Indian Journal of Endocrinology and Metabolism

ABSTRACTS
Year
: 2019  |  Volume : 23  |  Issue : 7  |  Page : 5--83

ESICON 2019 Abstracts


 

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. ESICON 2019 Abstracts.Indian J Endocr Metab 2019;23:5-83


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. ESICON 2019 Abstracts. Indian J Endocr Metab [serial online] 2019 [cited 2019 Dec 15 ];23:5-83
Available from: http://www.ijem.in/text.asp?2019/23/7/5/271346


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 DIABETES



 Serum Magnesium the Undervalued Marker of Diabetic Nephropathy



Jatin Agrawal, Veer Bahadur Singh, Babulal Meena, Rajesh Yadav

Department of Medicine, S P Medical College, Bikaner, Rajasthan, India.

E-mail: jatinagrawal1989@gmail.com

Diabetic nephropathy is a common cause of chronic renal disease. Its prevalence is increasing with an increase in the prevalence of diabetes. Hypomagnesemia considered as independent risk factor of diabetes, but its relation with microalbuminuria is still unresolved. Hence, our study aimed to find the corelation of microalbuminuria with serum magnesium (Mg). This cross-sectional study was conducted from June 2016 to December 2017 in S.P. Medical College and Associated Group of P. B. M. Hospitals, Bikaner. A total of 108 matched patients diagnosed as Type 2 diabetes mellitus were included. Diabetic patients were further divided into three groups according to the serum Mg concentration: Group 1: Mg <1.8 mg/dl, Group 2: Mg between 1.8 and 2.1 mg/dl, and Group 3: Mg ≥2.2 mg/dl. Microalbuminuria is defined as spot urine albumin creatinine ratio >30 mg/g but <300 mg/g). All three groups were compared. A total of 27 (25%) patients had microalbuminuria. The mean spot albumin urine creatinine ratio (SAUCR) among the groups was 28.29 ± 11.98, 22.55 ± 9.32, and 19.32 ± 6.52, respectively, with significant difference. There was also moderately significant negative corelation between the serum Mg and SAUCR. Thus, our study adds evidence to the association between low serum Mg and microalbuminuria.

Keywords: Magnesium, microalbuminuria, spot urine albumin creatinine ratio

 The prevalence of vitiligo and the role of thyroid antibody among patients with type 2 diabetes mellitus



Aneesh Ghosh

Department of Endocrinology, Ananthapuri Hospitals and Research Institute, Thiruvananthapuram, Kerala, India.

E-mail: ghoshkottan@gmail.com

Introduction: Diabetes mellitus is associated with many skin manifestations including vitiligo. Vitiligo occurs more commonly in type 1 diabetes mellitus. In India, however, few studies have focused on the association of autoimmune thyroid dysfunction with vitiligo and very few studies have been done to know the association of diabetes mellitus and vitiligo.[1],[2],[3] It has shown that thyroid dysfunction is present in up to 25% of patients with diabetes mellitus. Aims: The aims of this study were as follows: (1) to study the prevalence of vitiligo in type 2 diabetic patients and (2) to see the role of thyroid antibody (antithyroid peroxidase antibody) in this context. Settings and Design: This was a cross-sectional study conducted in a tertiary care hospital in Thiruvananthapuram. Materials and Methods: Two hundred consecutive patients of type 2 diabetes were included in the study group. All these patients were receiving standard medical care form a single consultant. Vitiligo was identified by thorough clinical examination using a magnifying lens. The first hundred patients included were having thyroid antibody-negative status and the subsequent hundred patients selected were positive for thyroid antibody. Patients were matched for age, gender, duration of diabetes, HbA1c, and other confounding factors. Statistical Analysis: Chi-square test was used for analysis with P =0.05 for significance. Results: Vitiligo was seen in 16% of patients with positive thyroid antibody status and 9% of patients with negative antibody status which was statistically significant (P <0.01). The preferred distribution was face, lips, forearm, hands, legs, and feet. Conclusion: Vitiligo is more commonly seen in type 2 diabetes mellitus even though there is no established causal association. This is the first study highlighting the possible role of thyroid autoimmunity in the prevalence of vitiligo in type 2 diabetes mellitus.

Keywords: Thyroid autoimmunity, type 2 diabetes, vitiligo

 References



Kumar KV, Priya S, Sharma R, Kapoor U, Saini M, Bisht YS. Autoimmune thyroid disease in patients with vitiligo: Prevalence study in India. Endocr Pract 2012;18:194-9.Dave S, D'Souza M, Thappa DM, Reddy KS, Bobby Z. High frequency of thyroid dysfunction in Indian patients with vitiligo. Indian J Dermatol 2003;48:68-72.Raveendra L, Hemavathi RN, Rajgopal S. A study of vitiligo in type 2 diabetic patients. Indian J Dermatol 2017;62:168-70.

 Assessment of footwear in diabetic patients with or without peripheral neuropathy



Anulekha Mary John, Jessilin K. Charley, Jibily Joy

Department of Endocrinology and Metabolism, Believers Church Medical College Hospital, Thiruvalla, Kerala, India.

E-mail: anulekhageorge@gmail.com

Introduction: Diabetic peripheral neuropathy, a well-known complication of diabetes mellitus, leads to foot ulcers. This can be very costly affecting the quality of life of an individual. Inappropriate footwear and walking barefoot increase the risk of ulceration in a neuropathic foot. Aims and Objective: The aim of this study was to assess the footwear of diabetic patients with or without peripheral neuropathy. Materials and Methods: Alternate patients with type 2 diabetes were selected. The feet of each patient were examined. Biothesiometry, monofilament, and footwear assessment were performed. Results: Among 230 patients who visited the diabetes clinic, 112 patients were enrolled. Of these, 69 (61.6%) were male and 43 (38.3%) were female. The mean age was 59.2 years and age ranged from 21 to 83 years. The mean age of men was 60.35. The mean age of females was 58.57. Duration of diabetes ranged from less than a year to 45 years. Seventy-five (66.96%) patients had diabetic peripheral neuropathy when assessed objectively using biothesiometry and 10-g Semmes Weinstein monofilament. Only 10 (8.9%) patients had footwear made of microcellular rubber. Only 15 (13.3%) wore a footwear with back strap. Among those with neuropathy, only 4 (0.5.3%) had an MCR footwear with a black strap. Optimal toe box was seen in 98 (87.5%) patients as most patients wore open footwear. Most of our patients wore a footwear that was too hard, with shore value on durometry ranging from 60 to 75. Only 5 (13.4%) patients had desirable soft insole. No patient had an optimal footwear that fulfilled all criteria required for a foot with diabetic peripheral neuropathy. Discussion and Conclusion: In addition to screening for neuropathy and regular checking of the feet, it is also important to look at a patient's footwear and make necessary amendments periodically. We have not received any financial grant from the Endocrine Society of India.

Keywords: Biothesiometry, diabetic foot ulcer, diabetic footwear, microcellular rubber, peripheral neuropathy

 Awareness of diabetic retinopathy among patients with type 2 diabetes mellitus, attending a tertiary care center



Anulekha Mary John, Ancy George, Anju K. Francis

Department of Endocrinology and Metabolism, Believers Church Medical College Hospital, Pathanamthitta, Kerala, India.

E-mail: anulekhageorge@gmail.com

Introduction: Diabetic retinopathy (DR) is a serious cause of irreversible blindness and is the most common microvascular complication of diabetes. Although various modalities of treatment are available, patients often present late in the course of the disease when treatment is more difficult. Aims and Objective: This study aimed to assess the level of awareness and current knowledge about DR. Materials and Methods: This study was conducted among patients with type 2 diabetes mellitus, attending a tertiary healthcare center in South India. A structured questionnaire was used to collect information. Data obtained was analyzed using Microsoft Excel 2007. Results: A total of 120 participants (62 [51.6%] males and 58 [48.3%] females) with type 2 diabetes were interviewed. The mean age ± standard deviation for the study population was 59.9 ± 12.18% years. Of the study population, 38% were aware that diabetes can affect the eyes and only a few patients were aware that DR could lead to blindness. Patients' compliance with routine retinal assessment was poor, with only a total of 39% of participants having had an eye examination in the previous year. Discussion and Conclusion: Only 38% of the study population was aware of diabetic retinopathy. More awareness-building initiatives to increase the effectiveness of DR screening program are warranted. Annual fundus examination in all diabetic patients aids in the prevention of blindness and allows early intervention.

Keywords: Blindness prevention, diabetic retinopathy, microvascular complication

 A study to evaluate the glucagon and incretin responses and identify the role of extrapancreatic glucagon in patients of fibrocalcific pancreatic diabetes



Shivendra Verma, Riddhi Dasgupta, Shajith Anoop, Nihal Thomas

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

E-mail: nihal_thomas@yahoo.com

Background: In tropical countries, one of the common causes for young-onset diabetes is “Fibro Calcific Pancreatic Diabetes” (FCPD). Despite widespread destruction of the pancreas in FCPD, glucagon has been found to be higher in various studies. We hypothesize that hyperglucagonemia in FCPD arises from gut. Aim: The aim of this study is to evaluate glucagon and incretin responses in patients with FCPD. Methods: Nine FCPD patients and six age- and body mass index-matched healthy controls were subjected to 75 g oral glucose tolerance test (OGTT) followed by isoglycemic intravenous glucose infusion (IIGI). Blood samples were analyzed for incretins and glucagon at nine pre-specified time-points over 3 h and the area under curve was calculated. Results: Glucagon was significantly higher during OGTT compared to IIGI in FCPD patients (98.8 ± 13 pg/ml vs. 63.4 ± 7 pg/ml, P = 0.03) and was also higher when compared to controls (98.8 ± 13 pg/ml vs. 65.8 ± 18 pg/ml, P = ns). FCPD patients showed very low basal and stimulated c-peptide (0.43 ± 0.14 ng/ml and 1.09 ± 0.3 ng/ml, respectively) and pancreatic polypeptide (12.3 ± 0.0pg/ml and 12.0 ± 0.6 pg/ml, respectively) levels. Glucagon-like peptide-1 (GLP-1) was significantly higher in cases on OGTT when compared to controls (44.5 ± 9.2 pM vs. 12.8 ± 7.5 pM, P = 0.02). Oxyntomodulin was also insignificantly higher in cases on OGTT when compared to controls (1252 ± 350 pg/ml vs. 859.8 ± 165 pg/ml, P = 0.43). GIP was lower in cases on IIGI when compared to controls (52.9 ± 23.9 pg/ml vs. 144.5 ± 36.1 pg/ml, P = 0.045) and there was blunted response on OGTT as well (106.8 ± 40.3 pg/ml vs. 557.8 ± 96.4 pg/ml, P = 0.003). Discussion: We found hyperglucagonemia in FCPD on OGTT, which was suppressed on IIGI. Increase in L-cell products: GLP-1 and oxyntomodulin and a good correlation between glucagon and GLP-1 during OGTT were suggestive of extrapancreatic glucagon production probably from L-cell. The blunted GIP could probably be due to: inadequate pancreatic enzyme supplements, a selective PC-2 enzyme up-regulation or a negative feedback regulation from extrapancreatic glucagon. Conclusion: Extrapancreatic glucagon does exist in FCPD and may contribute to postprandial hyperglycemia and lower GIP levels.

Keywords: Extra pancreatic glucagon, GIP, glucagon-like peptide -1, oxyntomodulin

 Assessment of achievement of American diabetes association targets in patients with type 2 diabetes mellitus at a tertiary care center in Eastern Nepal



Jouslin K. Baranwal, Robin Maskey1, R. K. Chaudhari, Ojaswee Sherchand

Departments of Biochemistry and1Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal.

E-mail: jouslin1984@gmail.com

Introduction: The goal of the management of type 2 diabetes is not mere maintenance of blood glucose, but to prevent vascular complications, improving the quality of life as well. Although the American Diabetes Association (ADA) has lain the target levels for hemoglobin A1c (HbA1c), blood pressure, and blood cholesterol levels, these are not being achieved in routine care. Aims and Objective: Hence, this study was undertaken to find whether the patients attending our diabetic clinic met these targets. Materials and Methods: Data were collected from the diabetic clinic records. Data of all the Type 2 Diabetes patients who have attended our clinic for past 1 year from the start of the study were enrolled despite the duration of Diabetes. Data of the pregnant women and patients with mention of conditions that interfere with measurement of HbA1c were excluded from the study. Results: We analyzed 336 records, 45.8% (n = 154) males and 54.16% (n = 182) females. The mean age of patients was 52.28 ± 11.9 years. Percentages of patients who had HbA1c < 7%, blood pressure <140/90 mm Hg and Low-density lipoprotein-c < 100 mg/dl were 56.5%, 72% and 56.3%, respectively. Only 37.8% of patients were found to have achieved all three targets laid by ADA. Higher percentage of females were found to have achieved all three targets as compared to males, 38.5% vs. 37% (P = 0.1). Furthermore, higher percentage of patients who were ≥50 years of age achieved all three targets as compared to those <50 years of age, 38.6% vs. 36.7% (P = 0.7). Discussion and Conclusion: Our study highlights that a substantial proportion of patients missed on achieving the ADA targets. Furthermore, several other studies conducted in both developing as well as developed countries have showed the achievement of these goals to be far from satisfactory. This is worrisome and further studies should be done to find out possible reasons behind this.

Keywords: Achievement, American Diabetes Association targets, Nepal

 Assessment of efficacy of epalrestat in diabetic symmetrical peripheral neuropathy with respect to erythrocyte sorbitol levels



Rujul Jain, S. K. Singh

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

E-mail: rujul1011@gmail.com

Introduction: Diabetic symmetrical peripheral neuropathy (DSPN) despite being the most common and most disabling complication of diabetes has very limited treatment options. There is renewed interest in epalrestat, an aldose reductase inhibitor due to its proposed disease-modifying properties. Aims and Objective: The aim of this study was to correlate baseline erythrocyte sorbitol levels with the therapeutic efficacy of epalrestat in DSPN. Materials and Methods: One hundred patients with duration of diabetes >5 years with Diabetic Neuropathy Symptom Score (DNSS) ≥1 were recruited in an open-label, prospective randomized control study. Participants were divided into two groups – Group 1: received placebo (containing Vitamin B12) and Group 2: received epalrestat 150 mg OD + placebo. DNSS, Numeric Pain Intensity Scale (NPIS) score, monofilament score, and vibration perception threshold (VPT) along with erythrocyte sorbitol levels (estimated by ELISA) were recorded at baseline and repeated 3 months later. Results: Both the groups were comparable in terms of mean age, duration of diabetes, and duration of neuropathy symptoms. There was a significant difference between improvement in DNSS (0.57 ± 1.04 in Group 1 vs. 2.39 ± 1.1 in Group 2; P < 0.001), NPIS score (0.41 ± 0.81 in Group 1 vs. 2.61 ± 1.26 in Group 2; P < 0.001), monofilament score (0.12 ± 0.93 in Group 1 vs. 2.82 ± 1.41 in Group 2; P = 0.001), and VPT (0.34 ± 1.14 mV in Group 1 vs. 3.48 ± 2 mV in Group 2; P = 0.001). There was a significant correlation between baseline sorbitol levels and improvement in VPT in the epalrestat group (r = 0.991; P < 0.001). Discussion and Conclusion: With paucity of treatment options in DSPN, epalrestat offers a ray of hope in ameliorating the symptomatology of DSPN. Baseline erythrocyte levels can help in predicting the efficacy of epalrestat. Epalrestat treatment may be clinically useful only in patients with excessive accumulation of sorbitol. This will pave the way for personalized medicine for DSPN in the future.{Figure 1}

Keywords: Diabetic neuropathy, epalrestat, sorbitol

 Prevalence, clinical profile, and follow-up of recurrent urinary tract infection in patients with type 2 diabetes mellitus



Tauseef Nabi

Department of Endocrinology, Government Medical College, Srinagar, Jammu and Kashmir, India.

E-mail: dr.tauseefnabi @gmail.com

Background: Patients with type 2 diabetes (T2D) are at increased risk of infections, with the urinary tract being the most frequent site, and good diabetic control has been recommended as a means of decreasing this risk. Adult women with diabetes are at increased risk of urinary tract infection (UTI), especially recurrences. The identification of risk factors can help pinpoint modifiable factors amenable to a disease prevention strategy for recurrent UTI. Objective: The aim is to study the clinical, etiological profile, complications, and follow-up of UTI in T2D patients. Patients and Methods: This was a hospital-based prospective study done on consecutive 200 T2D symptomatic UTI patients admitted in the endocrinology department having age >30 years. Various clinical, biochemical parameters and urine examination and culture were monitored. All the patients were followed for 6 months with respect to the number of UTIs, glycemic control and renal parameters. Results: UTI was more common in females (81%) as compared to males (19%). Lower UTI (cystitis) was present in 55.5% and pyelonephritis 44.5%, emphysematous pyelonephritis (EPN) in 9.5% and bacteremia in 58.1% of UTI patients. EPN was present only in females. Of the 169 T2D UTI patients followed till 6 months, 67 (39.6%) developed recurrent UTI. The presence of chronic kidney disease, uncontrolled diabetes, and renal calculi increased the risk of recurrent UTI in T2D females. While in males poor glycemia and lower estimated glomerular filtration rate increases risk of recurrent UTI. The recurrent UTI patients had significantly higher HbA1c at follow-up than at baseline, but renal parameters did no differ. Conclusion: Recurrent UTI is consequences of and leads to uncontrolled glycemia. Significant number of patients develop recurrent UTI on follow-up. Recurrent UTI patients have poor glycemic control on follow-up while renal parameters did not differ.

Keywords: Glycemic control, renal parameters, symptomatic bacteriuria, type 2 diabetes, urinary tract infections

 Insulin resistance and body composition in chronic liver disease



Preyander Singh Thakur, Nitin Kapoor, Ashish Goel1, H. S. Asha,

Riddhi D. Gupta, Uday Zachariah1, C. E. Eapen1, Grace Rebekah2,

Nihal Thomas, Thomas V. Paul

Departments of Endocrinology, Diabetes and Metabolism and1Gastrointestinal Sciences, CMC Vellore, Tamil Nadu, India,2Department of Biostatistics.

E-mail: preyander.thakur@gmail.com

Background: Patients with chronic liver disease (CLD) are at risk of metabolic complications such as diabetes mellitus (DM). Overt DM has been observed in 20%–40% and impaired glucose tolerance (IGT) in 60%–80% of patients with CLD. DM has a bi-directional relationship with CLD, as type 2 DM itself can cause liver disease. Second, CLD can lead to IGT and DM. Insulin resistance at the hepatic level, decreased clearance of insulin by the liver, and portosystemic shunting are the proposed mechanisms. Objectives: The aim of this study is to assess the insulin resistance and body composition in male patients with cryptogenic CLD and compare them with patients having hepatitis B-related CLD on antiviral therapy and age-matched controls. Methods: This was a cross-sectional study, conducted over a period of 18 months. Thirty male patients were recruited in each of cryptogenic CLD group, hepatitis B-related CLD group, and age-matched controls. Insulin resistance was assessed using homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI), and McAuley index. Relevant biochemical investigations for the calculation of these indices, i.e. fasting blood glucose, fasting insulin, and fasting triglyceride levels were checked. Body composition analysis in the form of total body fat, fat mass/h2, lean mass/h2, appendicular skeletal mass/h2, and visceral adiposity indices were assessed with Hologic DXA QDR 4500 Discovery A machine. Results: Mean age in cryptogenic CLD, hepatitis B CLD and healthy controls group was 39.33 ± 9.18 years, 39.77 ± 8.33 years and 39.33 ± 3.47 years and mean BMI was 23.07 ± 3.77, 24.81 ± 3.94, and 23.93 ± 1.48 kg/m2, respectively. Patients with hepatitis B-related CLD were found to have significantly higher levels of fasting insulin (9.25 ± 5.29 vs. 6.09 ± 3.94 IU/ml in healthy controls P = 0.02), HOMA IR (2.15 ± 1.37 vs. 1.48 ± 1.03 in healthy controls, P = 0.03) and lower levels of QUICKI (0.34 ± 0.04 vs. 0.38 ± 0.04 in healthy controls P = 0.009) and McAuley index (P = 0.01) than cryptogenic CLD and healthy controls. Patients with cryptogenic CLD had lower appendicular lean mass/h2 as well as lower fat mass/h2 compared to healthy controls. Conclusions: Patients with hepatitis B-related CLD had higher insulin resistance compared to cryptogenic cirrhosis as well as healthy controls. Cryptogenic cirrhosis patients had lower lean muscle and fat mass compared to healthy controls.

Keywords: Body composition, chronic liver disease, insulin resistance

 An institutional multidisciplinary inpatient consensus glucose management guideline – How and why diabetes patients and the institution could benefit from standardization



Roma Gianchandani, Jennifer Iyengar

Department of Internal Medicine, Division of Endocrinology and Metabolism, Michigan Medicine University of Michigan, Ann Arbor, MI, USA. E-mail: romag@umich.edu

Introduction: Patients with diabetes are seen by every specialty of medical care and are a vulnerable population, especially in inpatient areas. There are unequivocal data that hyperglycemia in the hospital setting increases morbidity, mortality, length of stay, and readmission rates. Therefore, a standardized approach to diabetes management can streamline hospital diabetes care, improve patient and hospital outcomes, and reduce costs and complication burden. Aims and Objectives: The University of Michigan Hospital sets out to build a consensus guideline with endocrinologists, hospital-based internists, anesthesiologists, surgeons, obstetrics and gynecology, pharmacists, nursing, house officers, and nutritionists. The aim was to establish a consensus inpatient guideline to standardize diabetes management for a 1200-bed teaching hospital and improve diabetes knowledge and outcomes. Materials and Methods: Enthusiastically supported by the University of Michigan's Office of Clinical Affairs, endocrinology and internal medicine led this process. The chair of each representative specialty selected representatives to the guideline committee. We had a multipronged approach based on moderate blood glucose targets, prehospitalization diabetes treatment and glucose control. Separate decision pathways were outlined for patients who required oral agents, noninsulin injectable, or insulin alone or those who used combination therapy. Pathways for type 1 diabetes, pumps, sensors, and newly diagnosed patients were also outlined. A separate focus of the guideline tackled consensus for diabetes management in specialty areas including preanesthesia, intraoperative procedures, postsurgery, obstetrics, and transition from hospital to home. Finally, management of challenging scenarios of severe insulin sensitivity as in dialysis patients and insulin resistance with high-dose steroids, tube feeds, and parenteral nutrition was also developed. Discussion and Conclusion: A multidisciplinary group created an inpatient diabetes consensus guideline which was evaluated, revised, and endorsed by each specialty. Details of the consensus guideline algorithms, its education, dissemination, and acceptance will be shared and be open to discussion during the presentation.

Keywords: Algorithms, diabetes, hospital, multidisciplinary

 An unusual case of severe hypoglycemia in a nondiabetic: Insulin autoimmune Syndrome



Harsha Pamnani, Asim Siddiqui, Subhash Kumar Wangnoo

Apollo Centre for Obesity, Diabetes and Endocrinology, Indraprastha Apollo Hospital, New Delhi, India.

E-mail: pamnaniharsha0@gmail.com

Introduction: Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare cause of hyperinsulinemic hypoglycemia characterized by autoantibodies to endogenous insulin without previous exposure to exogenous insulin and elevated insulin autoantibody titers. We report a case of IAS which did not respond to dietary measures. Case Report: An 83-year-old previously healthy woman was referred due to palpitations and sweating with disorientation, tremors, anxiety, and recurrent fainting attacks which were relieved on ingestion of food. Three days before admission, the patient had these symptoms, and sugar at home was 50 mg/dl, which was reverted by oral glucose. No history was suggestive of prior insulin or any antidiabetic medication use. At 3 am, when she had symptoms of hypoglycemia, glucometer blood sugar was 55 mg/dl, and samples were sent. Laboratories revealed blood sugar 40 mg/dl, serum insulin 16376 mIU/ml (2.6–24.9), C peptide 20.83 ng/ml (1.1–4.4), and ketonuria was absent. Antithyroid peroxidase and rheumatoid factor were negative. ANA (IF) and serum protein electrophoresis were normal. Ga-68 (DOTANOC) PET CT scan was also normal. Serum insulin antibody was 11.5 nmol/L (normal 0.00–0.02) by chemiluminescence immunoassay technique, Mayo Clinic Laboratories, Rochester, MN, USA. Even after following dietary measures, she had symptoms of hypoglycemia. She was started on 60-mg prednisolone daily; even then, she had episodes of hypoglycemia at home for which acarbose was added on follow-up. Gradually, acarbose was withdrawn. When she had no further hypoglycemia then after 1 month, steroid withdrawal was started. At present, she is on 5 mg of prednisolone and had no further hypoglycemic episodes and she is under follow-up. Conclusions: IAS is an uncommon condition that should be considered in the differential diagnosis of hypoglycemia in nondiabetic patients. It is important to obtain a detailed history, personal and family history of autoimmune or hematological disorders, use of drugs and health supplements, viral or bacterial infections, mode of hypoglycemia onset, and its response to sugar. It is a mostly benign condition and self-resolving in many patients.

Keywords: Anti-insulin antibody, hypoglycemia, insulin autoimmune syndrome, nondiabetics

 Low level of agreement in the evaluation of continuous glucose monitoring profiles



Jothydev Kesavadev, Elise Hachmann-Nielsen1, Kajsa Kvist2,

Richard M. Bergenstal3

Jothydev's Diabetes and Research Centre, Thiruvananthapuram, Kerala, India,1Novo Nordisk A/S, Copenhagen,2Novo Nordisk A/S, Søborg, Denmark,3International Diabetes Center, Minnesota, USA.

E-mail: jothydev@gmail.com

Introduction: Nearly 20 years after the introduction of continuous glucose monitoring (CGM), it is clear that CGM reports can effectively guide clinical decision-making, but the large amount of information contained in the CGM profile may also complicate the evaluation of the profiles. Aims and Objective: We hypothesized that there would be a relatively low level of agreement in the evaluations of CGM profiles performed by a diverse group of health-care professionals and patients, with higher level of agreement between diabetes experts. Methods: We investigated the interobserver variation in the two groups when asked to subjectively prioritize nine Ambulatory Glucose Profiles (AGPs) from “best” to “worst” through an Internet-based portal (www.glucoseprofile.com). Results: A total of 88 responses were collected. The groups were defined as nonexperts (n = 73) and self-evaluated experts (>10 years of experience and >1 CGM evaluation per week) (n = 15). The interobserver variation between the groups was calculated using interclass correlation coefficients (ICCs) showing moderate agreement among the nonexpert group (ICC = 0.60) and a good degree of agreement among the diabetes experts (ICC = 0.75) [Figure 1]. Discussion and Conclusion: Despite standardized CGM metrics and reports, there is still a relatively low level of agreement in the interpretation and ranking of CGM profiles even among diabetes experts. This may allow for undesirable variation in diabetes management. More tools are needed to optimize the use of CGM for clinical decision-making.{Figure 2}

Keywords: Continuous glucose monitoring, diabetes, experts, interobserver variation

 Outcomes of Type 2 diabetes clustering replicated in the DEVOTE trial



Samit Ghosal, Anna Rachel Kahkoska1, Elise Hachmann-Nielsen2,

Klara R. Klein3, Kristine G. Kongsbak4, Kajsa Kvist4, John B. Buse3

Nightingale Hospital, Kolkata, West Bengal, India,1University of North Carolina at Chapel Hill, Chapel Hill, NC, USA,2Novo Nordisk A/S, Copenhagen, Denmark,3University of North Carolina School of Medicine, Chapel Hill, NC, USA,4Novo Nordisk A/S, Søborg, Denmark.

E-mail: ramdasghosal@gmail.com

Introduction: Type 2 diabetes (T2D) is a heterogeneous disease. Aims and Objective: Individuals in the Swedish All New Diabetics in Scania (ANDIS) cohort with newly diagnosed T2D were grouped by six demographic and clinical variables to show four distinct T2D subtypes with differential risk for nephropathy and retinopathy. Methods: We tested the predictive validity of this clustering system for patients with advanced T2D in DEVOTE (a large, global, randomized, double-blind, cardiovascular outcome trial; median observation time: 1.99 years) for major adverse cardiovascular event (MACE)-free survival, severe hypoglycemia (SH)-free survival, and overall survival rates. Results: Individuals (n = 7637, mean age = 65 years, mean T2D duration = 16.4 years, mean glycated hemoglobin [A1C] = 8.43%) were assigned to a cluster for which they had the smallest Euclidean distance to the cluster center based on the following available baseline variables: A1C, body mass index, age, and age at diagnosis. Insulin resistance and sensitivity measures were not available. The four DEVOTE clusters showed baseline characteristics consistent with the original ANDIS clusters, with significant differences in MACE incidence and SH incidence [Table 1]. The results were confirmed using data from the LEADER trial (data not shown). Discussion and Conclusion: The study suggests that clusters derived from early T2D can be replicated in long-standing T2D. Future work should characterize differences in treatment response across clusters to improve outcomes across the heterogeneous T2D population.{Table 1}

Keywords: Adverse events, cardiovascular, clustering, prediction, type 2 diabetes

 Prescription feedback on the usage of empagliflozin and linagliptin combination in real-world practice



Subhash Kumar Wangnoo, S. Sridhar1, Soumik Goswami2, Prasun Deb3, Ksh Achouba Singh4, Ajay Gupta5, Maneesha Khalse6

Department of Endocrinology, Indraprastha Apollo Hospitals, New Delhi,1Department of Endocrinology, Diabetology and Metabolism, MIOT Hospitals, Chennai, Tamil Nadu,2Department of Endocrinology, Nilratan Sircar Medical College and Hospital, Kolkata, West Bengal,3Department of Endocrinology, Krishna Institute of Medical Sciences, Hyderabad, Telangana,4Department of Endocrinology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur,5Department of Endocrinology, CHL Group of Hospitals, Indore, Madhya Pradesh,6Medical Advisor, Lupin Limited, Mumbai, Maharashtra, India. E-mail: maneeshakhalse@lupin.com

Introduction: Empagliflozin and linagliptin combination (Empa/Lina) has shown good efficacy and tolerability in the treatment of type 2 diabetes mellitus (T2DM). Clinical data on its usage are limited in Indian patients. Aims and Objective: The present survey was intended to analyze feedback from the prescribers of Empa/Lina on utilization pattern in Indian clinical settings. Methods: A survey questionnaire on the usage of Empa/Lina was prepared, was validated in a small group of endocrinologists, and was then administered to physicians and endocrinologists across India. Results: A total of 1187 clinicians from all over India participated in the survey; 67% were consulting physicians, 14% were endocrinologists, 8% were cardiologists, and 11% were diabetologists. Forty-six percent perceived “better glycemic control” as the most appropriate clinical attribute for Empa/Lina combination followed by “end-organ protection” in addition to extraglycemic benefits such as reduction in body weight. Around 43.6% of the participants opined that they consider the addition of Empa/Lina for patients with HbA1c >8.5%, whereas endocrinologists suggested that high cardiovascular (CV) risk or established cardiovascular disease (CVD) and overweight/obese patients with T2DM are more appropriate for initiating this combination. Responding to the question of Empa/Lina as a suitable add-on, clinicians seem to prefer it as an add-on therapy to patients uncontrolled on metformin (45%) and metformin plus sulfonylureas (32%). Furthermore, many (35%) agreed that this combination demonstrates HbA1c reduction of 1.0%–1.5% when added to metformin. Sixty-four percent of the clinicians observed the associated genital mycotic infection as a common problem in 5%–10% in patients. However, this rate may even exceed 10% in their patients according to other participants (28%) where cautious approach needs to be exercised. Conclusion: The present survey shows that Empa/Lina is considered an efficacious and well-tolerated SGLT2i and DPP-4i combination agent; it is commonly prescribed due to its glycemic and cardiovascular benefits in T2DM patients in India.

