clinical presentation and positive TSH Receptor antibodies. Patients with history of thyroid surgery or radioiodine ablation, history of exposure to iodinated contrast, patients on anti-thyroid drugs, thyroxine, Amiodarone or lithium were excluded from the analysis. Results: The percentage of total radiotracer uptake varied from 2.1% to 44%. (Mean uptake 9.44%). Salivary gland uptake was decreased in all patients. 17.9% of patients (n = 7) had asymmetric radiotracer uptake on scintigraphy. One patient had increased uptake in one lobe (4.4%) with markedly suppressed uptake in contralateral lobe (0.5%). 10.2% patients (n = 4) had photopenic areas on scintigraphy. Two patients had focal avid uptake in the background of diffusely increased uptake suggestive of hot nodules. Conclusion: In majority of cases, Graves' disease is characterized by diffuse, symmetrical, avid uptake on Tc99m scintigraphy. However, a small subset of patients have asymmetric involvement. This may result from volume proportionate reduction in uptake or photopenic areas. Nodules identified on Tc99m scintigraphy may be useful in guiding further workup. In rare cases, unilateral involvement may lead to an erroneous diagnosis of autonomously functioning thyroid nodule. The wide variation in total radiotracer uptake may possibly represent background iodine status or timing of scan in relation to the disease process.

   Does elastography differentiate between benign and malignant thyroid nodules? Top

Awesh Shingare, Phulrenu Chauhan, Nishit Shah, Manoj Chadha, Raju Wadhwani1, Apoorva Wakade

Departments of Endocrinology and 1Radiology, P. D. Hinduja Hospital Mumbai, Maharashtra, India.

E-mail: [email protected]

Background: Thyroid nodules are extremely common and main clinical concern is to exclude malignancy. Malignant tissues have higher stiffness than benign lesions. Ultrasound elastography measures tissue stiffness and is used to differentiate benign and malignant lesions. Objective: (i) Primary: To evaluate diagnostic accuracy of ultrasound elastography to differentiate benign and malignant thyroid nodules. (ii) Secondary: To evaluate whether application of ultrasound elastography can decrease the need for FNAC in patients having a thyroid nodule. Materials and Methods: 44 consecutive patients with thyroid nodule(s), requiring FNAC based on clinical or ultrasound findings, attending Endocrinology OPD during the study period were enrolled. Patient's history, neck examination and ultrasound thyroid findings were recorded. Ultrasound elastography was performed and elastography score and strain ratio measured. After which patients underwent FNAC of the suspicious thyroid nodule. If patient underwent surgery subsequently histopathology findings were noted. Results: A total of 52 nodules in 44 patients were studied. On final diagnosis 9 nodules were malignant and 43 nodules were benign. Sensitivity, specificity and positive predictive value for elastography score in differentiating benign and malignant nodules was 88.89%, 88.37% and 61.54% respectively. The mean strain ratio for benign nodules was 2.72 and for malignant nodules was 4.52. Sensitivity, specificity and positive predictive value for strain ratio in differentiating benign and malignant nodules was 88.89%, 95.35% and 80% respectively. Conclusion: Both the elastography score and strain ratio are higher in malignant nodules than those in benign ones. Both elastography score and strain ratio have high sensitivity, specificity and accuracy for differentiating benign from malignant thyroid nodule. Elastography can be used supplementary to ultrasound and can reduce the number of patients undergoing unnecessary FNAC.

   Fasting versus postprandial thyroid function tests comparison in pregnant women Top

T. V. S. Pradeep, Ch. Sree Harsha Varma, K. Dileep Kumar, P. Amaresh Reddy

Department of Endocrinology, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India.

E-mail: [email protected]

Objective: To estimate whether a fasting or post prandial blood sample would make a clinically significant difference in the interpretation of thyroid function tests in pregnant women. Materials and Methods: We prospectively collected data from 55 pregnant women irrespective of their gestation. Both Euthyroid and Hypothyroid women are included and Hyperthyroid women are excluded. Thyroid Function tests were done in both Fasting state between 7-8 AM and Postprandial state between 10-11 AM. Tests are analysed with Chemiluminescence Immuno Assay (Beckman coulter). Fasting and postprandial blood glucose is done in all patients. Data was analyzed using SPSS for windows 22.0. Differences between two groups compared by student T test. Results: TSH was suppressed in 50 women (91%) after food intake irrespective of the fasting levels. Free T4 and T3 values did not change significantly. The mean TSH in the fasting state is 2.09 ± 1.37 and in postprandial state is 1.60 ± 1.04, which is highly statistically significant (P value <0.001). There is no significant change in FT3 and FT4 levels. The TSH fall is seen in women irrespective of trimester and thyroid status. On Pearson correlation, as the blood glucose difference increases the TSH fall is also increased but not statistically significant (p – 0.32). 11 out of 55 (20%) are reclassified as subclinical hypothyroidism based on the fasting sample whose TSH values were otherwise within range in the postprandial sample. This may have an impact on the diagnosis and management of hypothyroidism especially where even marginal changes in TSH may be clinically relevant as in Subclinical hypothyroidism and in pregnancy.

   Utility of IHC in detecting braf V600E mutation in papillary thyroid carcinoma Top

Nadeem Kocheri, Shipra Agarwal, Mehar C. Sharma, Chandrasekhar Bal1, Nikhil Tandon2

Departments of Pathology, 1Nuclear Medicine and 2Endocrinology, All India Institute of Medical Sciences, New Delhi, India.

E-mail: [email protected]

Background: Among thyroid tumors, BRAFV600E mutation is specific for papillary thyroid carcinoma, and has been variably reported to impart a poorer outcome. Targeted therapy has utility in recalcitrant cases. PCR-based methods are usually used for detection, but are not widely available. An easier and routinely available method like immunohistochemistry (IHC) would be a great deal if having comparable sensitivity and specificity. Objectives: To assess sensitivity and specificity of IHC for detecting BRAFV600E mutation in comparison with Sanger sequencing (SaS). Materials and Methods: It was an ambispective study. Consecutive PTC cases received in the department of Pathology, AIIMS, New Delhi, between March, 2015 and October, 2016, having adequate tissue in paraffin blocks were included. Tumour DNA was extracted and evaluated for BRAF mutation by PCR followed by SaS. VE1 mouse monoclonal antibody to BRAFV600E protein was used for IHC. Allred score was used to score IHC, and ranged from 0 to 8. Discrepant cases were reassessed using qPCR. Results: Fifty cases were studied. While 23 were scored 6; 10 scored 7, 14 scored 8, 1 scored 3 and 2 scored 0. SaS revealed that all with score less than 7 were wild type (wt). All which scored 8 were BRAF-mutant. Of the 10 which scored 7, 40% (4/10) were mutated by SaS. On statistics, IHC score of 7 or more had a sensitivity of 100% (95% CI 82.41%-100%) and specificity of 81.25% (95% CI-64.69%-91.11%), a positive predictive value of 75% (95% CI 55.1%-88%) and negative predictive value of 100% (95% CI 87.13%-100%). qPCR done on cases scored 7 but BRAF-wt, revealed low frequency of mutant DNA in these cases also. Conclusion: BRAF IHC is more sensitive and specific than SaS for detection of BRAFV600E mutation.

   Evaluation of PTEN expression in papillary thyroid carcinoma with lymphocytic thyroiditis Top

Sohini Banerjee1, Uma Nahar1, Gurjeet Kaur2, Anil Bhansali2, Rijuneeta Gupta4, Divya Dahiya3, Sanjay Bhadada2

1Department of Histopathology, 2Department of Endocrinology, 3Department of General Surgery, 4Department of Otolaryngology, PGIMER, Chandigarh, India.

E-mail: [email protected]

Introduction: Papillary thyroid carcinoma (PTC) is the most common variant of thyroid malignancies, shares some epidemiological and common molecular features with Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis (LT). There is increased risk of thyroid cancer reported in nodular HT. The wide distribution of this association may be related to differences in the level of morphological examination, autoimmunity as well as genetic background. Being tumour suppressor gene, Phosphatase and tensin homolog (PTEN) negatively regulates PI3K pathway by removing phosphate group from phosphoinositides by phosphatase activity. The aim of this study was to evaluate the expression of PTEN protein in PTC associated with chronic LT and its relevance in metastasis. Materials and Methods: A total of 10 PTC and 7 chronic LT cases were included both prospectively and retrospectively. All cases were investigated by means of thyroid function test (TFT), thyroid ultrasound (USG), and cytological examination before being operated. Immunohistochemical analysis for PTEN was performed in all cases and the results were correlated with histomorphological characteristics of PTC with its metastatic potential. Results: Coexistence of lymphocytic thyroiditis was seen in papillary thyroid carcinoma in 7 cases included in this present study. In cases of chronic LT pathologic changes like micropapillary structures and microfollicular hyperplasia was seen. Extensive lymphocytic infiltrates along with transformation of hyperplasia to neoplasia was seen in multifocal PTC with classical histological features. Clinically 2 patients were euthyroid and one patient presented with low TSH level with normal T3 and T4. Conclusion: Differential PTEN expression was evidenced in PTC cases which can be a risk factor for neoplastic transformation.

   Study the serum Vitamin D level in new onset hypothyroid patients and its correlation with thyroid related parameters and antibody titers Top

Subash Ranjan Behera, Arun Kumar Choudhury, Anoj Kumar Baliarsinha

Department of Endocrinology, S.C.B. Medical College, Cuttack, Odisha, India.

E-mail: [email protected]

Objectives: To compare serum vitamin D level in new onset hypothyroid patients versus controls. To correlate serum vitamin D levels with thyroid volume, hormonal status and anti TPO antibody titers in the hypothyroid patients. Materials and Methods: This is a cross sectional study conducted in the department of Endocrinology, S.C.B.Medical College, Cuttack. A total of 61new onset hypothyroid subjects in the age group of 18-60 years, from both sexes attending to the Endocrinology OPD were included. 40 age, sex and BMI matched healthy individuals were taken as controls meeting the exclusion criteria. After an overnight fast blood samples were collected for measurements of serum 25-hydroxyvitamin D [25(OH)D], FT3, FT4, TSH, thyroid peroxidase antibody (TPOAb), PTH, calcium and phosphorus from cases and controls. All subjects underwent thyroid ultrasonography. The cases were divided into three groups as per vitamin D level as vitamin D sufficient group (25 OHD = 30-100ng/ml) [VDS], insufficient group (25 OHD = 20-30ng/ml) [VDI] and deficient group (25 OHD <20ng/ml) [VDD] respectively. Anti TPO levels >34 kIU/L was considered as TPO positivity. Results: The mean value of vitamin D in cases (22.95 ± 8.59ng/ml) was significantly lower than the controls (27.9 ± 7.85ng/ml) (P < 0.01). As expected, the cases had significantly higher TSH, thyroid volume, anti TPO titres and lower FT3 and FT4 levels. When the hypothyroid group was divided into three groups basing on 25 OD levels, VDD group had significantly higher TSH, thyroid volume and anti TPO titres (P < 0.01 for each parameter) than VDI and VDS groups. No difference was observed in mean FT3 and FT4 levels between the groups. Conclusion: Serum vitamin D is significantly low in new onset hypothyroid patients than healthy controls. Hypothyroid patients with vitamin D deficiency have significantly higher TSH and antibody titres.

   Association between body mass index and thyroid stimulating factor Top

Ngairangbam Archana, Ranabir Salam, Lallan Prasad

Department of General Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India.

E-mail: [email protected]

Aims and Objectives: The study was conducted to determine any correlation between thyroid hormone function indicated by thyroid stimulating factor (TSH) and body mass index (BMI) by comparing BMI in hypothyroid individuals (with or without levothyroxine therapy) and euthyroid individuals with the respective TSH. Materials and Methods: Study design is a cross-sectional study. A total of 322 individuals (26 male and 296 female) out of which 22 individuals had subclinical hypothyroidism (SCH), 212 individuals had hypothyroidism and 88 individuals were euthyroid. TSH was estimated by Chemilluminence immune assay. Height (metre), weight (kilogram) and waist circumference (centimetre) were measured for all participants and comparisons were done according to gender and thyroid hormone status. Results: Mean TSH level in hypothyroid males and females was 24.53 ± 47.47and 36.69 ± 97.55 Vs 5.18 ± 1.13 and 7.29 ± 0.96 in males and females with SCH Vs 1.85 ± 0.88 and 2.88 ± 1.46 in euthyroid males and females. Mean BMI in hypothyroid males and females was 26.72 ± 3.03 and 25.60 ± 4.16 Vs 26.36 ± 3.51 and 26.93 ± 3.58 in males and females with SCH Vs 24.74 ± 3.54 and 25.77. r2 for hypothyroid group was 0.0003 (P = 0.80). r2 for subclinical group was 0.010 and (P = 0.65). r2 for euthyroid group was 0.006 and (P = 0.45). Conclusion: We concluded that there is no correlation between Thyroid Stimulating Factor and Body Mass Index. Further studies involving large number of subjects are needed to confirm the findings.

   Correlation between TIRADS imaging criteria and FNA - Bethesda system on thyroid nodules: A Tertiary centre experience Top

Annie A. Pulikkal, Nisha Bhavani, Nithya Abraham, Praveen V. Pavithran, Vasantha Nair, Harish Kumar, Arun S. Menon, Usha V. Menon

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India.

E-mail: [email protected]

Objective: To correlate TIRADS (Thyroid Imaging Reporting and Data System) ultrasound imaging criteria and Bethesda system of FNAC reporting on 200 consecutive thyroid nodules. Methods: A retrospective analysis was done of 200 thyroid nodules which presented in our OPD during the period of 6 months from February 2017 to July 2017. The nodules were classified into TIRADS 1 to 5 depending on the ultrasound features and FNAC was obtained from those which fulfilled the criteria according to ATA. TIRADS 1 and 6 and Bethesda 1 were excluded. Results: 79% of patients were females with a mean age of presentation of 51 ± 12.9 yrs. Majority of the nodules belonged to TIRADS 3 (62%). 29% were TIRADS 2, 8% were TIRADS 4 and 1% was TIRADS 5 (Figure 1). There was a significant correlation between TIRADs and Bethesda (P value 0.000). In patients with TIRADS 2 none of them had Bethesda 4 or 5. In patients with TIRADS 5 none of them had Bethesda 2or 3. Biopsy was done in 24 patients of which 13 (54%) were malignant. There was a significant correlation between TIRADS and biopsy results (Figure 2). Conclusion: Our study showed that TIRADs ultrasound imaging criteria correlated significantly with the Bethesda system of FNAC reporting for thyroid nodules. In those who underwent biopsy, TIRADs imaging criteria correlated with biopsy. Hence, TIRADS is a useful tool in deciding on performance of FNAC and surgical excision.
Figure 1: Correlation of TIRADS ultrasound criteria with Bethesda FNAC classification of thyroid nodules

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Figure 2: Correlation of TIRADS with biopsy reports

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   Prospective study of bethesda categories III and IV thyroid nodules: outcomes and predictive value of brafV600E mutation Top

Shiga Rappai Chirayath, V. P. Praveen, Vasantha Nair, Harish Kumar, Nisha Bhavani, Arun S. Menon, Usha Menon, Annie Pullikal, Nithya Abraham

Department of Endocrinology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India.

E-mail: [email protected]

Objective: This study aimed to analyse the outcomes, malignancy risk of indeterminate thyroid nodules along with utility of subjecting the FNA specimen for BRAFV600E mutation analysis. Method: The sonographic features, malignancy rate in surgically excised nodules and predictive value of BRAFV600E analysis were analysed. Results: Sixty-five patients-78.5% (51/65) females, 21.5% (14/65) males. Mean age of presentation 49.7+/- 13.55. Mean nodule size 22.2+/- 11.3 mm. 75.4% (49/65), 24.6% (16/65) categories III and IV. 38.5% (25/65) showed marked hypoechogenicity. 15.45% (10/65) showed microcalcification. One Cat III nodule showed irregular margins and two Cat IV nonparallel. Using ATA ultrasonographic pattern assessment, nodules were classified as having high (10.8%), intermediate (20%), low suspicion (64.6%), very low suspicion (3.1%) malignancy risk patterns. 61.5% (40/65) underwent surgical excision. Malignancy confirmed in overall 60% (24/40) by excision- of these 55.6% (15), 69.2% (9) were Cat III, Cat IV.38.5% (25/65) preferred follow up over excision. 7 underwent follow up FNA recategorised as Cat I (3/7), II (4/7). 80% (52/65) were advised excision by treating physician. 71% (37) complied with advice and 67% (25/37) were malignant. 20% (13/52) were advised follow up. 23% (3) underwent excision and none were malignant. BRAFV600Eanalysis was done on 67.7% (44/65) nodules of which 1 was positive. Malignancy was confirmed by surgical excision in that case. Conclusion: Malignancy risk in Cat III, IV were much higher than that described by ATA and by other studies published from centres around the world including that from North India. Strong consideration to surgery should be given to patients with FNA results suggesting these categories. Ultrasound findings were of limited value in predicting malignancy in our cohort of patients.

Malignancy Rate in Thyroid Nodules.

Classified as Bethesda Category III (AUS/FLUS).

Allen S. Ho, 1 Evan E. Sarti, 1 Kuna THYROID.

Volume 24, Number 5, 2014------------------------------ malignancy rate in cat 3 37.8%.


We thank the Department of Pathology, Amrita Institute of medical Sciences.

   Do we really have to wait for 4 weeks after thyroidectomy for radio-iodine scan? A follow up cohort study in patients with well differentiated thyroid cancer Top

Shriraam Mahadevan, Dhalapathy Sadacharan1, Vanishree Shriraam2, Subramanian Kannan3

Departments of Endocrinology and 2Community Medicine, Sri Ramachandra Medical College, 1Department of Surgical Endocrinology, Madras Medical College, Government General Hospital, Chennai, Tamil Nadu, 3Department of Endocrinology, Diabetology and Metabolism, Narayana Health City, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: A prospective study by Serhal et al. demonstrated that 14 days on average were required to reach serum TSH level of more than 30 mU/l after thyroidectomy, and 18 days were required after L-T4 withdrawal. Leboeuf et showed that serum TSH concentrations become supra-normal (>30 mIU) in 10 to 14 days after cessation of T4 or T3 therapy in patients with hypothyroidism. If TSH rise is indeed occurring earlier than 4 weeks, we might be able to expedite the Iodine WBS in these patients and minimise their morbidity related to hypothyroidism or avoid use of expensive Recombinant TSH. Aim: To study the time taken for TSH to elevate after total thyroidectomy in patients operated for WDTC. Methodology: After explaining about the nature of this study and getting informed consent we plan to recruit 30 patients undergoing total or near total thyroidectomy for indication of WDTC confirmed on histopathology. Preoperative Free T4 and TSH would be done on all patients with or without replacement therapy. Sample would be drawn for TSH on Days 4, 7, 14, 21, 28 and 35 of surgery (usual date of Whole Body Scan). Results: The mean (SD) age of the 30 member cohort was 39 (13) years with 26 female patients and their mean (SD) pre-operative TSH was 3.5 (1.4). At the end of the first week post-operatively, the mean TSH of the cohort was 25 (6) with 7 patients (23%) achieving the required cut-off of TSH >30 mIU/L. These 7 patients included 5 females and had a mean age of 45 years. At the end of the second week, the mean TSH was 53 (17) with all patients (100%) achieving a TSH level >30 mIU/ml. Conclusion: Iodine Whole Body scan can be safely performed in 2 weeks after total thyroidectomy instead of the usual wait time of 4 weeks. This could improve patient quality of life and obviate the need for rhTSH.

   Lower dose of once weekly thyroxine for thyroxine resistant hypothyroidism Top

Abilash Nair, Nandini Prasad, C. Jayakumari, Puthiyaveetil Khadar Jabbar, Saboora M. Beegum1

Departments of Endocrinology, and 1Biochemistry, Government Medical College, Thiruvanathapuram, Kerala, India.

E-mail: [email protected]

Background: The most common reason for poor control of hypothyroidism is non-compliance. Once weekly thyroxine (OWT) with doses less than 3 milligram/day have been shown to be a safe treatment alternative for hypothyroid patients but such a therapy has not been evaluated in Asians. Materials and Methods: Patients taking LT4 >3 mcg/kg/day were included in a consecutive manner. A baseline T4, FreeT4 and TSH was estimated. OWT was given for a period of six weeks. After the first dose T4 and FT4 were measured at 2 hrs and 24 Hrs. Each week the T4, Ft4 and TSH, were measured before administering and 2 hrs after (except TSH) after OWT administration. After the sixth week patients were advised to continue the procedure at home. Results: Twenty three (20 females) patients with mean age 38 (±9.85) yrs have been enrolled till now. The median TSH at baseline was 21.69 (IQR 10.5-45.02) μIU/ml. The average daily thyroxine dosage before enrollment was 262 (145) mcg/day and 4.73 (2.8) mcg/kg/day. They were now treated with 765 (128.3) mcg/week. In the 23 patients who completed 4-6 weeks the median TSH (± IQR) has changed from 21.7 (10.5-45.025) to 4.86 (1.065 -10.39) (P < 0.05). All except 3 patients showed a normalization of TSH values atleast once in the 6 weeks of directly observed treatment. Of the 16 patients who have completed 12 weeks (including six weeks of self-administration at home) 9 patients maintained euthyroidism, 2reverted back to hypothyroidism and 5did not achieve normalisation at 6 weeks. At 2 hrs of OWT administration T4 levels were around 1.71 times of basal levels. The mean T3 levels did not change significantly. Conclusion: OWT is effective in poorly controlled hypothyroidism but only around 60% of these patients maintained euthyroidism when allowed to continue OWT at home.

   Dual ectopic thyroid: A case report Top

Sunetra Mondal, Debmalya Sanyal1

Department of Endocrinology and Metabolism, IPGME&R, 1Department of Endocrinology and Metabolism, KPC Medical College and Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

Introduction: Ectopic thyroid tissue (ETT) is the commonest form of thyroid dysgenesis, majority being located in the midline along the tract of the thyroglossal duct. The aberrant migratory pathway is often associated with insufficient blood supply to support increased physiologic demand for thyroid hormones during puberty which is also often associated with an increase in size leading to the detection of previously undiagnosed ETT. Dual ETT is a rare entity as also underreported as they are mostly euthyroid or mildly hypothyroid. Case: 12y/F presented with a slowly progressive painless midline neck swelling for 2 yrs without any toxic features or compressive symptoms. A globular, soft-cystic suprahyoid mass was palpable that moved with deglutition and tongue protrusion. With a presumptive diagnosis of thyroglossal cyst, she was planned for surgery by otorhinolaryngologists and referred for evaluation of subclinical hypothyroidism. During tongue protrusion, another fleshy nodular swelling at the base of tongue with smooth overlying mucosa was noted. TSH was 8.06 μIU/ml with normal T4. USG revealed absence of eutopic thyroid gland with a hyopechoic nodule in midline suprahyoid location. The ectopic thyroid was confirmed on a 99mTc scan showing focal areas of increased tracer uptake in the submental region and base of the tongue with non-visualisation of orthotopic thyroid tissue. MDCT scan of neck identified well-defined thyroid tissue at two sites: infrahyoid region and at the foramen caecum. She was put on LT4 and followed up. There was regression in size of the neck swelling with lowering of the TSH levels. Conclusion: Though USG may be the initial investigation for detecting absent eutopic thyroid gland, it should be combined with thyroid scintigraphy and/or CT to locate areas of functioning thyroid tissue. This is essential prior to planning a surgical intervention for a thyroglossal cyst.

   Prevelance of autoimmune thyroid disease in type 1 diabetes Top

Sanjay Saran, Balram Sharma, Hardevaram Nehara, Vijay Kumar Bhavi

Department of Endocrinology, SMS Medical College, Jaipur, Rajasthan, India.

E-mail: [email protected]

Introduction: Type 1 diabetes is a common autoimmune disease of pediatric population and it is commonly associated with other autoimmune diseases especially autoimmune thyroid disease. Objectives: To see prevalence of thyroid autoimmune disorders in type 1 diabetes and its association with age, gender and duration of diabetes. Materials and Methods: A total of 134 patients were recruited among those attending outpatient department of Endocrinology and Metabolic Clinic of SMS Medical College, Jaipur, Rajasthan; in between april 2017 to August 2017. Diagnosis of Type 1 diabetes was established on ADA 2017 criteria. The patients were clinically examined, including thyroid gland palpation, blood pressure measurement and assessment of their pubertal status and growth. After achieving euglycemia blood sample was taken for hematological and biochemical test. HbA1c was done by HPLC, Anti TPO, TSH, T3, T4 was done by chemiluminescence method. The patients were clinically examined, including thyroid gland palpation, blood pressure measurement and assessment of their pubertal status and growth. Results: The prevalence of thyroid autoimmune disorders in 134 patients was 18.7%. The thyroid status of most of the patients with positive markers was euthyroidism (73%), but subclinical hypothyroidism (14%), overt hypothyroidism (4%), subclinical hyperthyroidism (3%) and overt hyperthyroidism (6%) were also present. Autoimmune thyroid disorders were the most prevalent immunological processes affecting diabetic patients. Conclusions: Thyroid autoimmunity is frequently present among T1DM patients, can be associated with increased age, female gender, long diabetes duration, and can imbalance the glycemic control of T1DM patients.

   Weekly dose of L-thyroxine as a first line treatment for hypothyroidism in young and middle aged working women Top

Satish Chander Wasoori, Manoj Hari Naik1, Chetan Bhardwaj2

Endocrinology and Metabolism, Paras Hospital, 2Internal Medicine, Park Hospital, Gurugram, Haryana, 1Internal Medicine, Sanjeevan Hospital, Thane, Maharashtra, India.

E-mail: [email protected]

Objective: To demonstrate the effectiveness and compliance to L-thyroxine in the treatment of hypothyroidism in a weekly dose of 7 times of normal dose as an alternative to daily dosing in young and middle aged women. Methods: Randomized trial on 40 female patients aged between 25 to 55 years with long standing hypothyroidism of 5 years or more, currently on daily dose of L-thyroxine, were assigned weekly dose of 7 times of normal dose. The patients were randomized in 2 groups G1 and G2. Group 1 (G1): 20 Female patients with an established diagnosis of hypothyroidism of 5 years or more with TSH value of 4.20mIU/L or less, currently on daily dose. The patients were assigned a weekly dose of L-thyroxine which was changed to 7 times of normal dose. Group 2 (G2): 20 Female patients with an established diagnoses of hypothyroidism of 5 years or more with elevated TSH value of more than 4.20mIU/L. The dose in this group was individualized as per the body weight and TSH value. All patients in both the groups were screened for malabsorption and were not receiving any drugs which interfere with the absorption of L-thyroxine. The minimum to maximum dose of L-thyroxine used in this study was 175-1050 mcg. Results: We achieved complete restoration of euthyroidism in all 20 patients in the G1 at D 84 and it continued to D 168. In G2 we achieved complete euthyroidism in 16 patients at D 84 and it increased to 18 patients with some dose adjustment at D 168. We could not achieve euthyroidism in 2 patients at D 168. The unlike cause can be attributed to other metabolic disorders like diabetes and obesity. Conclusion: Once weekly dose of L-thyroxine as an alternative to daily dosing regimen was shown to be efficacious and safe for the treatment of hypothyroidism in young and middle aged females. Once a week L-thyroxine can be considered as a first line therapy in young and middle aged working women facing impaired absorption due to early breakfast (no need to wait 30-45 min for breakfast).


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   Role of pre-ablative stimulated thyroglobulin in prediction of nodal and distant metastasis on iodine whole body scan Top

Meghana Prabhu, Sanju Samson1, Avinash Reddy, Sunil HV, Naveen Hedne Chandrasekhar2, Vijay Pillai2, Vivek Shetty2, Moni Abraham Koriokose2, Bushan Vaidhya2, Subramanian Kannan3

Departments of Nuclear Medicine, 1ENT, 2Head and Neck Surgical Oncology and 3Endocrinology, Diabetes and Metabolism, Narayana Health City, Bengaluru, Karnataka, India.

E-mail: [email protected]

Objective: Pre-ablative stimulated Thyroglobulin (ps-Tg) is an important investigation in the follow-up of patients with differentiated thyroid cancer (DTC) after surgery. The absolute cut off for thyroglobulin (Tg) level to detect persistent disease is unclear. The aim of the study was to derive the range of Tg level which portends the best sensitivity and specificity for detecting persistent disease in the neck and distant metastasis. Methods: 121 patients with DTC who had undergone total thyroidectomy, underwent thyroglobulin assessment before their 131I whole body scan (WBS). Patients with antibodies to Tg (Anti-Tg) were excluded. Patients were divided into 3 groups based on the findings on 131I WBS. Group 1 included patients with either no uptake, Group 2 included those with uptake only in the thyroid bed (remnant), Group 3 included patients with cervical (nodal metastasis) and Group 4 included those with metastasis outside the neck (extra-cervical metastases i.e. Lung, Bone, Others). Mean (SD) and median (IQR) of Tg level was calculated for each of the 4 groups. If patient had high levels of anti-Tg antibody those patients were excluded. Kruskal–Wallis test was used for the comparisons of means among the 3 groups. Results: Patients in Group 1 (n = 15; 13%) had a mean Tg level of 18 + 54 ng/ml (Median 0.8 and IQR 0.3-2.4). Two patients in group 1 had TENIS syndrome (Tg of 196 and Tg of 22.1 ng/dl with negative 131I-WBS scan and FDG-PET scan) and excluding those patients, rest of the patients had a ps-Tg level <4.5 ng/ml. Majority of patients belonged to Group 2 (n = 85; 70%) and had a mean Tg level of 25 + 63 ng/ml (Median 3.45 IQR 0.8-16.4); Group 3 (n = 13; 12%) patients had a mean Tg level of 45 + 63 ng/ml (Median 10.35 and IQR 3.8-77.6) and in Group 4 (n = 6; 5%) mean Tg was 558 + 296 ng/ml (Median: 500 and Range 241 to 1048) (P < 0.001 on comparison between the four groups). None of the patients had an upstaging of their disease stage on the post-therapy scan. Conclusions: A ps-Tg >240 ng/ml strongly suggests the presence of extra-cervical metastasis, while a value <2 ng/ml makes cervical metastasis unlikely.ESICON 2017 Abstracts

   Study of prevalence of autoimmune thyroid disease in women with polycystic ovary disease Top

Palanki Radha Rani, P. Amaresh Reddy1, K. Sreenivasa Rao2, Rushikesh Maheswari3

Department of Endocrinology and Metabolism, GGH, Kurnool, 1Consultant Endocrinologist, Max Cure Hospitals, Karimnagar, 2Department of Microbiology, Govt. Medical College, Guntur, Andhra Pradesh, 3Consultant Endocrinologist, Rushikesh Endocare Superspeciality Centre, Nanded, Maharashtra, India.

E-mail: [email protected]

Context: The relationship between polycystic ovary syndrome (PCOD) and thyroid dysfunction is complex and still not clear. Aim: In this study, we examined the effect of thyroid function tests and thyroid autoimmunity in polycystic ovarian disease. Methods: 25 adult patients of diagnosed cases of PCOD and 25 age matched controls were included in the study. Anthropometric data was recorded and analysis of thyroid function tests, insulin, fasting plasma glucose and lipid profile was performed. Results: In our study body mass index, waist circumference, fasting plasma glucose, total cholesterol, LDL cholesterol, triglycerides, insulin and HOMA IR are significantly high in cases compared to controls (P value < 0.001). Thyroid stimulating hormone (TSH) and Anti thyroid peroxidase antibodies (TPO) are higher among case compared to controls (mean TSH was 3.44 ± 2.58 vs 2.16 ± 0.9 mIU/l [P value - 0.031] mean TPO was 148 ± 322 and 4.35 ± 4.22 [P value- 0.035]). Free T3 and free T4 were not different between the cases and controls. Subclinical hypothyroidism is seen in significantly higher number of cases compared to controls (28% vs 4%; P - 0.02). TPO positivity is seen in 52% of cases and 12% of controls (p - 0.002). FT4 had a positive correlation with fasting plasma glucose (p - 0.04). Conclusion: Thyroid autoimmunity and subclinical hypothyroidism is highly prevalent in patients with PCOD.

   A prospective study of effect of levothyroxine replacement on cardiovascular risk factors and quality of life in subjects with subclinical hypothyroidism Top

Sattik Siddhanta, Pranab Kumar Sahana, Soumik Goswami, Nilanjan Sengupta, Arjun Baidya, Ravi Kumar, Arindam Ray, Ravindranath Sreenath

Department of Endocrinology, NRS Medical College, Kolkata, West Bengal, India.

E-mail: [email protected]

Context: Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular (CV) risk factors and quality of life. Objective: The objective of the study was to assess cardiovascular risk factors and patient-reported outcomes including quality of life after L thyroxine treatment. Materials and Methods: In this randomized open label hospital based prospective study consisting of patients attending the outpatient clinic of Department of Endocrinology, NRS Medical College and hospital and fulfilling the inclusion and exclusion criteria, patients were assigned either to receive treatment in the form of L-thyroxine or no treatment.Clinical and biochemical parameters and quality of life are being assessed at baseline and 6 and 12 weeks post intervention. The clinical parameters assessed included body weight, BMI, waist hip ratio and blood pressure. Biochemical parameters assessed included a fasting lipid profile, thyroid function test, Apo A1 and Apo B. Quality of life assessment was done my means of three validated questionarres-SF-36(v2), Underactive Thyroid symptom rating questionnaire (ThySRQ) and Thyroid treatment satisfaction questionnaire (ThyTSQ). Results: The baseline demographic and clinical characteristics suggest that the mean age of the patients is 41.8 years with a female preponderance. The patients are overweight but normotensive.Anti TPO antibody was positive in 64% of the patients recruited in the study.At baseline visit, there was no significant differences in the clinical and biochemical characteristics between the two groups. After 6 weeks of follow up, there was no significant change in the clinical and biochemical parameters in both the treatment and control arm. However, the quality of life (as assessed by the three questionnaires) improved significantly in the treatment arm compared to control. At 12 weeks of follow up, though most of the clinical and biochemical parameters improved on L-thyroxine supplementation, yet reduction of Waist Hip ratio, Total Cholesterol and LDLc only remained significant. During l-thyroxine supplementation, there has been significant improvements in the health related quality of life outcomes particularly tiredness and pain. However, there has been no significant improvement either in the clinical and biochemical parameters or in the subject reported quality of life outcomes in the control arm. Conclusion: Subclinical Hypothyroidism treated by L-thyroxine leads to improvement of many clinical and biochemical cardiovascular risk factors and improvement of the quality of life particularly at the end of 12 weeks. There also occurs improvement of symptoms particularly tiredness and pain.

   Presentation and management of Graves' disease: An IPGMER, Kolkata data Top

Subhodip Pramanik, Rana Bhattacharjee, Pradip Mukhopadhyay, Sujoy Ghosh, Subhankar Chowdhury

Department of Endocrinology, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: Graves' disease has varied presentation and preference for therapeutic modality varies from country to country. We report the presentation and mode of therapy that we prefer in a tertiary care center in Eastern India. Methods: This is a retrospective data of 60 patients with Graves' disease evaluated and treated at our facility. Patients were recruited consecutively between March 2017 and May 2017. Results: Baseline characteristics revealed median (±IQR) age of presentation 33.1 ± 10.1 years, F:M ratio 2.3:1, median duration 7.7 ± 6.8 months, BMI 20.7 ± 3.2 kg/m2 and 20% were smoker. Most common mode of presentation was tremor (93%), followed by palpitation (86.6%), weight loss (85%) and hyperdefecation (25%). Two patients presented with only eye symptoms. Overall 31 (51.6%) patients had eye signs and active eye disease was present in 5 (8.3%) patients. Only 30 patients were screened for glycemic status at disease onset and 12 (40%) were found to have dysglycemia, however categorisation of dysglycemia could not be done. Diagnosis of Graves' was mostly done by clinical examination (57%), followed by Isotope studies (38%) and only 3 (5%) patients by Anti TSH receptor antibodies (TRAb). Majority of the patients (70%) underwent medical therapy alone, followed by radioiodine ablation (21.6%) and surgery done in 5 (8.3%) patients only. Only 2 patients developed derangement of liver function and 1 patient developed recurrent rash with medical therapy leading to discontinuation. Average radioiodine dose was 11.9 ± 2.1 mCi and only 2 (13.3%) patient needed repeat dose. 2 patients out of 5 who underwent total thyroidectomy developed permanent hypoparathyroidism. Conclusion: A comprehensive overview of management of Graves' disease in Eastern India is described. There is high prevalence of dysglycemia but often not screened. Requirement of usage of TRAb is still minimal and restricted to special cases only.

   Study of serum vitamin D level in new onset Graves' disease and its correlation with thyroid related parameters Top

Swayamsidha Mangaraj, Arun Kumar Choudhury, Anoj Kumar Baliarsinha

Department of Endocrinology, S.C.B Medical College, Cuttack, Odisha, India.

E-mail: [email protected]

Objectives: We aimed to compare serum vitamin D level in new onset Graves' disease (GD) versus age and sex matched controls. To correlate serum vitamin D level with clinical and biochemical parameters of patients with GD. Materials and Methods: This cross sectional study was conducted at department of Endocrinology, S.C.B. Medical College and Hospital, Cuttack. 84 new onset Graves' disease (age 18-60 years) were enrolled as cases as per recommended criteria. Age and sex matched healthy individuals (18-60 years) meeting the exclusion criteria were taken as controls within same period as cases (±1 month). Biochemical and hormonal investigations included serum calcium, phosphorous FT3, FT4, TSH, 25(OH) D and PTH. TRAb was measured only for GD patients. All subjects underwent detailed thyroid ultrasonography. Sun exposure was assessed. Results: GD patients have significantly lower vitamin D levels as compared to controls (P = 0.019). Thyroid hormone levels, thyroid volume and TRAb titres did not differ significantly between vitamin D deficient GD group (mean 25 OHD <20 ng/ml) and vitamin D non deficient GD group (mean 25 OHD ≥20 ng/ml). Serum vitamin D level did not correlate with mean serum FT3, FT4, TSH, thyroid volume and TRAb titres in patients of GD. The odds ratio for vitamin D deficiency state for developing GD was 1.618 (95% CI- 0.767-3.411) (P = 0.205). Vitamin D sufficiency state was associated significantly with lower risk of GD (OR = 0.377) (95% CI 0.150-0.947) (P = 0.034).Conclusion: Our results reveal that serum vitamin D levels are significantly lower in new onset GD. No significant correlation between thyroid function, thyroid volume or TRAb titres with vitamin D status was found in GD. Vitamin D sufficiency state may be protective against GD.

   A rare case of ectopic ACTH production from medullary thyroid carcinoma Top

Sandeep Donagaon, Pramila Kalra, Anil Kumar1, Harish K2, Shamim Sheik3

Departments of Endocrinology, 1Oncology and 2Surgical Oncology, Ramaiah Medical College, 3Consultant Pathologist, Ramaiah Memorial Hospital, Bengaluru, Karnataka, India.

E-mail: [email protected]

Background: Ectopic ACTH production from medullary thyroid cancer is rare; over 50 cases have been reported all over the world till date. Ectopic ACTH syndrome is seen in 0.6% of cases of MTC (Medullary thyroid carcinoma). Here we present a case of elderly male presenting with features of cortisol excess leading to the diagnosis of MTC. Case Report: A 62-year-old man presented to the neurologist with paralysis and hypertension of recent onset, gradual onset swelling of face and weight loss. On further evaluation, he was found to have cushingoid features with hypokalemic alkalosis. Basal and dynamic biochemical testing was suggestive of ACTH dependent Cushing syndrome. MRI brain showed no evidence of pituitary adenoma. Gallium (Ga)-68 DOTANOC (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaceticacid-1-NaI3-octreotide)/fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed multiple cervical nodes with diffuse uptake in thyroid and bilateral adrenal hyperplasia. Ultrasound of the neck showed oval hypoechoic thyroid nodule with small foci of calcification and multiple enlarged lymph nodes in the cervical region. Deep cervical node biopsy was diagnostic of medullary carcinoma thyroid, staining positive for carcino-embryonic antigen (CEA), calcitonin, cytokeratin (CK)-7, synaptophysin, chromogranin, thyroid transcription factor (TTF-1) and negative for CK 20, inhibin and ACTH. Serum calcitonin level was 975 pg/mL. Patient underwent thyroidectomy with lymph node dissection. Histopathology revealed widely invasive MTC. Thyroidectomy and lymph node dissection confirmed the diagnosis. Discussion: Medullary thyroid carcinoma is a rare disease accounting for 3-4% of thyroid cancers. Biochemical evaluation lead to search for an ectopic source of ACTH. Ga68 DOTANOC/FDG PET-CT scan followed by histopathology clinched the diagnosis. Metastatic MTC has poor prognosis, and in our patient the hypercortisolemic state added to the morbidity. Conclusion: Ectopic ACTH syndrome from medullary carcinoma is a rare but well identified entity. Treatment has been varied with different chemotherapeutic and adrenolytic agents. Prognosis even after treatment has been dismal, when the disease is advanced.