Keywords: Empa/Lina, India, prescriber feedback, survey

 Estimated glomerular filtration rate loss with glucagon-like peptide-1 analog treatment: Data from sustain 6 and leader



Dharmalingam Mala, Perkovic Vlado1, Bain Stephen2, Bakris George3, Buse John4, Gondolf Theis5, Idorn Thomas5, Lausvig Nanna5, Mahaffey Kenneth6, Marso Steven7, Nauck Michael8, Pratley Richard9, Rossing Peter10, Zinman Bernard11, Mann Johannes12

Department of Endocrinology, Ramaiah Medical College, Bengaluru, Karnataka, India,1The George Institute, UNSW Sydney, Kensington, Australia,2Swansea University Medical School, Swansea, Wales, UK,3University of Chicago Medicine, Chicago, Illinois,4University of North Carolina School of Medicine, North Carolina, USA,5Novo Nordisk A/S, Gladsaxe, Denmark,6Department of Medicine Stanford Center for Clinical Research, Stanford School of Medicine, Stanford,7Research Medical Center, Kansas City, Missouri, USA,8Diabetes Center Bochum-Hattingen, St Josef Hospital (Ruhr-Universität Bochum), Bochum, Germany,9AdventHealth Translational Research Institute for Metabolism and Diabetes, USA,10Steno Diabetes Center Copenhagen, University of Copenhagen, Copenhagen, Denmark,12Friedrich Alexander University of Erlangen, Erlangen, Germany,11Lunenfeld–Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Canada. E-mail: drmaladharmalingam@gmail.com

Introduction: Previous SUSTAIN 6 and LEADER cardiovascular (CV) outcomes trials data indicate the glucagon-like peptide-1 analogs semaglutide and liraglutide may have beneficial effects on kidney function. Aims and Objectives: This post-hoc analysis investigated the semaglutide and liraglutide effects on change in estimated glomerular filtration rate (eGFR) evaluated as total eGFR slope. Materials and Methods: SUSTAIN 6 and LEADER assessed CV, kidney and safety outcomes with semaglutide and liraglutide versus placebo, in 3297 and 9340 patients with type 2 diabetes and at high CV risk, respectively. Median treatment duration was 2.1 and 3.8 years. In the current analysis, eGFR change over time was evaluated by the overall population and baseline eGFR subgroup (<60 vs. ≥60 mL/min/1.73 m2) for semaglutide (1.0 mg) and liraglutide versus placebo using a linear regression model with random slope and intercept; treatment differences between annual slopes were estimated (ETDs). Results: In the overall population, a slower rate of annual eGFR reduction was observed with semaglutide vs placebo (mean annual ETD of 0.87 mL/min/1.73 m2 favoring semaglutide); this effect appeared more pronounced for baseline eGFR <60 mL/min/1.73 m2, (annual ETD: 1.62 mL/min/1.73 m2 slower eGFR reduction, [Table 1]). In LEADER, the annual eGFR reduction was slower for liraglutide versus placebo for the overall population; the effect was more marked in patients with baseline eGFR <60 mL/min/1.73 m2 (annual ETD: 0.67 mL/min/1.73 m2 slower eGFR reduction [Table 1]). Discussion and Conclusion: Annual loss of kidney function was slower in patients treated with semaglutide or liraglutide versus placebo. The benefit appears more pronounced in patients with preexisting chronic kidney disease.{Table 2}

Keywords: Cardiovascular disease, chronic kidney disease, diabetes (type II), estimated glomerular filtration rate

 Diabetes duration did not moderate the reduction in severe hypoglycemia seen with degludec versus glargine U100 in DEVOTE



Ambrish Mithal, Anastasia-Stefania Alexopoulos1, Kajsa Kvist2,

Elise Hachmann-Nielsen3, John B. Buse4

Medanta – The Medicity, Gurugram, Haryana, India,1Durham,2Novo Nordisk A/S, Søborg,3Novo Nordisk A/S, Copenhagen, Denmark,4University of North Carolina School of Medicine, Chapel Hill, NC, USA.

E-mail: ambrishmithal@hotmail.com

Introduction: Hypoglycemia is associated with significant morbidity in type 2 diabetes (T2D). The progression of T2D leads to declining counterregulatory responses and heightened hypoglycemia risk. Aims and Objective: In this secondary analysis of data from DEVOTE, a CVOT with 7637 patients with T2D at high risk of cardiovascular events, we investigated diabetes duration as a moderator of severe hypoglycemia (SH) with the use of insulin glargine U100 (IGlar U100) versus insulin degludec. Methods: Patients in DEVOTE were categorized by diabetes duration in years: <10, 10–15, 15–20, and ≥20 years. The prevalence of SH was examined by treatment arm [Table 1] using a negative binomial model with log observation time as an offset term and diabetes duration categories as moderators. Results: Both proportion of patients with SH events and rate of SH increased with progression of disease in both arms. Degludec preserved its relative benefit over IGlar U100 for SH across diabetes duration groups, even in less progressed disease groups, i.e., an observed 52% relative risk reduction for degludec vs. IGlar U100 for patients within 10 years of disease onset (95% confidence interval: 0.29, 0.81). There was no significant difference in treatment ratios across categories (P value for interaction = 0.50). Similar findings were confirmed in the SWITCH 2 trial (data not shown). Discussion and Conclusion: Thus, diabetes duration did not moderate the relative reduction in rate of SH for degludec vs. IGlar U100 in DEVOTE.{Table 3}

Keywords: Severe hypoglycemia, glargine, degludec, reduction rate

 Effectiveness of empagliflozin and linagliptin combination in type 2 diabetes mellitus patients uncontrolled on triple oral drug therapy



Soumya Sengupta, Maneesha Khalse1, Amit Bhargava1

Dr Soumya Sengupta Diabetic Clinic, Singhbhum, Jharkhand,1Medical Affairs Division, Lupin Limited, Mumbai, Maharashtra, India. E-mail: maneeshakhalse@gmail.com

Introduction: Empagliflozin and linagliptin combination (Empa/Lina) has been introduced recently in Indian market, and data available are limited in Indian patients. Aims and Objective: The aim of this study was to evaluate the effectiveness of empagliflozin and linagliptin combination (Empa/Lina) as an add-on therapy in patients with type 2 diabetes mellitus (T2DM) with inadequate glycemic control with three oral antidiabetic drugs. Materials and Methods: Retrospective data with T2DM patients receiving Empa/Lina as an add-on therapy to the triple-drug therapy (metformin, sulfonylurea, and thiazolidinedione or dipeptidyl peptidase-4 inhibitor or alpha-glucosidase inhibitor) for at least 3 months were collected and analyzed. The effectiveness of Empa/Lina was assessed by analyzing the mean changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and glycosylated hemoglobin (HbA1c) after 3 months of duration. Results: Data of eligible 23 patients were included in the analysis. Empa/Lina 10/5 mg once daily was initiated in patients who were uncontrolled on triple-drug therapy. The mean age of the patients was 56.7 years, with a mean duration of diabetes 7.6 years and mean body weight 70.8 kg. Almost 75% of patients had comorbid conditions, hypertension (54%), and dyslipidemia (39%) being the most common. Metformin, glimepiride, and pioglitazone (82.7%) combination was the most preferred triple combination with a mean dose of 1.7 mg, 3.5 mg, and 13.8 mg, respectively. Statistically significant reduction was seen in HbA1c, FPG, and PPG at the end of 3 months by 1.34 ± 0.67%, 48.88 ± 22.7 mg/dl, and 64.36 ± 34.2 mg/dl from the baseline of 8.98 ± 1.8%, 170.20 ± 21.32 mg/dl, and 243.56 ± 45.03 mg/dl, respectively. At the end of 3 months, HbA1c target of <7% was achieved by 42% of patients receiving Empa/Lina. No adverse safety-related event was reported during 3-month duration. Discussion and Conclusion: Empa/Lina was found to be effective in the management of T2DM uncontrolled on triple oral therapy and was well tolerated.

Keywords: Empa/Lina, India, retrospective

 Switching to insulin degludec from other basal insulins reduces rates of hypoglycemia across patient subgroups in routine clinical care: The ReFLeCT study



Rakesh Sahay1,2, Harold W. de Valk3, Michael Feher4, Troels Krarup Hansen5, Johan Jendle6, Ángel Merchante7, Mette Marie Koefoed8, Ehsan Parvaresh Rizi8, Esther Zimmermann8, Gian Paolo Fadini91

Osmania Medical College,2Sahay's Endocrine and Diabetes Centre and Prime Hospital, Hyderabad, Telangana, India,3University Medical Center Utrecht, Utrecht, The Netherlands, 4Beta Cell Diabetes Centre and Lipid Clinic, Chelsea and Westminster Hospital, London, UK,5Steno Diabetes Center Aarhus, Aarhus, Denmark,6School of Medical Sciences, Örebro University, Långhuset, Örebro, Sweden,7Hospital General, Castellón de la Plana, Castellón, Spain,8Novo Nordisk A/S, Søborg, Denmark,9University of Padova, Padua, Veneto, Italy. E-mail: sahayrk@gmail.com

Introduction: ReFLeCT, a multicenter, prospective, observational study, evaluated the safety and effectiveness of switching from other basal insulins to insulin degludec (degludec) in patients with type 1 (T1D) or type 2 diabetes (T2D) in routine clinical practice. Aims and Objective: In prespecified subgroup analyses of the primary endpoint, we assessed if the overall result was robust in different subgroups. Methods: ReFLeCT comprised a 4-week baseline period (preswitch basal insulin) and 12-month follow-up period (degludec). The primary endpoint of overall hypoglycemia reported in patient diaries was reduced during the 12-month follow-up period versus baseline, without compromising glycemic control. We performed a prespecified subgroup analyses of the primary endpoint and assessed the robustness of the overall result in different subgroups, characterized according to baseline A1C (<7.5%, ≥7.5%–<8.5%, ≥8.5%–<9.5%, and ≥ 9.5%), diabetes duration (quartiles), and physician's reason for initiating degludec (hypoglycemia [yes/no]). Results: The estimated rate ratios of hypoglycemia were similar within subgroups (no significant interactions) and demonstrated overall lower rates (the majority significantly lower) during the 12-month follow-up periods versus baseline in patients with T1D or T2D [Figure 1]. Discussion and Conclusion: Irrespective of baseline characteristics or physician's reason for initiating degludec, switching to degludec from other basal insulins reduced the rates of overall hypoglycemia in patients with T1D or T2D in routine clinical practice.{Figure 3}

Keywords: Basal insulin, degludec, hypoglycemia, subgroup, switching

 Efficacy and safety of fast-acting insulin aspart compared with insulin aspart, both in combination with insulin degludec, in children and adolescents with type 1 diabetes: The onset 7 trial



Sunil M. Jain, Bruce Bode1, Violeta Iotova2, Margarita Kovarenko3, Lori Laffel4, Paturi V. Rao5, Henning Andersen6, Srikanth Deenadayalan6, Steffen Falgreen Larsen6, Thomas Danne7

Total Diabetes and Thyroid Center, BCM Health Island, Behind Bombay Hospital, Indore, Madhya Pradesh, India,1Atlanta Diabetes Associates, Atlanta, GA, USA,2University Hospital St. Marina, Varna, Bulgaria,3Department of Pediatrics, Novosibirsk State Medical University, Ministry of Healthcare of the Russian Federation, Novosibirsk, Russia,4Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA,5Diabetes Research Society, Hyderabad, Telangana, India,6Novo Nordisk A/S, Søborg, Denmark,7Children's Hospital Auf der Bult, Hanover, Germany.

E-mail: sunilmjain@gmail.com

Introduction: Efficacy and safety of fast-acting insulin aspart (FA) versus insulin aspart (IAsp) in a pediatric sample with type 1 diabetes (T1D) are unknown. Aims and Objective: The aim of this study was to confirm the efficacy and safety of FA versus IAsp in a pediatric sample with T1D. Materials and Methods: A treat-to-target, 26-week, multicenter trial randomized participants (1 to <18 years old) following a 12-week run-in period to double-blind mealtime FA (n = 260) or IAsp (n = 258), or open-label postmeal FA (n = 259), each with daily insulin degludec treatment (NCT02670915). All available information regardless of treatment discontinuation was used for evaluation. Results: At week 26, noninferiority (0.4% margin) for the primary endpoint, change from baseline in HbA1c, was confirmed for mealtime and postmeal FA versus IAsp, with a statistically significant difference in favor of mealtime FA (estimated treatment difference [95% confidence interval]: –0.17% [–0.30, –0.03] and –1.82 mmol/mol [–3.28, –0.36]). Change from baseline in 1-h postprandial glucose significantly favored mealtime FA versus IAsp at breakfast, lunch, and mean overall meals [Figure 1]. No significant differences in overall rate of treatment-emergent severe or blood glucose (BG)-confirmed hypoglycemic episodes (BG <3.1 mmol/L [56 mg/dL]) were observed. Mean total daily insulin dose on treatment was 0.92 U/kg (mealtime FA), 0.92 U/kg (postmeal FA), and 0.88 U/kg (IAsp). Discussion and Conclusion: Mealtime and postmeal FA with insulin degludec provided effective glycemic control (superior for mealtime FA) versus IAsp, with no additional safety risks in children and adolescents with T1D. Funding: Novo Nordisk A/S.{Figure 4}

Keywords: Diabetes (type I), fast-acting insulin aspart, pediatric

 Efficacy and safety of fast-acting insulin aspart compared with insulin aspart, both with insulin degludec with or without metformin, in adults with type 2 diabetes



Anil Bhansali, W. Lane1, K. Bozkurt2, E. Favaro2, H. C. Jang3, M. I. S. Kj'rsgaard4, A. Oviedo5, L. Rose6, P. Senior7, G. Sesti8, A. Soto Gonzalez9, E. Franek10

Department of Endocrinology, PGIMER, Chandigarh, India,1Mountain Diabetes and Endocrine Centre, Asheville, NC, USA,2Novo Nordisk A/S, Søborg, Denmark,3Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, North Korea,4Novo Nordisk A/S, Aalborg, Denmark,5Santojanni Hospital and Cenudiab, Ciudad Autonoma De Buenos Aires, Buenos Aires, Argentina,6Institute of Diabetes Research, Münster, Germany,7University of Alberta, Edmonton, AL, Canada,8University of Magna Graecia of Catanzaro, Catanzaro, Italy,9Hospital de A Coruña, La Coruña, Spain,10Mossakowski Clinical Research Center, Polish Academy of Sciences, Warsaw, Poland.

E-mail: anilbhansaliendocrine@gmail.com

Introduction: Information on the safety and efficacy of faster aspart compared with insulin aspart (IAsp) is limited. Aims and Objectives: We intend to evaluate the efficacy and safety of faster aspart compared with IAsp, both with insulin degludec with or without metformin, in adults with advanced type 2 diabetes (T2D) not optimally controlled with a basal–bolus regimen. Materials and Methods: This was a 16-week, multicenter, double-blind, treat-to-target trial. Following a 12-week run-in period to optimize basal insulin, participants were randomized (1:1) to mealtime faster aspart (n = 546) or IAsp (n = 545), both with insulin degludec. Results: Noninferiority (0.4% margin) regarding change from baseline in HbA1c 16 weeks after randomization (primary endpoint) was confirmed for faster aspart versus IAsp (estimated treatment difference [ETD] [95% confidence interval (CI)]: –0.04% [–0.11, 0.03] and –0.39 mmol/mol [–1.15, 0.37]). Faster aspart was superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD [95% CI]: –0.40 mmol/L [–0.66, –0.14] and –7.23 mg/dL [–11.92, –2.55]). Change from baseline in 1-h PPG increment based on self-measured blood glucose (BG) profiles was statistically in favor of faster aspart after lunch, the main evening meal, and over all meals [Figure 1]. Change from baseline in 1,5-anhydroglucitol also favored faster aspart over IAsp (ETD [95% CI]: 0.50 μg/mL [0.11, 0.89]). The overall rate of treatment-emergent severe or BG-confirmed (plasma glucose equivalent <3.1 mmol/L [56 mg/dL]) hypoglycemia was statistically significantly lower for faster aspart versus IAsp (estimated treatment ratio [ETR] [95% CI]: 0.81 [0.68, 0.97]), as was the rate within 4 h after a meal (ETR [95% CI]: 0.78 [0.63, 0.98]). Discussion and Conclusion: In combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia versus IAsp in adults with advanced T2D.{Figure 5}

Keywords: Basal–bolus regimen, Fast acting insulin aspart, type 2 diabetes

 The efficacy and safety of liraglutide versus placebo in children and adolescents with type 2 diabetes: The ELLIPSE randomized trial results



Rajesh Khadgawat, W. V. Tamborlane1, T. Barrett2, U. Fainberg3,

H. Frimer-Larsen3, M. Hafez4, P. M. Hale5, M. Y. Jalaludin6, M. Kovarenko7,

I. Libman8, P. V. Rao9, N. Shehadeh10, S. Turan11, D. Weghuber12,

M. Barrientos-Pérez13

Department of Endocrinology Metabolism and Diabetes, AIIMS, New Delhi, India,1Department of Pediatric Endocrinology, Yale University, New Haven, Connecticut, USA,2Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK,3Novo Nordisk A/S, Søborg, Denmark,4Department of Paediatrics, Cairo University, Cairo, Egypt,5Novo Nordisk Inc., Plainsboro, New Jersey, USA,6Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia,7Novosibirsk Medical University, Novosibirsk, Russia,8Division of Pediatric Endocrinology and Diabetes, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA,9Diabetes Research Society, Hyderabad, Telangana, India,10Endocrinology, Diabetes and Metabolism Institute, Rambam Health Care Campus, Haifa, Israel,11Department of Paediatrics, Subdivision of Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey,12Department of Paediatrics, Paracelsus Medical University, Salzburg, Austria,13Angeles Hospital of Puebla, Puebla City, Mexico.

E-mail: rajeshkhadgawat@hotmail.com

Introduction: Despite the burden of type 2 diabetes (T2D) in children and adolescents, only metformin and insulin are approved for use in this population. Aims and Objective: The ELLIPSE trial assessed efficacy and safety of the glucagon-like peptide-1 analog liraglutide versus placebo as an add-on to metformin ± basal insulin, as a new treatment option for youth with T2D. Materials and Methods: In this phase 3 trial, children aged 10 to <17 years were randomized 1:1 to liraglutide up to 1.8 mg/day (or maximum tolerated dose) or placebo for a 26-week, double-blind period, followed by a 26-week open-label extension (total: 52 weeks). Children with body mass index >85th percentile (age and gender matched) and hemoglobin A1C (HbA1c) (7.0%–11% [if diet and exercise] or 6.5%–11% [if on metformin ± basal insulin]) were included. Primary endpoint was change from baseline in HbA1c at 26 weeks. Changes in fasting plasma glucose (FPG) and safety were assessed. Results: Of 135 children randomized, 134 received treatment (liraglutide, 66 and placebo, 68). The mean age was 14.6 years (standard deviation: 1.7 years; range, 10.0–16.9 years; 30% aged 10–14 years) and 62% were female. At 26 weeks, HbA1c decreased from 7.87% to 7.13% with liraglutide and increased from 7.69% to 8.19% with placebo (estimated treatment difference [ETD]: −1.06%; 95% confidence interval [CI]: −1.65 to −0.46; P < 0.001; [Figure 1]). At 52 weeks, HbA1c decreased with liraglutide whereas increased with placebo (ETD: −1.30%; 95% CI: −1.89 to −0.70, P < 0.001; [Figure 1]). Liraglutide decreased FPG at 26 and 52 weeks (−19.4 and −18.5 mg/dL, respectively), whereas placebo increased (+14.4 and + 14.1 mg/dL, respectively). Similar proportion of children reported an adverse event (AE; 84.8% vs. 80.9%). Gastrointestinal AEs were more frequent with liraglutide (33.3% vs. 13.2%). Discussion and Conclusion: Liraglutide as an add-on to metformin ± basal insulin offers a new, efficacious, and durable treatment option, with an acceptable safety profile, for children and adolescents with T2D in need of improved glycemic control.{Figure 6}

Keywords: Children, diabetes, liraglutide

 The glucagon-like peptide-1 receptor agonists liraglutide and semaglutide improve cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of LEADER and SUSTAIN 6



Jayant Panda, Lawrence A. Leiter1, Stephen Bain2, Deepak L. Bhatt3,

John Buse4, C. David Mazer1, Richard Pratley5, Søren Lindberg6,

Søren Rasmussen6, Hrvoje Vrazic6, Subodh Verma1

SCB Medical College, Cuttack, Odisha, India,1St. Michael's Hospital and University of Toronto, Toronto, ON, Canada,2Institute of Life Science, Swansea University, Swansea, UK,3Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA,4University of North Carolina School of Medicine, Chapel Hill, NC,5Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA,6Novo Nordisk A/S, Søborg, Denmark.

E-mail: drjayantpanda@gmail.com

Aims and Objective: This post hoc analysis evaluated major adverse cardiovascular (CV) events (MACEs) and renal events in patients from LEADER and SUSTAIN 6 (CV outcome trials) with type 2 diabetes (T2D) and high CV risk who received liraglutide or semaglutide (vs. placebo) according to blood pressure (BP) categories: normal (<120/80 mmHg), elevated (systolic 120–129 mmHg and diastolic <80 mmHg), Stage 1 hypertension (systolic 130–139 mmHg or diastolic 80–89 mmHg), and Stage 2 hypertension (systolic ≥140 mmHg or diastolic ≥90 mmHg). Materials and Methods: LEADER and SUSTAIN 6 were global randomized CV outcome trials of liraglutide and semaglutide vs. placebo, in 9340 and 3297 patients, respectively, with T2D and high CV risk. Primary outcome was MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), with secondary outcomes including nephropathy. We evaluated the cardiorenal effect of liraglutide and semaglutide on the primary and secondary renal endpoints by baseline BP categories using Cox proportional hazards, with treatment and risk group as factors, adjusted for baseline characteristics related to cardiorenal risk. Results: In LEADER, 15%, 14%, 30%, and 41% of patients had normal BP, elevated BP, Stage 1 hypertension, and Stage 2 hypertension, respectively; proportions for SUSTAIN 6 were 13%, 13%, 31%, and 43%, respectively. Within each BP category, baseline demographics were generally well balanced across trial groups. The effects of liraglutide and semaglutide on MACE and secondary nephropathy endpoints across BP categories are shown in [Figure 1]. Discussion and Conclusion: Liraglutide and semaglutide demonstrated consistent improvements in CV and renal outcomes across most baseline BP categories.{Figure 7}

Keywords: Blood pressure, Cardiorenal, Cardiovascular disease, Cardiovascular disease prevention, Diabetes (Type II)

 The glucagon-like peptide-1 receptor agonists liraglutide and semaglutide improve cardiovascular and renal outcomes across most body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials



Arthur J. Asirvatham, Subodh Verma1, Stephen Bain2, Deepak L. Bhatt3, Lawrence A. Leiter1, C. David Mazer1, Darren K. McGuire4, Richard Pratley5, Bernard Zinman6, Søren Lindberg7, Søren Rasmussen7, Hrvoje Vrazic7,John Buse8

Arthur Asirvatham Hospital, Madurai, Tamil Nadu, India,1St. Michael's Hospital and University of Toronto, Toronto, ON, Canada,2Institute of Life Science, Swansea University, Swansea, UK,3Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA,4Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA,5Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA,6Lunenfeld–Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Canada,7Novo Nordisk A/S, Søborg, Denmark,8University of North Carolina School of Medicine, Chapel Hill, NC, USA. E-mail: drajasirvatham@yahoo.co.in

Introduction: Consistent cardiorenal benefits of liraglutide and semaglutide across body mass index (BMI) categories are unknown. Aims and Objective: We performed post hoc analyses on LEADER and SUSTAIN 6 data to evaluate cardiorenal efficacy by BMI groups in patients with type 2 diabetes (T2D) and high cardiovascular (CV) risk. Materials and Methods: LEADER and SUSTAIN 6 were randomized CV outcome trials of liraglutide and semaglutide vs. placebo in 9340 and 3297 patients, respectively, with T2D and high CV risk. The primary outcome was a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke (major adverse CV events [MACEs]), with secondary outcomes including nephropathy measures (new or persistent macroalbuminuria, serum creatinine doubling, end-stage kidney disease, or death from kidney disease). These cardiorenal outcomes were stratified by baseline BMI groups. Hazard ratios (HRs) for treatment vs. placebo were calculated using a Cox proportional hazards model with treatment and eligibility risk group as factors, adjusted for baseline characteristics related to cardiorenal risk within BMI groups. Results: In LEADER, 9%, 29%, 32%, and 30% of patients had a baseline BMI of <25 kg/m2, ≥25–<30 kg/m2, ≥30–<35 kg/m2, and ≥ 35 kg/m2, respectively; for SUSTAIN 6, this was 8%, 28%, 33%, and 31%. Baseline characteristics were mostly balanced within BMI groups. Both liraglutide and semaglutide improved MACE and nephropathy outcomes across most BMI groups vs. placebo [Figure 1]. In addition, more weight loss was observed with liraglutide (<25 kg/m2: −0.85 kg; ≥25–<30 kg/m2: −1.93 kg; ≥30–<35 kg/m2: −2.06 kg; and ≥35 kg/m2: −3.25 kg; P < 0.001) and semaglutide (<25 kg/m2: −3.34 kg; ≥25–<30 kg/m2: −3.09 kg; ≥30–<35 kg/m2: −3.65 kg; and ≥35 kg/m2: −3.99 kg; P = 0.09) vs. placebo. Discussion and Conclusion: In LEADER and SUSTAIN 6, liraglutide and semaglutide improved CV and renal outcomes with no apparent systematic differences across BMI groups.{Figure 8}

Keywords: Body mass index and waist circumference, cardiorenal, cardiovascular disease, cardiovascular disease prevention, diabetes (type 2)

 Liraglutide as add-on to sodium-glucose cotransporter-2 inhibitors in patients with inadequately controlled type 2 diabetes (LIRA-ADD2SGLT2i): a 26-week, randomized, double-blind, placebo-controlled trial



Vaishali Deshmukh, Lawrence Blonde1, Lidia Belousova2, Udi Fainberg3, Pedro A. Garcia-Hernandez4, Sunil M. Jain5, Margit S. Kaltoft3,

Ofri Mosenzon6, Jalal Nafach7, Mads Sundby Palle3, Rosangela Réa8

Deshmukh Clinic and Research Center, Pune, Maharashtra, India,1Ochsner Medical Center, New Orleans, Louisiana, USA,2Almazov National Medical Research Centre, Saint-Petersburg, Russia,3Novo Nordisk A/S, Søborg, Denmark,4Endocrinology Service, University Hospital, Monterrey, Mexico,5Department of Endocrinology, TOTALL Diabetes Hormone Institute, Indore, Madhya Pradesh, India,6Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel,7Dubai Diabetes Center, Dubai Health Authority, Dubai, United Arab Emirates,8Endocrinology and Metabolism Service, Universidade Federal do Paraná, Curitiba, Brazil. E-mail: deshmukhclinic@rediffmail.com

Introduction: Data are limited for combined use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes (T2D). Aims and Objective: LIRA-ADD2SGLT2i trial compared the effect on glycemic control of liraglutide (GLP-1RA) versus placebo added-on to SGLT2i ± metformin in patients with T2D. Materials and Methods: This phase 3b trial randomized (2:1) patients with T2D on a stable dose of SGLT2i ± metformin and HbA1c 7.06%–9.5% to either liraglutide 1.8 mg/day or placebo. Exclusion criteria were a history of diabetic ketoacidosis (DKA) while on SGLT2i and/or estimated glomerular filtration rate <60 mL/min/1.73 m2. Primary endpoint was change (Δ) in HbA1c from baseline at 26 weeks. Furthermore, Δ body weight (Bwt), percentage of patients achieving HbA1c <7%, and safety profiles were assessed. Results: Of 303 randomized patients, 280 (92.4%) completed treatment. Mean baseline values were HbA1c 8.0%, Bwt was 91.9 kg, and diabetes duration was 9.9 years. At week 26, mean ΔHbA1c from baseline with liraglutide was –0.98% (n = 203) versus –0.30% with placebo (n = 100) (estimated treatment difference [ETD]: –0.68%, 95% confidence interval [CI]: –0.89, –0.48; P < 0.001). Mean ΔBwt was –2.81 kg versus –1.99 kg, respectively (ETD: –0.82 kg; 95% CI: –1.73, 0.09, P = 0.077). In liraglutide group, 51.8% of patients achieved HbA1c <7.0% versus 23.2% in placebo group (odds ratio: 5.1, 95% CI: 2.67, 9.87; P < 0.001). A higher percentage of patients in liraglutide reported ≥1 treatment-emergent adverse event (AE, 66.3% vs. 47.0%). Nausea was the most frequent AE (26.2% vs. 6.0%). Hypoglycemic episodes were similar (8.9% vs. 8.0%); none were severe. Percentage of patients reporting serious AEs was low (2.5% vs. 1.0%). No fatalities occurred. There were no reports of acute renal failure, DKA, diabetic foot ulcers, or amputations with liraglutide + SGLT2i. Discussion and Conclusion: In patients with T2D, liraglutide add-on to SGLT2i ± metformin provided superior glycemic control versus placebo and safety profile was consistent with the known safety profile of both drug classes. The LIRA-ADD2SGLT2i is registered with ClinicalTrials.gov NCT02964247.