   Neuropsychological correlates of subclinical hypothyroidism Top

Pramila Kalra1, Kumaraswamy DR2, Ravi Yadav3, Mala Dharmalingam1, Jitender Saini4

Departments of 1Endocrinology and 2Neuropsychology, M S Ramaiah Medical College and Memorial Hospital Bengaluru, Departments of 3Neurology and 4Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.

E-mail: [email protected]

Introduction: There are conflicting studies about the presence of cognitive dysfunction in patients with subclinical hypothyroidism. It is prudent to identify subclinical cognitive abnormalities if any in patients with subclinical hypothyroidism to recommend/choose levothyroxine therapy. Aims and Objectives: To study the neuropsychological abnormalities in cases of subclinical hypothyroidism. Methods: Patients between 18 to 45 years of age, diagnosed with subclinical hypothyroidism and Thyroid stimulating hormone (TSH) values between 4.5 to 10 mIU/L with normal T4 values were recruited. Controls were healthy age, gender and education matched. All the cases and controls underwent detailed neuropsychological assessment which is a validated test for use in hypothyroid patients and age groups 18 to 60 years. Results: Twenty- nine patients with a mean age 30.9 ± 8.9 years (female:male ratio 27:2) and 16 controls (female:male ratio 7:1) with mean age 33.7 ± 6.04 years (P = 0.18) were enrolled. The mean TSH value in cases was 6.5 ± 1.81 mIU/L and in controls was 1.99 ± 1.54 mIU/L (P = 0.00). Patients were clinically screened for any nutritional deficiencies, and Diabetes mellitus was ruled out by HbA1c testing (values less than 6.5%) in both cases and controls. The visual memory delayed recall which is a function of the right temporal lobe was abnormal in 51.7% (N = 15) cases as compared to 6.25% (N = 1) controls (P = 0.012). The visual memory immediate recall which is also a function of right temporal lobe and response inhibition which is a function of bilateral superior medial prefrontal cortex showed a significant trend with abnormality in 44.8% (N = 13) and 17.2% (N = 5) cases and 18.75% (N = 3) and zero controls respectively (P = 0.09, P = 0.06). Conclusion: Patients with subclinical hypothyroidism have dysfunction in right temporal lobe and bilateral superior medial prefrontal cortex. This preliminary data would help to study the structural and functional MRI brain abnormalities in these patients.

   Adrenal: Unusual bilateral adrenal masses Top

Athulya Ashokan, Rajeev Philip1, Cherian Jacob, C. S. Abdul Kadar, Keshavan Charamelsankaran, R. N. Sharma

Departments of Medicine and 1Endocrinology, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: Unilateral adrenal masses are common with upto 4% of abdominal CTs picking up adrenal incidentalomas. Bilateral adrenal Masses are rarer, and usually are secondary to metastatic malignancy. But infrequently, we come across bilateral adrenal masses, which are treatable. We present two such cases. Case 1: A 48 year old female was referred for evaluation of b/l adrenal mass. She had history of weight loss and occasional fever for the last 6 months. She had uncontrolled diabetes, and a screening abdominal ultrasound abdomen was done, which showed b/l adrenal masses, 4.5 cms each. On evaluation for the adrenal mass, an MRI abdomen was done, which showed b/l adrenal masses, with imaging characteristics indeterminate for malignancy. A search for malignancy using a CT thorax, OGD was negative, and her hormonal status including cortisol, DHEAs, 24 hr urine cortisol, metanephrines were normal. A biopsy of the adrenal was done, and it showed inflammatory cells, macrophages with ingested PAS positive inclusions, s/o adrenal histoplasmosis. Patient was started on amphotericin and then switched over to itraconazole, after which she improved, and currently she is afebrile and is gaining weight. Case 2: A 68 year old male was brought to the casualty with shock. He had history of weight loss and occasional fever for the last 10 months. After initial resuscitation, he was evaluated and physical examination showed a thin built male with a BP of 90/70 with postural giddiness. He had significant hyperpigmentation over the knuckles and mucosal pigmentation. An ultrasound abdomen done showed b/l adrenal mass and a subsequent CT abdomen was done, which showed b/l adrenal masses, 5.2cm in diameter with good contrast washout. A search for malignancy using a CT thorax, OGD was negative. A base line AM cortiol was low, and corresponding ACTH was found to be high s/o primary adrenal insufficiency. A biopsy of the adrenal was done, and it showed granulomatous inflammation with caseous necrosis s/o tuberculosis. Patient was started on hydrocortisone and fludrocortisone, along with ATT. He improved with treatment, and has gained weight and afebrile now. Conclusion: Bilateral adrenal masses are rare, and when present, usually indicatesdisseminated malignancy. But rarely they can be due to treatable causes like histoplasmosis or tuberculosis. Adrenal biopsy, eventhough not routinely performed, helps us to pick up these treatable causes, and hence should be considered in cases of b/l adrenal masses if initial malignancy workup is negative.

   Unilateral adrenal hyperplasia as a cause of primary hyperaldosteronism Top

Jyoti Wadhwa, Smitha Nalla, I. Satish Rao1, Prasun Deb

Departments of Endocrinology and 1Pathology, KIMS, Secunderabad, Telangana, India.

E-mail: [email protected]

Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism. Here we report a case of 45 year old female patient who had hypertension for 20 years, diagnosed in her second pregnancy and was on regular antihypertensive medications since then. One year back, patient collapsed suddenly and was hospitalized for the same. Her potassium was then found to be 1.5 meq/L and she was started on tab eplerenone 50 mg OD by her treating physician. There was also history of chronic liver disease with portal hypertension with an episode of hematemesis two years back. She had presented to us a case of resistant hypertension on carvedilol, amlodipine, eplerenone and syp potklor with persistent hypokalemia. Eplerenone was stopped and changed to prazosin for evaluation of primary hyperaldosteronism. Her 24 hour urinary aldosterone was found to be 52.3 mcg/24 hrs (N <12 mcg/24 hrs), plasma aldosterone was - 37.5 ng/dL, plasma rennin activity was -0.3 ng/mL/hr with ARR of 125 ng/dL per ng/mL/hr. Her overnight dexamethasone test and urinary fractionated metanephrines were found to be normal. CT abdomen showed presence of right adrenal adenoma. Patient underwent laparoscopic right adrenalectomy with subsequent improvement in blood pressure and potassium levels. Histopathology from her right adrenal gland showed presence of two well defined yellowish nodules (1.5*1.5*1 cm) and (0.5*0.5*0.5cm) in size. Sections from larger uncapsulated nodule showed a nodular proliferation of adrenocortical cells with admixed zona fasiculata, zona glomerulosa and zona reticularis with normal adrenal tissue in the periphery. In view of presence of unencapsulated nodules, nodular adrenal cortical hyperplasia is being considered. We present this case for its rarity in literature and no reports from India so far.

   Clinical and hormonal profile of pheochromocytoma at a Tertiary Care Hospital in South India Top

Kotha Subbarao, B. Vivekanand, L. Brahmanandam, A. Mythili, Ramesh Jayanthy, K. A. V. Subramanyam

Department of Endocrinology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India.

E-mail: [email protected]

Objective: To study the clinical and hormonal profile of patients presenting with Pheochromocytoma to a Tertiary Care Hospital in South India. Materials and Methods: The study included 15 patients with Pheochromocytoma who attended the Department of Endocrinology, Andhra medical college from January 2016- June 2017. Clinical, hormonal, and radiological evaluation was done and analyzed. Results: Mean age of presentation was 35.6 years (14-60 yrs). Males were 47% and females were 53%. The most frequent symptoms were hypertension (60%), palpitations (53.3%), sweating (46.7%), headache (40%), anxiety (35.3%), diabetes (33%) and abdominal pain (26.6%). Hyper adrenergic spells were present in 33.3% of the patients. Hypertensive crises in 20%, normotension in 40% and incidentalomas were seen in 26.6% of the patients. One patient had hereditary pheochromocytoma syndrome. Biochemical evaluation revealed elevated metanephrines in 33.3%, nor metanephrines in 40% and both were elevated in 26.6% of patients. CECT abdomen showed intra adrenal mass in 80% of patients and extra adrenal mass in 20% of patients. Among adrenal masses 58.3% were on right side and 33.3% on left side and bilateral was seen in 8.3%. Conclusion: In our study, the mean age (35.6 years) of presentation seems to be relatively younger. The patients were often asymptomatic and normotensive. The present study confirms that the clinical presentation of pheochromocytoma can be variable and non specific and requires a high index of suspicion for early diagnosis.

   Profile of adrenal incidentalomas in a Tertiary Care Hospital Top

Don David, Rajeev Philip1, Cherian Jacob, C. S. Abdul Kadar, Keshavan Charamelsankaran, R. N. Sharma

Departments of Medicine and 1Endocrinology, PIMS, Thiruvalla, Kerala, India.

E-mail: [email protected]

Introduction: Adrenal incidentalomas (AI) are classically described to be present in in approximately 4-7% of patients in imaging studies. Majority are benign, but careful evaluation is warranted to rule out carcinoma and functional adenomas. The incidence of adrenal incidentalomas in an Indian setting is much lower than described in western literature. Aim: To study the profile of adrenal incidentalomas in a Tertiary Care Hospital. Materials and Methods: All patients referred for evaluation of adrenal masses in the medicine/endocrinology OPD were included in the study. Only masses more than 1 cms were evaluated. All patients underwent a Adrenal protocol CT, an overnight dexamethasone suppression test to look for Cushings, a Plasma Renin activity/Plasma aldosterone concentration, 24 hr urine meanephrine, and DHEAs, and if the masses were bilateral, an AM cortisol was done to look for adrenal insufficiency. Results: A total of 46 patients were studied. The mean age was 57.9 years, The male female ratio was 0.43. The average size of the adrenal was 3.18 cms (range 1.1-11.2 cms). 4 (8%) patients had bilateral adrenal masses. 10 patients (21%) had functional adrenal masses, which included 3 patients with Conns syndrome. 3 (6%) patients had pheochromocytoma, 3 (6%) patients had Cushings syndrome, one had Subclincal Cushings syndrome. 3 (6%) patients had myelolipomas. Rest patients (79%) had non functioning tumours. 2 (4%) patients had adrenocortical carcinoma, one patient had oncocytoma and one patient had teratoma.

   Rare case of CAH with hypertension: A case report Top

Chaitanya Konda, Vijay Sheker Reddy Danda, P. Sreedevi, P. Shalini, Madhavi Verpula, Sarath Aleti

Department of Endocrinology, Gandhi Medical College and Hospital, Secunderabad, Telangana, India.

E-mail: [email protected]

Background: Congenital adrenal hyperplasia (CAH) is a group of inherited disorders with a defect in cortisol biosynthesis with consequent overproduction of adrenocorticotropic hormone (ACTH) and secondary adrenal hyperplasia as a consequence. An enzymatic defect in 11-beta-hydroxylase is the second most common variant of CAH and accounts for approximately 5-8% of cases. We present a case of a CAH with Hypertension. Case History: A 6yr old female child, with a diagnosis of congenital adrenal hyperplasia, admitted for clitoral reduction surgery, was referred for endocrine work up. She was born of non-consanguineous marriage. She was noticed to have ambiguous genitalia at birth, without salt loosing crisis episodes. Diagnosed as CAH at age of 4 years of age and was started on hydrocortisone replacement. On examination her height was above 97th percentile, with +0.8SDS for IAP chart. External genitalia showed Prader stage 4 masculinisation, with single orifice at the base of phallus and a tanner staging of A2, P3, B1. Her blood pressure was 170/120 mm Hg. In view of severe hypertension she was evaluated to look for beta hydroxylase deficiency. A synacthen stimulated steroid profile was sent (LS/MS) which showed a suppressed cortisol, with moderately elevated 17 OHP and deoxycorticosterone elevated more than three times the upper limit. She was started on spironolactone 25 mg/day and up titrated to 125 mg/day over following eight weeks, with an add on calcium channel blocker, and was submitted for surgery after stabilisation. She underwent surgery and recovery was uneventful. Conclusion: Congenital adrenal hyperplasia is common disorder, with 21 hydroxylase deficiency being the most common cause. 11beta hydroxylase deficiency is a rarer presentation, which can present with late onset of hypertension. Early detection of this entity is very important to prevent consequences of persistent hypertension.

   Pheochromocytoma a case series of eight patients admitted in IPGMER, Kolkata in last 2 years with genotypic correlation Top

Debarati Bhar, Sunetra Mondal, Neha Agrawal, Sujoy Ghosh1, Pradip Mukhopadhyay1, Satinath Mukhopadhyay1, Subhankar Chowdhury1

Departments of Metabolism and 1Endocrinology, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Background: Pheochromocytoma in adrenal gland frequently exhibits an association with VHL mutation. This has been illustrated in the present case series of 8 cases of this disease admitted in our hospital. Results: Our case series had 8 patients of age group range between 2.5 months to 57 yrs. M:F-1:1. No s/o family h/o except sudden cardiac death in elder sibling of 1 patient and goitre and hypothyroid in 1st degree relative another. Hypertensive crises occurred in majority (5 out of 8). Raised urinary and/or plasma normetanephrines (with normal/borderline metanephrines) in all cases (incld. VHL + ve), extradrenal (hepatic) metastasis in 1, heterozygous for VHL mutation in 3 of 8. Tc99m hynic TOC (Octreotide derivative) couldn't localize the SOL though distinct on CT scan in 1 case. Of the 3 VHL + ve cases, all were large, cystic masses, 2 bilateral, 1 patient had asymmetric septal hypertrophy/HOCM?, 1 retinal angioma, brainstem microbleeds/CNS hemangioblastoma?. Largest SOL size was 90 mm in 1 patient, baseline (B) HU 42, absolute washout (AW) >60%, delayed washout (DW) >50%; other had SOL in right adrenal (R) 35 mm, left (L) 29 mm, baseline (B) HU 35, absolute washout (AW) >65%, delayed washout (DW) >40%; 3rd patient had SOL 27 mm (R), B 25 HU, AW >70%, DW >42%; 4th-SOL 46 mm (L), B 36 HU, AW >70%, DW >42%; 5th-SOL 70 mm (R), B 42 HU, AW >60%, DW >50%; 6th-SOL 60 mm; 7th- SOL 67 mm (R), 64 mm (L), others had T2 hyperintensities on adrenal MRI. Outcome- open and/or laparoscopic adrenalectomy with cure, no residual hypertension on follow up except 1 (demise in early postoperative period due to hemorrhagic shock). Case fatality was 1:8 or 12.5% for our study. SOL size range was from 18 -90 mm; bilateral in 50% (4 of 8). Conclusion: Our case series emphasizes value of directed genetic testing for VHL mutation in all norepinephrine secreting pheochromocytoma, even if they are purely in adrenal location.

   4A syndrome: A case report Top

Rajan Palui, Kalyani Sridharan, Harsh Durgia, Nandhini LP, Jayaprakash Sahoo, Sadishkumar Kamalanathan

Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

E-mail: [email protected]

Objectives: Triple A syndrome (also known as Allgrove syndrome) is characterised by Addison's disease, Achalasia and Alacrima. It occurs due to mutation in ALADIN gene in chromosome 12q13. When autonomic dysfunction is associated with this rare syndrome, it is called 4A syndrome. Here we report a 21-year-old man who had all the 4As - Addison's disease, Achalasia, Alacrima, and Autonomic dysfunction. Materials and Methods: This patient initially presented at 5 yrs of age due to lethargy, asthenia and progressive darkening of skin. At that time, baseline 8 am cortisol was 1.8 μg/dl and serum ACTH was >1250 pg/ml. He was started on oral hydrocortisone. After that the patient was lost to follow up but he was taking hydrocortisone from outside till 6 months back. Now this patient presented with addisonian crisis as he discontinued treatment due to dysphagia. His dysphagia was to both solids and liquids and was gradually progressive in nature for last 5 years. He also complained of alacrima, hyper nasal voice tone and bouts of dizziness. Results: On clinical examination he had postural hypotension and his autonomic function test was suggestive of dysautonomia (decreased heart rate variation with deep breathing and decreased heart rate response to standing). His Schrimer's test (bilaterally <5mm) and lacrimal scintigraphy were suggestive of alacrima. Barium swallow showed characteristic bird's beak appearance and upper GI endoscopy revealed dilated oesophagus. Oesophageal manometry was done and was suggestive of type 2 achalasia. Contrast enhanced computed tomography (CECT) of abdomen revealed bilateral atrophic adrenal glands. Conclusion: Based upon the clinical features and investigations, he was diagnosed as a case of 4A syndrome. All the components of this syndrome may not be present at the onset and long term follow up may be required to diagnose this rare syndrome.

   Pure testosterone secreting atypical adrenal mass causing long standing virilisation Top

Pramila Dharmshaktu, Yashdeep Gupta, Shipra Agarwal1

Departments of Endocrinology and 1Pathology, AIIMS, New Delhi, India.

E-mail: [email protected]

Introduction: Pure testosterone secreting benign adrenal lesions are very rare with less than 10 cases reported in literature till now. Case Summary: We present a case of 33 years old female who was symptomatic for past 10 years with secondary infertility, irregular menstrual cycles and progressive virilization. On examination, she had features of androgen excess with virilization and clitoromegaly. Biochemical steroid hormone evaluation revealed very high serum testosterone levels with marginally raised serum DHEAS levels. Patient was normotensive and not having any cushingoid habitus. Further low dose dexamethasone suppression test failed to suppress serum testosterone levels but suppressed serum cortisol and serum DHEAS levels suggesting tumoral origin of serum testosterone. Contrast enhanced CT scan of abdomen revealed a right adrenal mass of about 3*3 cms in size with poor radiological characteristics of an adenoma. Mass was further confirmed on MR adrenals in view of radiological characteristic of an adenoma and similar findings were obsereved of an adrenal mass. Patient underwent laparoscopic right adrenalectomy. Histopathology of the lesion revealed nodular adrenocortical adrenal hyperplasia. Within 2 days of surgery her testosterone levels came down to normal. Patient is on regular follow up. In her last follow up after 3 months of surgery, patient had resumed her menstrual cycles. Conclusion: Benign adrenal lesions hypersecreting androgens are rare. These tumors are usually associated with very high DHEAS levels also. This case highlights that adrenal lesions should be ruled out in patients with long standing virilisation and infertility.

   Prediction of adrenocortical insufficiency in clinically suspected patients using 9 am basal cortisol level in resource poor setting Top

G. P. Samarasinghe, E. M. S. B. Ekanayake, C. N. Antonypillai

Diabetes and Endocrinology Unit, Teaching Hospital, Kandy, Sri Lanka.

E-mail: [email protected]

Introduction: Hypothalamo pituitary adrenal (HPA) insufficiency is diagnosed by the presence of sub optimal cortisol response in standard short synacthen test (SST). The safe level of basal cortisol which would exclude the possibility of adrenal insufficiency is controversial.[1] Objectives: To identify a local reference cortisol value in the diagnosis of HPA insufficiency in clinically suspeced patients in Srilanka. Methods: All SST done for the evaluation of suspected HPA insufficiency, from January 2012 to January 2016 at Endocrinology Unit, Teaching Hospital, Kandy, Srilanka were retrospectively analyzed. A normal response to the SST was defined as a peak serum cortisol of >500 nmol/l at 30 min. The cut-off values of serum cortisol were determined in relation to the gold standard test. Results: Two hundred and seventeen patients suspected of having adrenal insufficiency were recruited, and 51% were females. There were 103 healthy and 112 diseased patients. The basal cortisol value (0900h) for the healthy adults was normally distributed with mean 336.5 and ± 123.7 SD. For the diseased adults the distribution was positively skewed with a median 144.7 and 97.5th percentile at 478. Conclusion: With 95% confidence, the adults who have basal cortisol levels less than 89.1 nmol/l are likely to be having HPA insufficiency and those who have values above 478 nmol/l are unlikely to be diseased. Adults who have values between 89.1 and 478 nmol/l need further tests (SST) to confirm or exclude HPA insufficiency.


  1. Kline GA, Buse J, Krause RD. Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay. Clin Biochem 2017;50:475-80.

   Clinical and biochemical profile of adrenal mass: Single centre experience Top

Prem Narayanan, Neeraj Kumar Agrawal, Jitendra Chouhan, Saurabh Arora, Surya Kumar Singh

Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

E-mail: [email protected]

Aim: To study the clinical and biochemical profile of adrenal masses evaluated in the endocrinology department in our hospital. Materials and Methods: It is a restrospective data analysis of patients with adrenal masses evaluated in our department from January 2014 – August 2017. The parameters such as gender, age, laterality of lesion, etiology, symptomatology, ABPM (Ambulatory Blood Pressure Monitoring) readings, biochemical profile (basal cortisol, ONDST, 24-hour urinary VMA) and size of the lesion (NCCT) were reviewed. Results: 28 patients were included in the study. There were 15 (53.5%) male and 13 (46.5%) female patients. The mean age of patients was 43.2 yrs (range – 8- 65 yrs). Of the 28 patients eleven had right adrenal mass (39.2%), six had left adrenal mass (21.4%) and eleven had bi lateral masses (39.2%). The most common aetiology was Benign adenoma (35.71%) followed by functioning adenoma (21.4%)(3 pheochromocytoma, 2 cortisol secreting, 1 androgen secreting), ACC (21.4%), infective (17.8%) and metastasis (3.5%). One patient with metastasis had the primary tumor in lung. Among the 11 patients with bilateral masses the most common cause was infective 45.4% followed by pheochromocytoma 27.2%. ABPM was used in all 3 patients with pheochromocytoma and it helped in demonstrating hypertensive spikes in all of them, of which 1 patient was normotensive on routine BP recordings. Among symptomatology 12 (40%) presented with abdominal pain, 4 (14.2%) with hypocortisolism, 3 (10.7%) with hyperadrenergic spells, 2 with hypercotisolism (7.1%), 8 (28.5%) were incidentalomas. Hypocortisolism was common in tuberculosis (100%). The largest size of lesion was 17 * 13 cm (ACC) and smallest was 1.2 * 1.0 cm (adenoma). Conclusion: Adrenal masses are quite common and our study shows no gender predilection. Majority of the adrenal masses occur in the middle age group with varied manifestations. Even though non functioning adenoma was the most common etiology in our study, infective etiology is the commonest in patients with bi lateral adrenal masses. Among functioning adenoma pheochromocytoma was most common followed by hypercortisolism. ABPM proved to be a good screening tool in the evaluation of pheochrocytoma and we suggest it to be further studied.

   ACTH stimulation test with long acting ACTH preparation for the diagnosis of adrenal insufficiency Top

C. Jayakumari, Geena Susan George, Abilash Nair, Puthiyaveetil Khadar Jabbar, S. J. Jessy1, T. P. Seena

Departments of Endocrinology and 1Biochemistry, Government Medical College, Thiruvanathapuram, Kerala, India.

E-mail: [email protected]

Background: Synacthen (Synthetic ACTH) stimulation test is the recommended method to diagnose adrenal insufficiency. In India availability of synacthen is poor and cost is prohibitively high. Long acting ACTH (Acton Prolongatum) is freely available as it is one of the therapeutic modalities for infantile seizures. In many centres in India, Acton prolongatum is being used for the purpose of diagnosing adrenal insufficiency but validation studies of its diagnostic accuracy are few. Materials and Methods: Ethics committee of Govt Medical College Thiruvananthapuram approved the study. Patients with suspected adrenal insufficiency (both primary and secondary) underwent stimulation test with 25 units of intramuscular Acton Prolongatum. Critically ill patients and those with impending adrenal crisis were excluded. Blood was drawn for serum cortisol estimation before the injection and 1 hour and 2 hours after the injection. The patients in whom the serum cortisol levels remained below 18 mcg/dl were further tested with IV Synacthen and blood was drawn for serum cortisol estimation at 0 (before injection), 30 and 60 minutes according to the standard procedure. An equal number of randomly selected patients who had a negative Acton prolongatum test were also tested with IV Synacthen. The tests were carried out on the Beckman Coulter Access 2 electro cheiluminicence system. Results: 31 patients with suspected adrenal insufficiency were identified over a period of 3 months. The mean age of the study patients was 33.4 years Twenty one of them were females. The clinical suspicion was of primary adrenal insufficiency in 11., secondary adrenal insufficiency in 2 and the rest were not having a classic setting of any particular type of adrenal insufficiency but were screened due to symptoms of weight loss, weakness or postural giddiness. Twenty four out of 31 patients achieved a robust cortisol peak after synacthen injection thus ruling out adrenal insufficency. Twenty six out of 31 patients had a higher 2 hour cortisol value than the one hour cortisol value indicating that the 2 hour value may be more important than 1 hour value in the diagnosis of adrenal insufficiency while using 'Acton prolongatum' in order to avoid false positive tests. Seven patients were found to have low (<18 mcg/dl) cortisol even after stimulation with acton prolongatum. When they were tested with synacthen all the seven were having values below 18 mcg/dl (False positive 0%, Specificity 100%). When the patients who had normal values with acton prolongatum were tested with synacthen they too showed stimulated values more than 18 mcg/dl. Conclusion: ACTH stimulation test with long acting ACTH preparation is sensitive and specific for the diagnosis of adrenal insufficiency. The blood samples for cortisol estimation when using acton prolongatum should be drawn for upto 2 hrs after the Acton Prolongatum Injection.

   Unusual cases with adrenal insufficiency: Adrenal histoplasmosis in immunocompetent Top

Vijay Kumar Bhavi, Balram Sharma, Anita Harsh1, Deepika Hemrajani1, Pratibha Maan1, Hardeva Ram Nehara, Sanjay Saran, Sandeep Kumar Mathur

Departments of Endocrinology and 1Pathology, SMS Medical College, Jaipur, Rajasthan, India.

E-mail: [email protected]

Background: Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. Histoplasmosis has been rarely reported from India.[1] Symptomatic adrenal involvement is more common in patients with immmunocompromised than immmunocompetent.[2] Objective: To determine the clinicopathological findings and treatment response in adrenal histoplasmosis. Materials and Methods: All 5 Male patients presented to Endocrine OPD with constitutional symptoms: weight loss, decreased appetite, postural dizziness, diffuse hyperpigmentation of skin. One patient also had diffuse cutaneous lesions of histoplasmosis. All cases underwent relevant biochemical investigations and hormonal evaluation. CECT adrenal imaging was performed. Diagnosis was made in each instance by percutaneous adrenal biopsy. Tissue was formalin-fixed, embedded in paraffin, sectioned at 4 μm and stained with H and E stain before examination (Figure 1). Fungal morphology was delineated using PAS stain to detect adrenal histoplasmosis (Figure 2).[3] Results: All cases were seronegative for HIV and had very low serum basal cortisol level at presentation. CECT imaging (Figure 3) showed bilateral adrenal involvement. Histoplasmosis was proven by histopathological examination.[4] They received amphotericin B followed by itraconazole treatment and steroids which led to symptomatic improvement with average follow up of one year.[5] Conculsion: Adrenal histoplasmosis should be considered in differential diagnosis of patients presenting with constitutional symptoms and unilateral or bilateral mass with or without AI.
Figure 1: Large areas of necrosis and granuloma formation noted in (x-100)

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Figure 2: HE stain showing numerous macrophages with intracytoplasmic fungal spores size with halo around them suggestive of histoplasmosis (X-1000)

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Figure 3: Bilateral adrenals are enlarged in size right adrenal 45 × 30 mm, left 50 × 28mm and are replaced by heterogeneous density lesion

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  1. Wheat LJ. Histoplasmosis: A review for clinicians from non-endemic areas. Mycoses 2006;49:274-82.
  2. Carlos F, Lopes B, Ronilson O, Bianca A, Leonardo S, Janaína S. Bilateral adrenal histoplasmosis in an immunocompetent man. Rev Soc Bras Med Trop 2007;40:230-3.
  3. Fitzhugh VA, Maniar KP, Kim MK, Chen H, Schainker BA. Adrenal histoplasmosis. Diagn Cytopathol 2010;38:188-9.
  4. Kumar N, Singh S, Govil S. Adrenal histoplasmosis: Clinical presentation and imaging features in nine cases. Abdom Imaging 2003;28:703-8.
  5. Arlt W. Disorders of the adrenal cortex. In: Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw Hill Publication. 2015. p. 2309.

   Adrenal incidentaloma cases: clinical, laboratory and imaging characteristics of 20 patients Top

Arindam Ray, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami, Sattik Siddhanta, Ravi Kumar, R. Sreenath

Department of Endocrinology, NRS Medical College, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: To study clinical, biochemical, radiological characteristics, different histopathological types of 20 individual subjects with adrenal incidentaloma in an attempt to give an idea of various types of adrenal lesions presenting as adrenal incidentaloma. Materials and Methods: 20 Subjects with adrenal incidentaloma from Endocrinology OPD of NRS Medical College, Kolkata during October, 2016 to July, 2017 has been included. As per Departmental protocol we evaluated for hormonal activity and CECT abdomen in all subjects. Surgical intervention has been suggested to those who are hormonally active, imaging suspicious for malignancy and size more ≥4 cm. Histopathology has been correlated with clinical, biochemical, radiological character of respective subjects. Results: GI symptoms constitute 77% at presentation. USG picks up 80% cases in our study as first imaging modality. After evaluation (n = 20), 60% has myelolipoma, 20% pheochromocytoma, 10% Conn syndrome, 5% Cushing's syndrome, 5% adrenocortical carcinoma. Subjects who has been surgically managed (n = 14), as per histopathology 43%has myelolipoma, 29% pheochromocytoma, 21% adrenal adenoma, 7% adrenocortical carcinoma. Conclusion: From our study: Apart from various clinical presentations, biochemical results and radiological picture of adrenal incidentaloma cases, Myelolipoma is the most common adrenal incidentaloma. Pheochromocytoma is the most common hormonally active adrenal incidentaloma. Conn syndrome patient may not have hypertension. Adrenocortical carcinoma can be clinically silent.

   73 year old male with bilateral adrenal haemorrhage Top

K. Divya, Mohan T. Shenoy, Harish Kareem, Simi M. Ismail

Department of General Medicine, Endocrinology and Gastroenterology and Radiology, SK Hospital, Thiruvananthapuram, Kerala, India.

E-mail: [email protected]

Objectives: Bilateral adrenal haemorrhage (BAH) is an uncommon but potentially catastrophic complication of thromboprophylaxis.[1] We report an elderly male who underwent a total knee arthroplasty and 3 weeks later, subsequently developed BAH from Apixaban (Oral factor Xa inhibitor). Corticosteroids were promptly started attained complete recovery by 72 hrs with no further complications. Materials and Methods: Case Report: A 73 year healthy gentleman underwent bilateral total knee replacement in July 2017. After 3 weeks, he reported to Emergency Room with abdominal discomfort and vomiting - noted to have hyponatremia (119) and hyperkalemia (5.5). CECT abdomen showed bulky isodense adrenals with significant perilesional fat stranding suggestive of BAH (Figure 1). He was hemodynamically stable with no evidence of sepsis; received intravenous Hydrocortisone 150 mg/day for five days followed by oral steroids. There was low cortisol level with lack of incremental response to Acton Prolongatum. He became symptomatically better with the normalisation of electrolytes due to early initiation of steroids (Table 1). Hence preventing acute adrenal crisis which contributes 15% fatality. Conclusion: Thromboembolism, a known complication in 40–80% total knee replacements requires appropriate thromboprophylaxis.[2] BAH presents a diagnostic challenge to treating physicians due to non-specific presentations that range from vague abdominal pain, nausea, vomiting, neuropsychiatric symptoms, hypotension or shock, and fever.[3] Timely intervention and early initiation of steroids is critical in the management can prevent acute and long term sequalae.
Figure 1: Serial biochemical parameter and CECT showing Bilateral adrenal hemorrhage

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Table 1: Serial electrolyte values in mEQ/L

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  1. LaBan MM, Whitmore CE, Taylor RS. Bilateral adrenal hemorrhage after anticoagulation prophylaxis for bilateral knee arthroplasty. Am J Phys Med Rehabil 2003;82:418-20.
  2. Stringer MD, Steadman CA, Hedges AR, Thomas EM, Morley TR, Kakkar VV. Deep vein thrombosis after elective knee surgery. An incidence study in 312 patients. J Bone Joint Surg Br 1989;71:492-7.
  3. Park KJ, Bushmiaer M, Barnes CL. Bilateral adrenal hemorrhage in a total knee patient associated with enoxaparin usage. Arthroplast Today 2015;1:65-8.

   Addison's disease due to bilateral adrenal histoplasmosis: An unusual cause of hypoglycaemia in a diabetic patient Top

Amarta Shankar Chowdhury, Debmalya Sanyal1

Department of Endocrinology, Rabindranath Tagore International Institute of Cardiac Sciences, 1Department of Endocrinology, Rabindranath Tagore International Institute of Cardiac Sciences, KPC Medical College, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: To report a case of hypoglycaemia in a Type 2 Diabetic patient due to adrenal insufficiency caused by bilateral adrenal histoplasmosis. Case Presentation: A 64 yr old lady, T2DM and hypertensive for 13 yrs on oral hypoglycemic agents presented with anorexia, nausea, generalized weakness, postural dizziness and weight loss for last 3 wks along with 2-3 episodes suggestive of hypoglycaemia, with one documented hypoglycaemia in the afternoon – managed without any assistance. On general examination her BMI was 19 kg/m2, pallor was present, B.P -130/76 mm of Hg (postural drop-34), with diffuse hyperpigmentation of buccal mucosa and palm. Power-4/5 b/l, ankle jerk-diminished. Her blood parameters revealed Hb- 8.0%, TC-7, 100, ESR: 58, Na-127, K- 4.4, HbA1c-7.6%. 8 A.M. Cortisol – 2.3 μg/dl, 8 A.M. ACTH –148 pg/ml. CT abdomen was consistent with b/l adrenal enlargement. FNAC from adrenal gland showed histiocytes and multinucleated giant cells with spores 2–3 μm in diameter located within histiocytes, giant cells and extracellular space. C/S confirmed it to be a case of Histoplasma. There was no evidence of disseminated histoplasmosis. She was treated with Itraconazole 200 mg twice daily and oral hydrocortisone. Conclusion: Adrenal insufficiency is an extremely rare cause of hypoglycemia in a T2DM patient. It has to be kept in the hindsight after excluding the usual causes of hypoglycemia in a diabetic patient. Adrenal histoplasmosis is rare but should be considered in any patient presenting with bilateral adrenal masses, constitutional symptoms and suggestive history.

   Quality of life and its correlations in male patients with primary adrenal insufficiency Top

Mahaveer Singh, Eesh Bhatia, Subhash Yadav

Department of Endocrinology, Sanjay Gandhi Post Graduate institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: To study the quality of life (QOL) and the frequency of hypogonadism in male patients with primary adrenal insufficiency (PAI). Materials and Methods: We conducted a single center, case-control study of 32 male patients [age 42 ± 11 years (range 26-70 years] with primary adrenal insufficiency and 64 control subjects matched for age, sex and BMI to assess their QOL. QOL was assessed by the SF 36v2 validated for Indian subjects. We studied the frequency of hypogonadism in PAI (morning testosterone <10.4 nmol/l on two occasions) and the association of serum testosterone and other variables with QOL. Results: The average hydrocortisone equivalent was (mean + SD) 20 ± 4 mg/day (range 15-30 mg/day). Four patients (12%) had hypogonadism (3 with secondary and 1 with primary hypogonadism). Patients had significantly higher frequency of hypogonadal symptoms when compared with healthy controls (P < 0.05). When compared with healthy controls, patients with PAI had a poor QOL in all 8 domains of SF-36v2 (P < 0.05 for each domain). All the domains of SF 36v2 except social functioning had negative correlation (P < 0.05) with average daily hydrocortisone equivalent. However, there was no correlation with serum testosterone. On multivariate analysis, average dose of hydrocortisone equivalent and T2DM were associated with poor performance in the SM-PCS (P < 0.05). Conclusion: Despite appropriate glucocorticoid replacement, male patients with PAI had a lower QOL and higher frequency of hypogonadism symptoms compared with controls. QOL was inversely related to average daily dose of glucocorticoid replacement but not with serum testosterone.

   Glucocorticoid misuse – A “Neglected Endocrine Disorder” affecting both mortality and morbidity: When will we acknowledge the nationwide impact? Top

Philip Finny, Lois Joy Armstrong1

Departments of Medicine and 1Research and Epidemiology, Duncan Hospital, Raxaul, Bihar, India.

E-mail: [email protected]

Objectives: Glucocorticoid misuse (GCM) is having a serious impact in India. We conducted small research projects to record the local impact in North Bihar and began collecting literature that highlighted this issue in Asia. Methods: At Duncan Hospital, Bihar there have been four research projects attempting to assess the problem of GCM. These studies are summarized and a review of both academic and non-academic literature has been used. Results: In a six-month, prospective, hospital-based study, 22 patients presented with Iatrogenic Cushing's syndrome or Hypo-adrenal crisis. The following complications were noted: cataracts (10), recent onset of diabetes (6), recent onset of hypertension (5), osteoporotic fractures of the spine (12). Ninety percent of these patients had been using glucocorticoids for more than two years. A community survey of 334 participants found 33.8% have taken glucocorticoids in the last six months. Eighty eight percent of these were inappropriate usage. One in fifteen people in Raxaul block potentially have a suppressed HPA axis due to GCM. In a six-month review of 102 hyponatraemic inpatients, 15 percent were diagnosed as being due to hypocortisolaemia. 253 verbal autopsies were collected in one year of community deaths. Verbal autopsies were used as only 7% had death certificates. At least 6 deaths, potentially have GCM implicated in their secondary medical diagnosis. COPD, a common local cause for GCM, was the most common cause of adult deaths in East-Champaran, Bihar. The death of a 55 year old, Nepali lady with Ludwig's Angina occurred after presentation to the Dental OPD. She had COPD and was a chronic GC misuser. Academic and non-academic literature reveals significant morbidity and mortality due to GCM from South Asia. Conclusions: A large, multidisciplinary study of the public health implications of glucocorticoid misuse is needed. Endocrinologists need to speak about systemic GCM to the relevant authorities, just as dermatologists are doing so about topical steroid misuse.

   Clinico-pathological characteristics in adrenocortical carcinoma: A single centre experience over a decade Top

Arun S. Menon, M. R. Bindhu, Annie Jojo, Ajith Nambiar, V. P. Praveen, Nisha Bhavani, Usha Menon, Nithya Abraham, Vasantha Nair, Harish Kumar

Department of Endocrinology, Amrita Institute of Medical Science, Kochi, Kerala, India.

E-mail: [email protected]

Introduction: Adrenocortical carcinoma (ACC) is a highly aggressive malignancy. Metastatic spread is common at presentation (21–52%) and almost invariable on follow up. All current medical and surgical treatments carry poor results. Low tumor incidence is a major obstacle to identifying effective treatment regimens and accurate prognostic markers. Introduction of standardized criteria like Weiss criteria has led to a more complete histopathological documentation and helps individual patient prognostication. Methods: We retrospectively studied the clinical and pathological characteristics of patients who presented over a 10 year period with a proven diagnosis of ACC. Those who underwent surgery had pathological characterization using Weiss criteria. Results: There were 24 patients during this period who had a diagnosis of adrenal cortical carcinoma confirmed by histology. The age at presentation was 45.1 ± 15.1 years (range 1- 73 years), with equal number of males and females. 16/24 patients presented with clinical features of Cushing's syndrome/virilisation, 4 had incidentally detected abdominal mass, and 3 presented with abdominal pain. 20 patients underwent surgery and thus had complete histopathological characterization. 12/20 were classified as Weiss 4 or 5 out of which 6 patients (50%) had no recurrence after more than 2 years of follow-up. All 8 who were classified as Weiss 6 or 7 had either metastases at presentation or recurrence within 12 months of follow-up. 4 patients did not undergo surgery as they had already developed metastases at presentation. The overall mortality was 18/24 patients within a year of follow-up. Conclusion: This data confirms the overall poor prognosis in ACC with a 12 month mortality of 75% regardless of the mode of presentation. Surgical treatment is the main stay with a uniformly poor response to chemotherapy. A standardized pathological grading system (Weiss criteria) helps in prognostication after surgery with a 50% chance of cure in those presenting with malignancy that is limited to the adrenal gland.

   Reproductive Endocrinology: Study of the clinical profile and etiology of various disorders of sex development presenting to endocrine OPD of a Tertiary Care Hospital Top

Ipsita Mishra, Arun Ku Choudhury, Anoj Kumar Baliarsinha

Department of Endocrinology, S.C.B. Medical College and Hospital, Cuttack, Odisha, India.