Keywords: Glucagon-like peptide, sodium-glucose cotransporter-2 inhibitor, type 2 diabetes

 DUAL VIII: More patients met treatment targets with insulin degludec/liraglutide versus insulin glargine 100 U/mL by week 26 in a 104-week randomized trial mirroring clinical practice



Krishna Seshadri, G. Sesti1, L. Bardtrum2, S. Daðdelen3, N. Halladin2,

M. Haluzík4, P. Őrsy2, M. Rodríguez5, V. R. Aroda6

Chennai Diabetes and Endocrinology Clinic and Apollo Speciality Hospitals, Vanagaram, Chennai, India,1University Magna Graecia of Catanzaro, Catanzaro, Italy,2Novo Nordisk A/S, Søborg, Denmark,3School of Medicine, Hacettepe University, Ankara, Turkey,4Institute for Clinical and Experimental Medicine and Institute of Endocrinology, Prague, Czech Republic,5Area of Endocrinology, Metabolism and Nutrition, Faculty of Medical Sciences, National University of Cuyo, Mendoza, Argentina,6Brigham and Women's Hospital, Boston, MA, USA. E-mail: krishnagseshadri@gmail.com

Introduction: Information on use of insulin degludec/liraglutide (IDegLira) as a first injectable therapy for patients with T2D is limited. Aims and Objectives: To report efficacy and safety data at week 26 in type 2 diabetes (T2D) patients to assess whether the benefits of IDegLira over insulin glargine 100 U/mL (IGlar U100) as an initial injectable therapy are observed in a durability trial. Materials and Methods: Patients (N = 1012) were randomized 1:1 to open-label IDegLira or IGlar U100. Starting dose was 10 U for both; only IDegLira had a maximum dose (50 U). Patients were instructed to titrate twice weekly to a fasting glucose target of 4–5 mmol/L. Results: Baseline characteristics were similar and representative of patients eligible for basal insulin initiation (overall mean diabetes duration: 10 years, HbA1c: 8.5%, FPG: 10 mmol/L). After 26 weeks, least square (LS) mean HbA1c reductions were significantly greater with IDegLira versus IGlar U100 (−2.0% vs. −1.5%, estimated treatment difference [ETD], 95% confidence interval [CI]: −0.47% [−0.58, −0.36]), as were the odds of patients achieving HbA1c targets and the composite endpoints of HbA1c targets without weight gain and/or hypoglycemia after 26 weeks [Figure 1]. Daily insulin dose was lower with IDegLira (35.4 U) versus IGlar U100 (48.4 U). LS mean change from baseline in body weight was 0.5 kg with IDegLira and 2.1 kg with IGlar U100 (ETD: −1.57 kg [−2.00; −1.13]). Hypoglycemia rates were 44% lower with IDegLira versus IGlar U100 (rate ratio: 0.56 [0.39, 0.82]). There were no unexpected safety findings. Discussion and Conclusion: After 26 weeks of treatment, more patients met HbA1c targets without weight gain and/or hypoglycemia with IDegLira versus IGlar U100 and with a lower insulin dose. These data support the use of IDegLira as a first injectable therapy for patients with T2D eligible for basal insulin initiation. Clinical Trial Registration Number: NCT02501161. Funding: Novo Nordisk A/S supported the study.{Figure 9}

Keywords: Diabetes (type II), hypoglycemia, injectable therapy, weight gain

 Diabetic peripheral neuropathy and foot care practices in Central Kerala



Anulekha Mary John, Anju K. Francis, Gloria Varghese

Department of Endocrinology and Metabolism, Believers Church Medical College Hospital, Thiruvalla, Kerala, India.

E-mail: anulekhageorge@gmail.com

Introduction: Foot complications in diabetic peripheral neuropathy are preventable. Awareness about neuropathy and regular foot care is essential for prevention. However, among well-educated population of Kerala, with high prevalence of diabetes, awareness studies about diabetic foot care are sparse. Aims and Objective: To assess the knowledge and compliance of foot care among those with diabetic peripheral neuropathy. Materials and Methods: This study was conducted among patients with type 2 diabetes mellitus in Kerala. A well-structured questionnaire was used to assess the knowledge and compliance regarding foot self-care practices. Michigan neuropathy screening instrument was used to identify those with diabetic peripheral neuropathy. Feet were examined using Semmes–Weinstein monofilament, muscle stretch reflex, and vibration sensation. Data were analyzed using Excel. Results: Among 375 patients interviewed, 197 (52.5%) were men and 178 (47.46%) women. Mean age ± standard deviation was 60.70 ± 12.99 years for men and 58.37 ± 9.77 for women. 112 (29.8%) patients had peripheral neuropathy. Only 53 (14.13%) patients were aware that they had neuropathy. Protective sensation was lost in (75) 20.43% of patients. Among patients with neuropathy, only very few 9 (0.08%) used appropriate footwear. Only 20 (17.85%) used footwear with back strap, and microcellular rubber was used by 15 (13.39%). Optimal toe box was seen in 73 (65.17%), and 19 (16.96%) had optimal shore value by durometry. 91.96% of patients needed modification of footwear. 89 (79.46%) patients with neuropathy were not aware of appropriate foot care practices and 45 (40.17%) had wrong practices. Discussion and Conclusion: Although one-third of our population had peripheral neuropathy, only <15% were aware of the same. Majority of patients with neuropathy did not use optimal footwear or follow regular foot care practices. It is important to spread awareness about diabetic peripheral neuropathy and foot care.

Keywords: Diabetic foot ulcer, foot care, microcellular rubber, peripheral neuropathy, vibration sense

 A case of insulin autoimmune syndrome



Pavan Kumar Reddy, Shafi Kuchay, Sunil Kumar Mishra, Ambrish Mithal

Department of Endocrinology, Medanta – The Medicity, Gurugram, Haryana, India.

E-mail: pavankumarreddy931@gmail.com

Introduction: Insulin autoimmune syndrome (Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. We describe a case of 57-year-old Indian female with type 2 diabetes, experiencing episodes of hypoglycemia, occurring mainly after meals. Case Report: A 57-year-old female who has had diabetes for 2 years was on metformin therapy till 2 months ago when she experienced recurrent episodes of hypoglycemia. During hypoglycemic episodes, she felt increased appetite, sweating, palpitations, and giddiness. Her documented glucose during the episode was 53 mg/dL, and symptoms alleviated after intake of glucose. She was evaluated in Medanta Hospital inpatient department and 72-h fasting test was performed. The critical sample analysis revealed high serum insulin and C-peptide levels, which confirmed diagnosis of endogenous hyperinsulinism. Contrast-enhanced computed tomography abdomen, endoscopic ultrasound, and Ga-DOTONAC did not reveal any lesion (s) favouring insulinoma. Insulin antibody testing was done to rule out Hirata's disease which were very high (>300 U/mL). The patient was put on steroid therapy (prednisolone) and alpha glucose inhibitors following which her frequency of hypoglycemic symptoms reduced drastically. She was maintained on prednisolone 5 mg per day and has been hypoglycemia free for the last 3 months. Her latest glycated hemoglobin was 7.2%. Conclusion: Autoimmune forms of hypoglycemia are rare, but should be taken into consideration in the setting of unsuppressed insulin/C-peptide levels, absence of lesion favouring insulinoma, and high antibody titers.

Keywords: Hypoglycemia, insulin autoantibodies, insulin autoimmune syndrome

References

Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P, et al. Autoimmune forms of hypoglycemia. Medicine (Baltimore) 2009;88:141-53.Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2009;94:709-28.

 Role of in vivo corneal confocal microscopy in early detection and prognostication of diabetic neuropathy



Satinath Mukhopadhyay, Subhankar Chowdhury, Shoeb Kaiser

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

E-mail: shoebkaiser786@gmail.com

Introduction: Diabetic neuropathy is a well-recognized microvascular complication of diabetes mellitus that results in significant morbidity in the form of pain, ulceration, infection, and lower limb amputation. Routine tests for neuropathy such as monofilament test, vibration perception threshold, and nerve conduction studies (NCSs) may be noninformative in the early stages of neuropathy when predominantly small unmyelinated C fibers are involved. There is pressing need for a rapid, noninvasive, objective, and quantitative diagnostic modality that assesses small unmyelinated C fibers. In vivo corneal confocal microscopy (CCM) is a new diagnostic modality for early demonstration of nerve fiber loss in diabetic neuropathy. Aims and Objective: To determine the ability of CCM in detecting early neuropathy in type 2 diabetes mellitus (T2DM) patients before abnormalities in routine tests for neuropathy and to evaluate the role of CCM in prognosticating the severity of diabetic neuropathy. Materials and Methods: Fifty adults with T2DM, recruited from the diabetic outpatient department of IPGME and R and SSKM Hospital, Kolkata, West Bengal, India, were subjected to routine tests for neuropathy (such as monofilament test and vibration perception threshold), warm perception threshold, NCSs, and bilateral laser scanning CCM. Fifty age-matched controls also underwent CCM. Results: CCM was abnormal in 15 (53%) out of 28 cases in which routine tests and NCS were normal. Among the 22 cases with clinically evident neuropathy and/or an abnormal NCS, CCM was abnormal in 18 cases. The degree of abnormality in the CCM parameters correlated with the severity of neuropathic deficits (P < 0.01). Discussion and Conclusion: CCM is a promising diagnostic modality for early diagnosis of subclinical diabetic neuropathy and also provides prognostic information in those with established neuropathy.

Keywords: Cornea, diagnosis, neuropathy

 Time to do more: An Indian perspective of addressing clinical inertia in the management of Type 2 diabetes mellitus in West India



Parag Rajnikant Shah, Uday Keshav Phadke1, Shankar Kumar2, Anup Vilas Thorat2

Gujarat Endocrine Centre, Ahmedabad, Gujarat,1Hormone and Diabetes Care, Galaxy Hospital, Pune,2Novartis Healthcare Private Limited, Mumbai, Maharashtra, India.

E-mail: uday@drudayphadke.com

Introduction: Despite the availability of a plethora of well-tolerated treatment options, optimal therapeutic targets for diabetes are often not met. Aims and Objectives: This study aimed to understand the attitudes and behaviors of physicians and patients toward the management of diabetes and to identify barriers beyond therapy. Materials and Methods: The basis of the survey in India was an extension to the global survey.[1] The survey in India was conducted in the form of a face-to-face interview among 641 patients and 638 physicians from mid-June 2018 to September 2018. West zone achieved a sample of 142 physicians and 131 type 2 diabetes patients, which is around 22% and 20% of the total survey of physician and patient sample, respectively. Mumbai, Palghar, Ahmedabad, Pune, and Bhopal were the cities which participated in this survey. The questionnaire was validated by leading endocrinologists from different parts of India and translated to local languages. The questionnaire was divided to cover the following three main aspects – diagnosis consultation, hypoglycemia awareness and reporting, and getting to glycemic goals. Results: Doctors spend on an average of ~16 minutes at the time of diagnosis consultation in the West Zone, which is slightly higher than that all over India. Patient understanding of topics discussed during consultation continues to be modest (only 40%–50%). Around 32% of the doctors feel that the incidence of hypoglycemia is underreported and attributes the common reason to be patients' lack of awareness on the seriousness of hypoglycemia. A higher proportion of the patients were prescribed medication immediately in the West zone as compared to that of all over India. Discussion and Conclusion: Due attention to diagnosis consultation, hypoglycemia reporting and challenges in management and getting HbA1c to goal will significantly enhance the understanding and alliance between physicians and patients and thereby improve diabetes care in India. There is a need to drive a joint ownership in the management of diabetes.

Keywords: Clinical intertia, diabetes, diabetes management, time to do more, West India

Reference

Strain WD, Cos X, Hirst M, Vencio S, Mohan V, Vokó Z, et al. Time to do more: Addressing clinical inertia in the management of type 2 diabetes mellitus. Diabetes Res Clin Pract 2014;105:302-12.

 Non-high-density lipoprotein cholesterol correlates with carotid intima-media thickness: A simple, cost-effective, outpatient-based marker for ischemic stroke in type 2 diabetes mellitus



O. Raghupathi, J. Siva Kalyani, B. Vivekanand, A. Mythili, K. A. V. Subrahmanyam, Jayanthi Ramesh

Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India.

E-mail: drjayanthyramesh@gmail.com

Introduction: Diabetes mellitus is a well-established risk factor for ischemic stroke and is associated with poor outcome. Studies revealed that non-high-density lipoprotein cholesterol (non-HDL-C) is independently associated with carotid atherosclerosis. Aim: To study and correlate non-HDL-C and carotid intima-media thickness (CIMT) in patients with ischemic stroke with type 2 diabetes mellitus (T2DM). Materials and Methods: This was a retrospective analysis which included 65 patients with T2DM with ischemic stroke confirmed by imaging done at King George Hospital, Visakhapatnam, during the period between August 2018 and July 2019. Demographic data, clinical history, and examination findings were noted. Non-HDL-C (in mg/dl) was calculated by subtracting HDL cholesterol from total cholesterol. The CIMT (in mm) was measured with B-MODE ultrasound system with linear transducer of 7.5 MHz. The mean value of both left and right CIMT was used for analysis. Results: Of the 65 patients included in the study, 60% (n = 39) were male and 40% (n = 26) were female. The mean age of the study population was 55.14 years. Hypertension was present in 69.2% (n = 45) of patients and 33.8% (n = 22) were smokers. The mean CIMT of all patients was 1.164 mm. No significant difference in the mean CIMT was seen between smokers (1.174 mm) and nonsmokers (1.160 mm) (P = 0.89). The mean CIMT was significantly higher in hypertensives (1.270 mm) compared to nonhypertensives (0.927 mm) (P = 0.001). Non-HDL-C showed strong correlation with CIMT, which was significant (r = 0.637, P = 0.00). Conclusion: Non-HDL-C has a strong and significant association with CIMT. Non-HDL-C can serve as a simple, cost-effective, outpatient-based marker and a modifiable risk factor in preventive strategies for ischemic stroke in T2DM patients.

Keywords: Carotid intima-media thickness, non-high-density lipoprotein cholesterol, type 2 diabetes

 Serum magnesium in type 2 diabetes mellitus and its association with the microvascular complications



Sajal Kamat, Dnyanesh Morkar1, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami

Department of Endocrinology, NRS Medical College and Hospital, Kolkata,

West Bengal,1Department of Internal Medicine, KLEs Jawaharlal Nehru Medical College, Belgaum, Karnataka, India.

E-mail: sajalsk21@gmail.com

Introduction: Hypomagnesemia has been associated with type 2 diabetic mellitus (DM), but the entity very often remains under-diagnosed and under-evaluated due to its usual asymptomatic presentation. Magnesium depletion has a negative impact on glucose homeostasis and insulin sensitivity and is a strong independent predictor of development of microvascular complications in type 2 DM. Aims and Objectives: This study aimed to evaluate serum magnesium levels in patients with type 2 DM and study its association with the microvascular complications. Materials and Methods: This cross-sectional study was done on 150 patients with type 2 DM from January 2014 to December 2014 in the Department of Medicine, Dr. Prabhakar Kore Hospital, Belgaum. Serum magnesium levels were assessed in patients with diabetes and they were also tested for the presence of microvascular complications. Results: In the present study, majority of the patients (71.33%) were males (2.48:1). Hypomagnesemia (<1.8 mg/dl) was seen in 41.33% of the patients. Diabetic retinopathy (DR) was present in 32% of the patients and 64.58% of patients with DR had hypomagnesemia (P = 0.001). Diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) were seen in 36% of the patients each and the incidence of hypomagnesemia in DN and DPN was 53.70% (P = 0.017) and 79.17% (P = 0.001) respectively. A significant association was found between serum magnesium levels, glycemic control, and duration of diabetes (P < 0.050). Conclusion: Hypomagnesemia is widely prevalent in patients with type 2 DM and seems to be a major risk factor for the development of microvascular complications.

Keywords: Diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, hypomagnesemia, type 2 diabetes mellitus

 Effectiveness of teneligliptin added in type 2 diabetes mellitus patients on insulin therapy: A subanalysis of Treat India-2 study



Mangesh Tiwaskar, Ameet Mohan Rathod1, Sachin Suryawanshi Yadav1, Hanmant Barkate1

Shilpa Medical Research Centre,1Glenmark Pharmaceuticals Ltd., Medical Service, Mumbai, Maharashtra, India.

E-mail: ameet.rathod@glenmarkpharma.com

Background: The incidence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate worldwide and in India. Incretins are being increasingly used in the treatment of T2DM. In India, recently introduced cost-effective gliptin, teneligliptin is widely prescribed as monotherapy and with other oral antidiabetics as well as with insulin therapy if uncontrolled. There is a lack of efficacy and safety data of usage of teneligliptin along with insulin. Aim: To evaluate the effect of teneligliptin in T2DM patients uncontrolled on insulin therapy through retrospective data analysis. Methods: For this retrospective study, a predesigned structured pro forma was used to collate information of T2DM patients from hospital records of 18 centers across India. Independent Ethics Committee (Suraksha Ethics Committee. Reg. No.: ECR/644/Inst/MH/2014/RR-17) approval was obtained before commencement of the study. Patients in whom treatment with teneligliptin was initiated and continued for a minimum period of 3 months were considered for the study. Data with respect to glycemic parameters along with insulin therapy with or without other antihyperglycemic agents (OHAs) were captured and further analyzed for the mean change in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), hemoglobin A1c (HbA1c), and the daily insulin dose from baseline to 3 months. Results: 150 patients out of 10,653 patients enrolled for Treat India-2 study were prescribed insulin therapy with or without other antidiabetic agents. From the data collected, it was observed that premix insulin (82.9%) was mostly prescribed to the patients on insulin therapy. It was observed that daily insulin dose was reduced from 25.28 ± 11.97 to 22.03 ± 12.21 IU with a difference of −3.25 IU/day (P = 0.0465) from baseline to 3 months after add-on teneligliptin. The mean change from the baseline to 12 weeks for FPG, PPG, and HbA1c was −72.7 mg/dL (P < 0.0001), −102.69 mg/dL (P < 0.0001), and −1.48% (P = 0.0001), respectively. Conclusion: Teneligliptin addition to insulin therapy with or without other OHA's significantly improved glycemic parameters and also reduced daily dose of insulin after 3 months of treatment.

Keywords: Gliptins, insulin therapy, teneligliptin, type 2 diabetes mellitus

 Perioperative glycemic control in patients undergoing cardiac transplantation and effect on outcome at a tertiary care center



Lohit Kumbar, Pramila Kalra, Nagamalesh, Ravi Shankar Shetty

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

E-mail: lohitlvk@gmail.com

Glycemic management in patients undergoing cardiac transplantation poses specific challenges, especially with cardiac tissue acceptance. These patients are being exposed to massive doses of steroids and immunosuppressive drugs. We present here our experience of managing 18 patients undergoing cardiac transplantation at our tertiary care center. Methods: Patients undergoing cardiac transplantation were monitored for glycemic status, and insulin infusion was given during the perioperative period. Postoperatively, these patients were followed up for glycemic control and cardiac tissue rejection. Results: A total of 18 patients with a mean age of 46.72 ± 16.94 years (mean ± SD) and a median age of 48.5 years underwent cardiac transplantation (males – 14 and females –4). Of these patients, four had postoperative diabetes mellitus. HbA1c preoperatively ranged from 5.4% to 12.5% (mean ± SD = 8.711 ± 2.47). The mean insulin requirement of insulin on postoperative day 0, 1, 2, and 3 was 1.396, 0.503, 0.490, and 0.537 (IU/kg/day) in patients with diabetes, whereas, in nondiabetic individuals, it was 1.955, 0.561, 1.19, and 0.61, respectively (P = NS). The mean insulin at the time of discharge in patients with diabetes was 0.698 ± 0.43 IU/kg/day (mean ± SD), while in nondiabetic individuals, it was 1.285 ± IU/kg/day (mean ± SD) (P = NS). Cardiac tissue rejection at <3 months and 3–6 months was not dependent on the glycemic status at baseline (P = NS), but perioperative glycemic control was the determining factor. The insulin requirements on day 0–3 among diabetics and nondiabetics were not significant (P = NS). Conclusion: In our experience, we found that perioperative and postoperative glycemic control was important in cardiac tissue acceptance. We found that the perioperative insulin requirement of our patients was higher compared to other perioperative patients as they are on a high dose of steroids. Perioperative and postoperative glycemic control is essential for successful cardiac transplantation and tissue acceptance.

Keywords: Cardiac transplantation, diabetes, insulin, perioperative

 A rare case of neonatal diabetes mellitus with glucokinase mutation



G. Arvind, Neelaveni, Rakesh Sahay

Osmania Medical College, Hyderabad, Telangana, India.

E-mail: arvind.dch@gmail.com

Background: Neonatal diabetes mellitus appears within the first 6 months of life, and permanent neonatal diabetes mellitus (PNDM) represents 50% of cases of neonatal diabetes, among which glucokinase (GCK) mutations cause 4% of PNDM. Homozygous mutations in the GCK gene cause neonatal diabetes, while heterozygous GCK mutations cause maturity-onset diabetes of the young. Case Report: We report a female neonate who was delivered by cesarean section at 34 weeks' gestation born to third-degree consanguineous marriage and mother being primipara with polyhydramnios with GDM requiring insulin therapy. Neonate had intrauterine growth retardation with birth weight of 1.4 kg. She presented on the 30th day of life with hypotension, dehydrated, hyperglycemia, and ketones negative, and she was treated with insulin infusion along with rehydration. Later, insulin infusion was stopped and started on injection insulin S/c 0.5 units tid as the baby was stable and breastfeeding. GRBS readings varied between 150–250 mg/dl. The initial insulin requirement ranged from 0.05–0.3 units/kg of body weight per day. Blood glucose control was difficult initially due to small doses of insulin and large variations in blood glucose concentrations. Investigations revealed C-peptide <0.05 ng/ml. Genetic analysis revealed an homozygous frameshift mutation in exon 2 of GCK gene (c.173del). Both parents are heterozygous for the same mutation. Parents are first cousins. Both the parents had impaired fasting glucose. Conclusion: We suggest that GCK-PNDM should be considered in an infant with PNDM, intrauterine growth restriction, gestational diabetes in mother, and a family history of consanguinity, and as a first investigation, the parent's fasting glucose should be checked even if there is not a clear history of diabetes.

 Fasting and postprandial lipid abnormalities in patients with type 2 diabetes mellitus



Ajay Hanumanthu, Sanjeev Rao Girimaji1, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami

Department of Endocrinology, NRS Medical College and Hospital, Kolkata, West Bengal,1Department of General Medicine, Apollo BGS Hospital, Mysore, Karnataka, India.

E-mail: ajay304304@gmail.com

Introduction: Postprandial hypertriglyceridemia has been linked with asymptomatic and symptomatic macrovascular disease in both normo- and hypertriglyceridemic individuals, and such abnormalities have been reported in type 2 diabetes mellitus, the increased risk of atherosclerosis among them, might, therefore, be related to the higher postprandial triglyceridemia. It is not clearly known whether patients with diabetes with macrovascular disease have greater abnormalities of postprandial triglyceride metabolism than those without. Aims and Objectives: This study aims to study the postprandial lipid abnormalities in patients with type 2 diabetes mellitus and to compare the relationship between fasting and postprandial lipids in those with type 2 diabetes mellitus and those without. Materials and Methods: This study was carried out in Apollo BGS Hospital, Mysore, Karnataka. It was carried out from January 2013 to December 2014. After 14 h fast, blood was collected for various biochemical parameters. The individuals were given a standardized fatty meal. Blood samples were drawn at baseline, 2, 6, and 8 h after the oral fat challenge. Results: In this study, cases had a mean triglyceride level of 160.32 ± 52.47 mg/dl in the fasting state and 176.48 ± 55.58 mg/dl in the postprandial state. The controls had a mean triglyceride level of 133.10 ± 60.34 mg/dl in the fasting state and 146.25 ± 62.12 mg/dl in the postprandial state. This association had a P = 0.013, which is statistically significant. Hence, there was a significant increase in the postprandial triglyceride level in the cases compared to that of the controls. Conclusions: The dyslipidemia of type 2 diabetes mellitus is characterized mainly by raised triglyceride, VLDL-c, and LDL-c. In the postprandial state, there was significant hypertriglyceridemia in cases when compared to that of the controls.

Keywords: Dyslipidemia, hypertriglyceridemia, type 2 diabetes mellitus

 Efficacy of remogliflozin etabonate in management of type-2 diabetes mellitus: Results of analysis of phase-III study stratified by baseline HbA1c



Mala Dharmalingam, Ramesh Goyal1, Hansraj Alva2, Jayashri Shembalkar, Rahul Kodgule4, Monika Tandon4, Sagar Katare4, Sachin Suryawanshi4, Hanmant Barkate4

MS Ramaiah Memorial Hospital, Bengaluru, Karnataka,1Apollo Hospital, Ahmedabad, Gujarat,2Vinaya Hospital and Research Centre, Mangalore, Karnataka,3Getwell Hospital and Research Institute, Nagpur,4Glenmark Pharmaceuticals, Mumbai, Maharashtra, India. E-mail: drdharmalingamesicon2019@outlook.com

Introduction: Remogliflozin etabonate (RE) is a novel SGLT2 inhibitor approved for use in type-2 diabetes mellitus (T2DM) in India. Objectives: This phase-III study evaluated the efficacy and safety of two different doses of RE versus dapagliflozin. Secondary efficacy analysis included comparison of HbA1c reduction with stratification for baseline HbA1c. Methods: This 24-week, double-blind, double-dummy three-arm study randomized T2DM patients with inadequate glycemic control (HbA1c ≥7% to ≤10%) on stable dose of Metformin monotherapy to either test arms of RE (100 mg BID; Arm-A) or RE (250 mg BID; Arm-B) or control arm of dapagliflozin (10 mg OD; Arm-C). Balanced randomization was ensured (in Arm-A and Arm-B) for stratification by baseline HbA1c levels, viz., 7%-7.9% (Strata-1), 8%–8.9% (Strata-2), and 9%–10% (Strata-3). The mean change in HbA1c from baseline was assessed at follow-up visits (week-1, week-4, and 4 weeks thereafter) analyzed in per-protocol and modified intention-to-treat population. Results: Of 612 randomized patients, 249 (Arm-A = 98; Arm-B = 90; Arm-C = 61), 223 (Arm-A = 82; Arm-B = 91; Arm-C = 50), and 139 (Arm-A = 44; Arm-B = 60; Arm-C = 35) were randomized to Strata-1, Strata-2, and Strata-3, respectively. The baseline HbA1c was comparable in all three treatment arms in each of predefined strata. All treatment arms demonstrated progressive reduction in HbA1c over 24 weeks in all three strata of patients. The mean change (standard error) in HbA1c from baseline to week-24 in Strata-1 was −0.36% (0.109%), −0.31% (0.112%), and −0.16% (0.133%) in Arm-A, Arm-B, and Arm-C, respectively. Similarly, in Strata-2, the change was −0.65% (0.141%), −0.86% (0.131%), and −0.96% (0.185%), whereas in Strata-3, the change was −1.73% (0.248%), −1.38% (0.233%), and −1.06% (0.305%) in Arm-A, Arm-B, and Arm-C, respectively. The mean difference in HbA1c in RE 100 mg or RE 250 mg versus dapagliflozin 10 mg arms was not found be statistically significant. Conclusion: The HbA1c reduction with two doses of RE was proportional to baseline HbA1c and comparable to dapagliflozin 10 mg in each of groups stratified for baseline HbA1c.

Keywords: Dapagliflozin, remogliflozin, SGLT2 inhibitor

 Efficacy of teneligliptin as an add-on to insulin monotherapy in patients with type 2 diabetes mellitus



Butungeshwar Pradhan, Sidharth Shankar Panigrahi

Department of General Medicine, VIMSAR, Sambalpur, Odisha, India. E-mail: sidshan.p@gmail.com

Introduction: Uncontrolled glycemic status is an independent risk factor for macrovascular and microvascular complications. Insulin therapy is ultimately required by a substantial number of individuals with type 2 diabetes mellitus (DM). Some patients do not adequately achieve therapeutic goals despite the titration of insulin dose. Dipeptidyl peptidase-4 (DPP) inhibitors increase the concentration of glucagon-like peptide-1 and glucagon-dependent insulinotropic peptide. It has been reported that addition of DPP-4 inhibitors is more effective than dose escalation of insulin. Objective: To find the efficacy of teneligliptin add-on to insulin monotherapy in patients with uncontrolled type-2 DM. Methods: It was a prospective open-label observational study of 40 patients with inadequate glycemic control with insulin. Keeping the baseline insulin dose fixed, teneligliptin 20 mg was added daily for 12 weeks. The primary outcome measure was measured by change in HbA1c, FBS, and PPBS at 12 weeks. Results: In 40 patients, teneligliptin was used as add-on treatment in patients receiving insulin as monotherapy. From baseline to 12 weeks, there was a change in mean HbA1c (9.50% ±2.07%–8.015% ±1.34%, P = 0.0003), mean FBS (250.08 ± 107.6–155.2 ± 58.7 mg/dl, P = 0.0001), and mean PPBS (303.3 ± 118.31–200 ± 44.4 mg/dl, P = 0.0003). Reduction in these glycemic parameters was thus found to be significant in patients with teneligliptin as add-on to insulin. Overall, 20% of patients reached the target HbA1c of < 7% after 12-week treatment. Conclusion: Teneligliptin is a useful add-on in patients of uncontrolled glycemic status with insulin monotherapy. Conflicts of Interest: There is no conflict of interest in this study.