E-mail: [email protected]

Objective: To study the clinical profile and etiology of patients of various disorders of sex development presenting to endocrine OPD of a Tertiary Care Hospital. Materials and Methods: We retrospectively assessed the records of patients who were evaluated for hypogonadism and genital ambiguity between March 2014 to June 2017, in our endocrine unit. The patients were classified on the basis of clinical features, hormonal investigations, imaging studies, karyotype and laparoscopy/biopsy studies as indicated. Results: Distribution of DSD by category were 46XYDSD (41.6%), 46XXDSD (27.3%), SCD DSD (30.9%). Distribution of DSD by subtypes were 46XYDSD;-5 αReductase (37.1%), IHH (20.1%), Kallman Syndrome (14.28%), B/L Anorchia (11%), PAIS (8.5%), CAIS (2.8%), CAH (2.8%); 46XXDSD–CAH (34.1%), IHH (21.7%), 46XXOTD (13%), ACC (8.6%), Classic CAH (4.3%); SCDDSD– KFS (53.8%), TS (38.4%), MGD (7.69%). Mean age of presentation of DSD; 5αReductase (7.5 yr), PAIS (14.33 yr), CAH (9.3 yr), KFS (25 yr) and TS (17 yr). Conclusion: 46XYDSD comprises 41.6% of cases of which 5αReductase deficiency is the most common etiology. CAH was the main subtype of 46XXDSD. KFS was the main subtype of SCD DSD. DSD pose a serious challenge not only in terms of gender role, identity and sex reassignment but also in terms of fertility issues, social acceptance and risk of gonadal malignancy in certain subtypes.

   Correlation of level of androstenedione with clinical hyperandrogenism in polycystic ovary syndrome Top

Apoorva Sharadchandra Wakade, N. F. Shah, Phulrenu Chauhan, Manoj Chadha, Awesh Shingare

Department of Endocrinology, P. D. Hinduja Hospital, Mumbai, Maharashtra, India.

E-mail: [email protected]

Objective: (i) Primary: To evaluate the usefulness of Androstenedione (A4) in assessing clinical hyperandrogenism, in patients with polycystic ovary syndrome (PCOS), especially as compared to testosterone (TT). (ii) Secondary: To compare the level of androstenedione and testosterone in obese and non-obese subgroups of PCOS patients. Materials and Methods: 40 consecutive patients with PCOS diagnosed by Rotterdam 2003 criteria, attending Endocrinology OPD during the study period were enrolled. They were assessed clinically as well as biochemically for hyperandrogenism. Hirsutism was defined as Ferriman-Gallwey (FG score) of ≥8. Results: Androstenedione level was significantly higher among hirsute patients as compared to non-hirsute patients. Androstenedione was elevated in 77% of patients having hirsutism; whereas testosterone was elevated in only 16% of these patients. FG score was significantly positively correlated with androstenedione level (r = 0.352; P = 0.026); whereas it was significantly negatively correlated with the ratio of testosterone to androstenedione (TT/A4), (r = 0.412; P = 0.008). Out of 40 patients, 21 were obese (BMI ≥25 kg/m2). Androstenedione level was higher in non-obese than obese PCOS patients. A significant positive correlation was demonstrated between BMI and testosterone levels. Conclusion: Androstenedione is a better marker of PCOS related androgen excess as compared to testosterone, even in obese patients. Although testosterone correlated positively with BMI; the TT/A4 ratio, which reflects the activity of 17β hydroxysteroid dehydrogenase, did not depend on obesity.

   Clinical and hormonal profile of 46 × Y disorders of sexual development at a tertiary hospital in South India Top

Sravani Tanna, L. Brahmanandam, B. Vivekanand, A. Mythili, Jayanthy Ramesh, K. A. V. Subhramanyam

Department of Endocrinology, Andhra Medical College, Visakahapatnam, Andhra Pradesh, India.

E-mail: [email protected]

Objective: To study the clinical presentation and Hormonal profile of 46 × Y DSD patients at a Tertiary hospital KGH in Visakhapatnam, Andhra Pradesh. Materials and Methods: The study included 25 patients with 46 × Y DSD who attended the Department of Endocrinology, KGH, Andhra medical college from Jan 2015 to May 2017. Clinical, Hormonal and Radiological evaluation was done. Results: Mean age of presentation is 8.24 yrs. Among 25 patients 12 were diagnosed with 5α Reductase deficiency (48%), 4 with PAIS (16%), 3 with 17β HSD Deficiency (12%), 2 with CAIS (8%), 1 with Mixed gonadal dysgenesis (4%), 1 with PMDS (4%). In 2 patients definitive diagnosis could not (8%) be made. 16 patients presented with Ambiguous genitalia (64%), 5 patients with Primary amenorrohea (20%), 2 patients with isolated Hypospadias (8%), 1 patient with isolated Micropenis (4%), 1 patient with abdominal distension due to Germ cell tumor (4%). Among 16 patients with Ambiguous genitalia 10 were with Hypospadias and Micropenis (62.5%), 4 with Cryptorchidism and hypospadias (25%), 1 with labioscrotal swellings (6.25%), 1 with bifid scrotum and hypospadias (6.25%). Among 25 patients 19 had palpable gonads (76%) and 6 patients had Non palpable gonads (24%). Conclusion: In our study 5 α reductase deficiency is more common followed by PAIS. Most common presentation is Ambiguous genitalia followed by primary amenorrohea.

   Cytogenetic and clinical characteristic of turner syndrome patients in West Bengal Top

Shanoli Ghosh, Sanchita Roy1, Pritha Pal, Atreyee Dutta, Ajitesh Roy2, Ajanta Halder

Departments of Genetics and 2Medicine, Vivekananda Institute of Medical Sciences, 1Department of Anatomy, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: To categorize the TS patients according to their cytogenetic profile and to correlate the karyotype with their clinical characteristics. Methodology: After obtaining ethical clearance from the institutional ethics committee patients attending the genetics OPD of VIMS referred from different endocrineology, gynaecology OPD were screened for TS. Detailed clinical features were recorded administering a proper questionnaire with expert opinion of clinician. Peripheral venous blood samples were taken on patients consent for human leukocyte culture and Karyotyping was done. 25 patients with TS karyotype were selected for study. Result: Out of 30 patients 17 patients showed 45, X karyotype and 13 other showed mosaic karyotypes. In mosaic variants five iso-chromosome karyotype was found, two of them showed pure form [46Xi (X) (q10)] two were mosaic with monosomy X karyotype [46, X/46Xi (X) (q10)] and one patient had three cell lines [46, XX/45, X/46Xi (X) (q10)]. Four patients showed Mosaicism with male karyotype [45, XO/46, XY] and one patient with normal female karyotype [45, XO/46, XX]. One patient revealed an isodicentric X cell line in mosaic form with classical monosomy X [45X/46, X idic (X) (q25)]. There were wide variations in presenting characteristics of these patients. Two patients revealed 46, XY mosaic cell line presented with ambiguity of genitalia, one patient with classical monosomy X had a rare finding of absence of distal portion of lower limb ant the patient having an isodicentric X cell line presented with mullerian agenesis. Conclusions: Proper cytogenetic analysis of TS is very important as that can help in proper genetic counselling and risk and lifestyle management of the patients.

   Clinical, biochemical and radiological profile of cases of 46XY disorders of sexual development in a tertiary centre Top

Sowrabha Bhat, Subhankar Chowdhury, Satinath Mukhopadhay, Pradip Mukhopadhyay, Sujoy Ghosh, Dibakar Biswas, Rana Bhattacharjee, Arijit Singha

Department of Diabetes and Endocrinology, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Objectives: 46XY DSDs may present with a wide spectrum of phenotypes ranging from unambiguously female genitalia to ambiguous male genitalia with hypospadias. The aim of this study was to evaluate the clinical presentation and diagnosis of cases of 46XY DSD admitted in the inpatient department of our institute. Methods: All patients of 46XY DSD, both new and old, who were admitted in the inpatient department for evaluation between July 2011 and July 2017 in our centre were included in this study. Clinical, hormonal and radiological evaluation was done for these patients to arrive at a diagnosis. Results: Of the 23 patients of 46XY DSD included in this study, 8 were diagnosed with 5 alfa reductase deficiency, 4 with partial androgen insensitivity syndrome, 1 with complete androgen insensitivity syndrome, 1 with persistent Müllerian duct syndrome, 1 with 17 beta HSD3 deficiency, 1 with 17,20 lyase deficiency, 1 with gonadal dysgenesis and 1 with vanishing testes syndrome. Interestingly, one of the patients with biochemical tests suggestive of 5 alfa reductase deficiency was found to have a phenotype compatible with a diagnosis of Smith-Lemli-Opitz syndrome. Most patients of 46XY DSD were raised as male except 1 case each of PAIS, CAIS and 17 beta HSD3 deficiency who were reared as female. In 5 patients a definite diagnosis could not be arrived at as they didn't follow up after discharge from our institute. Subsequent management was discussed with the parents of the patients based on the preferred gender of rearing. Conclusion: In the current study in our institute, a wide range of presentations of 46XY DSDs were observed. The most common cause among these was 5 alfa reductase deficiency. In the recent years an 'epidemic' of steroid 5 alfa reductase deficiency is being noted. ELISA method was used for measurement of DHT levels post hCG stimulation which is being done in a lab outside our set up unlike the other hormones tests. Whether this is causing a falsely low value of DHT and leading to an over diagnosis of 5 alfa reductase deficiency is still an enigma. Hence an accurate diagnosis of 46XY DSD largely depends on the reliability of the hormonal assays used. Plan of management in these patients depends on the choice of gender of rearing.

   Cardiovascular profile of polycystic ovary syndrome in Northeastern India Top

Abhamoni Baro, Dipti Sarma, Uma Kaimal Saikia

Department of Endocrinology, Gauhati Medical College and Hospital, Guwahati, Assam, India.

E-mail: [email protected]

Objective: To study the cardiometabolic characteristics and cardiovascular (CV) risk factors in polycystic ovary syndrome [PCOS] in northeastern India. Materials and Methods: This is a case control cross-sectional study analyzing 98 PCOS and 50 controls in the age group of 16–35 years. Cardiometabolic parameters including body mass index (BMI), waist circumference, blood pressure, oral glucose tolerance test, fasting lipid profile, fasting insulin and carotid intima media thickness [IMT] were compared between cases and controls. Differences in the CV risk factors were also compared between hyperandrogenic and PCOS with normal testosterone levels. Results: The mean testosterone level in cases and controls were 75.50 ± 32.21 ng/dl and 19.42 ± 12.42 ng/dl respectively (P = 0.004). The cases had significantly higher systolic blood pressure (125.37 ± 11.63 vs 114.49 ± 8.67 mmHg), diastolic blood pressure (81.22 ± 4.90 vs 75.31 ± 6.49 mmHg), impaired fasting (95.5 ± 26.6 vs 81.98 ± 9.4 mg/dl, P = 0.0007) and impaired first hour post prandial glucose (156.5 ± 72.4 vs 121.5 ± 16.2 mg/dl, P = 0.001), high cholesterol (179.2 ± 31.89 vs 124.65 ± 11.09 mg/dl), HDL (45.24 ± 8.22 vs 52.61 ± 2.73 mg/dl), triglycerides (143.96 ± 82.4 vs 97.57 ± 7.21 mg/dl) and VLDL (25.46 ± 14.37 vs 17.22 ± 5.49), higher insulin levels (20.82 ± 25.62 vs 3.63 ± 1.76 uIU/ml) and IMT (0.63 vs 0.49 mm, p= <0.0001), compared to controls. On linear regression analysis significant correlation was found between IMT and BMI, IMT and cholesterol, LDL and HDL but no correlation was noted with testosterone. Women with hyperandrogenic PCOS presented with a worse cardiometabolic profile and a higher prevalence of CV risk factors, such as obesity and overweight, hypertension, impaired glucose tolerance, dyslipidemia and insulin resistance, compared to PCOS with normal testosterone. Conclusion: Women with PCOS, specially those with hyperandrogenemia, have a worse cardiometabolic profile compared to women without PCOS. Therefore, all cases of PCOS should be screened for the presence of CV risk factors, since these derangements at a young age imply an elevated risk for the development of CV disease later in life.

   Cardiovascular disease risk assessment in the siblings of women with polycystic ovary syndrome Top

Karthik Subramaniam, V. P. Vipin1, Aditya Kapoor2, Archana Tripati, Preeti Dabadghao

Departments of Endocrinology and 2Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 1Consulatant Endocrinology, Aster Medcity, Kochi, Kerala, India.

E-mail: [email protected]

Objectives: (1) To assess cardiovascular disease risk in the siblings of PCOS patients using brachial artery flow mediated dilatation (FMD) and carotid intima-media thickness (CIMT). (2) To correlate CIMT and FMD with clinical, hormonal and metabolic parameters. (3) To assess the degree of correlation in hormonal, biochemical and CIMT/FMD parameters between probands and siblings. Materials and Methods: This was a prospective cross-sectional case control study conducted in a tertiary care centre. 54 brothers and 38 sisters (age 12-40 years) of patients with PCOS (diagnosed by Rotterdam criteria) were compared with 38 men and 32 women who were age, sex, and BMI matched. CIMT and FMD were done by standard procedure and the operator was blinded for siblings and controls. Based on a previous pilot study, sample size was calculated to be 44 brothers and 40 sisters. Results: FMD was significantly low in brothers as compared to controls (median = 12.5% vs 18.9%) but was not significant in sisters. CIMT was significantly elevated in sisters (median = 4 cm vs 3 cm in controls) while was not different in brothers. Serum HDL levels and waist-hip ratio (WHR) correlated negatively with CIMT (r = - 0.38) and FMD (r = -0.29) respectively in brothers. Brothers had significantly higher prevalence of acanthosis, waist circumference, elevated blood pressure, metabolic syndrome as compared to controls respectively whereas sisters had significantly higher ferriman-gallway score. Presence of family history of diabetes conferred risk of higher BMI, WHR and lower FMD in brothers. Conclusions: Siblings of PCOS individuals show evidence of structural and functional endothelial dysfunction at an early age. Brothers are at higher risk of metabolic syndrome especially in the presence of family history of diabetes mellitus. Hence, it is prudent to do routine screening for metabolic parameters in siblings of PCOS women as even they are at higher risk of cardiovascular disease.

   Aromatase deficiency in two siblings: A rare form of familial DSD Top

Debasish Patro, Arun Kumar Choudhury, Anoj Kumar Baliarsinha

Department of Endocrinology, S.C.B. Medical College and Hospital, Cuttack, Odisha, India.

E-mail: [email protected]

Objectives: To report a very rare form of disorders of sex development (DSD) caused by aromatase deficiency in two siblings. We report the clinical phenotypes and hormonal parameters of the siblings in this report. Materials and Methods: A 12 years female child presented for evaluation of non development of secondary sexual characters. She had ambiguous genitalia since birth and had undergone clitoroplasty at 3 years of age. Her younger sibling aged 3 yrs also has ambiguous genitalia with additional history of maternal virilization during second pregnancy. Necessary imaging and hormonal investigations were done to arrive at the diagnosis. Results: Basal and stimulated 17-OH progesterone levels were normal on repeated occasions in past as well as now. Bone age was significantly delayed as compared to chronological age. USG of abdomen and pelvis revealed bilateral enlarged multicystic ovaries without any presence of wolffian structure. Hormonal evaluation revealed elevated gonadotropins and testosterone. Serum estradiol level was significantly low. Serum TSH, DHEAS and 17OHP were normal. Karyotype was 46 XX. Ovarian tumor markers were negative. Basing on these clinical and biochemical parameters a diagnosis of Aromatase deficiency was made. Genetic testing could not be done due to unavailability at our institution. A trial of low dose estrogen therapy was given. After 6 months of therapy there was significant decrease in the gonadotropins and testosterone levels as well as the size of bilateral ovaries. Conclusion: Aromatase deficiency though extremely rare should be thought of while evaluating cases of virilizing DSD. Maternal virilization during pregnancy, though a classically described association may be conspicuously absent in certain cases.

   Polycystic ovary syndrome: The pros and cons of various diagnostic criteria and investigation to find out associations of various factors implicated with PCOS Top

Ashutosh Halder, Hemant Kumar, Amanpreet Kaur Kalsi, Manish Jain

Department of Reproductive Biology, AIIMS, New Delhi, India.

E-mail: [email protected]

Objectives: To assess pros and cons of various diagnostic criteria of PCOS. To evaluate etio-pathologic associations of various factors implicated with PCOS. Materials and Methods: About 258 suspected PCOS cases were evaluated from February 2014 to April 2017. About 153 cases were found compatible with primary PCOS and 16 with secondary PCOS (e.g. CAH, hypercortisolism, 46, XY DSD, ovarian insufficiency, etc). All primary PCOS cases were investigated for additional biomarkers (DHT, androstenedione, AMH, inhibin B, etc) as well as implicated etio-pathogenetic factors such as BMI, insulin, inflammatory markers (IL4 and INFγ), leptin, bisphenol A (BPA), DNA methylation, etc. Results: We observed Rotterderm criteria or revised NIH (2012) criteria picks up maximum cases without influencing specificity and sensitivity. Also showed similar associations in comparison to other criteria with BMI, hyperandrogenemia, hyperandogenism, AMH level, hyperinsulinemia, immune alterations, etc., We observed BMI of >25 in 51% cases (obesity in 17.6% cases), oligomenorrhoea/amenorrhoea in 93.5%, polycystic and/or enlarged ovarian morphology in 81.7% cases, FG score of > 8 and/or AMH of >5 ng/ml in 78% and high total testosterone only in 26.5% cases. High fasting insulin was observed in 7.2% and DHEAS in 3.5% cases. We did not find any difference in inflammatory markers. BPA level was significantly higher in PCOS group and >3SD level was observed in 37.5% of PCOS cases. Extreme DNA methylation was observed in 8% cases (4% each with extreme hypomethylation and hypermethylation). Conclusion: We conclude best available diagnostic criteria is Rotterdam/revised NIH 2012 criteria. Hyperandrogenemia was rare in North Indian PCOS cases. High BMI was common but insulin resistance was rare. AMH level of >5 was as good as ovarian morphology. BPA seems play role but inflammatory markers do not show any association. Epigenetics factor seems play some role in a subset but need to test gene wise methylation changes to confirm epigenetic role.

   Study of cardiovascular risk factors and continuous ambulatory blood pressure monitoring in adolescent girls with polycystic ovary syndrome Top

Haritha Galla, K. Neelaveni, Rakesh Kumar Sahay

Department of Endocrinology, Osmania Medical College and General Hospital, Hyderabad, Telangana, India.

E-mail: [email protected]

Background: Insulin resistance is a common underlying factor in the pathogenesis of PCOS. Although insulin resistance can predispose to the later development of hypertension, young girls with PCOS are generally normotensive. Single office blood pressure measurements used in most studies are not sensitive enough to detect mild derangements in blood pressure regulation which could be early abnormalities in those who later go on to develop hypertension. Ambulatory blood pressure recording may be able to identify these early abnormalities in young women with PCOS who are predisposed to diabetes, hypertension and cardiovascular disease in later life. Objective: To study the cardiovascular risk factors and 24 hour pattern of blood pressure with Ambulatory BP monitoring systems in adolescents with PCOS. Materials and Methods: Study design is hospital-based cross sectional study. Criteria for the diagnosis of PCOS was based on Endocrine society clinical practice guidelines. 27 cases in the age group 14 to 18 years and 26 healthy age and weight matched controls were taken. Metabolic and hormonal parameters were evaluated. Ambulatory BP values were obtained from every subject with a portable, automated non-invasive monitoring device (Meditech, ABPM-05). The monitors were programmed to record BP every 30 minutes. The average systolic BP, diastolic BP and hourly recordings during daytime and night time were obtained. Dipper and non dipper status was determined. Meditech ambulatory blood pressure monitors are configured and recorded data are analysed by Easy ABPM Holter software solutions. Data analysis was carried out using the Statistical Package for Social Sciences (SPSS version 21). Results: HOMA IR was significantly higher among girls with PCOS when compared to controls. (5.97 vs 2.41, P value <0.001). HDL cholesterol levels were lower among cases. (39.51 vs 45.15 mg/dl, P value 0.001). Triglyceride levels of cases were higher. (113.4 vs 84.23 mg/dl, P value 0.001). There was no significant difference in the day time systolic and diastolic BP between cases and controls. Nocturnal systolic and diastolic BP was significantly higher among cases. Night time systolic BP was 104.7 vs 97 mm Hg for cases and controls respectively, P value 0.002. Night time diastolic BP was 60.92 vs 56.19 mm Hg for cases and controls respectively, P value 0.01. Non dippers were 70% and 30% among cases and controls respectively (P value 0.019). Conclusion: This cross-sectional study revealed a higher prevalence of cardiovascular risk factors and a non-dipping BP pattern in this group of young women with PCOS which was independent of BMI, WC and insulin resistance. Presence of these risk factors and the non-dipping pattern in the ABPM indicates a very high risk for future development of hypertension and cardiovascular disease.

   Clinical, hormonal and radiological profile of disorders of sexual development in 20 patients at a Tertiary Care Centre Top

Ravikumar, Nilanjan Sengupta, Pranab Kumar sahana, Arjun Baidya, Soumik Goswami, Sattik Siddanta, R. Sreenath, Arindam Ray

Nilratan Sircar Medical College, Kolkata, West Bengal, India.

E-mail: [email protected]

Objectives: Disorders of sexual development (DSD) present with spectrum of phenotypes ranging from unambiguous female genitalia to ambiguous male genitalia with hypospadias or dysgenetic gonads or ambigious female external genitalia.Diagnosis and subsequent management of these patients depends on the cause of DSD, degree of feminization or virilisation, age at presentation, and gender orientation. The aim of this study was to evaluate the presentation and management of patients with DSD at our center. Patients and Methods: All new and old patients of DSD attending the endocrinology outdoor of NRSMCH kolkata in a period of 24 months were included in this study. Clinical, karyoptype, hormonal, and radiological evaluation were done to identify the cause of DSD. Results: Among 20 patients, 12 patients and 8 patients were raised as males and females respectively. The mean age at presentation 4 year. Out of 20 patients 7 patients had CAH, 5 patients were diagnosed with 5 alpha reductase deficiency and 3 patient had AIS, 2 patients Diagnosed with ovotesticular DSD and other 3 patients with MGD. Conclusions: CAH was the most common DSD in our patients followed by 5 alpha reductase deficiency.Management of patients with DSD depends on etiology, gender assignment, genital surgery, and consequent psychosocial implications.

   Body composition, metabolic characteristics and insulin resistance in obese and non-obese women with polycystic ovary syndrome Top

Anil Satyaraddi, Nitin Kapoor, Sahana Shetty, Kripa Elizabeth Cherian, T. K. Aleyamma1, Mohan Shashikant Kamath1, Nihal Thomas, Thomas Vizhalil Paul

Departments of Endocrinology and 1Reproductive Medicine, CMC, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Objectives: To compare body composition, metabolic characteristics and insulin resistance indices between obese PCOS (BMI ≥25 kg/m2), non-obese PCOS (BMI <25 kg/m2) subjects and their age and BMI matched controls. Materials and Methods: A total number of 81 PCOS subjects (Obese-42; Non-obese-39) and controls (Obese-42; Non obese-44) were recruited in this cross sectional study. A Rotterdam criterion was used for the diagnosis of PCOS. All patients underwent detailed clinical, anthropometric and assessment of metabolic parameters including insulin resistance. All of them had an evaluation of body composition and visceral adipose tissue [VAT] (assessed by DXA scan). Results: A total of 22 out of 81 (27%) PCOS subjects {80%-obese PCOS; 20%- non-obese PCOS} had a diagnosis of metabolic syndrome based on international diabetes federation (IDF) criteria. Six (7%) PCOS subjects (4 obese PCOS; 2 non-obese PCOS) were diagnosed to have diabetes mellitus. Twenty eight (35%) PCOS subjects had an impaired glucose tolerance test (IGT) with 46% of them belonging to obese PCOS group and 54% to non-obese group. Insulin resistance was seen in around 80% of obese PCOS subjects, 20% in non-obese PCOS subjects [cut-off values for determining insulin resistance: fasting Insulin ≥12.2 μU/ml; HOMA-IR ≥2.5%]. Total body fat and estimated VAT were significantly increased in both obese and non-obese PCOS subjects when compared to their age and BMI matched controls (P = 0.0001), and the difference was significant even after correcting for body weight (P = 0.0001). Estimated VAT corrected for body weight was not significantly different between obese and non-obese PCOS.Conclusion: Both obese and non-obese PCOS when compared with their age and BMI matched controls are metabolically worse and have more visceral adiposity which can lead to increased risk of metabolic complications. Non-obese PCOS subjects had similar amount of visceral adipose tissue as that of obese PCOS even after correcting for body weight.

   Spectrum of 46XY disorders of sex development Top

Shravan Ankathi, K. Neelaveni, Rakesh Kumar Sahay

Department of Endocrinology, Osmania Medical College, Hyderabad, Telangana, India.

E-mail: [email protected]

Background: The term disorders of sex development (DSD) refers to congenital disorders associated with conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. The spectrum of the 46XY (DSD) is broad ranging from unambiguous female genitalia to ambiguous male genitalia with hypospadias or dysgenetic gonads. In this study, we reviewed the clinical spectrum and presentation of patients with 46XY DSD at our center. Materials and Methods: All old and new patients of 46XY DSD attending the endocrine OPD in a period of 24 months were included in this study. Clinical, hormonal, radiological and cytogenetic evaluation were done to identify the cause of DSD. Results: During the period a total of 21 patients were seen with 46XY DSD due to variable etiologies. Among them, 14 were diagnosed with disorders of androgen synthesis and action, 1 with complete androgen insensitivity (CAIS), 5 with partial AIS, 8 with 5 alfa reductase deficiency, 4 were diagnosed with disorders of gonadal development, 2 with complete gonadal dysgenesis, 1with partial gonadal dysgenesis, 1 with ovotesticular DSD. Definitive diagnosis could not be made in 3 patients. Conclusion: A wide spectrum of causes were noted. 5 alfa reductase deficiency was most common followed by PAIS. Due to overlapping clinical and biochemical parameters only preliminary etiological diagnosis can be made. Management of these patients depends on etilogy, gender assignment, gender orientation and psychosocial aspects of treatment. Gonadectomy, corrective genital surgeries, hormonal treatment are mainstay of treatment.

   Primary amenorrhea: An endocrine perspective Top

Nikita Shah, Nikhil Bhagwat, Gayatri Ghanekar, Chaitanya Yerawar, Manoj Chaddha, Premlata K. Varthakavi

Department of Endocrinology, Topiwala National Medical College, B. Y. L. Nair Ch. Hospital, Mumbai, Maharashtra, India.

E-mail: [email protected]

Background: Primary Amenorrhea (PA) not only poses a diagnostic challenge but also causes psychosocial distress to the patient and the family. Aim: To study the clinical, hormonal and cytogenetic profiles of patients with primary amenorrhea. Methods: Primary Amenorrhea is defined as absence of menarche till the age of 14 years in absence of secondary sexual characteristics and till the age of 16 years in presence of secondary sexual characteristics. In this retrospective analysis, patients who presented to endocrine clinic with PA from August 2011 to June 2017 were included. Results: Out of 54 subjects who presented with PA, 7 patients were lost to follow up before etiological diagnosis could be made. The records of 47 patients was analyzed. (1) The mean age of presentation was 18.94 ± 1.37 years. (17.57 years-20.31 years). (2) The Etiology was classified as: (a) Normogonadotrophic hypogonadism-21.28%, Mullerian agenesis (14.89%), PCOS (2.1%), XY DSD-Complete androgen insensitivity syndrome (4.25%). (b) Hypogonadotrophic hypogonadism-27.66%, Isolated hypogonadotrophic hypogonadism (14.89%), Hypothalamic amenorrhea (4.26%), CDGP (6.38%), ACTH and prolactin cosecreting pituatary macroadenoma (2.1%). (c) Hypergonadotrophic hypogonadism-51.06%, Turner Syndrome (34.04%), Premature ovarian failure (8.51%), XY DSD (8.50%). (3) Six patients who sought advice for PA had XY DSD (two presented to endocrine services post gonadectomy). (4) Unique karyotype 45XO: 46XX: 47XXX mosaicism, 46XO iso (Xa), 45XO: 46XYand 46 dicentric (X) q28 were found on cytogenetic analysis. (5) Thyroid dysfunction was associated with Turner patients (43.7%) and Premature Ovarian Failure (25%). Conclusions: (1) In our country, patients delay seeking medical advice for PA. (2) The commonest etiology of PA was Hypergonadotropic hypogonadism out of which commonest cause being Turner syndrome. (referral bias could be the reason, as outflow tract abnormalities are managed by gyneacologists). (3) Cytogenetic abnormalities were present in 48.9% patients. (4) Prolactin levels should not be overlooked in patients with PA.(5) The medical and paramedical community need to be sentisized regarding DSD.

   Study of fertility outcome in patients with pcos needing fertility treatment: Experiance in tertiary centre in South India Top

Jaideep Khare, S. Vyjayanthi1, Prachi Srivastava2, Jyoti Wadhwa, Smitha Nalla, Prasun Deb

Departments of Endocrinology, 1Department of Infertility, Reproductive Medicine & Surgery and 2Dermatology, Krishna Institute of Medical Sciences, Secunderabad, Telangana, India.

E-mail: [email protected]

Aims and Objective: In this prospective observational study, we have tried to find out the fertility outcome in PCOS patients treated with different assisted reproductive procedures. Material and Methods: 115 PCOS patients were included in our prospective observational study who attended the Infertility clinic of Krishna Institute of Medical Sciences and met the inclusion criteria. Basic hormonal and metabolic work up was done. On the basis of patient's willingness and previous history of treatment for fertility, patient was treated and allocated to ovulation induction alone (OI), Ovulation induction with intrauterine insemination (IUI) or assisted reproductive technology like IVF protocol. Results: Mean age, BMI and infertility duration was 28.26 + 4.58 years, 26.93 + 3.84 kg/m2 and 4.20 + 2.91 years respectively. OI group included 25 patients who received 40 OI cycles. Total Pregnancy (TP) and Ongoing Pregnancy (OP) rate per OI treatment cycle was 27.5% and 17.5% respectively. Overall TP and OP rate was 44% and 28% respectively. IUI group included 56 patients who received 89 IUI cycles. TP and OP rate per IUI cycle was 21.35% and 15.73% respectively. Overall TP and OP rate was 33.93% and 25% respectively. IVF group included 34 patients who received 47 fresh IVF cycles and 19 frozen embryo transfer cycles. The cumulative pregnancy rate and OP rate in IVF group was 73.53% and 55.88% respectively. Ovarian hyperstimulation syndrome as a complication was seen in one patient of IVF and two patients of IUI group, whereas multiple pregnancies and ectopic pregnancy was seen in one patient each in IVF group. Conclusion: Amongst three methods of assisted reproduction, IVF is most effective treatment for infertility but because it is more invasive and more expansive it should be last resort if earlier methods fail.

   Vanishing testes syndrome: Report of two cases Top

Neeraj Sinha, A. K. Basu, A. Maiti, A. Sinha, T. C. Das, S. Raghuvanshi, S. Ghosh

Department of Endocrinology, Medical College Kolkata, Kolkata, West Bengal, India.

E-mail: [email protected]

Introduction: Vanishing testes or Testicular Regression Syndrome (TRS) is a condition which is considered to be due to subsequent atrophy and disappearance in fetal life of an initially normal testes. This absence of testes in otherwise 46XY male is assumed to be a consequence of intrauterine or perinatal torsion or infarction. Case 1: 23 year old phenotypic male came with underdeveloped sexual characteristics. His scrotum was not well developed, testes not palpable (since birth) and he had micropenis with single urogenital opening at tip of penis (SMR P2, SPL 3 cm) and B/L Gynaecomastia with disc size 4 cm. HE was found to have hypergonadotropic hypogonadism with karyotype 46 XY. On MRI, a small hypointense lesion was found in left inguinal region. The tissue was surgically removed. Histopathological examination confirmed it to be TRS without any features of malignanacy. Patient is on testosterone replacement therapy and his present SMR is P5, with SPL 10 cm. Case 2: 25 year old male comes with complain of unilateral testes since birth. His SMR was P5, SPL11 cm, scrotum well developed, right testes not palpable, left testes 25 ml, no gynaecomastia. His testosterone levels were normal. MRI revealed testicular like tissue on right inguinal region which on biopsy confirmed to be TRS without any feature of malignancy. Conclusion: TRS is not an uncommon disorder. While TRS occurs in 5% of cryptorchidism cases but in those cryptorchidism with non palpable testes, it accounts for 35-60% of cases. Malignancy potential of remnant tissue of TRS is not established.

   Miscellaneous: DXA measured visceral adipose tissue, total fat, anthropometry and cardiometabolic risk factors in mother-daughter pairs Top

Sahana Shetty, Nitin Kapoor, Nihal Thomas, Thomas Vizhalil Paul

Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: [email protected]

Visceral fat is the pathogenic fat depot associated with diabetes, dyslipidemia and cardiovascular diseases. Estimation of visceral adipose tissue (VAT) by Dual-energy-X-ray absorptiometry (DXA) is a newer technique with less radiation exposure, shorter scanning time and lower cost as compared to the other imaging modalities. Aims and Objectives: To look at the relationship between cardiometabolic risk factors and DXA measured VAT, total fat percent (TF%) and anthropometry. To study the changes in body composition indices with menopause. The familial resemblance of VAT and TF% in mother-daughter pair was also compared. Methodology: Cross sectional community study of 300 women (150 postmenopausal mothers and 150 premenopausal daughters) on the body composition indices, visceral adipose tissue and lean mass indices measured by DXA and metabolic parameters. The association between VAT, TF% and anthropometric measures and cardiometabolic risk factors were studied by correlation, ROC curves and multiple logistic regression analysis. Results: VAT indices were significantly higher and lean indices lower in postmenopausal women as compared to premenopausal women. One fourth of postmenopausal women were categorized as metabolically obese normal weight (MONW). DXA-VAT was a better predictor of cardiometabolic risk factors as compared to waist circumference, BMI and TF% in postmenopausal women (AUC: 0.68 vs 0.62, 0.60 and 0.5 respectively), whereas BMI had a better prediction in premenopausal women (AUC: 0.68). VAT area >100 cm2 had a significant association with the presence of >2 cardiometabolic risk factors (P = 0.04, OR-2.2, CI: 1.0-4.7) in the postmenopausal women. Daughters of the mothers with higher TBF% were found to have a higher TBF% compared to daughters of mothers with normal TBF% (36.2 + 4.2 Vs 32.2 + 4.4, P = 0.03). Conclusion: VAT increases and lean mass decreases with age and menopause. DXA measured VAT is a better predictor of cardiometabolic risk in postmenopausal women but not in premenopausal women. Total body fat may have a familial resemblance, but not the visceral adipose tissue which is determined by age, menopause and probable life style factors.

   An adolescent male with Blount's Disease: A doubly rare presentation Top

V. Madhavi, Vijay Sheker Reddy Danda, Sreedevi Patnala, Srinivas Rao Paidipelly, Shalini Patlolla, Chaitanya Konda

Department of Endocrinology, Gandhi Medical College and Hospital, Kaloji Narayana Rao University of Health Sciences, Secunderabad, Telangana, India.

E-mail: [email protected]

Introduction: Blount's disease is a disorder of unknown etiology, affecting the growth plates of proximal tibia of growing children. It has been noted to be more common in African-American children. Incidence in Indian children is unknown. Common presentation is in infancy or early childhood, and is more common in girls. We present a case of adolescent male with Blount's disease. Case Report: A 14-year-old boy presented with excess weight gain over past 4 years. In the last one year, he noticed progressive bowing of both legs with pain during activity, for the past six months. He has insignificant sun exposure, limited physical activity, further decreased recently due to pain, has limited dairy and meat intake. He was born of non-consanguineous marriage. Antenatal, natal, and post natal periods were uneventful. His birth weight was 3 kg. He started walking at 12 months of age. There was no bowing of legs or pain during childhood. His paternal uncle has skeletal dysplasia with short right lower limb and kyphoscoliosis. On examination, he had bowed legs with laxity around the knee joints. There were no clinical signs suggestive of rickets. Charted on IAP 2015 growth chart, height was at 5th percentile, weight at 95th percentile, BMI in severe obesity range (35.7 kg/m2). Remaining general and systemic examination was unremarkable. Albumin-adjusted calcium was 9.12 mg/dl, phosphorous 4.7 mg/dl, Alkaline phosphatase 536 IU/L, 25(OH) Vitamin D was 12.65 ng/dl. Deficiency of vitamin D was present but there was no radiological or clinical evidence of rickets. X-ray of knee showed medial beaking of tibia with increased tibio-femoral angle. His ABG and Renal parameters were normal. He was started on appropriate supplements and is due for surgery. Conclusion: A genetic predisposition, and biomechanical factors due to obesity are likely the etiological factors in this child.

   The unsolved puzzle of Bartter type 3 or Gitelman syndrome: A case report Top

Soumita Mandal, Sujoy Ghosh, Pradip Mukhopadhyay, Rana Bhattacharjee, Subhankar Chowdhury

Department of Endocrinology, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

Background: Both Bartter and Gitelman syndrome are causes of salt losing tubulopathy chacterized by persistent hypokalemia, metabolic alkalosis. As phenotypically often similar, Bartter syndrome type 3 and Gitelman syndrome show diagnostic ambiguity. Case: 28 years old lady came to our OPD with recurrent episodes of tetany, muscle cramps and GTCS since late childhood. There was no h/o significant vomiting, diarrhoea. She had no history of neck surgery, irradiation, known malignancy, congenital cataract, no h/o diuretics or laxative use with h/o adequate milk intake and sun exposure. Initial presentation prompted us to investigate for primary hypoparathyroidism. Her biochemical reports were as Total Calcium- 6.8 mg%, Inorganic Phosphorus 6 mg%, iPTH- 14.6 pg/ml, 25 OH vitamin D 23.22 ng/ml, Potassium- 2.5 mmol/L, creatinine 0.6 mg%. Work up for persistent hypokalemia revealed ABG-pH 7.5, HCO3- 32 mmol/lit, 24 hrs urinary potassium 55 mmol/day, spot urine calcium: creatinine ratio 0.2 [molar ratio s/o borderline hypercalciuria], serum Magnesium 1.6 mg%. In view of the above the diagnosis is considered as either Bartter Syndrome type 3 or Gitelman Syndrome or overlap in between these two. Patient was managed with oral calcium, calcitriol, potassium supplementation, spironolactone and oral Magnesium. Conclusion: The distinction between Bartter type 3 and Gitelman syndrome is often blurred, demanding proper work up.

   Russell silver syndrome - A study of 2 cases Top

Nikhil Lohiya, Rashmi Lote-Oke1, Anuradha Khadilkar1, Vaman Khadilkar1, Nikhil Phadke2, Meenal Agarwal2, Kavita Khatod2, Nikita Gogate2

Department of Pediatrics, Bharati Hospital and Research Centre, 1Hirabai Cowasoji Jehangir Medical Research Institute, Jehangir Hospital, 2GenePath Dx, Phadke Hospital, Pune, Maharashtra, India.

E-mail: [email protected]

Background: Russell Silver syndrome (RSS) presents with distinctive facial features and growth retardation. RSS has a heterogeneous etiology and molecular causes may be identified in around 60% cases. Reports from India describing genetic etiology and response to growth hormone (GH) therapy are scarce. Objective: We present here 2 cases of RSS diagnosed at different ages by clinical suspicion and confirmed by genetic analysis; both were treated with GH, we also describe the response to GH treatment. Methods and Results: Case 1: 6 yrs 9 months old girl child brought with the complaints of failure to thrive and clinical features were suggestive of RSS. He was stunted (Z score = -2.3) with weight 14.1 kg (Z score= -1.87). Genetic analysis showed altered methylation pattern/hypomethylation in the IC1 region involving the 11p15 chromosomal locus in an apparent mosaic state, consistent with diagnosis of Russell-Silver syndrome. She was then started on GH therapy and showed good catch-up growth (height velocity Z score = 2.4). Case 2: 7 months old infant boy was brought with the complaints of not gaining adequate weight and height. He was having clinical features pointing towards RSS. Anthropometric measurements concluded stunting (Z score = -5.7) and wasting (Z score=-2.14). Genetic analysis was suggestive of hypomethylation of at DMR1, upstream of H19 gene at 11p15. He was then started on GH therapy showed good response (Height velocity Z score = -0.2). Conclusion: Children with clinical suspicion of Russell silver syndrome need genetic analysis for hypomethylation in the IC1 region involving the 11p15 chromosome as first line genetic analysis, which is most common. Response to GH therapy is good in Indian children with RSS.

   Opportunistic infection in an immunocompromised patient Top

Suresh Damodharan, S. Sriram1, Nancy Ann George2, Merrin Joseph2

Sri Ramakrishna Hospital, 1Department of Pharmacy Practice, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Science, 2College of Pharmacy, Sri Ramakrishna Institute of Paramedical Science, Coimbatore, Tamil Nadu, India.