Keywords: Efficacy of teneligliptin

 Prevalence and determinants of B12 deficiency in patients with type 2 diabetes mellitus of Indian origin



Gautham Kolla, Shivaprasad Channabasappa, Sridevi Atluri, Ramdas Barure

Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India. E-mail: kollagautham@gmail.com

Introduction: Diabetes mellitus is one of the most common endocrine disorders, and metformin is the most commonly used antidiabetic agent which is well known to cause B12 deficiency. B12 deficiency occurs due to effect on calcium-dependent membrane action in the terminal ileum, leading to malabsorption of Vitamin B12. Objectives: The objective of our study is to estimate the prevalence of B12 deficiency and to identify its determinants in patients with type 2 diabetes mellitus of Indian origin. Materials and Methods: We conducted a retrospective analysis of 2802 adult patients with type 2 diabetes mellitus attending the outpatient clinic of endocrinology department. Serum B12 levels were assessed by Beckman–Coulter immunoassay system, and B12 deficiency was defined as values <200 pg/ml. Biochemical parameters including fasting blood sugar, A1C, creatinine, serum calcium, thyroid profile, lipid profile, and hemoglobin were also estimated. Results: The prevalence of B12 deficiency in patients with type 2 diabetes was 28.9% in our study. B12 deficiency was found to be associated with metformin therapy. Conclusion: B12 deficiency is common in patients with type 2 diabetes, especially those who are on metformin therapy. B12 deficiency can lead to the progression of diabetic peripheral neuropathy. Regular annular screening and treatment for underlying B12 deficiency are warranted for patients with type 2 diabetes on metformin therapy.

Keywords: B12 deficiency, metformin, type 2 diabetes mellitus

 Diabetes and hearing loss



Srivalli Madhira1,2, Ramesh Jayanthy3,41SIE's Speciality Clinics, Visakhapatnam, Andhra Pradesh,2SIE's Speciality Clinics,3Sai's Institute of Endocrinology, Hyderabad, Telangana,4Sai's Institute of Endocrinology, Visakhapatnam, Andhra Pradesh, India. E-mail: drsrivallient@yahoo.co.in

Introduction: The incidence of hearing loss in diabetes is twice more as compared to people without diabetes. The early detection of hearing loss is important to qualify and quantify hearing loss. The duration of diabetes and the degree of glycemic control are also important. Objective: The objective of this study is to study the effects of diabetes on hearing and also the association with duration of diabetes, glycemic control, type of diabetes, and degree of hearing loss. Materials and Methods: The control group had 50 patients who were age matched and had no diabetes. The case group had 50 patients with diabetes and hearing symptoms of which 40 had type 2 diabetes and 10 had type 1 diabetes. Detailed ENT examination along with tuning fork tests was done. The pure tone audiometry was done for all frequencies. The glycemic evaluation included HbA1c, fasting blood glucose, duration, clinical history, and evaluation of other diabetes complications. Discussion: The sensorineural hearing loss was more in type 2 diabetes as compared to type 1 and controls. The literature review suggests that the endolymph glucose level is a reflection of blood glucose. The poorer glycemic control, repeated hypoglycemia, and associated neuropathy may also affect the hearing thresholds, strial damage, and outer hair cell defects. Results: Our results confirm that diabetes mellitus is associated with increased risk of sensorineural hearing loss, especially more in younger adults, with significant greater pure tone thresholds at all frequencies. In older diabetes patients, the higher frequencies were more effected. The patients with poor glycemic control and longer duration had more hearing loss. Conclusion: Routine audiological assessment will impact the quality of life of the diabetes patients and early intervention for the management of hearing loss with better prognosis on the hearing.

Keywords: Audiologic evaluation, diabetes, hearing loss

References

Lin SW, Lin YS, Weng SF, Chou CW. Risk of developing sudden sensorineural hearing loss in diabetic patients: A population-based cohort study. Otol Neurotol 2012;33:1482-8.Sunkum AJ, Pingile S. A clinical study of audiological profile in diabetes mellitus patients. Eur Arch Otorhinolaryngol 2013;270:875-9.Horikawa C, Kodama S, Tanaka S, Fujihara K, Hirasawa R, Yachi Y, et al. Diabetes and risk of hearing impairment in adults: A meta-analysis. J Clin Endocrinol Metab 2013;98:51-8.

 “Let food be thy medicine” – Reversing diabetes with vegan diet: A case report



Hemi Soneja, Junior Anand Gupta, Jasmine Chanana

Max Smart Super Specialty Hospital, Saket, Delhi, India.

E-mail: hemisoneja@gmail.com

Introduction: Type 2 diabetes, as we all know, is a disease of complications and is increasing at an alarming rate worldwide. The concept of diabetes reversal is now being increasingly recognized, and we have evidence from several trials including the DiRECT study. Diet has a significant impact on management, but often compliance is a major issue. Here, we discuss a patient who was initiated on customized vegan diet, made by professionally trained chefs, under direct supervision of dieticians, keeping into consideration the patient preferences and taste, and delivered on a daily basis. Case Presentation: A 56-year-old male presented with type 2 diabetes (17 years' duration); hypertension (14 years); osteoarthritis; obesity; on metformin 1 g BID; injection liraglutide 1.8 mg s/c once daily; glimepiride 2 mg BID; dapagliflozin 5 mg once daily; injection lispro (U-100) – 24 units three times a day; and injection degludec 54 units once daily. His HbA1c was 7.9, with frequent episodes of fluctuations in his blood sugar levels with episodes of hypoglycemia, averaging twice a week. He was started on 1700 calorie vegan diet (protein 20%; fat 20%; and carbohydrate 60%) and sugars were monitored via Flash Glucose Monitoring. He continued to show improvement in his sugar levels, the dose of insulin was gradually titrated down, and on day 35, the insulin was stopped altogether. Other hypoglycemic medications continued to be the same. He lost 8 kg weight in 75 days. It is now been 40 days that he has been off insulin and his latest HbA1c was down to 7.1 in 75 days. Discussion and Conclusion: Vegan diet can help with halting the progression of diabetes and help decrease medication requirement over a period of time. The provision of customized meals, which are scientifically planned, based on a home delivery model, can significantly improve patient compliance and can be an important add-on to conventional therapy.

Keywords: Diabetes, reversal, vegan diet

 Association of subclinical Cushing's syndrome in patients of type 2 diabetes mellitus



Swapnil Suresh Jagtap, Pramod Gandhi1, Rajesh V. Gosavi2

IGGMC,1Kingsway Hospitals,2GMC, Nagpur, Maharashtra, India. E-mail: ssjagtap89@gmail.com

Introduction: Type 2 diabetes mellitus (DM) is a common disorder that may be sustained by several endocrine diseases; subclinical Cushing's syndrome (SCS) is one of them. SCS is defined as autonomous cortisol production in patients without typical signs and symptoms of hypercortisolism. Aims and Objective: The aims and objectives were to study the association of SCS with type 2 DM patients, to study the correlation of SCS in type 2 DM patients with metabolic syndrome and also with poor control of diabetes. Materials and Methods: This observational study was performed in tertiary care center from November 2016 to October 2018 enrolling total 121 patients (81 type 2 DM cases and 40 nondiabetic controls). Both cases and controls were screened with 1 mg overnight dexamethasone suppression test (ODST), with serum cortisol of ≥1.8 mcg/dl being considered as abnormal (screening positive). The screening test-positive patients were further evaluated with confirmatory test 48-h low-dose dexamethasone suppression test (LDDS). LDDS test was performed after gap of at least 1 week, and serum cortisol level of ≥1.8 mcg/dl was considered abnormal. The serum cortisol levels in type 2 DM patients and in controls were compared. Serum cortisol levels were also compared in patients with long duration of diabetes, poorly controlled diabetes, and metabolic syndrome. Results: Screening test (ODST) was positive in 3 (3.7%) patients among 81 type 2 DM cases and was negative in all controls. Confirmatory test (LDDS) was negative in all the ODST-positive patients. Discussion and Conclusion: In our study, no association of SCS with type 2 DM was found. Screening test (ODST) positivity was significantly associated with poor control, with longer duration of diabetes, and also with metabolic syndrome (P = 0.038, 0.0031, and 0.048, respectively).

Keywords: Overnight dexamethasone suppression test, subclinical Cushing's syndrome, type 2 diabetes mellitus

 Comparison of ambulatory glucose profile among patients with type 1 diabetes mellitus and type 2 diabetes mellitus



Sandeep Ganta, Alok Sachan, V. Suresh, Raghavendra Katakam, Sree Divya

Departments of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India. E-mail: gsreddy1210@gmail.com

Background: Flash glucose monitoring (FGM) is an interstitial glucose monitoring system. Objective: To assess the various factors related to glycemic control from ambulatory glucose profile (AGP) and to compare the AGP profiles among patients with type 1 diabetes mellitus (DM) and type 2 DM. Methods: Patients with type 1 and type 2 DM attending outpatient services at a tertiary care hospital, who underwent FGM with free-style liber pro (Abbott), were included. Sensor was worn for 14 days. Relevant data, such as type of DM, treatment details, and recent HbA1c, were collected. Results: Complete data (sensor AGP with corresponding clinical information) were obtained for 112 patients with type 1 DM (n = 35, 32%) and type 2 DM (n = 77, 68%), irrespective of therapy. Aggregated analysis of AGP data comparing patients with type 1 DM versus type 2 DM revealed poorer glycemic control among patients with type 1 DM (estimated HbA1C 9.35 ± 2.9% vs. 7.15% ± 1.7%, respectively, P = 0.0001; average blood glucose 219 ± 84.6 mg/dL vs. 156.2 ± 47.3 mg/dL, respectively, P = 0.0001). Time spent within target range (70–180 mg/dL) was more among patients with type 2 DM compared to patients with type 1 DM (54.7% ± 21.3% vs. 29.1% ± 14.5%, P < 0.0001) whereas time spent below target (hypoglycemia) was lesser among patients with type 2 DM. High glycemic variability was found among 30/35 patients with type 1 DM (85%) compared to 17/77 patients with type 2 DM (22%). Moderate positive correlation was observed between estimated HbA1C by AGP versus measured HbA1C among patients with type 2 DM (r = 0.5599) and type 1 DM (r = 0.6128). Conclusions: Patients with type 1 DM have poorer glycemic control when compared to patients with type 2 DM. At the same time, patients with type 1 DM also have more episodes of hypoglycemia. Estimated HbA1C by AGP was lower compared to measure HbA1c in the laboratory.

Keywords: Advanced glucose sensing technologies, ambulatory glucose profile, flash glucose monitoring

 Significance of serum gamma glutamyl transferase level in first-degree relatives of type-2 diabetic patients



Silima Subhasnigdha Tarenia, Partha Sarkar1, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami

Department of Endocrinology, NRS Medical College and Hospital,1Department of General Medicine, CNMC and H, Kolkata, West Bengal, India. E-mail: drsilimatarenia@gmail.com

Introduction: Possibility of an association between serum gamma glutamyl transferase (GGT) levels and diabetes has been suggested in previous studies, albeit more strongly in females and impaired fasting glucose patients. Obesity is also associated with type-2 diabetes mellitus (T2DM) and metabolic syndrome, and studies have shown this association to be stronger if GGT levels are in the high normal range. Liver being the central metabolic powerhouse connects the above observations by its role in insulin clearance, maintenance of fasting and postprandial glucose homoeostasis, as well as being the source of GGT. However, insights into the nature and possible implications of these associations are lacking. Better understanding of these relations might pave way for a possible diagnostic role of GGT in the early detection of those at risk of future diabetes. Aims and Objectives: (1) To study level of GGT in first-degree relatives (FDRs) of T2DM patients. (2) To derive a relationship of serum GGT with metabolic profile (fasting blood glucose [FBG], postprandial blood glucose, lipid profile, blood pressure, blood pressure) and physical status (waist-hip ratio). Materials and Methods: Study site: General Medicine Department of CNMC and H. Study population: 30–80-year-old nondiabetic FDR of T2DM. Study period: 1 year. Sample size: 100. Study type: This was a cross-sectional study. Results: Increase levels of FBG, low-density lipoprotein cholesterol (LDLC), triglyceride (TG), LDL: high-density lipoprotein (HDL) ratio, total cholesterol (TC):HDL ratio, and HbA1C were associated with increased GGT levels (correlations were statistically significant). Discussion and Conclusion: This study showed a positive correlation between increasing GGT levels with FBS, LDLC, TG, LDL: HDL, TC: HDL, and HbA1C levels. These findings among FDRs of diabetes patients potentiate the possibility of using GGT as an early novel marker in population at risk.

Keywords: Gamma glutamyl transferase, type 2 diabetes mellitus

 Prevalence of coronary artery calcification and other cardiovascular disease risk factors in young adults with type 2 diabetes mellitus



Saroj Kumar Sahoo, Tony P. Joseph, Nikunj S. Kotecha1, H. B. Chetan Kumar1, Neeraj Jain2, Sunil Kuma2, Aditya Kapoor1, Eesh Bhatia

Departments of Endocrinology,1Cardiology and2Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. E-mail: drsarojsahoo21@gmail.com

Introduction: Cardiovascular complications are the major causes of morbidity and mortality in patients with diabetes mellitus. There is a paucity of studies on a detailed evaluation of subclinical atherosclerosis in young adults with type 2 diabetes (T2DM). Aim and Objectives: The objective of the study is to study the prevalence of coronary artery calcium (CAC) score, carotid intima–media thickness (CIMT), flow-mediated dilation (FMD) along with other traditional cardiovascular risk factors in young adults with T2DM. Materials and Methods: Sixty-two patients with T2DM, age between 30 and 50 years, and duration of diabetes >5 years (median age 44.5 years, 71% males) and 60 age-, sex- and BMI-matched healthy controls were evaluated for CAC score, CIMT, and FMD. All were subjected to 2D-Echocardiography and electrocardiography. Framingham risk score (FRS) and serum high-sensitivity C-reactive protein were assessed in all. Results: A positive CAC score was comparable between the cases with T2DM and controls (14.5% vs. 11.7%, P < 0.64). The patients with T2DM had a significantly higher CIMT (0.54 ± 0.15 vs. 0.49 ± 0.10 mm, P = 0.014), FRS (8.87 vs. 4.23, P < 0.001), and a lower FMD (9.0% vs. 10.7%, P = 0.009) compared to controls. The heart rate (83 ± 13 vs. 74 ± 11, P < 0.001), QTc (402 ± 20 vs. 382 ± 21, P < 0.001), interventricular septal (IVS) thickness (10 vs. 9 mm, P < 0.001), and posterior wall thickness (10 vs. 9 mm, P < 0.001) were also significantly higher in the patients with T2DM compared to controls. Hypertension (42% vs. 7%, P < 0.001) and metabolic syndrome (76% vs. 35%, P < 0.001) were more prevalent in the patient group. Age and IVS thickness were independent predictors for a worse CIMT. Discussion and Conclusion: There was a high prevalence of cardiovascular disease risk factors among asymptomatic young adults with T2DM. CAC score was not be a useful tool for the assessment of subclinical atherosclerosis in young adults with T2DM, whereas CIMT and FMD were more appropriate.

Keywords: Carotid intima-media thickness, coronary artery calcium score, flow mediated dilatation, type 2 diabetes, young-adults

 The prevalence of short stature and overweight/obesity in children and adolescents with type 1 diabetes mellitus: A South Indian experience



Krishna Reddy Thaduri, Vijay Sheker Reddy Danda, Sreenivas Paidipally, Chaitanya Konda, Madhavi Verpula, D. Sandeep Reddy

Department of Endocrinology, Gandhi Hospital, Secundrabad, Telangana, India.

E-mail: kisnareddy@gmail.com

Introduction: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease due to autoimmune destruction of pancreatic beta cells resulting in insulin deficiency. Growth failure and malnourishment are common features of T1DM in children and adolescents. Overweight and obesity are also surfacing as concerns. Aim: The aim is to study the prevalence of short stature in T1DM and its relation to HbA1C, thyroid function testing, celiac disease, and nutritional parameters and to study the prevalence of obesity/overweight in T1DM. Materials and Methods: One hundred consecutive T1DM children presenting to the Department of Endocrinology, Gandhi Medical College/Hospital, Hyderabad, Telangana, India, during 2017–2018, were recruited in the study after due ethical clearance. Anthropometry, HbA1C, and nutritional parameters were assessed. A cross-sectional analysis was done. Results: The mean height standard deviation score (SDS) was lower than the Indian national standard (−1.72), 39% of the children were short with a height SDS >−2SDS. Stature had a significant positive correlation with body mass index, hemoglobin, albumin-corrected calcium albumin levels. Ten out of thirty-nine children with short stature and 5/61 normal stature had overt hypothyroidism. Of the 39 short children, one child was overweight. Four cases are positive for anti-Ttg in short stature group, none in the normal stature group. About 11% of children were overweight/obese, 4% were underweight. HbA1C was significantly lower in the obese/overweight children. Discussion and Conclusion: The prevalence of obesity is increasing worldwide, which is also observed in T1DM, likely being due to lack of physical activity, recurrent hypoglycemic episodes with defensive eating and psychological factors. In our study, short stature is higher compared to previously publish Indian data. This could be due to the effect of hypothyroidism, chronic disease, low socioeconomic status, nutritional factors, and calorie restriction.

Keywords: Obesity, shortstature, type 1 diabetes mellitus

 Concurrent type 1 diabetes mellitus and glutamic acid decarboxylase antibody-associated cerebellar ataxia in an Indian patient: A rare occurrence



Karthik Prabhakar, Ashwitha Shruti Dass, Uday Murgod1

Departments of Diabetes and Endocrinology and1Neurology, Manipal Hospital, Bengaluru, Karnataka, India.

E-mail: karthik.prabhakar@manipalhospitals.com

Case Report: A 36-year-old female presented with generalized -weakness, giddiness, dry mouth, polydipsia, and polyuria for 7–10 days and also she reported gradual difficulty in walking for 2 months. There was no history of ethanol abuse or head injury. Clinically, she was dehydrated, tachycardic, tachypneic, with ketone breath, had normal cognition, nystagmus, diplopia, impaired limb coordination, and gait ataxia and normal limb power, reflexes, and sensation. RBS 317 mg/dL, serum bicarbonate 12 mmol/L, severe glycosuria and ketonuria; hemoglobin A1c: 11.3%; renal functions, serum calcium, complete blood cell, creatine phosphokinase, erythrocyte sedimentation rate, C-reactive protein, and Vitamin B12 were normal. She was treated with intravenous (IV) fluids, IV insulin infusion for diabetic ketoacidosis, and then subcutaneous insulin; thiamine injections were administered for neurodeficits. Magnetic resonance imaging-brain, whole-body positron emission tomography–computed tomography, cerebrospinal fluid-analysis, and antinuclear antibody-profile were all normal. Thyroid function test was normal with thyroid autoantibody positive. Diabetic retinopathy, microalbuminuria, and gluten sensitivity were excluded. Anti-glutamic acid decarboxylase (GAD)-65 antibodies were positive with high titers; hence, “type 1 diabetes mellitus (T1DM) with GAD-65-antibody-associated cerebellar ataxia (CA)” was diagnosed. She received IV immunoglobulins for 5 days with brief neuroimprovement. Recurrent cerebellar symptoms necessitated IV methylprednisolone, but this precipitated diabetic ketosis needing IV insulin infusion. Further neurological deterioration was treated with rituximab infusion. So far, she has received four doses of 1000 mg IV rituximab infusion; she can walk indoors independently. Glycemic control was achieved with basal-bolus regime. Discussion: T1DM associated with autoantibody-mediated CA is a unique condition, occurring rarely but generally seen in females. Very high anti-GAD antibody titers tend to indicate central nervous system disorders such as CA, stiff person syndrome, limbic encephalitis, and occasionally paraneoplastic etiologies; other autoimmune endocrine disorders (thyroid/polyglandular syndromes) may also be seen. Diabetes either precedes or follows CA, but in our patient, happened together. She remains under close follow-up for other autoimmune conditions.

Keywords: Cerebellar ataxia, glutamic acid decarboxylase-65 antibodies, type 1 diabetes mellitus

 A study on factors influencing mean amplitude of glycemic excursion in patients with type 1 diabetes mellitus



R. S. Riyas, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami, Rahul Valsaraj

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

E-mail: azmiriyas0331@gmail.com

Introduction: Type 1 diabetes mellitus (T1DM) is the progressive loss of β-cell function resulting in absolute insulin deficiency. Multiple factors such as glycemic variability are involved in glycemic control and also development of complications. Glycemic variability can be quantified by intermittent glucose determinations using the continuous glucose monitoring (CGM) system. The mean amplitude of glycemic excursion (MAGE) is one of the most common indices used to calculate glycemic variability. Aim and Objective: To find the correlation between age of patient, duration of diabetes, antibody profile, hemoglobin A1C (HbA1C), and C-peptide with MAGE in T1DM. Materials and Methods: Thirty T1DM patients were included and MAGE was measured by a CGM device (Medtronic MiniMed, Northridge, CA). Results: The mean age of patients was 15.6 ± 5.99 years. 16 (53.7%) patients were male and 14 (47.3%) were female. The mean duration was 44.6 ± 06 months. The mean HbA1C was 8.14% ± 1.06%, and the mean total daily insulin dose was 39.6 ± 16.9 units. The association between variables was found out by Pearson's correlation: age (r = −0.126, P = 0.507), duration (r = 0.099, P = 0.602), insulin dose (r = −0.127, P = 0.503), HbA1C (r = 0.059, P = 0.758), and C-peptide (r = −0.224, P = 0.234). Duration of the disease and HbA1C showed signal toward positivity, while others not. Conclusion: T1DM has some heterogeneity in its clinical expression. Severity of metabolic instability as manifested by MAGE showed a trend toward positive correlation with duration of disease and HbA1C, but not with total daily dose and C-peptide which may have implications on management.

Keywords: Continuous glucose monitoring, mean amplitude of glycemic excursion, type 1 diabetes mellitus

 Clinical profile of small fiber neuropathy by in vivo corneal confocal microscopy in pediatric type 1 diabetes



Mainak Banerjee, Sujoy Ghosh, Pradip Mukhopadhyay, Madhurima Basu, Shatabdi Ghosh

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

E-mail: mainak18y@gmail.com

Introduction: Corneal subbasal nerves, a plexus of small unmyelinated nerve fibers, are believed to be involved earliest in diabetes. In vivo corneal confocal microscopy (IVCCM) has been validated as a surrogate marker for small fiber neuropathy (SFN). IVCCM data in pediatric type 1 diabetes with relation to puberty is lacking. Aims and Objectives: We aimed to evaluate the clinical profile of SFN in type 1 diabetes children with IVCCM. Materials and Methods: IVCCM was performed on 51 type 1 diabetes cases (age 12.8 ± 3.1, 19 males, 11 prepubertal) and 51 healthy controls (age 11.96 ± 3.87, 21 males, 16 prepubertal) to determine corneal nerve fiber length (CNFL), density (CNFD), and branch density (CNBD). SFN was diagnosed after clinical and NCV testing of patients. Receiver operating characteristic (ROC) curve analysis was done to determine area under the curve (AUC) and optimal thresholds for SFN identification in patients. Results: SFN, as evidenced by warm perception threshold ≥42°C, was present in 10 (19.6%) individuals. All had normal NCV or vibration perception testing. CCM parameters were significantly lower in T1DM cases as compared to controls, but not in prepubertal children. There was no correlation between CCM parameters and diabetes duration or HbA1C. CNFL and CNFD, with the exception of CNBD, were significantly lower in T1DM patients with SFN in comparison to those without SFN. In ROC curve analysis for SFN, AUC was greatest for CNFL (manual: 0.905 and automated: 0.902) compared with CNFD (automated: 0.77, automated: 0.79) and CNBD (manual: 0.71, automated: 0.75). The threshold value that optimized sensitivity and specificity for diagnosing SFN was a CNFL (M) of 13.53 mm/mm2 (sensitivity 100%, specificity 68.3%) and CNFL (A) of 12.54 mm/mm2 (sensitivity 100%, specificity 75.6%). Conclusion: CNFL was the best discriminatory CCM parameter for diagnosing pure SFN. The proposed cutoff can be used as marker of SFN for Indian children with type 1 diabetes.

Keywords: Corneal confocal microscopy, pediatric type 1 diabetes, small fibre neuropathy

 Hypoglycemia in a child – Unusual cause



Suresh Damodharan, Vijai J. Dharshan, Renny Rozario1

Department of Diabetology and Endocrinology, Sri Ramakrishna Hospital,1Sri Ramakrishna Institute of Pharmaceutical Sciences, College of Pharmacy, Coimbatore, Tamil Nadu, India.

E-mail: rozariorenny@gmail.com

Introduction: Hypoglycemia is a heterogeneous disorder with many different possible etiologies, including hyperinsulinism, glycogen storage disorders, fatty acid disorders, hormonal deficiencies, and metabolic defects, among others. This condition affects newborns to adolescents, with various approaches to diagnosis and management. Hypoglycemia may be caused by various defective pathways in the production and metabolism of glucose, as well as defective pathways to maintain euglycemia. Case Presentation: A 3-year-old boy was admitted with persistent hypoglycemia and he was subjected to fasting protocol and plasma insulin; C peptide levels and ketone levels were checked during hypoglycemia. Other routine investigations were done.

Investigations:

Insulin antibody: Normal

Newborn screening (tandem mass spectrometry): Normal

Imaging: Ultrasonography of the abdomen: Normal study. Discussions: When children present with symptoms of hypoglycemia, it is important to thoroughly investigate potential etiologies. Even though there was a reduction in insulin levels it was not completely suppressed, but with very low C – peptide levels, hyperinsulinemia might or might not be the cause. Normal cortisol, Insulin-like growth factor, thyroid-stimulating hormone, and liver function test ruled out other hormonal causes for hypoglycemia. Screening for fatty acid oxidization disorders and glycogen storage disorders might help in assessing other metabolic disorders leading to hypoglycemia. The patient blood glucose has been maintained with a high carb diet, intravenous dextrose. Awaiting screening results: (1)What other investigations can be done to diagnose hypoglycemia? (2)Is it appropriate to start on diazoxide? (3)What would be the next step in management?

Keywords: Glycogen storage disorder, hyperinsulinism, hypoglycemia

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 Leukocyte, insulin, and glucose response to high-carbohydrate and high-fat meals: A comparative study



Anshul Agarwal, V. P. Praveen, Ullas Mony, Nisha Bhavani, Usha Menon, Harish Kumar, Vasantha Nair, Arun S. Menon, Nithya Abraham, Prem Narayanan

Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India. E-mail: anshul5371@gmail.com

Introduction:

Food substances induce an inflammatory state. Postprandial inflammatory state of the leukocytes may be important in atherogenesis

Aims and Objectives:

The aim of this study is to assess the pre- and post-prandial increase (0, 2, 3, and 4 h) in total leukocyte count (TLC), differential count (DC), insulin and glucose levels in response to four different type of diet.

Rich in carbohydrate mealRich in saturated fatty acid (coconut oil)Rich in w3 unsaturated fatty acid (canola oil)Rich in w6 unsaturated fatty acid (sunflower oil).

Materials and Methods:

Eight normal healthy, nonmetabolic syndrome adults (5 females, 3 males), median age of 23 years were given four different diet at a gap of 1 week each. Pre- and post-prandial levels of TLC, DC, glucose, and insulin levels were compared.

Results:

2-h postprandial increase in TLC was significant in coconut, olive, and sunflower rich diet (P = 0.02, 0.02, and 0.05, respectively) while increase was insignificant in carbohydrate diet (P = 0.158)2-h postprandial neutrophil increase was significant in coconut, olive and sunflower containing diet (P = 0.07, 0.02, and 0.02, respectively) while lymphocyte significantly increased in carbohydrate diet (P = 0.02)2-h postprandial increase in monocyte was significant only in coconut diet (P = 0.02). There was significant increase in monocyte postprandially with coconut rich diet as compared to carbohydrate rich diet (P = 0.020)Median insulin level after 2 h of carbohydrate, coconut, olive, and sunflower diet was 46.55, 23.38, 25.31, and 24.43 uIU/mL, respectively. Insulin increase was significantly more in carbohydrate as compared to coconut, olive, or sunflower rich diet (P = 0.004, 0.0104, and 0.028, respectively).

Discussion:

Postprandial increase in TLC and neutrophils seen with fat rich diet and not with carbohydrate rich diet may suggest that fatty diet may cause more inflammation as compared to carbohydrates.

Keywords: Fatty diet, inflammation

 To study the relationship between the mean platelet volume, immature platelet fraction, and glycemic control in type 2 diabetes mellitus patients



Sonali Shivaji Kagne, Phulrenu H. Chauhan1, Awesh Shingare1, Shanaz Khodaiji1, Dia Mansukhani2, N. F. Shah1, Manoj Chadha1

Department of Endocrinology, P. D. Hinduja National Hospital and MRC,1Consultant, P. D. Hinduja National Hospital and MRC,2Department of Lab Medicine, P. D. Hinduja National Hospital and MRC, Mumbai, Maharashtra, India.

E-mail: sonalikagne2011@gmail.com

Introduction: Mean platelet volume (MPV) and immature platelet fraction (IPF) have been shown to be surrogate markers of platelet size and activity, respectively. In patients with diabetes mellitus, altered platelet activity is one of the contributing factors for atherothrombosis. We studied the effect of chronic hyperglycemia on MPV and IPF in patients with type 2 diabetes mellitus (T2DM). Aims and Objective: The objective of the study was to find the correlation between MPV, IPF, and HbA1c in patients with T2DM and to study the impact of improvement in glycemic control on MPV and IPF. Materials and Methods: We prospectively evaluated 60 patients with T2DM and 38 nondiabetic healthy controls. Patients were divided into two groups based on their glycemic status (Group A [n = 23]: HbA1c ≤7% and Group B [n = 37]: HbA1c >7%). MPV, IPF, and HbA1c were measured in the study and control populations at baseline and only in Group B patients at 3 months. Results: In diabetic patients, average MPV (Group A: 9.82 ± 0.62 fl, Group B: 10.14 ± 0.77 fl, vs. controls: 9.51 ± 1.35 fl, P = 0.02) and IPF (Group A: 1.78 ± 0.79, Group B: 2.47 ± 1.4 vs. controls: 1.59 ± 0.82, P = 0.001) values were significantly higher compared to controls. Seventeen of 37 patients (46%) in Group B achieved a target HbA1c level (<7%) on follow-up. MPV was significantly decreased in these 17 patients compared to their baseline MPV (9.72 ± 0.70 fl vs. 10.15 ± 0.72 fl, P = 0.00153); however, the reduction in mean IPF was not significant (2.42 ± 1.67 vs. 2.13 ± 1.11, P = 0.152). Conclusions: Platelet activity, as measured by MPV and IPF, is significantly higher and correlates with glycemic control in T2DM patients when compared to healthy nondiabetic controls.

Keywords: HbA1c, immature platelet fraction, mean platelet volume, type 2 diabetes mellitus

 Mutational profile of maturity-onset diabetes in the young in India differs from that seen in the Western population



Kalyani Sridharan, Aaron Chapla, Hesarghatta Shyamasunder Asha, Thomas V. Paul, Denny Varghese, R. Parthibhan, Simon Rajaratnam, Felix Jebasingh, Riddhi Das Gupta, Sandeep Kumar Agarwal, R. Lavanya, J. Jabasteen, Sarah Mathai1, Sophy Korula1, Anna Simon1, Nihal Thomas

Departments of Endocrinology, Diabetes and Metabolism and1Paediatrics, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: sridharan.kalyani22@gmail.com

Background: Maturity-onset diabetes of the young (MODY) is an important etiology of early-onset diabetes mellitus. The genetic landscape of MODY in the Indian population has been shown to be different from that of the West. Aims: The aim of this study is to assess the mutational profile of patients with young-onset diabetes mellitus with a clinical suspicion of MODY referred for genetic testing. Methods: This is a retrospective observational study conducted between 2012 and 2018. Patients, who were clinically suspected to have MODY by the referring physician and referred to our center for genetic testing, were included in the study. A multiplex polymerase chain reaction-based target enrichment was established, followed by next-generation sequencing on the Ion Torrent Personal Genome Machine. All the mutations and rare variants were confirmed by Sanger sequencing. Results: We included 231 patients who were clinically diagnosed with MODY and had the relevant clinical data. Eighty-four of them had MODY-related variants; 31 (13.4%) were pathogenic or likely pathogenic (5 in HNF1A, 3 in ABCC8, 4 in HNF4A, 2 in WFS1 1 in HNF1B, 1 in INS, and 1 in EIF2AK3) or variants of undetermined significance (VUS) present in more than one subject (6 in PDX1 E224K, 4 in NEUROD1 H241Q, 2 in PDX1 P33T, and 2 in PAX4 R105C). The rest of the variants were benign or likely benign or VUS present in only a single subject. Seven patients had two MODY-related variants each and 1 had 3 variants. Conclusion: The mutational profile of subjects with MODY in India shows a preponderance in HNF1A, ABCC8, HNF4A, PDX1, and NEUROD1 which is different from that in the Western population.

Keywords: Maturity-onset diabetes in the young, mutations in maturity-onset diabetes of the young, young-onset diabetes

 TRHYROID



 High prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus



Vipan Talwar, Gourav Talwar1

Departments of Endocrinology and1Golden Hospital, Jalandhar, Punjab, India.

E-mail: vtalwarendo@gmail.com

Objective: The aim of this study is to determine the prevalence of thyroid dysfunction (TD) in diabetic patients and to assess the correlation between these two endocrine disorders. Methods: The study population were 650 type 2 diabetes mellitus (DM) patients with no history of TD or treatment, attending outpatient department of our endocrine center and were assessed from January 2019 to June 2019. The anthropometric indices including weight, height, waist, and hip circumferences were measured, and laboratory tests including hemoglobin A1c (HbA1c), thyroid profile, and lipid profile were done. Data were analyzed using Microsoft Excel data software, P < 0. 05 was considered as statistically significant. Results: Of 650 patients (310 males and 340 females), 493 (75.9%) are euthyroid 157 patients have thyroid dysfunction, i.e. the prevalence rate of 24.1%. Subclinical hypothyroidism is present in 102 (15.6%) patients, 40 (6.2%) have clinical hypothyroidism, 10 (1.5%) have subclinical hyperthyroidism, and 5 (0.8%) have hyperthyroidism. Patients with higher body mass index, higher HbA1c, high cholesterol, microvascular complications have higher prevalence of thyroid dysfunction. Subclinical hypothyroidism is more common among females and elderly population. The duration of diabetes has no relation to the prevalence of thyroid disorders. Discussion: DM and TD are the two common endocrine disorders that frequently coexist and studies have documented higher prevalence of TD in patients with diabetes than the general population. Our study has reported the prevalence rate of 24.2% in asymptomatic diabetic patients, which is quite significant. Thyroid hormones affect glucose metabolism through several mechanisms in diabetes and unrecognized TD may adversely affect metabolic control and add more risk to an already predisposed scenario for cardiovascular diseases. Conclusion: Screening for thyroid disease among diabetic patients should be routinely performed in view of high prevalence, as an undiagnosed TD can cause aggravation of the classical risk factors such as hypertension and dyslipidemia.

Keywords: Thyroid dysfunction, type 2 diabetes mellitus

 Cardiopulmonary dysfunction in patients with subclinical hypothyroidism



Tauseef Nabi

Department of Endocrinology, Government Medical College, Srinagar, Jammu and Kashmir, India.

E-mail: dr.tauseefnabi @gmail.com

Background: Subclinical hypothyroidism (SCH) represents the earliest stage of hypothyroidism. SCH is defined biochemically as a high serum thyroid-stimulating hormone (TSH) and normal serum free thyroxine (fT4) and triiodothyronine (fT3) concentrations. Cardiopulmonary fitness reflects the overall capacity of the cardiovascular and respiratory system. VO2 max, also known as maximal oxygen uptake, is the measurement of the maximum amount of oxygen a person can utilize during intense exercise. Objective: The aim of this prospective observational case–control study was to evaluate the cardiopulmonary fitness of patients diagnosed with SCH. Methods: The study comprised 140 participants (80 patients with SCH and 60 healthy controls) in the age-group of 18–55 years. VO 2 max was estimated indirectly by following the protocol of Queen's college step test (QCT) method to assess cardiopulmonary fitness. Results: The patients of SCH and controls were comparable for age, gender, weight, waist circumference, body mass index, and hemodynamic parameters. TSH was significantly elevated in SCH than controls, while fT4 and fT3 were comparable. The patients of SCH showed a significant reduction VO2 max as compared to controls 46.4 ± 8.6 and 49.8 ± 9.8 ml/kg/min, respectively (P = 0.029). VO2 max was significantly reduced in females SCH than males SCH (P = 0.001). Conclusion: Cardiopulmonary functions were affected in patients with SCH. A mild cardiopulmonary dysfunction was seen in patients with SCH, particularly in females.

Keywords: Cardiopulmonary fitness, Queen's College step test, subclinical hypothyroidism, VO2 max

 Study of thyroid hormone profile in hospitalized patients with diabetes and its correlation with glomerular filtration rate



Vahid S. Bharmal, Asha Ranjan, Rujul Jain, S. Dhananjaya, Saurabh Arora, N. K. Agrawal, S. K. Singh

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

E-mail: vsbharmal@gmail.com

Introduction: Patients with diabetes have higher prevalence of thyroid disorders than the general population. Hypothyroidism has effect on glomerular filtration rate (GFR), which declines with time in patients with diabetes. The present study compared the levels of thyroid hormones with GFR in 200 hospitalized diabetic patients. Materials and Methods: Thyroid hormone profile was obtained from 200 (male/female – 105/95) hospitalized patients with diabetes. Their estimated GFR was calculated by Modification of Diet in Renal Disease-Epidemiology Collaboration formula. Statistical analysis was done using Chi-square test. Results: Mean serum triiodothyronine (T3), serum thyroxine (T4), and thyroid-stimulating hormone (TSH) in patients with GFR <60 were 60.0244 ± 25.27 ng/dl, 6.46 ± 2.27 μg/dl, and 4.23 ± 4.23 mIU/ml, respectively. These values in patients with GFR >60 were 78.85 ± 28.73 ng/dl, 6.18 ± 2.48 μg/dl, and 3.33 ± 3.57 mIU/ml, respectively. Raised TSH was found in 21 out of 80 patients with GFR <60 and 18 out of 120 patients with GFR >60 (P = 0.0423) with statistically significant difference. Low T3 was found in more (54/80) patients with GFR <60 than patients (50/120) with GFR >60 (P = 0.00034). Low T4 was found in 19 out of 80 patients with GFR <60 and in 23 out of 120 patients with GFR >60 (P = 0.43). Conclusions: We concluded that diabetic patients with reduced GFR had low T3, raised TSH, and normal T4. Defect in the conversion of T4 to T3 in diabetic patients with reduced GFR should be the basis of treatment of subclinical or overt hypothyroidism with T3 rather than with T4 sodium for improving GFR in such patients.

Keywords: Diabetes, glomerular filtration rate <60, low triiodothyronine, raised thyroid-stimulating hormone

 Analysis of the prognostic value of sodium iodide symporter and deiodinase mRNA expression in gastric cancer



Alok Mishra, Ashutosh Shrivastava

Center for Advance Research, Molecular Biology Unit, King George's Medical University, Lucknow, Uttar Pradesh, India.

E-mail: ashutoshshrivastava@kgmcindia.edu

Introduction: The Na+/I− symporter (NIS) is a transmembrane glycoprotein that facilitates active iodine transport in primary thyroid and other tissues. NIS protein has been known to overexpress in cancer cases of breast and gastrointestinal organs. Deiodinases form a group of enzymes essential for thyroid hormone activation and deactivation maintaining its homeostasis. Recent studies show a possible role of deiodinases in various cancers. We used data mining analytical approach to evaluate prognostic roles of NIS and deiodinases in gastric cancer patient's overall survival (OS). Aims and Objectives: The aim was to study the prognostic significance of NIS and Deiodinases-1, 2 and 3 (DIO 1-3) in gastric cancer patients using the Kaplan–Meier plotter (KM plotter) database. Materials and Methods: “The KM plotter” database was used for direct in silico validation in clinically relevant 876 gastric cancer patients with >15 years of follow-up information. After obtaining KM survival plots, Hazard ratio and Log-rank Pvalue were calculated. Results: There was observation of worsening overall survival for NIS and DIO1-3, indicating that dysregulation of these genes is critical for gastric cancer. NIS high expression correlated with significantly worsen OS in intestinal-type cancer patients, but not in diffuse-type cancer patients. Deiodinase-1 increased mRNA expression correlated significantly to worsen OS for all gastric cancer patients. Further, prognostic roles of mentioned genes were assessed in different types of gastric cancer morphologies and different clinicopathological features. Discussion and Conclusions: Based on these analyses, in summary, we found an indication of prognostic values of these genes. This information will contribute to a better understanding of managing complex and heterogeneous gastric cancer. Further these findings may be beneficial as a companion diagnostic predicting more accurate gastric cancer prognosis.

Keywords: Biomarkers, deiodinases, gastric cancer, Kaplan–Meier, Kaplan–Meier plot, survival

 Role of programmed cell death-1 checkpoint in papillary thyroid carcinoma associated with lymphocytic thyroiditis



Sohini Banerjee, Uma N. Saikia, Divya Dahiya1, Sanjay K. Bhadada2, B. D. Radotra

Departments of Histopathology,1General Surgery and2Endocrinology, PGIMER Chandigarh, India.

E-mail: sbanerjee0311@gmail.com

Introduction: Tumor-associated lymphocytic thyroiditis is frequently seen in tumor microenvironment (TME) of papillary thyroid carcinomas (PTC). The programmed cell death-1 (PD-1) and its ligand PDL-1 perform a vital role in tumor progression and survival of tumor by escaping tumor neutralizing immune response generated in TME. The engagement of PDL-1 expressed in tumor cells, and APCs and PD-1 expressed on T lymphocytes may create T-cell exhaustion and attenuation of immune responses. Aims and Objectives: The aim was to correlate the expression of PDL-1/PD-1 in TME and the efficacy of PD-1 checkpoint in PTC. Materials and Methods: A total of 212 cases were operated for PTC from 2015-2019, of which we analyzed immunohistochemical expression of PD-1, PDL-1, FoxP3 and CD8 on formalin-fixed paraffin-embedded tissue of 12 classical PTC with LT. In addition, characterization of lymphoid cells on fine-needle aspiration cytology by flow cytometry (FCM) of CD8 and CD25 surface markers were evaluated. Results: About 33% of the total had an associated LT. The CD8 + T lymphocytes were abundant in all the 12 cases of PTC; however, only four cases showed expression of FoxP3 and this observation was confirmed by FCM with CD8:CD25 ratio of 4.85. Nearly 65% of cases showed both PD-1 and PDL-1 positivity ranged from 1.2% to 15.6% for PD-1 and up to 14.25% for PDL-1. Discussion and Conclusion: We observed an antitumor CD8+ T cell responses generated in TME in patients of classical PTC which could be correlated with the involvement of PD-1/PDL-1 and blocking antitumor immune response. Anti-PD-1 therapy or inhibitors blocking the interaction of PD-1 and PDL-1 can be effective to modulate immune cell-tumor cell interaction and enhance specific antitumor immune response in these cases to act as immune checkpoints for monitoring the patient survival.{Figure 10}{Figure 11}

Keywords: Papillary thyroid carcinoma, tumor microenvironment

 Van Wyk–Grumbach syndrome – Isosexual pseudoprecocious puberty to secondary true precocious puberty: A case report



Ankush Desai, Prachi Prabhu1

Goa Medical College, Bambolim,1Consultant, Goa, India.

E-mail: pprachi1981@gmail.com

Introduction: Van Wyk–Grumbach syndrome (VWGS) is a rare presentation of juvenile hypothyroidism in girls, characterized by isosexual pseudoprecocious puberty and multicystic ovaries. It uniquely presents with short stature and delayed bone age unlike other causes of precocious puberty. Early diagnosis and prompt levothyroxine replacement can avoid unnecessary investigations and surgical intervention in girls presenting with premature menarche and ovarian cyst. The development of secondary true precocious puberty upon treatment with levothyroxine has not been reported. Aims and Objective: The aim of this study was to describe a case of VWGS who subsequently developed true precocious puberty. Materials and Methods: We report a 7-year 9-month-old girl with worsening short stature, chronic constipation, weight gain, abdominal distension, and recent-onset vaginal bleeding. On evaluation, she had elevated thyroid-stimulating hormone (TSH), low T3 and T4, delayed bone age, elevated follicle-stimulating hormone with prepubertal luteinizing hormone, and multicystic ovaries confirming the diagnosis of VWGS. She was initially started on levothyroxine 25 mcg once daily and titrated to target T4 and TSH in normal range. Results: All the features of the syndrome improved after adequate levothyroxine replacement. However, on subsequent follow-up, she was found to have developed secondary true precocious puberty with advanced bone age and a pubertal response on gonadotropin-releasing hormone (GnRH) stimulation. Discussion and Conclusion: Most of the earlier cases of VWGS have reported normal puberty postlevothyroxine replacement. Our patient evolved to secondary true precocious puberty with menarche before 10 years (around 2 years postlevothyroxine replacement). This was confirmed by advanced bone age and pubertal response on GnRH analog stimulation. A close follow-up is essential for timely diagnosis of secondary true precocious puberty for any potential therapy to be considered to achieve optimum height in girls with VWGS.

Keywords: Delayed bone age, juvenile hypothyroidism, precocious puberty

 Assessment of gonadal functions in women with subclinical hypothyroidism in Western Uttar Pradesh



Manish Srivastav, Alankar Tiwari

Department of Human Metabolism and Endocrinology, Meerut, Uttar Pradesh, India.

E-mail: tiwarialankar@gmail.com

Introduction: In females, hypothyroidism can cause menstrual disturbances, mainly oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility and pregnancy complications. Several studies have been done to evaluate gonadal dysfunctions in overt hypothyroidism, but very few studies are available regarding subclinical hypothyroidism. The present study evaluates the gonadal functions of women with subclinical hypothyroidism. Aims and Objective: This study aimed to assess the basal gonadotropin and estradiol levels in women of reproductive age group with subclinical hypothyroidism and compare them with euthyroid controls. Materials and Methods: Twenty females of age 18–35 years with newly diagnosed subclinical hypothyroidism were taken as cases and twenty age- and body mass index (BMI)-matched healthy females were taken as controls. Both in cases and controls, basal follicle-stimulating hormone, luteinizing hormone (LH), and estradiol were measured on the 3rd or 4th day of menstrual cycle at 8 AM on fasting. Thereafter, leuprolide 20 μg/kg was given subcutaneously on the same day. One hour after injection, LH and estradiol were measured. Basal and stimulated values were compared between both groups. Results: Basal LH was significantly higher in controls (6.63 ± 2.38 mIU/ml) when compared to cases (6.06 ± 2.10 mIU) with P = 0.01 (< 0.05). No significant differences were found between stimulated LH and estradiol in both the groups. Discussion and Conclusion: In mild thyroidal failure, the response of pituitary gonadotrophs to leuprolide is normal in contrast to overt hypothyroidism where the response is sluggish. This is the first study to be done in subclinical hypothyroid patients to asses both basal and stimulated gonadotropin levels. Further studies are required in large samples to confirm these findings.

Keywords: Gonadal dysfunction, subclinical hypothyroidism in females, subclinical hypothyroidism

 Conversion of Hashimoto's hypothyroidism to Graves' hyperthyroidism: Two cases



Ankush Desai, Prachi Prabhu1

Goa Medical College, Bambolim,1Consultant, Goa, India.

E-mail: pprachi1981@gmail.com

Introduction: Hashimoto's thyroiditis with hypothyroidism and Graves' disease (GD) are autoimmune thyroid disorders known to occur within families. The combination in the same individual is also well known with the evolution of GD into Hashimoto's hypothyroidism (HH) being common. Aims and Objectives: The aim of this study was to describe two cases of HH evolving into GD. Materials and Methods: We report two middle-aged women with this rare autoimmune switch who first presented with symptoms suggestive of hypothyroidism. On evaluation, both had high thyroid-stimulating hormone (TSH) and normal T3 and T4 with strongly positive antithyroid peroxidase antibody titers confirming the diagnosis of HH. They were treated with levothyroxine and the dose was titrated to target TSH with regular follow-up. Results: The first patient, at 7 years of levothyroxine replacement, developed features of thyrotoxicosis with low TSH and high T3 and T4 despite tapering and omitting levothyroxine. Subsequent technetium-99m thyroid scan showed diffuse increased uptake, and TSH receptor antibody (TRAb) titers were elevated confirming the diagnosis of GD. Similarly, the second case was diagnosed to have evolved into GD 5 years after the diagnosis of HH with positive TRAb and technetium-99m thyroid scan showed diffusely hyperfunctioning gland. Withdrawal of levothyroxine and treatment with oral carbimazole lead to resolution of symptoms of thyrotoxicosis and normalization of TSH in both the patients. Discussion and Conclusion: HH and GD may follow one another in the same individual and the clinical state depends on the balance between the activities of the two TRAbs, the thyroid-stimulating antibody implicated in GD and the thyroid-blocking antibody in HH. The switch from HH to GD is considered rare, probably due to lack of a critical mass of functioning thyroid tissue in individuals with long-standing HH. In conclusion, the occurrence of this switch emphasizes the need for careful patient monitoring.

Keywords: Autoimmune switch, Graves' hyperthyroidism, Hashimoto's hypothyroidism

 Rituximab in the treatment of steroid-refractory Graves' ophthalmopathy



Sajal Kamat, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami

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

E-mail: sajalsk21@gmail.com

Introduction: Graves' disease is an autoimmune thyroid disease defined by a clinical triad consisting of hyperthyroidism, diffuse goiter, and thyroid eye disease, also referred to as Graves' ophthalmopathy (GO) or thyroid-associated ophthalmopathy. GO occurs in about one-fourth of patients with Graves' disease and is believed to be related to immunologic cross-activity between thyroid and orbital tissue antigens. Glucocorticoids are the principal medical therapy for active moderate-to-severe GO but are not very effective in many patients and additional treatment options are needed. Rituximab, an anti-CD20 monoclonal antibody that leads to B-lymphocyte depletion, shows promise as an effective therapeutic agent for GO. This case series aims to determine the safety and efficacy of intravenous (IV) rituximab in steroid-refractory GO. Aims and Objectives: To assess the efficacy of rituximab in steroid-refractory GO. Materials and Methods: This series included three patients of steroid-refractory active GO (clinical activity score [CAS] of 4 or more). These patients received two 1 g doses of IV rituximab 2 weeks apart. Each patient underwent clinical assessment (CAS), thyroid function tests, and TSH receptor antibody (TRAb) evaluation before and after rituximab therapy. Results: There was a significant reduction in the TRAb levels and CAS in all patients treated with rituximab. A significant improvement in the CAS was also seen in all three patients. However, there was no improvement of proptosis noted in the patients after treatment. There were no adverse reactions to rituximab demonstrated in any of the patients. Conclusion: This case series adds to the growing literature demonstrating that rituximab, administered in our patients, is safe and clinically effective in the treatment of active steroid-refractory GO. Larger randomized control trials are needed to confirm the efficacy of rituximab in GO.

Keywords: Graves' ophthalmopathy, rituximab

 Prospective study of clinical, hormonal, serological profile and quality of life in patients of Graves' disease and response to treatment over 12 months



Ashu Goyal, Pranab Kumar Sahana, Nilanjan Sengupta, Arjun Baidya, Soumik Goswami

Department of Endocrinology, N.R.S Medical College, Kolkata, West Bengal, India.

E-mail: drashugoyal@gmail.com

Introduction: Graves' disease is the most common autoimmune disease, affecting 0.5% of the population in the US, and represents 80% of cases of hyperthyroidism. Graves' hyperthyroidism results from the production of IgG antibodies that bind and activate the thyroid-stimulating hormone (TSH) receptor on the surface of thyroid follicular cells. Objective: To study the clinical, hormonal (thyroid function test), and serological profile (TSH receptor antibody) in patients of Graves' disease and the quality of life by SF-36. Materials and Methods: This was a nonrandomized, prospective interventional study (sample size-40 patients). Baseline evaluation was done by history, clinical examination, routine investigation, hormonal (FT4, total T3, and TSH), and serological profile (TSH receptor antibody). Patients were given either carbimazole or radioiodine therapy. During follow-up, we evaluated the patients by clinical examination, thyroid function test (free T4, total T3, and TSH), and serological test (TSH receptor antibody titer) for 12 months. We also assessed their quality of life at the baseline and at the end of 12 months of study by SF-36. Results: The mean age was 34.43 ± 13.22 years. Sex ratio (F = 52%, M = 48%). Mean body mass index was 19.67 kg/m2 [Table 1]. Conclusion: Findings suggest that administration of carbimazole causes improvement in thyrotoxicosis symptoms. There are statistically significant improvements for the different parameters. There is significant (statistically) improvement in quality of life over 12 months.{Table 4}

Keywords: Autoimmune, Graves' disease

 Effect of Vitamin D supplementation on thyroid autoimmunity among the subjects of autoimmune thyroid disease in coastal Odisha, India



Kishore Kumar Behera, Gautom Kumar Saharia1, Debasish Hota2, Madhusmita Sethy3

Departments of Endocrinology,1Biochemistery,2Pharmacology,3Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India.

E-mail: endocrin_kishore@aiimsbhubaneswar.edu.in

Introduction: Autoimmune thyroid disorders (AITD) have been linked to Vitamin D deficiency, but whether Vitamin D supplementation is reversal is not established. Objective: Whether Vitamin D supplementation could reduce thyroid autoantibodies and improve thyroid function test. Setting: The study was conducted in Endocrinology Outpatient Department, AIIMS, Bhubaneswar, Odisha, India. Methods: Twenty-two female patients and one male patient were included and followed for 6 months. All the participants were given weekly supplementation with 60,000 IU Vitamin D3 for 2 months, then once a month for 4 months was given. Outcome Measure: Difference in preintervention and postintervention antithyroid peroxidase antibody (TPOAb) levels. Additional outcomes were differences in thyroid-stimulating hormone (TSH). Results: There were significant differences in change after 6 months of vitamin supplementation on TPOAb (746.835 ± 332.24 to 954.09 ± 459.76; P = 0.006) and TSH (7.23 ± 3.16 to 3.04 ± 2.62; P = 0.01) [Table 3]. Mean serum 25(OH) D3 increased from 15.33 ± 5.71 to 41.22 ± 12.24 after Vitamin D3 supplementation [Table 2]. Conclusion: There was a significant increase TPOAb titer after Vitamin D3 supplementation and improvement of thyroid function test who had low Vitamin D3 levels at baseline.{Table 5}{Table 6}{Table 7}

Keywords: Antithyroid peroxidase antibody, autoimmune thyroid diseases

 Clinical utility of TSH receptor antibody in differentiating Graves' disease from other causes of thyrotoxicosis



Tittu Oommen, Mathew John, Rejitha Jagesh, G. Deepa

Providence Endocrine and Diabetes Specialty Centre, Trivandrum, Kerala, India. E-mail: drtittu@gmail.com

Introduction: In subjects with suppressed TSH, diagnosing Graves' disease (GD) will make a difference in management. GD is conventionally diagnosed with clinical features and nuclear scintigraphy in India although the use of TSH receptor antibody (TSHRAb) is gradually increasing. Methods: This was a retrospective analysis of all the patients who underwent TSHRAb in private endocrine practice. The clinical utility of TRAB was assessed against thyroid technetium (Tc) uptake in subjects where both were available and against clinical and follow-up diagnosis in all patients. TSHRAb was done by ECLIA method in Roche e411. The cutoff of positivity in the assay was >1.75 IU/L. For interpretation of Tc scans, the initial diagnosis at reporting and reporting by a treating endocrinologist was considered separately. Results: Over 3 years, 198 patients underwent TRAB testing. Of these in 171 patients, TSHRAb was used for differentiating GD from other causes of thyrotoxicosis. The final diagnosis of follow-up was GD in 99 patients, thyroiditis in 65 patients, gestational toxicosis in 4 patients, and toxic MNG or AFTN in 1 patient. Of 97 patients in whom Tc scans were available, 76 (78.35%) patients had concordant results in their clinical features, Tc scans, and TRAB. In 99 patients with GD, 88.89% (88 patients) of subjects had TSHRAb positivity. In 25 (38.46%) subjects, despite TSHRAb positivity, the final diagnosis was thyroiditis on follow-up. In patients where a Tc scan was done, the initial diagnosis of the Tc scan did not correlate with final diagnosis in 21 (21.65%) patients. Of 88 patients with TSHRAb positivity where the titer of TSHRAb was >3, the sensitivity of TSHRAb was 94.32%.

Keywords: Graves, thyrotoxicosis, TRAB

 Thyroglobulin antibodies in thyroid carcinoma: Prevalence, correlation with clinicopathological characteristics, and implications on disease outcome



Lakshmi Nagendra, Revathy Vinu, Vasantha Nair, Usha V. Menon, Nisha Bhavani, Praveen V. Pavithran, Arun S. Menon, Harish Kumar, Nithya Abraham, Prem Narayanan

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

E-mail: drlakshminagendra@gmail.com

Introduction: Differentiated thyroid cancer (DTC) is the most common endocrine cancer. Serum thyroglobulin (Tg) assays and neck ultrasonography are currently the mainstays of postoperative surveillance in patients with DTC. The impact of thyroglobulin antibody (TgAb) on outcome of DTC is controversial. Many, but not all studies, have shown that trends in TgAb help to assess recurrence and progression of DTC. Aims: (1) To assess the prevalence of TgAbs in patients with thyroid cancer and the correlation of TgAb with clinicopathological features, risk category, and treatment-related factors. (2) To study the characteristics, natural history of TgAb, and its implications on disease outcome. Materials and Methods: A total of 722 patients in The Amrita Thyroid Cancer Database with DTC were retrospectively assessed. Further, patients with antibody positivity at 6 months were studied for the correlation between the TgAb trend, recurrences, and clinical end point at the end of 3 years. Results: Prevalence of TgAb in DTC patients in our study was 39.1%. Presence of TgAb at 6 months was significantly higher in female sex, younger patients (age <55 years), and patients with lymphocytic infiltration on histopathology. The presence of TgAb positivity at 6 months did not correlate with tumor size, high-risk histology, capsular invasion, vascular invasion, tumor foci, or metastasis. At the end of 3 years, 31.8% (64/201) of patients with a stable/decrease in TgAb trend had no evidence of disease compared to 0% (0/8) of patients with increasing antibody trends. However, the difference was not significant (P = 0.127). Recurrence was seen in eight patients over the 3-year follow-up period. Of the eight patients, five patients had declining TgAb trend, two patients had a stable antibody trend, and one patient had an increasing TgAb trend. Discussion and Conclusion: Presence of TgAb positivity was not associated with any markers of disease severity at 6 months. TgAb trend did not correlate with clinical end points or disease recurrence.