E-mail: [email protected]

Introduction: Mucormycosis is alifethreatening infection that occurs in patient who are immunocompromised. It refers to several different diseases caused by infection with fungi in the order Mucorales. Case Study: A 39 year old male patient was admitted with complaints of fever, cough with expectoration, abdominal pain for one week, and history of type II diabetes mellitus for past three years. On examination patient was drowsy, arousable. HbA1C: 17%, RBS: 445 mg/dl. The ABG revealed acidosis. pH: 7.04, Serum bicarbonate: 6.4mEq/L. CT shows consolidation in both lower lobes and started on imipenem, vancomycin, amphotericin-B (conventional), Bronchoscopy showed greyish white lesions in the left main bronchus, upper and lower lobe with distorted appearance. Bronchial washing, brushing and biopsy was done for further evaluation, showed non septate fungal hyphae causing ischemic necrosis of pulmonary parenchyma, suggestive of invasive mucormycosis. The treatment switched over to liposomal amphotericin B in view of rising renal parameters. Discussion: Effective management requires a 3 pronged combination of medical and surgical modalities along with correction of the predisposing underlying conditions. Amphotericin B or its newer lipid formulation –liposomal amphotericin B along with extensive surgical debridement to remove the necrotic tissues remains the main stay of therapy. Conclusion: Lethal or progressive life threatening infection of mucormycosis can happen in immunocompromised patients. Early diagnosis and aggressive treatment might reduce the mortality associated with devastating fungal infection and we have to be aware of this and treat accordingly.

   Blount's disease - A close mimicker of rickets Top

Partha Sarathi Choudhury, Rana Bhattacharjee, Sujoy Ghosh, Pradip Mukhopadhyay, Subhankar Chowdhury

Department of Endocrinology, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

E-mail: [email protected]

A 2 yr old male child presented with progressive bowing of both legs for last 1 yr. His immediate post natal history and developmental milestones were unremarkable and he started walking at age of 11 mths. His lower limb deformity was neither associated with irritability, myalgia, bone pain, muscle weakness, carpopedal spasm nor failure to thrive. He was born of non consanguineous marriage with an uneventful normal vaginal delivery. He was exclusively breast fed for 6 mths and at the time of presentation he was having complimentary breast feeding. Clinical examination revealed Height-88 cm (75th -97th percentile) with an upper segment: lower segment ratio of 1.4: 1; He was obese with Weight- 18.3 kg (>97th percentile) with no stigmata of hypercortisolism/hypothyroidism or Albright's hereditary osteodystrophy. His head circumference was normal with no frontal bossing; He had bilateral genu varum but he had no evidence of widening of ankles and wrists, prominent costochondral junctions, scoliosis or kyphosis and dental anomalies. Biochemical investigations including complete blood count, liver function test, renal function test, electrolytes and arterial blood gas analysis were normal; Serum calcium - 9.8 mg/dl (albumin 4 g/dl); phosphorous-5.2 mg/dl; Alkaline phosphatise-315 U/l; 25 OH vitamin D -45.36 ng/ml; iPTH and thyroid function test were within age specific normal reference range. Plain radiograph of both legs including knees revealed tibia vara with beaking of medial aspect of proximal tibial metaphysis along with minimal widening of femoral and tibial metaphysis without any features of fraying or cupping. All these suggest the diagnosis of Blount's disease which is a close mimicker of rickets and thus it is to be considered in the differential diagnosis of bilateral genu varum particularly in an obese child.

   A rare case of Hayek Peake syndrome Top

Rahul Kamath, Prem Kumar Asokumar

Department of Endocrinology, SKS Hospital, Salem, Tamil Nadu, India.

E-mail: [email protected]

Introduction: Hayek Peake syndrome is a rare disease presenting with hypernatremia and hypothalamic dysfunction with no organic lesion in hypothalamus. Case Report: A 17 year old female was reviewed in view of chronic persistent hypernatremia and delayed puberty. Symptoms of the patient started at the age of 9 months. Patient had recurrent episodes of seizures, severe weakness and self-limiting fever. Investigations showed high sodium levels. Birth history was uneventful and milestones were appropriate for age till 9 months of age. After that she had been admitted multiple times for recurrent seizures and had poor performance in school. On examination, Short statured, BP was 90/70 mm Hg and Tanners stage – A1, P1, B2. Investigations suggestive of Hypernatremia (Na – 157 meq/L), Growth Hormone levels – <0.050, T4 – 9.39, FSH – 1.6, LH – 0.01, Prolactin – 0.87 and FBS – 184 PPBS - 305. MRI imaging of brain was normal and Ultrasound abdomen showed small sized uterus and ovaries. Management and Outcome: Patient required spironolactone 200 mg/day for sodium correction. She is being managed with metformin, growth hormone and E2 for puberty induction. Discussion: Patient had chronic adipsic hypernatremia, short stature, Panhypopituitarism with hyperprolactinemia with no abnormality detected in MRI brain and being followed up for 5 years. She has poor response to GH and E2. Conclusion: Hayek Peake syndrome is a rare hypothalamic syndrome manifesting as adipsic/hypodipsic hypernatremia with multiple endocrinopathies with incompletely studied natural history and possesses many challenges in management.

   Sobbing, Siblings, SERAC1ing: New gene in Asian Indian family with Perrault Syndrome Top

Abhilasha Manvatkar, Altamash Shaikh, Nivedita D. Moulick, Sameer Yadav, Tushar Bandgar

Endocrine Division, Medicine Department, LTMMC and LTMGH, Sion Hospital, Mumbai, Maharashtra, India.

E-mail: [email protected]

Objectives: Perrault syndrome (PS) is rare cause of POF/POI (PRIMARY OVARIAN INSUFFICIENCY) 46XX gonadal dysgenesis with sensorineural deafness. It has diagnostic difficulty because of the phenotypic and genetic heterogeneity. Data on genetics are globally sparse and none is from India. Hence the objectives are: 1. To study genetics of Perrault syndrome. 2. Management challenges. Materials and Methods: History and examination of all siblings was done. Blood samples of siblings were sent for biochemistry, karyotyping and Imaging (USG, MRI). Genetic analysis was done followed by Exome sequencing by Sangers. Results: Out of 4 siblings, two had amenorrhoea (one primary, one secondary). Both had POF. All had sensorineural deafness, two had marfanoid habitus, One with primary infertility presented with real management issues and was sent for In vitro Fertilisation (IVF) with donor oocyte. High FSH, Very low AMH, We identified a novel gene, SERAC1 (SERine Active site Containing 1), for the first time in the world in both sisters. The targeted exome sequencing revealed homozygous novel pathogenic mutation c.738+1G>T mutation, present in both cases. Conclusion: This is the first time genectic data from India is available on Perrault Syndrome, and first evidence in the world of SERAC1 gene mutation c.738+1G>T, suggesting that mitochondria may play pivotal role in the development of PS. This has been identified as the sixth gene responsible for PS.

   Wolcott Rallison syndrome: A case report Top

Nalini B. Wagmode, Patanjali Bhatta, Vageesh S. Ayyar, Ganapathi Bantwal, Vivek Mathew, Belinda George

Department of Endocrinology, St. Johns Medical College Hospital, Bengaluru, Karnataka, India.

E-mail: [email protected]

Introduction: It a rare disorder characterized by neonatal diabetes, skeletal dysplasia, hepatic dysfunction and growth retardation. Classically, they present with diabetes requiring insulin absolutely before infancy, presenting with diabetic ketoacidosis at the time of initial diagnosis. Hepatic failure is recurrent and most common cause for mortality. Case Report: We here report the case of 2 year 6-month old female infant born out of 2nd degree consanguineous marriage. She was diagnosed with type 1 Diabetes mellitus at the age of 2 months, when she was admitted for DKA. She had one episode of jaundice at age of 8 months. She had no signs of developmental delay or intellectual impairment. X-ray of spine and major joints showed signs of skeletal dysplasia. Dysplastic changes on knee radiographs are illustrated by enlarged and irregular metaphyses with prominent beaks. Femoral and tibial epiphyses are flattened. On the hand, the carpal bones and phalanges show tabulation defects and appear short and enlarged. The carpal centres are small and irregular, the proximal phalanges show dense and cone-shaped epiphyses. At the spine, the characteristics relate to those of mild platyspondyly. Vertebrae show irregular upper and lower plates with frequent ossification defects at the anterior edge. She was tested for anti-GAD antibodies and found to be negative. Genetic testing was done and showed a homozygous mutation in the exon 17 of EIF2AK3 gene which produces a truncated protein with a loss of 52 amino acids which results in loss of function of the protein. Conclusion: WRS should be suspected in cases of early onset diabetes. Prognosis is poor with death occurring due to multi organ failure.

   Allan–Herndon–Dudley syndrome (AHDS) – A case report Top

C. P. Patanjali, Nalini B. Wagmode, Vageesh S. Ayyar, Ganapathi Bantwal, Vivek Mathew, Belinda George

Department of Endocrinology, St. Johns Medical College Hospital, Bengaluru, Karnataka, India.

E-mail: [email protected]

Introduction: It is one of the first X-linked mental retardation (XLMR) syndromes reported. Initially it was described on the basis of childhood hypotonia, muscle hypoplasia, severe cognitive impairment, poor head control, dysarthria, and athetoid movements. MCT 8 mutations were found in all the cases described. Gene encoding MCT8 (SLC16A2) is located on chromosome Xq13.2. Case Report: We here report a case of a 2yr 1 mnth old male who was under evaluation for global delay in development. Born of a non consanguinous marriage, 1st in birth order delivered by caesarean section in view of non progressive labour. He developed feeding difficulties at age of 1 month and was started on formula feeds. He had global developmental delay in the form of absent neck holding, inability to pivot in bed, sit, stand or vocalize appropriately for his age. On examination he had microcephaly, nuchal hypotonia with spasticity of both lower limbs, severe cognitive impairment, asthenic build Work up for inborn errors of metabolism-negative EEG was normal, MRI brain- s/o hypomyelination His thyroid function tests showed high total and free T3 levels, mildly elevated TSH and low normal T4 levels. Hence we suspected a Possibility of MCT8 mutation- Allan Herndon Dudley Syndrome which was confirmed with genetic analysis. Conclusion: Prognosis is poor with usually death occurring in childhood or early adult life. Allan Herndon Dudley syndrome may be a rare cause of delayed developments in infants.

   Madness, coma, white matter lesions: The (Un) usual suspect Top

Jyothi Idiculla, G. D. Ravindran

Department of Internal Medicine, St. John's Medical College, Bengaluru, Karnataka, India.

E-mail: [email protected]

Case: A 42 year old lady with retroviral infection of 8 years presented with aggressive behaviour, crying spells of one month and also gradual memory loss. Clinical examination revealed a mini- mental state examination (MMSE) score of 19/30. Apart from slurring of speech and sluggish reflexes, there was no other deficit. Blood Investigations were normal but for mild anaemia. CSF analysis was negative for pyogenic/tubercular/cryptococcal/viral infections. Thyroid function tests were suggestive of primary autoimmune hypothyroidism (TSH >150, total T4 4 and ATPO >1200). The MRI revealed non-enhancing white matter lesions. On achieving euthyroidism, her MMSE improved to 26/30, with partial resolution of the lesions on MRI. Subsequently she was admitted with myxedemic coma from which she recovered with therapy. Discussion: Although subtle thyroid dysfunction of various aetiologies is reported in over 30% of patients, overt disease occurs in a minority. In patients with retroviral infection thyroid dysfunction is usually not considered as a cause of cognitive decline White matter lesions in hypothyroidism is a rare entity. Conclusion: The case illustrates the importance of considering hypothyroidism in a patient with retroviral infection and higher mental dysfunction and ensuring compliance.

   A multifaceted presentation in a case of renal tubular acidosis Top

Amarta Shankar Chowdhury, Debmalya Sanyal1

Department of Endocrinology, Rabindranath Tagore International Institute of Cardiac Sciences, 1Department of Endocrinology, Rabindranath Tagore International Institute of Cardiac Sciences, KPC Medical College, Kolkata, West Bengal, India.

E-mail: [email protected]

Objective: To report a case of Renal tubular acidosis presenting with disproportionate short stature, bony abnormalities and hypokalemic periodic paralysis. Case Presentation: A 13 yr old boy presented with sudden onset, gradually progressive weakness of all 4 limbs without any diurnal variation preceded by an episode of loose motion and non bilious vomiting. He had stunted growth with knock knees along with delayed dentition. Developmental milestones were normal. He had already received multiple courses of Vitamin D and calcium supplementation. On examination, he had disproportionate short stature with antalgic gait, kyphoscoliosis, anterolateral bowing of tibia and angulation of forearm. He had widening of wrist and ankle joint. Power was 1/5 in all 4 limbs with diminished deep tendon reflexes. Investigations revealed corrected calcium of 10.82 mg/dL, hypokalemia, hypophosphatemia. Urine pH was alkaline. Blood pH was 7.3 and bicarbonate was 9.5 mEq/L. iPTH was normal. Vitamin D was 70 ng/mL. Radiographs revealed Cupping and splaying of metaphysis. Discussion: HCO3- being <10, normal PTH values and phosphopenia points out to a diagnosis of Type 1 distal renal tubular acidosis. Raised level of Vit D and calcium may be due to overzealous calcium and vitamin D supplementation. Meticulous approach will aid in proper management in form of potassium citrate supplementation thereby preventing further deleterious consequences. Conclusion: Type 1 RTA is easier to treat because of the lower alkali requirement (3 to 4 mEq/kg per day) to maintain acid-base equilibrium. Overcorrection of acidosis should be avoided to prevent paradoxical increase of the urinary calcium excretion. Nevertheless, prognosis is excellent if diagnosis has been performed early in life. Adequate alkali therapy restores growth in children and prevents the progression of nephrocalcinosis at all ages.

   Association of dietary intake and physical activity with body composition and growth in 3-18 year old Indian Children Top

Nikhil Lohiya, Anuradha Khadilkar1, Shashi Chiplonkar1, Vaman Khadilkar1, Veena Ekbote1, Neha Kajale1, Raja Padidela2

Department of Pediatrics, Bharati Hospital and Research Centre, 1Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital, Pune, Maharashtra, India, 2Department of Paediatric Endocrinology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, England.

E-mail: [email protected]

Background: Body composition and growth are influenced by nutrient intake and lifestyle choices. Asian Indian children and adolescents have higher body fat percentage at lesser body mass index (BMI) and their final height is short in comparison to WHO standards. Objective: To investigate relationships of dietary nutrient composition and physical activity with growth and body composition in Indian 3-18 year old school children. Methods: It is a cross-sectional study done in 4747 school children (2623 Boys, 3-18 yrs). Height, weight, body composition (body impedance analyser), activity and nutrient intakes were recorded. Results: Mean daily intakes of energy and protein (as percentage of Recommended Dietary Allowance, (RDA)) reduced significantly in children (P < 0.01) above 6 years. Mean micronutrient intakes decreased up to 55% below requirements in older age groups. Body fat percentage did not correlate with diet but in boys there was a marginal negative association with moderate physical activity (P < 0.1), a positive association with inactivity (P < 0.05) and with percentage muscle and bone mass (P < 0.1). Similar results were seen by regression analysis (R2 = 0.22, P < 0.01). In girls, a negative association of micronutrient intake (antioxidant) and light sports activity with body fat percentile (R2 = 0.19, P < 0.05) was observed. Height for age Z scores (HAZ) were positively associated with mid-parental HAZ (β=0.45, P = 0.0001), as well as protein density (β=0.103, P = 0.014), and negative association with inactivity was noted (β = -0.0001, P = 0.049- boys) (girls-R2 = 0.104, P < 0.01) on multiple regression analysis. Conclusion: Dietary composition of Indian children needs to be focussed towards a balanced diet with increased intakes of energy, protein as well as micronutrients along with increased physical activity to achieve optimal growth and decrease risk of adiposity.

   Case series of autoimmune hypoglycemia: A rare but important diagnosis Top

Uttio Gupta, Rakhi Malhotra, Hiya Boro, Charandeep Singh, Yashdeep Gupta, Rajesh Khadgawat

Department of Endocrinology and Metabolism. All India Institute of Medical Sciences, New Delhi, India.

E-mail: [email protected]

Introduction: Insulin autoimmune syndrome (IAS) is an uncommon cause of hyperinsulinemic hypoglycemia characterized by autoantibodies to endogenous insulin in individuals without previous exposure to exogenous insulin. In IAS, the insulin and C-peptide levels are markedly elevated and insulin antibodies are present in high titre. Case Series: Here we present our experience of management of three cases (Table 1) of IAS, presented in Endocrinology OPD. CT abdomen, Ga-DOTANOC scan and EXENDIN scan for localization were negative in all. All the patients were put on frequent small carbohydrate meals to avoid prolonged fasting of more than 4-5 hours. At 6 month follow up two patients have spontaneous resolution of hypoglycemia, insulin autoantibody titre decreased to 1.23 nmol/l from 300 nmol/l in first case. In third patient the magnitude and frequency of hypoglycemia improved significantly. Conclusion: Proper diagnosis of this rare condition will avoid needless pancreatic surgical procedures.
Table 1: Profile of three patients of IAS

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   VIT D levels in preeclampsia/eclampsia Top

Aadil Ashraf, Ahmad Wajeed Yousuf, Irfan Gul, Sabreena Qadri1 Nivenjeet Kaur, Shazia Rashid2

Departments of Medicine, 1Psychiatry and 2Obstetrics and Gynaecology, Govt Medical College, Srinagar, Jammu and Kashmir, India.

E-mail: [email protected]

Background: Pregnancy induced hypertension (PIH) is a common gestational disorder which complicates 10% of pregnancies globally and it is associated with maternal, fetal and neonatal morbidity and mortality. Yet the etiology of this disorder is little understood. Alterations in Vitamin D and serum calcium (Ca) levels have been suggested as effective factors in causing PIH. Objectives: To evaluate levels of 25 hydroxy vitamin D and calcium in preeclampsia and eclampsia. Methodology: This study included all the patients reporting to Out Patient Department (OPD) and also those admitted in LD hospital, an associated hospital of Government Medical College, Srinagar with preeclampsia or eclampsia. A total of 140 patients were enrolled in the study, with 70 in each study group (55 with preeclampsia/15 with eclampsia) as well as control group. Appropriate inclusion and exclusion criteria were applied and serum vit D levels and serum calcium levels were measured as per standard protocols. Results: The mean values of serum calcium in study group and control group were 8.66 ± 1.22 mg% and 9.58 ± 0.98 mg% respectively (p < 0.01). The Mean values of serum 25-hydroxyvitamin D levels in study group and control group were 19.66 ± 2.1 nmol/l and 24 ± 1.2 nmol/l respectively (p < 0.04).

   A study of obesity in school children Top

Rushikesh Maheshwari, P. Amaresh Reddy1, P. Radha Rani2

Rushikesh Endocare superspeciality Centre, Nanded, Maharashtra, 1Department of Endocrinology, Maxcure Hospital, Karimnagar, Telangana, 2Consultant Endocrinologist, Kurnool, Andhra Pradesh, India.

E-mail: [email protected]

Objectives: To find prevalence of obesity in adolescents and analyze the relationship between obesity with risk factors causing obesity in adolescents.

Materials and Methods:

Description of the Study Area and Location:

Nellore: Nellore district is the southernmost coastal district of Andhra Pradesh. Administratively the district is divided into 46 Mandals, covering three revenue divisions with head quarters at Nellore, Gudur and Kavali. Nellore is famous for paddy production and education. Nellore municipality is constituted during the year 1885. In 2005, Nellore is upgraded from municipality to corporation. It consists of 50 wards. According to census 2011, total population of Nellore corporation is 505,258 (males-257,043 and females-240,215).

Ethical clearance: Institutional ethical committee, Narayana Medical College, Nellore, accorded ethical clearance for this study.

Sample size: Sample size is calculated from the previous prevalence studies data on obesity by using appropriate sample size calculation method.

VV Khadilkar et al conducted multicentre study in 2011, total 20,243 students studied from five zones in India, prevalence of overweight and obese was 23.9%. Taking prevalence as 24%, allowable error 15%.

n = (Zα)2 pq/L2

Where n = Sample size, p = Prevalence, q = (100-p), L = Allowable error


p = 24%

q = (100 – p) =100-24 = 76

L = 15% of p = 15% of 24


Sample is rounded off to 850 students.

Sampling unit: Sampling unit is the school.

Study subjects: 850 subjects from 4th to 10th classes are selected for the study..

Study period: The study is conducted from October 2013 to November 2014.

Inclusion & Exclusion Criteria

Inclusion criteria: All the boys and girls from 4th to 10th class.

Exclusion criteria

  1. Children who were absent on the day of examination
  2. Children with anatomical abnormalities
  3. Non-cooperating children
  4. Children who were unwell were excluded from the study.