Keywords: Disease outcome, thyroglobulin antibody trend

 Technetium MIBI scintigraphy in Indian patients with amiodarone-induced thyroiditis: imaging characteristics and response patterns



P. R. Manjunath, V. P. Praveen, P. Shanmugha Sundaram, Nisha Bhavani, Vasantha Nair, Harish Kumar, Arun S. Menon, Usha Menon, Nithya Abraham, Prem Narayanan

Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India. E-mail: dr.manjunathpr@gmail.com

Aims and Objective: Technetium (Tc) MIBI in amiodarone-induced thyroiditis (AIT) management in the Indian context is not well described. In this case series, we describe varying types of Tc MIBI patterns and responses in patients with AIT. Materials and Methods: Retrospective data of patients from hospital information system of 13 patients with AIT from 2017 to 2019 were used in this case series. Homogenous increased and decreased uptake in Tc MIBI was taken as type 1 and type 2, respectively. Inhomogenous uptake or requiring dual therapy as mixed forms. Statistical analysis for was performed with SPSS Version 17. Results: Majority of the patients in this series were males 11 (61.1% vs. 11.1%) with a median age of 57 ± 16.8 years. The median dose of amiodarone was 200 mg/day. The median time to thyrotoxicosis from the initiation of amiodarone was 27.5 months. Type 2 AIT was the most common pattern (6, 46.2%) seen. One patient with Type 1 AIT responded spontaneously without treatment. Median carbimazole dose and duration in type 1 AIT were 30 mg/day and 25.1 months, respectively. In patients with Type 2 AIT, two patients who were scintigraphically Type 2 required sequential introduction of steroids and antithyroid drugs. Median dose of steroids was 30 mg/day and duration was 10 ± 9.6 months, respectively. Median dose of carbimazole was 40 mg/day and duration was 3.5 ± 5.5 months in patients with Type 2. Two patients with mixed AIT became euthyroid by the 2nd month after therapy. In mixed forms, the median dose of steroids was 25 mg/day and duration was 2 months with carbimazole dose 30 mg/day and duration was 8 ± 6.1 months. Discussion and Conclusion: MIBI can be a single diagnostic scan for patients suspected to have AIT. Patients with AIT Type 1 responded earlier than AIT Type 2 patients. Significant number of patients had mixed AIT (3/13). Few times both imaging findings and clinical response needs to be considered for final decision in these patients.

Keywords: Amiodarone-induced thyroiditis, technetium MIBI

 Rescue plasma exchange followed by emergency total thyroidectomy in Grave's disease associated thyrotoxicosis complicated with carbimazole induced hepatitis and pancreatitis: A case report



Aprajita Pradhan, Khalid J. Farooqui, Sunil Kumar Mishra, Mukesh Nandal1, Sukrit Sud1

Departments of Endocrinology and Diabetology and1Gastroenterology, Medanta –The Medicity, Gurgaon, Haryana, India. E-mail: Aprajitapradhan@gmail.com

Introduction: The management of a patient with Grave's thyrotoxicosis with liver dysfunction is challenging. We present an unusual case of severe hyperthyroidism and hepatitis in which rescue plasmapheresis was used as a bridge to definitive therapy with thyroidectomy. Case: We report a case of a previously healthy 52-year-old male who was diagnosed as having hyperthyroidism due to Grave's disease on investigation for weight loss and was started on carbimazole. Consequently, the patient developed abdominal pain, pruritus, progressive icterus and presented to hospital, with concomitant transaminasemia, direct hyperbilirubinemia, and hyperamylasemia with pancreatitis. His initial TSH <0.015 uIU/ml, free T3 19.2 pg/ml with free T4 >6.9 ng/dl. Carbimazole was withdrawn, and he was conservatively managed on beta-blockers till the resolution of acute pancreatitis. However, he continued to worsen and was readmitted with recurrent vomiting, decreased oral acceptance, odynophagia, and persistent pruritus. The use of an oral steroid for the management of thyrotoxicosis was negated due to esophageal candidiasis. Radioiodine treatment was not an option as the patient had already received iodinated contrast for abdominal imaging. In lieu of paucity of therapeutic options, trial of therapeutic plasma exchange was given to improve hyperbilirubinemia and decrease serum thyroxine level before total thyroidectomy was done. The patient is currently stable on replacement thyroxine. He has since shown recovery of liver functions. Discussion and Conclusion: In the presence of concomitant hepatic dysfunction, therapeutic options for treating thyrotoxicosis are limited, but this strategy can be a way around. We could not find any similar case report of carbimazole-associated hepatitis and pancreatitis, treated with plasma exchange and total thyroidectomy.[1],[2]

Keywords: Carbimazole, hepatitis, plasma exchange, thyrotoxicosis

References

Ahmeti I. Thyrotoxicosis associated with cholestatic jaundice treated with therapeutic plasma exchange–case report. Thyroid Disord Ther 2017;6:211.Akmal A, Kung J. Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity. Expert Opin Drug Saf 2014;13:1397-406.

 Genetic spectrum of dyshormonogenesis in childhood hypothyroidism



Sonali Appaiah, Dipti Sarma1, Kandarpa Kumar Saikia2, Madhuchanda Sarma2

Department of Endocrinology, St. John's Medical College and Hospital, Bengaluru, Karnataka,1Department of Endocrinology, Gauhati Medical College,2Department of Bioengineering and Technology, GUIST, Gauhati University, Guwahati,Assam, India.

E-mail: sonaliappaiah2@gmail.com

Introduction: Dyshormonogenesis (DH) is one of the most common causes of primary hypothyroidism (PHT) in children and adolescents along with Hashimoto's thyroiditis. Molecular basis of DH involves genetic variation in seven genes involved in thyroid hormone biosynthesis, namely thyroglobulin (TG), thyroid peroxidase (TPO), dual oxidase 2 (DUOX2), dual oxidase maturation factor A2 (DUOXA2), iodotyrosine dehalogenase 1, sodium iodide symporter (SLC5A5), and pendrin (SLC26A4). Severe defect in thyroid hormone biosynthesis presents itself as congenital PHT, while milder defect can have delayed presentation in children and adolescents. Aims and Objective: To study the clinical and genetic profile in children with PHT due to DH. Materials and Methods: The present study was conducted in the Department of Endocrinology, Gauhati Medical College Hospital, in thirty children (<18 years) with PHT due to DH. DH was diagnosed in cases with PHT based on the presence of goiter clinically with eutopic thyroid gland in thyroid ultrasonography, uptake on technetium 99 scintigraphy of thyroid, normal anti-TPO titer, normal spot urine iodine levels, and normal fine needle aspiration cytology findings. Mutation in TPO, DUOX2, DUOX2, TG, and NIS genes was screened in these cases. Results: The mean age of patients with DH at presentation was 8.06 ± 4.89 (0.91–18) years, and the male-to-female ratio was 1:1.7. Goiter was present clinically in all patients. History of delayed developmental milestones was seen in 33.3% (10) and short stature in 53.28% (16) of patients, and family history of PHT was seen in 30% (9) of patients. The median (range) thyroid-stimulating hormone of patients with DH was 79.7 (6.15–100) μIU/mL, T4 was 46.8 (8–151.8) nmol/L, and TG levels was 323 (0.04–500) ng/mL. Subclinical PHT was seen in 30% (9) of patients. We detected mutation in the TPO gene in 11 (36.63%) patients, with adenosine deletion at position 1542480. Cytosine deletion at position 1542461 with frame shift mutation in the TPO gene was also seen in 1 (3.33%) patient. Discussion and Conclusion: DH has variable presentation in childhood, including both mild subclinical PHT and severe forms of PHT presenting with neurocognitive and growth impairment. TPO gene mutation was found to be the most common cause of DH in our study, which is similar to data from the West. A study from South India found NIS to be the most common cause of DH. Gene mutation screening in these children could facilitate genetic counseling and early identification of subsequent cases in the same family.

Keywords: Childhood hypothyroidism, dyshormonogenesis, genetic study

 Thyroid-related adverse effects of alemtuzumab in patients with multiple sclerosis



Aprajita Pradhan, Candy Sze1

Department of Endocrinology and Diabetology, Medanta - The Medicity, Gurgaon, Haryana, India,1Queen Mary University and St. Bartholomew's Hospital, London, UK. E-mail: aprajitapradhan@gmail.com

Background: Alemtuzumab (anti-CD 52 monoclonal antibody) has been approved for the treatment of multiple sclerosis (MS). The most important side effect of alemtuzumab is novel autoimmunity and takes the form of thyroid autoimmunity in most patients.[1] Aim: The aim of this study is to investigate the incidence, course, and outcome of endocrinological adverse effects in patients of multiple sclerosis, treated with anti-CD 52 antibody. Material and Methods: Data were collected from a prospective registry maintained at The Royal London Hospital of patients who were started on alemtuzumab between November 2014 and March 2017. The progression to endocrine adverse effects, clinical course, and clinical management were recorded. Results: Ninety-seven consecutive patients were included in this study. Eleven patients (11.34%) developed thyroiditis. Patients were predominantly female (7/11), with median age of 28.5 years (25–48). Around one-third (36%) of the affected patients eventually developed overt hypothyroidism requiring thyroxine replacement. Conclusion: The incidence of thyroid-related adverse effects was lower (11.39 vs. 30%)[2] in our study as compared to the existing literature. All the patients had thyroiditis in contrast to the previous studies in which the predominant thyroid-related adverse event noted was Graves' disease.[2] Thyroid disease is a common side effect of monoclonal antibody treatment, and the development of a detection and treatment pathway would be helpful in these cases.

Keywords: Alemtuzumab, multiple sclerosis, thyroid autoimmunity

References

Jones JL, Coles AJ. Mode of action and clinical studies with Alemtuzumab. Exp Neurol 2014;262 Pt A: 37-43.CAMMS223 Trial Investigators, Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, et al. Alemtuzumab vs. Interferon beta-1a in early multiple sclerosis. N Engl J Med 2008;359:1786-801.

 Immunoglobulin 4-related orbital disease masquerading as eosinophilia in thyroid-associated orbitopathy



Vaibhav Pathak, A. K. Baliarsinha, Arun Kumar Chaudhury, Rukma Rajnedra Narakar

Department of Endocrinology, SCB Medical College, Cuttack, Odisha, India. E-mail: drvaibhavpathak@gmail.com

Objectives: Immunoglobulin G (IgG) 4-related disease is an immune-mediated systemic condition characterized by the enlargement of affected organs caused by lymphoplasmacytic infiltration with a predominance of IgG4-positive plasma cells. Herein, we report a case of IgG4-related ocular disease mimicking thyroid-associated orbitopathy (TAO) constituting a unique clinical entity. Materials and Methods: A 72-year-old male, a known case of hypothyroidism and diabetes mellitus, presented with bilateral eyelid swelling (L > R) and redness for the last 3 months. He had similar episode 3 years back during which he was found to have hypothyroidism and treated as TAO with course of steroids. During the present evaluation, he was found to have eosinophilia, raised absolute eosinophil counts with raised erythrocyte sedimentation rate and C-reactive protein, which was suggestive of some alternative cause. Results: On further evaluation, his IgG4 levels were found to be raised, and computed tomography orbit showed diffuse muscle thickening with tendon sparing. He was treated with oral steroids with which he responded well. Further screening for other organ involvement was done which showed atrophic pancreas. To our surprise, in spite of the high doses of steroids, his glycemic status was normal all the time which led to a suspicion that his diabetes could be because of IgG4 disease-related involvement of pancreas. Conclusion: IgG4-related disease mimicking TAO suggests a common etiology as an autoimmune-like disease among autoimmune thyroid disease, TAO, and IgG4-RD. For diagnosis, this case highlights small clues such as raised eosinophils which should not be ignored.

Keywords: Eosinophilia, immunoglobulin G4-related disease, thyroid-associated orbitopathy

 PITUITARY



 Bone mineral density in hyperprolactinemia



Amanpreet Kaur Kalsi, Manish Jain, Ashutosh Halder

Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India.

E-mail: ashutoshhalder@gmail.com

Purpose: Hyperprolactinemia patients have been reported to have low bone mineral density (BMD). This study aimed to compare BMD and associated factors in hyperprolactinemia. Patients and Methods: A total of 35 hyperprolactinemia patients (>100 ng/ml serum prolactin levels) and 10 controls participated in the study. Hyperprolactinemia cases were classified into macroprolactinemia and true hyperprolactinemia by polyethylene glycol precipitation. Serum levels of prolactin, estradiol, calcium, phosphate, and alkaline phosphatase were measured. BMD was measured at lumbar vertebrae, left femur, and left wrist by dual-energy X-ray absorptiometry (DEXA) scan. Results: The prevalence of osteopenia/osteoporosis was 50% in macroprolactinemia patients, 70% in true hyperprolactinemia patients, and 60% in controls (P = 0.517). Pearson's correlation analysis did not find any significant correlation of prolactin, estradiol, calcium, phosphate, or alkaline phosphatase with T score or Z score at lumbar spine, femur, or wrist in hyperprolactinemia patients and controls. The only significant correlations were found between body mass index (BMI) and prolactin levels (r = 0.473, P = 0.003) and between BMI and total femur T score (r = 0.360, P = 0.015) and Z score (r = 0.362, P = 0.015). Mean BMI was also significantly high (P = 0.029) in hyperprolactinemia patients with normal DXA (28.7 ± 5.3 kg/m2) compared to those with osteopenia/osteoporosis (24.7 ± 4.8 kg/m2). Conclusion: There was no significant difference in incidence of osteopenia/osteoporosis in macroprolactinemia and true hyperprolactinemia patients. The only significant correlation of BMD was found with BMI suggesting high BMI to be a protective factor against osteoporosis in hyperprolactinemia patients.

Keywords: Body mass index, bone mineral density, hyperprolactinemia, macroprolactinemia, prolactin

 Our experience with macroprolactinomas



Simon Rajaratnam, Nihal Thomas, Thomas V. Paul, H. S. Asha, Nitin Kapoor, Ari George Chacko1, Bylis Vivek Joseph1, Vedantam Rajshekhar1

Departments of Endocrinology and1Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: simonrajaratnam@yahoo.com

Objective: The objective was to study the clinical profile and treatment response of macroprolactinomas. Methods: Between 2002 and 2018, 884 patients were diagnosed as prolactinomas and 373 had macroprolactinomas. Those coming for >1 year were included in this study. Those who had surgery or radiation therapy (RT) elsewhere were excluded. Classification: macroadenomas (M): tumors 1–3 cm, not invading surrounding structures; invasive macroadenomas (IM): tumors >3 cm, invading surrounding structures; and giant adenomas (GA): tumors >4 cm, invading surrounding structures. Results: This study included 100 (M), 66 (IM), and 40 (GA) patients. These tumors occurred mostly in men in the third decade. Patients with large tumors (IM and GA) presented with headache (47.5% and 57.6%) and decreased vision (59% and 60%). The median tumor volume (cm3) was 27 (M), 139 (IM), and 161 (GA). The median prolactin level (ng/dL) was 1003 (M), 4980 (IM), and 5676 (GA). Hypogonadism was very common in 89% (M), 86% (IM), and 83% (GA). Hypothyroidism occurred in 20% (M and IA) and 21% (GA). Hypocortisolism was seen in 8% (M), 16% (IM), and 11% (GA). All patients were treated with cabergoline; the median dose was 2 mg/week (range, 1–4.5 mg/week). Ten patients with M, 3 with IM, and 2 with GA underwent surgery as they could not afford medical treatment long term. Two patients with M also underwent RT. The median follow-up was for 4 years (range, 1–16 years). Median prolactin level (mg/dL) reduced to 6.9 (M), 12.2 (IM), and 13.9 (GA). Median tumor volume (cm3) decreased to 7 (M), 49 (IM), and 51 (GA). No tumor was seen in 28% (M), 20% (IM), and 21% (GA). Visual improvement occurred in 76% (M), 81% (IM), and 75% (GA). Hypogonadism improved in 63% of patients with (M), and 16/19 women with primary infertility conceived with treatment. Conclusion: Even large tumors (IM and GA) respond well to cabergoline, adjuvant treatment is usually not required. In patients with smaller noninvasive tumors (M), the gonadal axis usually recovers and fertility may be restored. Most patients will need to continue cabergoline long term.

Keywords: Giant adenomas, invasive macroadenomas, macroadenomas

 Predictors of hypopituitarism due to vasculotoxic snake bite with acute kidney injury



Sowrabha Bhat, Pradip Mukhopadhyay, Arpita Roychoudhury1, Subhankar Chowdhury, Sujoy Ghosh

Departments of Endocrinology and Metabolism and1Nephrology, IPGMER, Kolkata, West Bengal, India.

E-mail: sowrabhas@gmail.com

Aims and Objectives: Hypopituitarism frequently develops following vasculotoxic snake bite complicated by acute kidney injury (AKI). Well-defined prospective studies of the prevalence of hypopituitarism and its predictors in vasculotoxic snake bites complicated by AKI are unavailable. Methods: Fifty-one consecutive patients of AKI following vasculotoxic snake bite were evaluated for various clinical/biochemical parameters (including Free thyroxine4, thyroid-stimulating hormone, cortisol, adrenocorticotropic hormone, total testosterone, follicle-stimulating hormone, LH, prolactin, and insulin-like growth factor-1). Diabetes insipidus was evaluated in relevant cases. 20-min whole-blood clotting time (WBCT) at presentation was measured in all. Magnetic resonance imaging of hypothalamo-pituitary region was done at 3 months in patients with hypopituitarism to rule out structural lesion. Results: About 21.6% (11/51) patients developed hypopituitarism at baseline (within 7 days) and 39.3% (13/33) at 3 months developed hypopituitarism. Cortisol deficiency was the most common abnormality. Patients who developed hypopituitarism at baseline were younger compared to those without hypopituitarism (35.67 years vs. 46.59 years, P = 0.032) and required more sessions of hemodialysis (8 vs. 3, P = 0.041). Binary logistic regression confirmed that development of hypopituitarism could be predicted by increased number of sessions of hemodialysis (odds ratio [OR]: 1.51, P = 0.008) and 20 min WBCT (OR: 1.2, P = 0.038). Discussion and Conclusion: Hypopituitarism is common following vasculotoxic snake bite subjects who develop AKI. Hypopituitarism could develop as early as 7 days following snake bite and should be evaluated for particularly in younger patients, especially those requiring increasing number of session of hemodialysis and in patients with abnormal 20 min WBCT at presentation.

Keywords: Acute kidney injury, hypopituitarism, vasculotoxic snake bite

 A rare case of relapsing lymphocytic hypophysitis



Monika Goyal, C. M. Batra

Department of Endocrinology, Diabetes and Metabolism, Indraprastha Apollo Hospital, New Delhi, India.

E-mail: drmonika0889@gmail.com

Introduction: Lymphocytic hypophysitis is a rare autoimmune disease of the pituitary gland, although it is the most common histologic variant. Occur commonly during and shortly after parturition, rarely in menopausal women, 15% of cases have been reported in men presenting primarily with headache, visual impairment, hyperprolactinemia followed by hypoadrenalism and other pituitary dysfunction. Diagnosis is based on magnetic resonance imaging (MRI) suggestive of thickened pituitary stalk in the background of relevant clinical history. Management includes replacement of deficient hormone and steroids, and rarely, surgery is indicated. Usually self-limiting disease, but secondary adrenocortical cell atrophy is common, and resultant empty sella is frequent outcome. Recurrence is very rare phenomenon in lymphocytic hypophysitis with only 8 cases reported. We are discussing one such case. Case Report: A 34-year-old male presented with symptoms of headache for 6 months, decreased libido, erectile dysfunction, polyuria, and polydipsia for 3 months. MRI brain revealed an enlarged pituitary gland with thickened pituitary infundibulum and mildly elevated optic chiasma. An investigation done for pituitary dysfunction showed that the patient had luteinizing hormone (LH) with hypogonadotropic hypogonadism (HH) with central hypothyroidism (CH) without neuro-ophthalmologic compromise and diabetes insipidus, with new-onset diabetes mellitus type 2. The patient was started on wysolone and injectable HCG and OHA. Serial MRI showed reduction in lesion, and steroids were tapered slowly over a period of 6 months. Within a week of steroids withdrawal patient presented with adrenocortical insufficiency (AI) with repeat MRI showed again enlarged pituitary with thickened stalk and was diagnosed with LH relapse. The patient was initially treated with high-dose steroids. Serial MRI showed reduction in pituitary enlargement. Steroids were gradually withdrawn slowly over a period of 1 year. It has been 6 months that the patient is off steroids with partial recovery of pituitary dysfunction, i.e. AI but persistent HH and CH. Conclusion: LH is a rare disease, usually self-limiting, and may present with relapse like other autoimmune conditions, emphasizing the need of periodic follow-up of these patients.{Figure 12}{Figure 13}{Figure 14}{Figure 15}

Keywords: Hypogonadotropic hypogonadism, lymphocytic hypophysitis, relapsing

 A rare case of adult-onset Langerhans cell histiocytosis presenting with diabetes insipidus



Sandeep Sahu, Arun Kumar Choudhury, Anoj Kumar Baliarsinha

Department of Endocrinology, SCB Medical College and Hospital, Cuttack, Odisha, India.

E-mail: docsandy.rihan@gmail.com

Introduction: Langerhans cell histiocytosis (LCH) is characterized by a clonal proliferation of Langerhans cells from single organ to multisystem involvement. About half of the cases have hypothalamic-pituitary involvement. Immunohistochemistry is essential for the diagnosis, and the treatment protocols are controversial. Objective: LCH is often misdiagnosed because of its various clinical features and laboratory results. In view of this, its clinicopathological, histopathological, immunohistochemical features are to be analyzed for correct diagnosis. Materials and Methods: A 30-year-old female patient presented with complaints of swelling over the scalp, ear discharge, hearing loss, amenorrhea, excessive thirst, and urination. There was no history of trauma. There was no evidence of any skin lesions. There was no history of pain or swelling of both eyes. Results: On evaluation, she was found to have diabetes insipidus. Other routine parameters and screening for anterior pituitary hormones were within the normal limits. Magnetic resonance imaging of pituitary revealed relatively hypovolemic pituitary and thickened pituitary stalk. X-ray skull revealed multiple lytic lesions. Punch biopsy of the skull was suggestive of Langerhans cell histiocytosis. Based on history, examination, and histopathological findings, a diagnosis was Langerhans cell histiocytosis was made. She was managed symptomatically, put on desmopressin nasal spray and planned for radiation therapy. Conclusion: LCH has high rate of misdiagnosis and definitive diagnosis depends on pathological biopsy and X-ray examination. The prognosis is related to the onset age and the quantity of affected organs. Although specific therapeutic approach has not been well established, combined chemotherapy for multisystem lesions and surgical operation or radiotherapy for unifocal lesions may improve the therapy.

Keywords: Adult, diabetes insipidus, langerhans cell histiocytosis

 Evaluation of cardiovascular risk factors in Sheehan syndrome



Mayur Agrawal, Subhash Yadav, Sheo Kumar1, Krishnarpan Chatterjee2

Departments of Endocrinology,1Radiology and2Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. E-mail: mayuragrawal2006@gmail.com

Introduction: Sheehan syndrome (SS), also known as postpartum pituitary necrosis, is a rare cause of hypopituitarism in the developed countries but still common in the developing world and is associated with increased mortality. One of the important causes of SS is cardiovascular disease. Aims and Objective: In this cross-sectional study, we aimed to find out the cardiovascular risk factors associated with SS. Materials and Methods: Forty-five women diagnosed with SS attending the outpatient department at Sanjay Gandhi Post Graduate Institute of Medical Sciences on standard replacement therapy were included in the study. All patients underwent history, clinical examination, hormonal evaluation (T4, insulin-like growth factor-1, 8-AM cortisol, SST, adrenocorticotropic hormone, follicle-stimulating hormone, prolactin), oral glucose tolerance test, lipid, insulin, interleukin-6, high-sensitivity C-reactive protein, carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD), and two-dimensional echocardiography. Results: Forty-five patients were recruited. The mean age and body mass index of the patients was 48.3 ± 9.6 years and 23.7 ± 3.9 kg/m2, respectively; 82.2% of the patients had a history of postpartum hemorrhage, 93.33% had lactation failure, and 97.7 had amenorrhea. Nearly 40% of the patients were hypertensive, whereas 22.2% were diagnosed to have Type 2 diabetes mellitus. The prevalence of metabolic syndrome in our cohort was 37.7%. The mean CIMT was 0.624 ± 0.107, which is statistically significantly higher than normative data (P = 0.0084) and mean FMD change was 20.7 ± 11.08%. Discussion and Conclusion: SS patients have increased mortality due to various causes. Growth hormone deficiency is the most common reason according to literature; also, unphysiological steroid replacement, inadequate thyroxine replacement, and sex steroid replacement may contribute to this increased risk. These patients have an increased risk of metabolic and cardiovascular risk factors.

Keywords: Cardiovascular risk, carotid artery intima-media thickness, flow-mediated dilation, hypopituitarism, Sheehan syndrome

 Pituitary adenomas in children and adolescents: Clinicobiochemical profile, genetic background, and treatment outcomes



Satyam Singh Jayant, Rimesh Pal, Liza Das, Pinaki Dutta

Department of Endocrinology, PGIMER, Chandigarh, India. E-mail: drsatyam9680@gmail.com

Introduction: Pituitary adenomas in children and adolescents are rare with only 2%–6% of surgically treated adenomas occurring in children and adolescents. Aims and Objectives: To find the clinicobiochemical profile, genetic background, and treatment outcomes in young-onset pituitary adenomas diagnosed in our tertiary care hospital. Materials and Methods: Patients of 20 years of age or younger at presentation with confirmed diagnoses of pituitary adenoma on imaging and/or histopathology were retrospectively analyzed from January 2010 to December 2018. Results: A total of 74 cases were identified with a median age at diagnosis of 15 years and a male: female ratio of 1.6:2.1. The most common subtype was corticotropinoma (32.4%), followed by somatotropinoma (25.7%), prolactinoma (23%), nonfunctioning pituitary adenoma (16.3%), thyroid-stimulating hormone-oma (1.3%), and pituitary blastoma (1.3%). 75.6% of cases were macroadenoma and 24.4% microadenoma. At baseline, hypocortisolism was the most common hormone deficiency observed in 44.5% of cases, followed by hypothyroidism (25.6%), hypocortisolism (19%), and growth hormone deficiency (12.2%) cases. 65 cases underwent genetic analysis of which three were familial pituitary adenoma. Of these three familial cases, two patients were found to have AIP and GNAQ gene mutation, respectively. No mutation was identified in the third familial case. X-linked acrogigantism microduplication was identified in one girl with somatotropinoma. Sixty (81%) patients underwent surgical tumor excision; the rest 14 patients were managed medically. At a median follow-up of 24 months, 56.7% of the patients achieved clinical and biochemical remission. Conclusion and Discussion: pituitary adenomas cause neuro-ophthalmological symptoms and deter normal growth and puberty. Prolactin is critical in the diagnostic workup as patients with prolactinomas can be effectively managed with primary medical therapy. In all other adenomas, surgery forms the mainstay of therapy with or without adjuvant radiotherapy/pharmacotherapy.

Keywords: Pituitary adenoma children, TSS

 Prevalence of colonic polyps and colonic malignancy in patients with acromegaly



Priyamvada Tyagi, Purnima Agarwal1, Praveer Rai2, Sushil Gupta

Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh,1Department of Endocrinology, VMMC and Safdarjung Hospital, New Delhi,2Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

E-mail: 1priyamvada.tyagi@gmail.com

Introduction: Active acromegaly predisposes to colonic polyps and colonic malignancy. However, there is limited information about their prevalence in Indian subjects. Aims and Objective: In this case–control study, we studied the prevalence of colonic polyps and malignancy in patients with acromegaly and assessed risk factors. Materials and Methods: Ninety-eight (51 males/47 females) patients with biochemically confirmed acromegaly underwent full length (unsuppressed GH after oral glucose load and/or elevated IGF-1 matched for age and gender) and histopathology of colonic lesions. The control group (n = 200) was subjects of IBS undergoing colonoscopy. Clinical and biochemical parameters in acromegalic patients with colonic polyp were compared to those without a polyp. Results: Twelve acromegaly patients (12.2%) had colonic polyps as compared to 11 (5.5%) in the control group (P = 0.013). All acromegaly patients had active disease at the time of colonoscopy. FBS was higher in those with polyps (P = 0.024) as compared to patients without polyps. We did not observe significant correlation between presence of polyps and IGF-1 levels, acanthosis nigricans and skin tags, or presence of occult blood in stools. Discussion: The prevalence in this study is 12.2%, which is statistically significant as compared to the control population. Low-grade dysplasia was seen in 4/12 patients and none had adenocarcinoma. Conclusion: The present study shows increased the prevalence of colonic polyps among patients with acromegaly, mandating screening of all patients with acromegaly.

Keywords: Acromegaly, colonic polyps

 Respiratory comorbidities in patients with acromegaly: A case–control study



Priyamvada Tyagi, Ravi Mishra1, Zia Hashim1, Alok Nath1, Sushil Gupta

Departments of Endocrinology and1Pulmonary Medicine, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. E-mail: 1priyamvada.tyagi@gmail.com

Introduction: Respiratory and cardiovascular comorbidities occur in more than 50% patients with acromegaly and predispose to higher morbidity and mortality. Aims and Objectives: In this cross-sectional study, we studied respiratory complications in subjects with acromegaly by polysomnography, pulmonary function tests (PFTs), and high-resolution computed tomography chest. Transthoracic echocardiography and other cardiovascular risk factors were studied. Materials and Methods: Thirty-four patients with biochemically diagnosed and active acromegaly (17 men and 17 women; mean age, 50 ± 13 years) were enrolled. A group of 34 healthy subjects (19 men and 15 women; mean age, 54 ± 18 years) with no symptoms or signs of any severe disease served as controls. Results: The mean duration of symptoms of acromegaly was 5.59 ± 5.1 years. Patients with acromegaly had higher body mass index as compared to controls (P < 0.05). There was no significant difference in apnea–hypopnea index between acromegaly and control subjects. However, patients with acromegaly had significantly higher prevalence of apnea (40%) as compared to controls. This difference was observed in mixed type, central, and obstructive types of apnea. On PFT, 14 (41%) had restrictive lung disease, 4 (11.7%) had obstructive, and rest had normal results. On two-dimensional echo, there was no difference between left ventricular mass in patients and controls. Discussion: There is high prevalence of sleep apneas in acromegaly patients as compared to controls. Majority had hypertension and diabetes but no difference in echocardiography findings. Conclusion: Respiratory comorbidities are highly prevalent in patients with acromegaly. Screening and regular follow-up are indicated for all patients.

Keywords: Acromegaly, respiratory, sleep apnea

 The assessment of gonadal function in male prolactinoma who are in remission: Single-center experience



Manjeetkaur Sehemby, Anurag Lila, Swati Jadhav-Ramteke, Virendra Patil, Nalini Shah, Tushar Bandgar

Department of Endocrinology, King Edward Memorial Hospital, Mumbai, Maharashtra, India.

E-mail: anuraglila@gmail.com

Introduction: Macroprolactinomas constitute half of all functioning pituitary macroadenomas. Because of delay in diagnosis, males harbor larger tumors at presentation as compared to females. Gonadal axis involvement in macroprolactinoma could be either due to suppression of GnRH secretion or due to direct pressure effect of expanding tumor mass on gonadotrophs leading to their permanent damage. Hence, not all patients have recovery of gonadal axis on the remission of prolactinoma. The present study is conducted to determine the status of gonadal axis in male prolactinomas who are in remission on medical management. Aims: The aim is to assess the status of hypothalamic–pituitary–gonadal axis in male patients with macroprolactinoma who are treated medically and are in remission. Secondary Objectives: The objective of the study is to assess the status of hypothalamic–pituitary–adrenal axis, thyroid axis, and growth axis. Materials and Methods: Prospective analysis of 28 patients from 2001 to 2018 was done. Male macroprolactinoma patients who were hypogonadal at presentation and who achieved remission on medical management were enrolled in the study. Injection testosterone was discontinued for 3 months before and the analysis of gonadal function was done. Results: Totally 28 patients were enrolled in the study. About 22% of patients achieved eugonadism at remission. Other axes were rarely involved at presentation (hypothyroidism 7%, hypocortisolism 3.5%, and growth axis 27%). On remission, hypothyroidism, hypocortisolism, and growth axis involvement was seen in 3.5%, 7%, and 3.5%, respectively. It was seen that other axes were involved (at presentation and remission) only in those patients who remained hypogonadal at remission. Baseline median prolactin level in patients who achieved eugonadism was significantly lower than patients who remained hypogonadal (1640 vs. 3770, P = 0.03), baseline serum luteinizing hormone (LH) was higher in patients who achieved eugonadism as compared to patients who remained hypogonadal (4.05 ± 2.8 vs. 1.76 ± 1.02, P = 0.0032). Conclusion: Compared to world literature, in our cohort, recovery of gonadal axis at remission is poor (22%). Baseline high prolactin and low serum LH are predictors for persistent hypogonadism. Although other axes involvement is uncommon, the involvement is seen only in those patients who remain persistent hypogonadal.

Keywords: Cabergoline, macroprolactinoma, male hypogonadism, recovery

 Genotype and phenotype in Kallmann syndrome with a report of novel mutations: A case series



Piyush Dilip Lodha, Vijay Sheker Reddy Danda, P. Sreenivas Rao, Madhavi Verepula, Chaitanya Konda, Krishna Reddy Thaduri

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

E-mail: piyushlodha001@gmail.com

Introduction: Congenital-isolated hypogonadotropic hypogonadism presents with the absence of puberty and if left untreated leads to infertility. It has a considerable clinical and genetic heterogeneity. Aim and Objective: To study the clinical, biochemical, radiological, and genetic characteristics of the cases of anosmic hypogonadotropic hypogonadism. Materials and Methods: We analyzed five subjects presenting to our department with hypogonadotropic hypogonadism. Phenotypic features and hormonal studies were analyzed along with clinical exome by targeted gene sequencing (next-generation sequencing). Forty relevant genes were tested in the analysis. Results: All cases had severe reproductive phenotype. Four subjects out of five had absent olfactory bulbs on magnetic resonance imaging while one subject had normal olfactory apparatus. 2/5 had bimanual synkinesia. One of these two subjects had unilateral renal agenesis and the other had submucosal cleft palate. Mutations were found in four out of five subjects. One mutation was X linked and the rest were autosomal. Of the 5 subjects clinically labeled as Kallmann syndrome, 2 out of 5 had mutations in KAL1 gene. Two siblings had similar heterozygous mutation at the same location in CHD7 gene with autosomal dominant inheritance. The mutation in CHD7 gene was at exon 2 variant 1565G>T (p.Gly522Val) which was confirmed with Sanger sequencing. One out of five subjects had no mutation detected. Conclusion: In our series, 4 out of 5 cases had genetic mutations, most of them being autosomal. There was significant diversity in the mutations and phenotype. Severe reproductive phenotype irrespective of genetic mutations was seen. Few new variants were found as a large number of genes were analyzed. We report a novel heterozygous mutation in CHD7 gene with pathogenic phenotypic spectrum without other features of CHARGE syndrome.

Keywords: Genetic mutations, hypogonadotropic hypogonadism, phenotype–genotype correlation

 A case of central diabetes insipidus as a cause of unexplained hydroureteronephrosis



Giridhar Adapa, Rakesh K. Sahay, K. Neelaveni

Osmania Medical College, Hyderabad, Telangana, India.

E-mail: giri.adapa@gmail.com

Background: Prolonged polyuria as a cause of bilateral, nonobstructive hydronephrosis was first described by Osler in 1892. Since then, excessive urine flow and extensive dilatation of the urinary tract have been most frequently documented not only in young children with nephrogenic diabetes insipidus (DI), often hereditary and X-linked, but also in patients with central DI (CDI) and psychogenic polydipsia. Case Report: We report a 19-year-old girl admitted to the nephrology ward in May 2019 because of polyuria, acute kidney injury (AKI), and hypokalemia (serum creatinine 1.4 mg/dl, creatinine clearance 65 ml/min/1.73 m2, and serum potassium 1.7 mEq/l) associated with bilateral hydronephrosis and hydroureters. On further investigations, hydronephrosis was nonobstructive and the cause was unexplained, referred to endocrinology for evaluation of polyuria and polydipsia. Relevant history included compulsive water drinking and polyurea from the age of 12 years. On examination, the patient weighed 32 kg and she was normotensive. Urinalysis was normal. 24-h water intake was 6 l and output was 6.5 l. Urine osmolarity was 65 mOsm/kg and serum osmolarity 290 mOsm/kg, suggesting DI. Water deprivation test was carried and found to have CDI. Magnetic resonance imaging brain showed absent pituitary bright spot and started desmopressin spray 10 mcg/day. Polyurea and polydipsia subsided and creatinine and hypokalemia improved. Repeat ultrasound after 1 month of treatment showed partial improvement in hydroureteronephrosis. Conclusion: DI can be a cause of unexplained hydroureteronephrosis. Appropriate evaluation and medical management avoid unnecessary surgical procedures and improve patient conditions.

Keywords: Diabetes insipidus, hydrouretronephrosis, polyurea

 Prevalence and patterns of postoperative polyuria and hyponatremia in the immediate course after transsphenoidal



Avinash Patil, V. Suresh, Alok Sachan, Sree Divya

Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India.

E-mail: dravinashptl@gmail.com

Objective: This study was performed to examine the prevalence and predictors of polyuria and hyponatremia after a complete and selective removal of pituitary adenomas through the transnasal–transsphenoidal approach. Introduction: Surgery in the sellar region is often accompanied by disturbances of water/electrolyte metabolism and osmoregulation, probably due to manipulation and/or vascular alterations of the neurohypophysis. The water and electrolyte disturbances manifest as Diabetes insipidus (DI) and/or hyponatremia. DI is the result of a lack of ADH, and hyponatremia is probably primarily due to an SIADH. The aim of this study was to study the prevalence of these disorders in the postoperative period and their course. Design: Fifty-four patients with pituitary adenomas, operated between 2014 and 2019 in the department of neurosurgery, were evaluated retrospectively in the postoperative period for 10 days. The prevalence of patterns of DI and SIADH was studied. Results: The study included 54 patients with a mean age of 42.8 ± 13.82 years. About 57.4% of them were females and 43.6% were males. About 70.4% of patients harbored nonfunctioning tumors and 29.6% had functionally active pituitary adenomas. Among the cases, 93% of patients had macroadenomas (>10mm) and only 7% had microadenomas (<10mm). Central hypothyroidism was seen in 53.7% and adrenal insufficiency in 42.6% both of which were corrected preoperatively. Postoperative water and electrolyte disturbances occurred in 65.4% of the patients; in 27.4% as isolated DI; in 35.2% as isolated hyponatremia; and in 15.7% as combined DI-hyponatremia. The maximum amount of diuresis in patients with isolated DI occurred on a postoperative day 2 with the highest value of median sodium level of 146 mmol/L. Nadir of medians of hyponatremia (132 mmol/L) in patients with isolated hyponatremia occurred on postoperative day 7 with the lowest value of median sodium of 128 mmol/L. Altogether, 27.8% of the patients had to be treated with vasopressin transiently. Of all the patients with hyponatremia, 20.8% were treated by transient fluid-intake restriction due to a sodium level of <130 mmol/L with or without clinical symptomatology. Conclusion: Water and electrolyte disturbances occurred in the majority of patients undergoing transsphenoidal resection of the tumor and were usually transient. DI usually occurs during the 1st or 2nd postoperative day and resolves in the majority of cases. Hyponatremia usually occurs at the end of the 1st postoperative week and resolves in most cases within 5 days. Very few patients will need treatment other than fluid-intake restriction to avoid serious complications. Thus, careful monitoring of the water and electrolyte disturbances in patients undergoing transsphenoidal pituitary adenoma surgery is mandatory for the first 7 postoperative days.

Keywords: Diabetes insipidus, pituitary, polyuria, SIADH

 Diabetes insipidus – Varied clinical presentations



Devireddy Sandeep Reddy, D. Vijay Sheker Reddy, P. Srinivas Rao, V. Madhavi, K. Chaitanya, T. Krishna Reddy

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

E-mail: slahssandy@gmail.com

Introduction: Diabetes insipidus (DI) is a relatively uncommon clinical problem and has varied clinical presentations ranging from significant polyuria disturbing daily activities to being masked under other hormonal deficiencies only to be unmasked after treatment. Aims and Objectives: The aim is to study clinical characteristics of cases of DI. Materials and Methods: We analyzed the varied presentations of patients diagnosed as DI, at the Department of Endocrinology, Gandhi Hospital, Hyderabad, during the year 2018–2019. Results: We have studied six cases of DI and the initial clinical presentation of each subject was as follows: (1) Episodic hypokalemic periodic paralysis (2) Polyuria from neonatal period associated with diminished vision (3) Short stature (4) Polyuria (5) Acute gastroenteritis with shock and secondary amenorrhea (6) Acute gastroenteritis in child with polyuria. Discussion and Conclusions: In our study, we found that high degree of suspicion should be present as some patients might not have large urine output as expected. Hypernatremia in a conscious patient with access to water should lead to suspicion of adipsic DI. Genetic central DI presents later in childhood but AR forms can present earlier. Solute and water diuresis can coexist. Polyuria can worsen after replacement of levothyroxine and unmasking of DI can occur with cortisol replacement in Sheehan's syndrome. Nontreatment or partial treatment might be judicial in patients with cardiac failure. Presentation in early childhood points toward nephrogenic DI. Water deprivation test, the standard test in evaluation of DI was not performed in any of our cases, despite an indication in one case. We conclude that water deprivation test may be skipped even in cases where it is indicated, in limited resource setting or patient limitations, by integrating all other clinical parameters and therapeutic response to DdAVP.

Keywords: Clinical presentation, diabetes insipidus, water deprivation test

 The assessment of body composition with dual-energy X-ray absorptiometry scan in acromegaly patients



Satinath Mukhopadhyay, Anusha Handral

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

E-mail: anuhandral@gmail.com

Introduction: Acromegaly has a variable effect on bone mineral density (BMD) based on the presence or absence of hypogonadism. Excess Growth hormone and insulin-like growth factor-1 causes increase in lean body mass and low total body fat. To the best of our knowledge, the present study is the first Indian study looking at BMD and body composition together in acromegaly patients; hence, we conducted the present study. Aims and Objective: The aims of the study are (1) to compare BMD of cases with controls, (2) to evaluate the effects of sex, gonadal status, and activity of disease on BMD in postoperative acromegaly patients, (3) to evaluate fat percentage in cases and compare it with controls. Materials and Methods: The present study is a cross-sectional observational study, patients with a diagnosis of acromegaly postsurgery attending endocrine outpatient department during the study. Thirty cases and thirty healthy controls were included in the study. All relevant investigations were done, dual-energy X-ray absorptiometry (DXA) scan performed using GE lunar prodigy machine at following sites hip, L1-L4 spine for BMD, whole body for total body fat percentage. Results: BMD (g/cm3) at hip in cases 1.00 and controls 0.99 with Pvalue (0.641) and spine in cases: 1.05 and controls: 1.11 with Pvalue (0.105) showed no statistically significant difference between active and inactive cases (P value at spine: 0.341 and hip: 0.253); similarly, BMD compared in eugonadal with hypogonadal patients, male with females showed no statistically significant difference. The total body fat percentage was lower in cases when compared to controls with Pvalue (0.48). Discussion and Conclusion: The present study shows that BMD in postoperative acromegaly cases was comparable to controls demonstrating the fact that acromegaly patients with coexisting hypogonadism, if treated early, are known to have preserved BMD but may have poor bone quality which cannot be assessed by DXA. Further studies will be required to assess the microarchitecture of bone and hence, the utility of trabecular bone score.

Keywords: Acromegaly, dual-energy X-ray absorptiometry

 Ultrasound-guided internal jugular vein sampling using arginine vasopressin for the localization of adrenocorticotropic hormone-dependent Cushing's syndrome: A tertiary care center experience



T. Ajeesh, S. Soumya1, Abilash Nair2, C. Jayakumari, Ramesh Gomez2, Darvin V. Das2, R. Sreenath2, P. K. Jabbar2

Departments of General Medicine,1Pediatrics and2Endocrinology and Metabolism, Government Medical College, Thiruvananthapuram, Kerala, India. E-mail: abhimck@gmail.com

Background: The anatomical localization of pituitary adenoma using inferior petrosal sinus sampling for the diagnosis of Cushing's disease (CD) is technically challenging and CRH is not marketed in India. Aim of the Study: To assess the performance of internal jugular vein (IJV)/peripheral vein adrenocorticotropic hormone (ACTH) gradient using arginine vasopressin (AVP) for determining the etiology of ACTH-dependent Cushing's syndrome (CS). Materials and Methods: Patients with ACTH-dependent CS underwent IJV blood sampling under ultrasound guidance. Blood was collected sequentially from the right and left IJV for ACTH, cortisol, and prolactin after stimulation with 1 unit of AVP at 5 and 8 min. Peripheral blood for ACTH, cortisol, and prolactin was taken simultaneously from a heparinized intravenous cannula in the antecubital vein at 0, 5, 8, 15, 30, 60, 90, and 120 min. Results: Retrospective data from eight patients (seven females and one male) with ACTH-dependent CS were included for analysis. CD was confirmed in four patients based on positive ACTH staining in the resected tumor. All the three patients with suspected CD had a high-dose dexamethasone suppression test of more than 50%; of them, two had visible tumor on magnetic resonance imaging sella but deferred surgery and one was a patient with recurrent CD with no definitive tumor currently on medical management. IJV: peripheral ACTH ratio of ≥1.6 identified all the seven cases as CD, and in one patient with suspected ectopic source of ACTH, based on aggressive clinical course and hypokalemic metabolic alkalosis, the IJV: peripheral ACTH ratio was <1.6. Conclusion: AVP-stimulated IJV: peripheral ACTH gradient was observed in 100% of patients with CD. As the sample size is small, larger studies are required for further confirmation.

Keywords: Cushing's disease, Cushing's syndrome, internal jugular vein sampling, vasopressin

 Baseline characteristics and surgical outcomes in an acromegaly cohort



Silima Subhasnigdha Tarenia, Nilanjan Sengupta, Pranab Kumar Sahana, Arjun Baidya, Soumik Goswami

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

E-mail: drsilimatarenia@gmail.com

Introduction: Acromegaly is a rare disease caused by growth hormone hypersecretion, predominantly due to pituitary adenoma. The annual incidence is between 0.2 and 1.1 cases/1 lakh people. As this condition is associated with increased morbidity and mortality, screening is recommended for all patients presenting with clinical features of acromegaly. Aims and Objectives: To analyze the patients with acromegaly focusing on baseline characteristics, morbidities, and efficacy of surgery on outcome. Materials and Methods: Study site – Department of Endocrinology, NRS Medical College and Hospital; study population – patients of acromegaly visiting the department of endocrinology; study period – 2-year; sample size – 13; and study type – prospective study. Results: In total, there were 10 male and 3 female patients with the mean age of presentation of 40.23 years. 84.61% of patients had headache. All patients had enlargement of hands and feet, coarsening of facial features, macroglossia, prognathism, oily skin, and fleshy lips. 30% of patients had bitemporal hemianopia; 7.69% of patients had right temporal visual field loss, and 61.53% of patients had no visual disturbance. The frequency of both diabetes mellitus and hypertension at diagnosis were 23.07%. The colonoscopic findings were within normal limits in most of the cases. Obstructive sleep apnea was present in 30.76% (n = 4) of the cases. Of the 13 patients, 2 had microadenoma and 11 had macroadenoma. Eight patients underwent surgery. At 1-month follow-up, insulin-like growth factor 1 was still high in five patients, whereas in three patients, it was reduced. Review magnetic resonance imaging at 3 months showed no residual tumor in three patients (all were microadenoma), whereas five patients had residual tumor who received radiotherapy with medical management. Discussion and Conclusion: Acromegaly presents with myriad of symptoms which require early identification by screening. Surgical outcomes of macroadenoma were less successful than microadenoma. Postsurgery patients often require radiotherapy, medical treatment, or a resurgery for control of disease.

Keywords: Acromegaly, pituitary

 Endocrine adverse effects after immune checkpoint inhibitor therapy in patients with metastatic melanoma



Aprajita Pradhan, Candy Sze1

Department of Endocrinology and Diabetology, Medanta - The Medicity, Gurgaon, Haryana, India,1Queen Mary University and St. Bartholomew's Hospital, London, UK.

E-mail: aprajitapradhan@gmail.com

Background: Immune checkpoint inhibitors are known to cause immune-related adverse events (IRAEs) including endocrinopathies. Endocrinopathies have been reported previously, but this study adds to the frequency of the incidence and the clinical management of these patients. Objective: This is a comprehensive retrospective case review to analyze the incidence, course, and outcome of endocrine adverse effects in patients with metastatic melanoma, treated with immune checkpoint inhibitors. Materials and Methods: Data were collected from a prospective registry of patients at St. Bartholomew's Hospital, London, who were started on immune checkpoint inhibitors for metastatic melanoma between 2012 and 2017. The progression to endocrine adverse event during this period, the clinical course, and management were analyzed. Results: A total of 137 patients were included: 18% developed at least one endocrine adverse event over the period of analysis. Following ipilimumab, the overall incidence of hypophysitis was 8%. Among these patients, the majority (81.8%) were symptomatic and needed hormonal replacement therapy. Radiological involvement was found in six patients (4.4%). After receiving pembrolizumab, 26% of patients developed thyroid-related adverse events, either thyroiditis or hypothyroidism. Conclusion: The incidence of ipilimumab-induced hypophysitis in our study population was comparable to that of the existing literature.[1] However, the incidence of thyroid-related adverse event following pembrolizumab was slightly higher than that of previous studies.[2] Clinical, biochemical, and periodic radiological follow-up plays a very important role in the management of these patient cohort.

Keywords: Endocrinopathies, hypophysitis, immune checkpoint inhibitors

References

Faje AT, Sullivan R, Lawrence D, Tritos NA, Fadden R, Klibanski A, et al. Ipilimumab-induced hypophysitis: A detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab 2014;99:4078-85.de Filette J, Jansen Y, Schreuer M, Everaert H, Velkeniers B, Neyns B, et al. Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab. J Clin Endocrinol Metab 2016;101:4431-9.

 Central diabetes insipidus: Experience from a tertiary care center



Dipti Sarma, Manoj Gedam

Department of Endocrinology, Guwahati Medical College, Guwahati, Assam, India.

E-mail: dr.manojvgedam@gmail.com

Introduction: Central diabetes insipidus (DI) is a rare disorder caused by vasopressin deficiency. Objective: The objective was to assess the etiological, biochemical, clinical, and radiological spectrum of central DI in our institute and to compare between organic and idiopathic central DI. Materials and Methods: Thirty-two patients with central DI admitted in the Department of Endocrinology, Gauhati Medical College, Assam, in the last 2.5 years, were included in the study. Detailed clinical assessment, biochemical evaluation, and magnetic resonance imaging brain were done in all the patients. Central DI patients without any identifiable cause were considered idiopathic and those with structural lesion in hypothalamic pituitary region were considered organic. Results: Out of the 32 (n = 14 males and n = 18 females) patients, there were 12 idiopathic DI and 20 organic central DI (craniopharyngioma – 7, Rathke's cyst – 2, granulomatous hypophysitis – 3, adenoma – 6, and meningioma and glioma – 1). The median age of presentation was 37 years (range: 6–57 years) in idiopathic and 36 years (range: 8–62 years) in organic DI (P = 0.3). The median duration of symptoms was 21 (10–48) months in idiopathic and 12 (6–24) months in organic DI (P = 0.04). Patients with organic DI more commonly present with neurological symptoms (headache 2 vs. 10, visual disturbance 6 organic DI, seizure 3 organic DI, vomiting 5 organic DI). Mean serum sodium idiopathic versus organic was 146 ± 1.8 mmol versus 146 ± 1.9 mmol, P = 0.59, serum osmolality idiopathic versus organic was 289 ± 8.9 mosm versus 290 ± 7.8, P = 0.78, urine osmolality idiopathic versus organic was 100 ± 39.5 mosm versus 101 ± 34.6, P = 0.52, and urine-specific gravity idiopathic versus organic was 1.003 ± 00 versus 1.001 ± 00, P = 0.52. Post desmopressin serum sodium idiopathic versus organic was 144 ± 2.7 mmol versus 143 ± 2.3 mmol, P = 0.32, serum osmolality idiopathic versus organic was 276 ± 10 mosm versus 279 ± 11 mosm, P = 0.42), and urine osmolality idiopathic versus organic was 438 ± 69 mosm versus 425 ± 70 mosm). Organic DI more commonly presents with pituitary dysfunction hypocortisolism (13 [60%], P = 0.01), hypothyroidism (11 [50%], P = 0.04), hypogonadism (8 [25%], P = 0.02), and hyperprolactinemia (14 [70%], P = 0.002). Pituitary bright spot was absent in 12 (100%) versus 13 (65%) patients, present in 7 (21.8%) organic DI and pituitary stalk thickening was present in 1 (8.3%) versus 8 (40%). Conclusion: Organic DI is more likely found to have acute onset of presentation than idiopathic DI. Organic DI should be suspected in patients presenting with symptoms of DI with anterior pituitary dysfunction even in the absence of neurological symptoms.

Keywords: Central diabetes insipidus, idiopathic diabetes insipidus, organic diabetes insipidus

 An unusual for cause for primary amenorrhea – A case study



Suresh Damodharan, Vijai J. Dharshan, Renny Rozario1

Department of Diabetology and Endocrinology, Sri Ramakrishna Hospital,1Sri Ramakrishna Institute of Pharmaceutical Sciences, College of Pharmacy, Coimbatore, Tamil Nadu, India.

E-mail: rozariorenny@gmail.com

Introduction: The Gonadotropin-releasing hormone (GnRH) pulse generator is the primary structure that drives the menstrual cycle. In the absence of a functional GnRH pulse generator, the gonadotropes remain unstimulated and the ovaries dormant. The GnRH pulse generator is the hypothalamic structure that releases GnRH, a decapeptide that stimulates luteinizing hormone and follicle-stimulating hormone synthesis and release from the pituitary. Normally, this dysfunction can commonly occur as a functional problem, but structured lesions are also possible among which craniopharyngioma is the most common. Case Presentation: A 13-year-old female patient with onset of puberty at 12 years reported with symptoms of irregular menstrual cycle and occasional headache during stress, and her secondary sexual characters were seen to be developing slow.

Investigations:

Imaging: Ultrasonography abdomen: Small uterus with multifollicular ovaries. Magnetic resonance imaging of the brain: Small poorly defined infiltrating T2-hyperintense lesion 22 mm × 12 mm × 10 mm involving the right caudate nucleus, ventromedial thalamus, and adjoining right hypothalamus at subependymal location; mild choline peak. Magnetic resonance imaging pituitary: Normal pituitary gland. Discussions: The girl was started on glucocorticoid and levothyroxine replacement. Neurosurgeon opinion was obtained. With suboptimal pituitary function, the precise and early diagnosis of hypothalamic was made. Hypopituitarism can prevent negative physical and psychological sequelae, preserve normal peak bone mass, and restore fertility in affected patients. (1)Will surgical decompression relieve and restore the possible hypothalamus dysfunction? (2)Should we replace with sex hormones? (3)Should we wait for puberty sprout?

Keywords: Craniopharyngioma, pituitary, primary amenorrhea

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 Clinical characteristics of patients with acromegaly: A single-center experience in East India over 1 year



Rahin Mahata, Chandan Kumar Mishra, Partha Pratim Chakraborty, Anirban Sinha, Animesh Maiti

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

E-mail: rahin.mahata@gmail.com

Acromegaly is a rare disease caused due to hypersecretion of growth hormone (GH). Most of the cases of acromegaly are caused by pituitary adenoma which can be macroadenoma or microadenomas, are never malignant, but can have significant morbidity and mortality. We report nine cases of acromegaly who presented with classical presentation of acromegaly with coarse facial features and progressive enlargement of hands and feet. There were four males (44%) and five females (56%) who were diagnosed on the basis of serum insulin-like growth factor-1 and GH suppression test. Mean age of the patients was 43 years, and median duration of diagnosis of the disease since the appearance of clinical features was 3 years. Among them, there were headache in seven patients (78%), diabetes mellitus in seven patients (78%), hypertension in three patients (33%), visual impairment in five patients (55%), panhypopituitarism in three patients (33%), and colonic polyp in one patient (11%). On pituitary magnetic resonance imaging, we found macroadenoma in eight patients (89) and microadenoma in one patient (11%). One of the nine patients was a case of postoperative relapse (relapse occurred at 3 years after transsphenoidal surgery). Of the nine patients, three patients were undergone surgical resection of pituitary adenoma, and subsequently on follow-up, four patients were not willing to take any kind of definitive therapy and two patients on medical therapy with octreotide LAR.{Figure 16}{Figure 17}{Figure 18}{Figure 19}{Figure 20}

Keywords: Coarse facial features, diabetes mellitus, headache, macroadenoma, panhypopituitarism, visual impairment

 An unusual case of central diabetes insipidus



S. N. Gadage, J. D. Mulchandani, V. Shah, S. Gupta, Milind Patil

Inlaks and Budhrani Hospital, Pune, Maharashtra, India.

E-mail: milindpmed@gmail.com

Introduction: Central diabetes insipidus (CDI) is a heterogeneous condition characterized by the presence of polyuria and polydipsia due to a deficiency of vasopressin. In 1950, the first case of CDI associated developing in the setting of infective endocarditis was reported. We hereby report a similar case of diabetes insipidus (DI) complicating a case of bacterial endocarditis. Aims and Objective: We aim to discuss the rare case of DI with infective endocarditis and to review the literature. Materials and Methods: A 54-year-old woman presented with high-grade fever and loss of appetite. She had undergone aortic valve replacement with coronary artery bypass graft surgery 1 month back. Investigations revealed prosthetic valve endocarditis secondary to coagulase-negative Staphylococcus. During a hospital stay, the patient had a cardiac arrest. Postresuscitation patient developed refractory shock. Echocardiography showed new-onset septoapical hypokinesia and paravalvular abscess. The diagnosis of myocardial infarction due to embolism of the vegetation was considered. The patient showed gradual improvement with antibiotics, mechanical ventilation, and supportive care. While recovering, the patient developed persistent polyurea. Laboratory abnormalities included hypernatremia, elevated serum osmolality, and low urine osmolality. She improved with fluid, desmopressin and sodium levels were stabilized. Based on clinical, laboratory, and magnetic resonance imaging findings and response to desmopressin, the diagnosis of CDI was made. On follow-up, the patient is maintaining sodium and urine output on daily 100 mcg desmopressin. Results: Thus, we report a case of permanent DI developing in the setting of infective endocarditis. Discussion and Conclusion: The ischemic insult to pituitary either due to embolization of posterior pituitary or hypoperfusion secondary to cardiac arrest may have resulted in DI. The case highlights monitoring for DI in the setting of cardiac arrest and infective endocarditis. Early recognition and correction of hypernatremia may prevent further brain injury.

Keywords: Cardiac arrest, diabetes, endocarditis

 Vanishing sphenoidal mass



Adlyne Reena Asirvatham, Karthik Balachandran, Satish Kumar, Shriraam Mahadevan

Department of Endocrinology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India.