Study Area: This study is conducted in the Narayana school of Nellore city. Study Design: This is a community based cross-sectional study. Sample Size: Sample size is calculated from the previous prevalence studies data on obesity by using appropriate sample size calculation method. Results: As in (Table 1). Conclusions: (1) Prevalence of overweight and obesity in our study is 17.4% and 8.1% respectively. (2) Factors associated with overweight and obesity, (a) Unemployed mothers, (b) Other family member obese, (c) Skipping breakfast, (d) Eating while TV viewing, (e) Motor transport to school, (f) Spending more time for TV viewing, (g) Playing Computer/viedeo games on school days, (g) Playing indoor games for more time, (h) Hotelling, (i) Bad sleeping habits, (3) Of those factors, (a) Other family member obese, (b) Frequent Hotelling, (c) Sleeping less, were more at risk of obesity. These factors should be addressed during the management of obesity. (4) Acanthosis and both systolic/diastolic blood pressure was significantly more among obese compared to nonobese.
Table 1: Results

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   Metabolic profile pre and post transplant in liver transplant recipients Top

Tittu Oommen, Arun S. Menon, Nithya Abraham, Nisha Bhavani, V. P. Praveen, Vasantha Nair, Usha Menon, Harish Kumar, S. Sudhindran

Department of Endocrinology and Surgical Gastroenterology, Amrita Institute of Medical Science, Kochi, Kerala, India.

E-mail: [email protected]

Objectives: New-onset diabetes after transplantation (NODAT) and Post transplant Metabolic syndrome (PTMS) are frequently observed after liver transplantation with reported rates ranging between 9-30% and 44- 58% respectively. These are associated with increased cardiovascular morbidity and mortality, more severe infections, higher incidence of rejection, and poorer graft survival. Methods and Results: We prospectively studied the metabolic parameters pre and post transplant in 51 liver transplant recipients for a mean duration of 11 ± 3.5 months. 49% (25/51) of the study population were known to have type 2 diabetes prior to transplantation. There was no significant difference in age (47.56 ± 8.0 vs 43.88 ± 10.81 years), body weight (67.76 ± 11.87 vs 70.23 ± 18.62 kg), lipid profile (TC 97.08 ± 34.23 vs 86.98 ± 47.64 mg/dl), MELD score (20.22 ± 5.73 vs 23.10 ± 5.147) and HOMA-IR (4.79 ± 3.92 vs 2.16 ± 1.56) between patients with or without pre-existing diabetes. 52% of those with diabetes were already on insulin treatment and 42% on oral agents. 10/26 patients without pre-existing diabetes developed NODAT. No significant difference was observed in age (47.70 ± 5.43 vs 41.5 ± 12.70 years), body weight (70.70 ± 15.72 vs 69.94 ± 20.73 kg), lipid profile, MELD score, pre transplant HOMA-IR (2.352 ± 1.80 vs 2.08 ± 1.56) or length of hospital stay (25 ± 8 vs 24 ± 7 days) in patients who developed NODAT. The cumulative steroid dose and mean tacrolimus levels also did not seem to have any correlation with development of NODAT. Conclusions: Our results suggest that pre-existing diabetes is not associated with worsening of metabolic parameters after transplantation. Metabolic abnormalities pre-transplant did not seem to predict the risk of developing NODAT or PTMS. We conclude that traditional metabolic risk factors are not sensitive enough in predicting cardiovascular risk post liver transplant. Newer markers/risk models may be required to identify and treat this at-risk group.

   Evaluation of Vitamin D levels in metabolic syndrome and its correlation with glycemic profile and cardiovascular risk factors Top

Saurabh Nandwani, Manoj Mathur, Piyush Saxena, Ajeet Chaurasia

Department of Medicine, MLN Medical College, Allahabad, Uttar Pradesh, India.

E-mail: [email protected]

Objectives: Vitamin D, a regulator of bone metabolism, has been recently been linked with energy homeostasis and metabolic disorders in western countries. The aim of the present study was to know the relationship between vitamin D concentration and the components of metabolic syndrome and glycemic profile. Methods: Plasma 25(OH) D was measured in a cross sectional sample of 28 men and 23 women aged 18–65 years attending Swaroop Rani Nehru hospital, Allahabad. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asians. Fasting plasma glucose, post prandial glucose, lipid profile, A1C, and inflammatory markers (hsCRP) were measured. Anthropometric data were also obtained for this cross sectional observational study. Results: The mean of plasma 25(OH) D was 21.97 ng/ml and percentages of vitamin D deficiency [vit D <20ng/ml] and insufficiency [vit D: 20-30 ng/ml] were 45.16% and 38.70% respectively in metabolic patients group. The mean of plasma 25(OH) D was 28.57 ng/ml and percentages of vitamin D deficiency [vit D <20ng/ml] and insufficiency [vit D: 20-30 ng/ml] were 25% and 20% respectively in control group. Unpaired t test was used to compare vitamin d values between the case and control groups. P value was 0.0201 (<0.05). Significant inverse associations existed between 25(OH) D and individual metabolic syndrome components plus A1C and hsCRP except with blood pressure. Conclusion: In the study, significant inverse association were present for vitamin D with central obesity, hyperglycemia, hypertriglyceridemia and hsCRP. The findings of this investigation revealed that vitamin D deficiency may have an important role in metabolic syndrome and its components.

   Type 1 autoimmune polyendocrinopathy without mucocutaneous candidiasis: Discussion of genetic analysis Top

Subramanian Kannan, R. Rengaraj1, Siddaram J. Patil2, Anuradha Rao3, Ghazala Zaidi4, Saroj Sahu4, Eesh Bhatia4

Departments of Endocrinology, 2Genetics and 3Dermatology, Narayana Health City, 1Oxford Medical College, Bengaluru, Karnataka, 4Department of Endocrinology, SGPGI, Lucknow, Uttar Pradesh, India.

E-mail: [email protected]

Objective: To report an unusual case of a Type 1 Autoimmune Polyendocrinopathy in a nine year old girl and discuss its genetic analysis. Methods: A 9 y 8 m old girl child born out of consanguineous marriage had an uneventful neonatal and infantile years. Her growth (height 127 cm and weight 28 kg) and milestones were normal. She first experienced seizure episodes at the age of 4y and was started on phenobarbitone without much improvement in seizure frequency. After 6 months, she developed depigmented macules and patches over forehead followed by over hands and feet. She progressed to have complete loss of scalp hair and eye brow hair within a span of few months. At the time of clinical presentation she was noted to have alopecia totalis, vitiligo patches in the torso, face, lips and extremities. Oral cavity demonstrated enamel dysplasia and gum hypertrophy with no evidence of candidiasis. Nails were dystrophic and KOH mount of nail scrapings were negative for fungal elements. She has positive Trousseau and Chvostek sign. Slit lamp examination of cornea was normal. Labs were significant for a TSH of 9.559 mIU/L, fT4 of 0.88 ng/dl, TPO >1300 IU/ml, Calcium (albumin corrected) 7.68 mg/dl, phosphorus 7.37 mg/dl, PTH was <4 pg/ml, 8AM cortisol 17.8 mg/dl and fasting glucose of 83 mg/dl. A clinical diagnosis of Type 1 Polyendocrinopathy (APS-1) with hypoparathyroidism, primary hypothyroidism, alopecia, vitiligo was made. CT brain revealed multifocal symmetric calcification including cortical and subcortical areas. She was started on oral calcium, calcitriol and thyroxine and she has been slowly weaned off phenobarbitone over a period of 4 months and currently remains seizure free. Repeated probing of the mother and the patient about oral lesions, or oesophageal symptoms related to candidiasis was negative. Results: Her serum had a high titre of interferon alpha antibody [1.89 units (normal <0.02)] which is a marker of APS-1. Genetic analysis of the AIRE gene exons 1-14 (exon 12 and 13 pending at time of submission) were done. In exon 7 the mutation g. 774 C > G (p. 278 S > R)] was noted. However this mutation was present in homozygous state in the father and heterozygous state in the mother, and as they are clinically unaffected this is unlikely to be a pathogenic mutation. Conclusion: We report a case of APS-1 with lack of muco-cutaneous candidiasis and no clearly demonstrable pathogenic mutation in the AIRE gene.

   Bardet-Biedl Syndrome: A rare case report affecting two siblings Top

T. C. Das, A. Maiti, A. K. Basu, A. Sinha, P. Devarbhavi, S. Swar, N. Sinha, Sayan Ghosh, Raghubanshi Somnath

Department of Endocrinology, Medical College Kolkata, Kolkata, West Bengal, India.

E-mail: [email protected]

Introduction: Bardet Biedl Syndrome (BBS) is a autosomal recessive condition with a wide spectrum of clinical features involving multiple organ system. The accepted major criteria for diagnosis include retinitis pigmentosa, obesity, polydactyly, mental retardation, hypogonadism, and renal dysfunction. We have presented two sibling exhibiting characteristic features of Bardet Biedl Syndrome. Case Report: Two siblings presented with like difficulties in night vision, weight gain and hyperphagia and delayed developmental milestone with poor scholastic performances. On examination -normal stature, post axial polydactyly, central obesity, acanthosis nigricans, moderate intellectual impairment, in male had micro penis and small testis. Fundoscopy showed black pigmentation, thin vessels and bony spicules suggestive of retinitis pigmentosa, OCT showed loss of choroidal architecture and thinned out retinal pigment epithelium. USG abdomen showed fatty liver, no renal abnormality. Conclusion: The uniqueness of this case is it's rarer incidence and involvement of two siblings. Clinicians must be aware of this syndrome, for which an early diagnosis and multidisciplinary approach will significantly improve mortality and morbidity in patients.

   Hypertensive form of congenital adrenal hyperplasia presented with seizure disorder: An uncommon association Top

Ranajit Bari, Arijit Singha, Rana Bhattacharjee, Sujoy Ghosh, Pradip Mukhopadhyay, Subhankar Chowdhury

Department of Endocrinology and Metabolism, IPGMER, Kolkata, West Bengal, India.

E-mail: [email protected]

A 8 year old boy born out of consanguineous marriage was presented to emergency department with generalized tonic clonic seizures. He was having episodic seizures since last one year in spite of getting two antiepileptic drugs regularly. He had history of accelerated height gain, appearance of pubic and axillary hair, body odor, acne, for 3 years. His one elder brother died of similar type of illness at the age of 4. He had normal birth and developmental history. There was no history of salt wasting crises, headache, visual disturbance, meningitis, encephalitis or cranial irradiation. On examination, he was hypertensive, on amlodipine 10 mg, with SBP 130 mm of Hg (>99th percentile) and DBP 80 mm Hg (95th percentile). There was generalized hyperpigmentation. His tanner stage was A1, P4. His Stretched penile length was 8 cm and Testicular volume 4 ml bilaterally. His auxological parameters were as following - height 143 cm (>97th percentile), height age 11-11.5 years, height SDS + 3.32, weight 35.7 kg (>97th percentile), weight age 11 years. There was no focal neurodeficit or any abdominal lump. Other systemic examinations were within normal limits. The Baseline laboratory parameters, Testosterone 228 ng/dl, LH <0.05 miu/ml were suggestive of peripheral precocity. The 17OH progesterone 26.4 ng/ml, cortisol 13.5 mcg/dl, DHEAS 52.9 mcg/dl, sodium 143 mEq/L and potassium 1.9 mEq/L were suggestive of hypertensive variant of CAH probably due to 11 beta hydroxilase deficiency. USG showed bilateral enlarged adrenals. His bone age was 11 years. MRI H-P region did not reveal any abnormality except mild superior bulge of pituitary. MRI Brain was within normal limit. The association of classic salt wasting CAH with seizure episodes due to hyponatremia was well described. But it was not been reported earlier in case of 11 beta hydroxylase deficiency.

   Dulaglutide treatment reduces glycemic excursions in people with type 2 diabetes: A post-hoc analysis of 6 phase 3 randomized clinical trials Top

Indranil Bhattacharya, Guillaume Charpentier1, Luis-Emilio García-Pérez, Vivian T. Thieu, Nan Jia, Jennie G. Jacobson, Valeria Pechtner2

Eli Lilly and Company, Indianapolis, IN, USA, 1Centre Hospitalier de Corbeil, Evry, 2Lilly France, Neuilly-sur-Seine Cedex, Lille, France.

E-mail: [email protected]

Objectives: The once-weekly GLP-1 receptor agonist dulaglutide (DU) demonstrated a significant HbA1c reduction and the potential for weight loss in adults with uncontrolled type 2 diabetes (T2D) in the AWARD phase 3 clinical program. DU has also demonstrated significant reductions in fasting, pre- and postprandial glucose levels. Materials and Methods: To further understand the glycemic effects of DU 1.5 mg and 0.75 mg, we performed a post-hoc analysis examining glycemic excursions (morning, midday, evening, and daily mean) obtained by self-monitored blood glucose testing at 6- or 12-month time points. Analysis was performed by individual study (AWARD-1, -2, -3, -6, -8 and -9), given the different background therapies (DU + metform + pioglitazone, DU + metform + glimepiride, DU monotherapy, DU + metform, DU + glimepiride, DU + insulin glargine ± metform, respectively). Glycemic excursions were derived by subtracting blood glucose values before each meal from blood glucose values 2 hours after the meal (LOCF). Results: Treatment with DU 1.5 mg resulted in significant reductions from baseline in daily mean glucose excursions (change: -7 to -15 mg/dL, P < 0.05) in all six trials. The effect of DU 1.5 mg on glycemic excursions was most evident in the morning (change: -12 to -24 mg/dL, P < 0.5; change in evening: -3 to -14 mg/dL). The trend of the glycemic excursion reductions from baseline with DU 1.5 mg and DU 0.75 mg were similar. Conclusion: The effect of DU treatment on glycemic excursions may contribute to overall improvements in glycemic control in patients with T2D treated with DU. Disclosures: This study was supported and conducted by Eli Lilly and Company. This is an encore of an abstract presented at ADA 2017; San Diego, CA, USA; June 9-13, 2017.

   Study on reduced effectiveness of levothyroxine when co-administered with herbal drinks Top

Anulekha Mary John, Sherin Sarah Mathew, Jibily Joy

Department of Endocrinology and Metabolism, BCMCH, Thiruvalla, Kerala, India.

E-mail: [email protected]

Objectives: (1) Describe the general practice of thyroxine-administration among participants. (2) To compare effectiveness of thyroxine when co-administered with herbal-drinks as against water. (3) To study the effect of change in practice. Materials and Methods: This prospective study was conducted in a tertiary care institute in Kerala during January-May 2017. Healthy adult out-patients diagnosed primary hypothyroidism, meeting inclusion criteria (age 18-75 years, non-pregnant, on adequate dose of thyroxine) were interviewed regarding thyroxine-administration, type of drink taken with thyroxine and time-gap between medication and food. TSH (Thyroid Stimulating Hormone) was measured using Immunochemiluminometric assay (ICMA) and details entered into proforma. Patients were instructed to take thyroxine early morning, with water, wait 30 minutes before first drink (other than water) and repeat TSH after 6 weeks. Dose of thyroxine was adjusted according to TSH value at 6 weeks. Results: There were 121 patients who met the inclusion criteria. 61 (50.4%) took thyroxine with water and 60 (49.6%) with herbal-drinks. These included karingali (cutch tree)-21 (35%), pathimugham (sappan wood) 14 (23.3%), Tulsi (basil) 3 (5%), jeera (cumin) 4 (6.6%) and the rest took with dhahashamini (mixed herbs) 18 (30%). Among patients taking thyroxine with water 45 (73.8%) had normal TSH and 16 (26.2%) had elevated TSH. Among patients taking thyroxine with brewed herbs, 25 (41.7%) had normal TSH and 35 (58.3%) had elevated TSH. This difference was significant with a Chi square of 8.33 and P value 0.004. Among patients who took thyroxine with water, 16 (26.2%) and among patients with herbal drinks, 13 (21.6%) did not keep adequate time-gap between thyroxine and food. After education, all except one were able to normalize TSH at 6 weeks, on current dose of thyroxine. TSH was suppressed in 8 (13.1%) among water and 16 (26.7%) among herbal-water, on current dose, thus enabling reduction to more physiological dose. Conclusions: (1) Fifty percent of patients on thyroxine-replacement, take it with herbal-water. (2) Taking thyroxine with herbal-water reduced effectiveness. (3) Taking thyroxine with water, with adequate time-gap before next drink improved efficacy.

   Study of thyroid autoimmunity in patients of thyrotoxicosis without hyperthyroidism our experience Top

P. Amaresh Reddy, Palanki Radha Rani1, Rushikesh Maheswari2, K. Srinivasa Rao3

Department of Endocrinology, Maxcure Hospitals, Karimnagar, Telangana, 1Department of Endocrinology and Metabolism, GGH, Kurnool, Andhra Pradesh, 2Consultant Endocrinologist, Department of Endocrinology, Rushikesh Endocare supespeciality Centre, Nanded, Maharashtra, 3Prof & Head, Department of Microbiology, Guntur Medical College, Guntur, Andhra Pradesh, India.

E-mail: [email protected]

Context: Thyroiditis, is an inflammatory thyroid condition. Should Thyroid autoimmunity be used as marker for thyroiditis. Aims: To study the prevalence of thyroid auto immunity in patients of thyrotoxicosis without hyperthyroidism in a tertiary care centre. Materials and Methods: We studied 20 patients with features of thyrotoxicosis with out hyperthyroidism. After complete physical and clinical evaluation, biochemical analysis for Thyrod profile, erythrocyte sedimentation rate (ESR) Thyroperoxidase antibodies (TPO), Ultrasound of thyroid were done. Tc99 thyroid scan was done for all patients. Results: in the study subjects 6 were males and none of the patients were in the post partum period. The mean age was 32.7 ± 12.9 years. The presenting complaints observed were tremors, palpitations and diffuse painless enlargement of thyroid. On ultrasonography bulky thyroid was seen in 11.1%cases. Mean TSH, free T4, free T3 and FT3/FT4 ratio were 0.06 ± 0.06 Miu/l, 4.8 ± 2.65 ng/dl, 1.88 ± 1.02 pg/ml, and 2.65 ± 0.57 respectively. Elevated ESR was seen in all patients (52 ± 13.7 mm in 1st hr). Technetium 99 thyroid scan was uniformly showing decreased uptake in all cases. Anti thyroperoxidase antibody positivity is seen in 40% cases. Discussion: ESR and Tc 99 thyroid scan are better investigative modalities for differentiation of thyroiditis in toxic phase and Graves' disease. TPO antibodies should not be used for differentiating the two conditions due to the high positivity rates in patients with thyroiditis as described in our study which was not described previously. Conclusion: High TPO antibody titres should not be used for the differentiation of graves disease and thyroiditis.

   Insulin sensitivity and beta-cell function in Graves' disease and their changes with carbimazole induced Euthyroid state Top

Nandhini Lakshmana Perumal, Jayakumar Selvi, Kalyani Sridharan, Jayaprakash Sahoo, Sadishkumar Kamalanathan

Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

E-mail: [email protected]

Objective: Thyroid hormones play an important role in intermediate metabolism and abnormal glucose tolerance is often observed in patients with hyperthyroidism. Several pathogenic mechanisms have been proposed as contributors. However, there is no conclusive evidence in the existing literature regarding the predominant underlying pathophysiology and its changes with the restoration of a euthyroid state. Our objective was to (1) determine the changes in insulin resistance parameters in patients with Graves' disease following restoration of a euthyroid state and (2) to study beta-cell function in these patients and its changes with the restoration of the euthyroid state. Materials and Methods: This study was designed as an observational study with a before- after study design. Forty-five treatment-naïve consenting adults with Graves' diseases were included and thirty six completed the study. Oral glucose tolerance test was performed at baseline and after three months of achieving a euthyroid state, to assess glucose tolerance, insulin sensitivity and beta cell function. All patients were treated with anti-thyroid medication. Outcome measures studied were HOMA2-IR, Matsuda index and ISSI-2 index. Results: Two-thirds of the patients had abnormal glucose tolerance at baseline. Among those with abnormal glucose tolerance at baseline, 34.7% had persistent abnormality during follow-up. There was no significant change in the indices of insulin resistance from baseline, after achieving a euthyroid state. Patients with abnormal glucose tolerance had a significantly lesser ISSI-2 index at baseline and it improved after achieving a Euthyroid state. Conclusion: In conclusion, abnormal glucose tolerance is a significant metabolic consequence in patients with Graves' disease. Decreased beta-cell function was observed among those with abnormal glucose tolerance and it improved during follow-up. In a proportion of patients, abnormal glucose tolerance persisted after three months of achieving a euthyroid state, emphasizing the need for continued follow-up.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]


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