E-mail: adlynereena@yahoo.co.in

A 53-year-old woman presented to an oto-rhino-laryngologist with headache for 2 years. There was no history suggestive of raised intracranial tension. She was postmenopausal and had five children. In view of chronic headache, she underwent magnetic resonance imaging (MRI) of the head which revealed a sphenoidal sinus tumor with empty sella [[Figure 1], Panel A, arrow]. She underwent endoscopic biopsy of the tumor to rule out malignancy. Surprisingly, histopathology was suggestive of pituitary adenoma, and she was referred for further evaluation. On examination, she had expressive galactorrhea from both breasts. Laboratory studies showed a prolactin level of 2200 ng/ml (normal range, 15 to 28), thyrotropin level of 3.7 μU/ml (normal range, 0.5 to 4.9), and free thyroxine level of 1.0 ng/dl (normal range, 0.8 to 1.8). Her follicular-stimulating hormone and luteinizing hormone levels were inappropriately low. Other pituitary hormones were normal. A diagnosis of ectopic sphenoidal sinus prolactinoma was made, and cabergoline 0.5 mg once weekly was started. Ectopic pituitary adenomas most commonly occur in sphenoid sinus possibly due to remnant of precursor cells during the development of anterior pituitary. At 1 year of follow-up, her headache had resolved, the prolactin level had normalized, and a recheck MRI showed complete resolution of the tumor [[Figure 1], Panel B].{Figure 21}

Keywords: Ectopic pituitary adenoma, prolactinoma, sphenoidal prolactinoma

 ADRENALS AND NET



 An unusual case of paraganglioma



Harsha Pamnani, Asim Siddiqui, Subhash Kumar Wangnoo

Department of Endocrinology, Indraprastha Apollo Hospital, New Delhi, India. E-mail: pamnaniharsha0@gmail.com

Background: Castleman's disease (CD) or angiofollicular lymph node hyperplasia is a rare disorder characterized by the benign proliferation of lymphoid tissue. It can involve the whole body, and approximately 70% occurs in the chest, 15% in the neck, and 15% in the abdomen and pelvis, involving mainly lymphatic tissues. Extralymphatic sites may also be involved such as lungs, larynx, parotid glands, pancreas, meninges, and muscles. The exact pathogenesis is unknown. We report a case of a 27-year-old male who was suspected to have paraganglioma but later histologically confirmed to have hyaline-vascular variant of CD. Case Report: A 27-year-old male presented with complaints of abdominal pain for 3 months unassociated with loss of appetite, fever, dysuria, weight loss, headache, and seizures. There was no significant past medical and surgical history. Clinical examination and routine blood biochemistry were within normal limits. Ultrasonography abdomen revealed a heterogeneous mass in the right adrenal region. Contrast-enhanced computed tomography (CT) abdomen revealed oval-shaped lesion (73 mm × 57 mm × 53 mm) in the right anterolateral aspect of the prevertebral space at L4 and L5 vertebral levels (CT attenuation: 99–111 HU). Twenty-four-hour urinary normetanephrine was 4203.01 mcg/24 h (73–808) and metanephrine was 95.51 mcg/24 h (74–297). After adequate preoperative preparation, he underwent abdominal mass excision and specimen was sent for histopathological examination. HPE of retroperitoneal mass revealed localized nodal CD (hyaline-vascular type). Two-month postoperative 24-h urinary normetanephrine was 4770.16 mcg/24 h and metanephrine was 95.51 mcg/24 h. The repeated values of 24-h urinary metanephrines and normetanephrines were normal after 7 months of surgery. No other adjuvant treatment was given. The patient did not report any recurrence till date and is under follow-up. Conclusion: CD commonly presents as a unicentric disease with a hyperenhancing lymph nodal mass and should be suspected in any lymphoproliferative disease of uncertain origin, which should always be confirmed by histopathology. It can also mimic paraganglioma.

Keywords: Aangiofollicular lymph node hyperplasia, Castleman's disease, hhyaline-vascular type, paraganglioma

 Renal medullary nephrocalcinosis as a sequale of primary hyperaldosteronism



Raiz Ahmad Misgar, Mir Iftikhar Bashir, Arshad Iqbal Wani, S. Arun Viswanath

Department of Endocrinology, SKIMS, Srinagar, Jammu and Kashmir, India. E-mail: drarunviswanath3289@gmail.com

Introduction: Primary hyperaldosteronism (PA) is emerging as one of the most common causes of secondary hypertension. It is now widely believed that PA exists as a spectrum from normotension to severe hypertension, and the current guidelines place more emphasis on detecting only overt cases of PA and thereby missing several cases. Aims and Objective: The clinical spectrum of PA is getting expanded with time. Nephrolithiasis and nephrocalcinosis have been reported infrequently in association with PA. Materials and Methods: The clinical course of two cases of PA who had associated incidentally discovered nephrocalcinosis is being discussed here with plausible causal association between these two conditions. Results: Our first case, a middle-aged female with poorly controlled hypertension for 5 years and recurrent hospitalization with spells of unconsciousness due to ventricular tachycardia and hypokalemia. She was found to have PA due to the right adrenal adenoma and was subjected to right adrenalectomy with prompt remission of hypertension and correction of hypokalemia. She presented 6 months after surgery with incidentally detected medullary nephrocalcinosis on abdominal sonography and did not have any established cause of medullary nephrocalcinosis on workup. Our second case is again a middle aged female with poorly controlled hypertension for 6 years who presented with acute pure motor quadriparesis due to hypokalemia and was found to have PA due to the right adrenal adenoma. During evaluation, she was found to have early medullary nephrocalcinosis with no other cause apparent to attribute this finding. Discussion: Hyperaldosteronism induced chronic hypokalemia, hypocitraturia and hypercalciuria are possible mechanisms explaining nephrocalcinosis/nephrolithiasis in PA. Conclusion: We propose that nephrocalcinosis could be a rare manifestation of PA; hence, it should be enlisted as a cause of medullary nephrocalcinosis and evaluation for PA should be incorporated into the diagnostic workup of nephrocalcinosis.

Keywords: Clinical spectrum, nephrocalcinosis, nephrolithiasis, primary hyperaldosteronism, sequale

 Management of a difficult case of insulinoma with radiofrequency ablation



Srinivas Kandula, Geeta Aurangabadker, Vaibhavi Modi1, Sundeep Lakhtakia2, K. D. Modi

Department of Endocrinology, Care Hospital,1VRK Medical College,2Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India.

E-mail: srinivaskandula09@gmail.com

Insulinoma is a rare functioning pancreatic neuroendocrine tumor (PNET). It is characterized by symptomatic hypoglycemia with endogenous hyperinsulinemia. Proper biochemical diagnosis, localization, and surgical removal of the tumor is the mainstay of the treatment. Alternate therapy such as radiofrequency ablation (RFA) and local injection of concentrated ethanol are reported successful in some cases. We report one such case of insulinoma located in the uncinate process of the pancreas in close vicinity to main pancreatic duct (PD) and common bile duct (CBD) that was successfully managed with RFA. A 41-year-old female presented with repeated episodes of symptomatic hypoglycemia for the last 1 year every time recovering with intravenous or oral glucose. On fasting challenge test after 1 h, she was found to have hypoglycemia with blood glucose of 40 mg/dl. Serum insulin and c-peptide were disproportionately high. Imaging with magnetic resonance imaging (MRI) revealed 1.7 cm × 1.2 cm-sized T1 hypointense and T2 hyperintense mass in the uncinate process of the pancreas. The mass was in close vicinity of CBD and main PD. After explaining treatment options and complication risk, the patient expressed unwillingness for surgery. RFA was suggested as alternative therapy with its limitations and risks. Endoscopic ultrasonography (EUS) showed hyperechoic mass in the head of the pancreas with increased vascularity. EUS-guided fine-needle cytology aspirate was positive for immunohistochemistry-pancytokeratin, chromognanin, and synoptophysin, suggestive of PNET, well-differentiated WHO Grade I. Initially, she was subjected for ERCP, and a PD stent was placed to protect the main PD. After 20 days, she underwent EUS-guided RFA for pancreatic mass. Post procedure, she had developed acute pancreatitis, which was managed conservatively. Blood glucose was monitored regularly. There was no episode of hypoglycemia after RFA. On the 5th day, she was discharged with normal blood glucose. She was asymptomatic and was re-evaluated 2 and 6 months after RFA with normal blood glucose. Repeat MRI abdomen showed shrinkage in tumor size with cystic area surrounding the lesion.

Keywords: Hypoglycemia, insulinoma, radio frequency ablation

 Adrenocortical carcinoma: Experience from a tertiary care center



Ayan Roy, Niya Narayanan, Chandhana Merugu, Sadishkumar Kamalanathan, Dukhabandhu Naik, Jayaprakash Sahoo

Department of Endocrinology, JIPMER, Puducherry, India.

E-mail: drayanroy9@gmail.com

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with varied clinical presentation. ACC is often present with features of hormone excess and in some cases may be functionally silent. It has a very poor prognosis, and more so with cortisol-producing tumors. Here, we report a case series of ACC with different spectrum of clinical and biochemical presentation, posing a challenge in the diagnosis and management. Methods: This is a retrospective study conducted on the clinical, hormonal, and histological profile of ten ACC patients between 2010 and 2019. Results: A total of ten cases were analyzed. One patient was adolescent (age: 13 years); nine patients were adults with a mean age ± standard deviation (SD) of 45.2 (±11 years). Eighty percent of the patients (n = 8) were female. The most common clinical presentation was abdominal pain (60%), with duration of symptoms ranging between 7 days and 4 months. Three patients had Cushing's syndrome, and two patients had virilizing features at presentation. Fifty percent of the patients reported significant weight loss. One patient presented with low-grade fever for 4–6 months. Hypertension was noted in 80% (n = 8) of cases, with one patient presenting with hypertensive crisis. Diabetes mellitus was found in 40% (n = 4) of cases. The mean 8 AM basal cortisol level was 25.9 ± 11.7 μg/dl. Midnight cortisol during sleep was elevated in eight patients. Seven patients (70%) had elevated 24-h urinary cortisol, out of which three patients had very high urinary cortisol (>1000 μg/dl) level. Five patients (50%) had unsuppressed serum cortisol level on overnight dexamethasone suppression test. Adrenocorticotropic hormone levels were not suppressed in five patients (mean ± SD: 23.5 ± 6.49 pg/ml). Serum dehydroepiandrosterone sulfate (DHEAS) level was elevated in six patients, whereas three patients had normal levels. 17-hydroxyprogesterone levels were available for four patients; all were within normal range. Modified Weiss score range was between 3 and 6. Three patients died with survival period ranging between 2 and 10 months. All of them had very high urinary-free cortisol. One patient had tumor recurrence after 1.5 years. Rest of the patients are under periodic follow-up. Conclusion: ACC can have a myriad of clinical presentations. Comorbidities such as diabetes and hypertension are common. Biochemical abnormality with an excess cortisol production was detected in a significant number (30%) of patients without features of Cushing's syndrome. DHEAS was normal in 30% of patients of adrenocortical tumors. Very high cortisol level at presentation predicts poor prognosis. Periodic monitoring is important to identify recurrences.

Keywords: Adrenocortical carcinoma, cortisol, cushing's syndrome

 Etiological and temporal profile of adrenal incidentalomas: A single-center experience



K. Raja Mohan Reddy, B. Vivekanand, A. Mythili, K. A. V. Subrahmanyam, Jayanthy Ramesh

Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India.

E-mail: drjayanthyramesh@gmail.com

Introduction: Adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. The prevalence of adrenal incidentalomas increases probably due to advances in abdominal imaging and their widespread availability. Most of the adrenal incidentalomas are nonfunctioning. Aim: To study the etiological and temporal profile of adrenal incidentalomas in our hospital. Materials and Methods: Twenty-four patients with adrenal incidentalomas who presented to King George hospital, Visakhapatnam, between January 2017 and August 2019, were included. Patients' clinical data were noted. Imaging and hormonal assessment according to the guidelines were done and analyzed. Results: Among 24 patients, 66.7% were female and 33.3% were male. 37.5% of patients were between 30 and 40 years of age. 58.3% of lesions were present in the right adrenal, 37.5% on the left side, and 4.1% had bilateral lesions. 54% of the cases had incidentaloma of size <4 cm and 33.3% had >6 cm size. Functional incidentalomas were seen in 29% (n = 7) of cases. Among functional lesions, pheochromocytoma was detected in 6 (25% of total lesions) patients and 1 was adrenocortical carcinoma with autonomous cortisol secretion. Pheochromocytomas were predominantly norepinephrine secreting (5/6) and 2 among them had size <4 cm. One patient had adrenal insufficiency with bilateral lesions – ?infective etiology. Among nonfunctional incidentalomas, 8 were adenomas, 2 were cystic lesions, 2 were myelolipomas, 1 adrenocortical carcinomas, 1 ganglioneuroma, 1 schwannoma, and 1 hyperplasia. Of 24 patients, 12 met the criteria for surgical excision and their histopathology showed 6 pheochromocytomas, 2 adrenocortical carcinoma, 2 adenomas, 1 ganglioneuroma, and 1 schwannoma. Discussion and Conclusion: Our study shows (1) high prevalence of incidentaloma in young (58.3% were 20–40 years of age) and (2) detailed evaluation of incidentalomas can unmask significant number of functioning tumors (25% of total incidentalomas were pheochromocytomas).

Keywords: Adrenal incidentaloma, adrenocortical carcinoma, asymptomatic adrenal tumors, functional adenoma, pheochromocytoma

 Uncommon congenital adrenal hyperplasia: Congenital adrenal hyperplasia other than 21-hydroxylase deficiency



Shakun Chaudhary, Rama Walia, Anil Bhansali

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

E-mail: shakunchaudhary@yahoo.co.in

Introduction: Congenital adrenal hyperplasia (CAH) other than 21-hydroxylase deficiency is uncommon. Here, we present five cases of uncommon CAH with unique presentation in each individual. Objective: The objective of the study is to describe clinical profile and treatment outcome inpatient of CAH other than 21-hydroxylase deficiency. Materials and Methods: Patients of CAH other than 21-hydroxylase deficiency who visited our OPD were subjected to detailed medical history, physical examination, biochemical and hormonal investigations. A prospective follow-up was done for outcome measures. Results: A total of five patients were identified. Among these three patients had 11β-hydroxylase deficiency, one had 17α-hydroxylase deficiency, and one patient had 3β-hydroxysteroid dehydrogenase deficiency. Among patients with 11β-hydroxylase deficiency, Case – 1 (19-year-old female) presented with secondary amenorrhea along with features of androgen excess and was initially managed as polycystic ovarian disease. The alternate diagnosis was suspected because of clitoromegaly and virilization. Case – 2 (18-year-old female) presented at birth with clitoromegaly but was misdiagnosed as 21-hydroxylase deficiency. The diagnosis was revised later on after evaluation for hypertension and secondary amenorrhea. Case – 3 (14-year-old male) presented with short stature and macroorchidism. Case – 4 (14-year-old female) was diagnosed to have 17α-hydroxylase deficiency in whom presentation was primary amenorrhea. The diagnosis of 17α-hydroxylase deficiency was considered due to the presence of concurrent hypocortisolism. Case – 5 (8-year-old male) was diagnosed as 3β-hydroxysteroid dehydrogenase deficiency who presented with premature adrenarche and obesity. The diagnosis was delayed due to the alteration of hormonal profile by intake of exogenous steroids for atopic dermatitis. Patients were managed with hydrocortisone and fludrocortisone (if indicated), which resulted in substantial improvement of clinical and hormonal profile. Conclusion: CAH other than 21-hydroxylase deficiency is rare, and data regarding clinical phenotype and outcome are scarce in literature. Hence, it becomes pertinent to be aware of the different modes of presentation, clinical profile, and outcome of CAH other than 21-hydroxylase deficiency.

Keywords: 11β-hydroxylase, 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, congenital adrenal hyperplasia

 An array of adrenal masses: A case series



Chhavi Agrawal, Saurav Shishir Agrawal, Partha Pratim Chakraborty, Anirban Sinha, Animesh Maiti, Asish Kumar Basu

Department of Endocrinology, Medical College, Kolkata, West Bengal, India. E-mail: drchhaviagrawal@gmail.com

Introduction: Adrenal masses are commonly found in the course of abdominal investigations and present diagnostic challenges. Important issues are whether the mass is the cause of the symptoms being investigated, whether the adrenal mass is benign or malignant, and if it is functional or nonfunctional, as the further management depends on these primary results. Materials and Methods: We present here a series of 15 patients, retrospectively analyzed, with adrenal masses seen in endocrine outpatient department from August 2017 to August 2019. Results: The mean age of patients was 42 years, with an almost equal distribution between sexes (7 females, 8 males). Three of the 15 patients had incidentaloma, while 12 patients were symptomatic due to adrenal mass. Of the 15 patients, three had bilateral adrenal masses and others had unilateral mass. All three patients with bilateral adrenal masses were males and were diagnosed with primary adrenal insufficiency due to adrenal histoplasmosis. Adrenal pheochromocytoma was the most common diagnosis in our patients with unilateral adrenal mass (5 of 12); three of them were normotensive. Three patients were diagnosed with primary aldosteronism due to adrenal adenoma, and all of them were hypertensive and two had hypokalemic paralysis at presentation. Three patients were operated due to large adrenal masses, two of which on histology were myelolipoma and one was diagnosed as a case of adrenocortical carcinoma. One patient had clinical features, suggestive of Cushing's syndrome, and the source of excess steroids was localized to adrenal gland. Conclusion: In the present study, we found that among the functional tumors, pheochromocytomas were the most frequently observed. Adrenal biopsy should be used selectively and was done for the evaluation of bilateral adrenal masses with high suspicion for infectious or infiltrative disease, and it is imperative that a biochemical assessment be performed before this procedure to avoid a potential hypertensive crisis.{Figure 22}{Figure 23}

Keywords: Adrenal histoplasmosis, pheochromocytoma

 Novel allele-specific PCR and next-generation sequencing-based comprehensive genetic screening for congenital adrenal hyperplasia



R. Lavanya, Aaron Chapla, H. S. Asha1, Sophy Korula2, Deny Varghese, Parthiban, Simon Rajaratnam1, Sarah Mathai2, Anna Simon2,

Thomas V. Paul1, Nihal Thomas1

Molecular Endocrinology Laboratory, Department of Endocrinology Diabetes and Metabolism, Christian Medical College,1Department of Endocrinology Diabetes and Metabolism, Christian Medical College,2Department of Paediatric Endocrinology and Metabolism, Paediatric Unit 1, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: lavanyaravichandran1992@gmail.com

Introduction: Congenital adrenal hyperplasia (CAH) encompasses a heterogeneous group of autosomal recessive disorders resulting in a clinical spectrum of abnormalities associated with adrenal insufficiency. Several genes have been implicated in CAH, and CYP21A2 mutations of 21-hydroxylase (21-OH) deficiency are the most persistent cause in 90% of the patients. With substantial challenges in molecular analysis imposed by the pseudogene CYP21A1P, genetic diagnosis is not well established and widely available in India. Aims and Objectives: To establish an extended, cost-effective genetic diagnosis for CYP21A2, CYP11B1, CYP17A1, CYP19A1, and POR genes in CAH using allele-specific PCR (ASPCR) and next-generation sequencing (NGS)-based techniques. Methods: Fifty-five patients with clinically diagnosed 21-OH deficiency and five patients with 11β-OH deficiency were recruited in the study. Conventional DNA extraction and primary amplification of CYP21A2 and CYP21A1P with specific long-range primers were followed. The long-range CYP21A2 PCR product was utilized to genotype eight common hotspot mutations in CYP21A2 using in-house designed novel ASPCR primers – P30L, I2G, 8BPdel, I172N, E6clus (I236N, V237E, and M239K), V281L, Q318X, and R356W. The other four genes and those negative for CYP21A2 hotspots were subjected to targeted NGS for five-gene panel. The results were validated using Sanger sequencing. Results: 25 out of 34 (73.5%) pediatric patients and 8 out of 21 adults (38%) were found positive for different hotspots using ASPCR. NGS strategy is being used to identify other mutations (data analysis in progress). Discussion and Conclusion: The ASPCR genotyping was found to be highly specific and sensitive for eight hotspots screening for 55 patients. I172N had the highest frequency in adults (71%) and 12G splice variant (81%) in children. Six adults and 13 children were either being compound heterozygous or with one homozygous and multiple heterozygous mutations. The phenotype–genotype correlation was high in I2G, I172N, and Q318X. Thus, we suggest ASPCR approach as first-tier genetic testing to provide cost-effective and robust genetic screening of the most common hotspots in CYP21A2 for clinically suspected pediatric patients and carrier testing. This largely voids the need for direct NGS-based or multiplex ligation-dependent probe amplification techniques.

Keywords: 21-hydroxylase deficiency, allele specific PCR, congenital adrenal hyperplasia, genotyping, next generation sequencing

 Diagnostic accuracy of Acton Prolongatum® stimulated salivary cortisol in adrenal insufficiency as compared to standard Synacthen test



Geena Susan George, Nandini Prasad, Abilash Nair, C. Jayakumari, Darvin V. Das, Puthiyaveettil Khadar Jabbar

Department of Endocrinology and Metabolism, Government Medical College, Thiruvananthapuram, Kerala, India.

E-mail: abhimck@gmail.com

Introduction: Salivary cortisol measurement is noninvasive and corresponds to serum-free cortisol levels. In India, the availability of Synacthen is difficult whereas injectable long-acting porcine sequence, ACTH 1–39 (Acton Prolongatum®) is easily available. Aims and Objectives: To find the diagnostic accuracy of stimulated salivary cortisol using Acton Prolongatum® (Acton Prolongatum salivary stimulation test [APSST]) in comparison with Synacthen (short Synacthen test [SST]) for the diagnosis of adrenal insufficiency (AI). Methods: Subjects with suspected AI on the basis of clinical features underwent an SST with 250 μg Synacthen followed by APSST after 3 days. Salivary cortisol collected by passive drooling method was collected at 0, 60, and 120 min following injection of 30 units Acton Prolongatum®. Salivary cortisol was measured with ECLIA using Cobas e 411 analyzer and the lower limit of assay was 0.054 μg/dl. Stimulated peak cortisol cutoff of <18 μg/dl on SST was considered as AI. Results: A total of 67 patients (mean age 36.72 ± 17.83 years) with suspected AI were enrolled for the study. Based on SST, 38 were classified as having AI whereas 29 were found to be normal. Those who had AI were classified as having primary (n = 20) or secondary (n = 18) AI based on clinical settings and ACTH levels. Area under receiver operating characteristics for APSST (at 60 min) was 0.960 when compared to SST, thus proving its high accuracy. A salivary cortisol cutoff of 0.90 μg/dl at 60 min following stimulation with Acton Prolongatum® had a sensitivity of 90.9% and specificity of 100%. Conclusion: Salivary cortisol measurements following ACTH stimulation test using Acton Prolongatum® is an accurate, noninvasive, and economical alternative to SST in the diagnosis of AI. Funding: This study has received fund from the Endocrine Society of India (Trainee Grants).

Keywords: Acton Prolongatum, adrenal insufficiency, salivary cortisol

 Normotensive pheochromocytoma presenting as adrenal incidentaloma



Naveen Charantimath, K. Neelaveni, Rakesh Kumar Sahay

Osmania Medical College, Hyderabad, Telangana, India.

E-mail: naveen.charantimath@gmail.com

Introduction: Pheochromocytomas are tumors originating from the chromaffin cells, more common in the third and fifth decades of life. Clinically, the patients present with headache, palpitation, and hypertension (0.1%–1% of all secondary hypertension cases), but a number of incidentally discovered pheochromocytomas present with atypical symptoms and may not be associated with hypertension. The characteristics of normotensive pheochromocytomas are poorly understood. Aims and Objectives: We report two such cases of incidentally discovered normotensive pheochromocytomas. Case Scenarios: Case 1: A 29-year-old woman presented with pain abdomen for 2 months was incidentally detected to have right adrenal incidentaloma by ultrasonography abdomen. On clinical examination, she was normotensive. 24-h urinary metanephrines and normetanephrine were elevated; computed tomography showed intense postcontrast enhancement suggestive of pheochromocytoma. As the patient did not tolerate α and β blocked, the patient underwent surgery without antihypertensive therapy with close monitoring of blood pressure (BP). Right adrenalectomy was uneventful, and histopathological examination confirmed pheochromocytoma. Case 2: A 24-year-old male patient presented with nonspecific symptoms for 1 month incidentally detected to have a left adrenal mass on ultrasonography of the abdomen. On clinical examination, he was normotensive. 24-h urinary metanephrines and normetanephrine were elevated; computed tomography showed intense postcontrast enhancement suggestive of pheochromocytoma. The patient underwent surgery without antihypertensive therapy with close monitoring of BP. Left adrenalectomy was uneventful, and histopathological examination confirmed pheochromocytoma. Conclusion: This case series illustrates an unusual presentation of normotensive pheochromocytoma as adrenal incidentaloma. Perioperative preparation in these patients can be achieved without adrenergic blockade; however, close monitoring of BP is recommended.

Keywords: Normotensive pheochromocytoma

 Late-night salivary cortisol normative data and its use as a screening test for endogenous Cushing's syndrome



Nandini Prasad, Geena Susan George, Abilash Nair, C. Jayakumari, K. H. Ratheesh1, Puthiyaveettil Khadar Jabbar

Departments of Endocrinology and Metabolism and1Community Medicine, Government Medical College, Thiruvananthapuram, Kerala, India.

E-mail: abhimck@gmail.com

Background: Late-night salivary cortisol (LNSC) is used as a screening test for Cushing's syndrome (CS). However, there are no community-based normative data till now. Objective: The primary objective was to determine the upper (97.5th centile) reference range of LNSC in South Indian population with an assessment of its diagnostic accuracy in endogenous CS as the secondary objective. Materials and Methods: Multistage cluster sampling was followed to identify eligible participants from eight rural and six urban anganwadi areas in Trivandrum district for domiciliary collection of late-night saliva. Participants were provided with prelabeled plain bottles to collect 3 ml saliva at 11.00 pm after giving proper instructions. Salivary cortisol was measured with ECLIA using Cobas e 411 analyzer. Lower detection limit was 0.054 μg/dl. Salivary cortisol levels of patients admitted with suspected endogenous CS under Endocrinology Department Medical College, Thiruvananthapuram, were also assessed for a diagnostic cutoff value. Results: In the community, out of the 481 normal subjects screened, 474 were enrolled for the study whereas the other seven were excluded due to errors in sample collection. The 97.5th centile of LNSC in normal subjects was found to be 0.28 ± 0.089 μg/dl. Twenty-six patients with suspected CS were included in hospital part of the study of whom 15 were confirmed to have hypercortisolemia. The cutoff of 0.28 μg/dl gave a sensitivity of 85% and specificity of 100% for diagnosing CS. No patient with CS had an LNSC value <0.15 μg/dl. Conclusion: The reference range for late-night salivary cortisol in our population was 0.28 ± 0.089 μg/dl, and this is well applicable to CS patients also with good diagnostic accuracy. Funding: This study has received fund from the Endocrine Society of India.

Keywords: Cushing's syndrome, late-night salivary cortisol, normative data

 Adrenal cortical carcinoma case series: Clinicopathological features and outcomes



Anshul Agarwal, Arun S. Menon, B. Nisha, V. P. Praveen, Harish Kumar, Vasantha Nair, Usha Menon, Nithya Abraham, Prem Narayanan

Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India. E-mail: anshul5371@gmail.com

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy associated with grave prognosis. ENSAT staging and Weiss score are useful tools in assessing prognosis. The impact of secretory functionality of the tumor on the prognosis of the disease remains unclear. Aims and Objectives: To analyze the clinical and pathological features in ACC patients and identify any prognostic factors. Materials and Methods: Twenty-nine histopathologically proven ACC were retrospectively assessed. Weiss scoring and ENSAT staging were done. Based on clinical presentation, the cases were classified into autonomous hormonal excess (increased cortisol, androgen, estrogen, or mineralocorticoid), incidentally detected by imaging for other purpose or nonspecific symptoms from an abdominal mass. Results: The mean age was 52 ± 14 years. Size of the mass at presentation was 8.7 ± 4.2 cm on imaging, ENSAT staging was 2.3 ± 0.7, and the mean Weiss score was 4.9 ± 1.5. 65.5% presented with autonomous hormonal excess, 48.3% were incidentally detected, and 13.8% had nonspecific symptoms. 10/29 patients had distant metastasis at presentation. 13/19 developed either recurrence or metastasis at distant sites within 2 years of follow-up. Average Weiss scoring at presentation for those who had recurrence was 5.6. Weiss score showed positive correlation with recurrence of ACC within 2 years (P = 0.004). Age, sex, computed tomography size, or hormone overproduction did not show any correlation with the recurrence of ACC. Discussion and Conclusion: Of six patients who were disease-free till 2 years of follow-up, five had Weiss score at or below 4, thus aiding prognostication. Recurrence in patients with ACC was significantly associated with tumor staging and Weiss scoring. Tumor size or secretory activity did not show any correlation with either the metastasis at presentation or recurrence.

Keywords: Adrenal cortical carcinoma, Weiss score

 Case of familial pheochromocytoma and the role of next-generation sequencing



Sandeep K. Mathur, Anshul Kumar, Balram Sharma, Naincy, Himanshu Sharma

Department of Endocrinology, SMS Medical College, Jaipur, Rajasthan, India. E-mail: anshul.singh2910@gmail.com

Introduction: The case highlights how next-generation sequencing helped us to diagnose a patient with bilateral adrenal pheochromocytoma as von Hippel–Lindau syndrome, and then subsequent screening helped us to find three other asymptomatic cases in the blood relatives who also had bilateral adrenal pheochromocytoma. Case Presentation: Here, we present a case of a 31-year-old male. On visiting his family physician, he was found to have raised blood pressure with significant postural fall. He also reported a significant history of spells. Investigations showed raised 24-h urinary meta and normetanephrines. Contrast-enhanced computed tomography chest and abdomen showed that in addition to the bilateral adrenal pheochromocytoma, the patient also had found to have a large paravertebral mass. Metaiodobenzylguanidine scan showed an abnormal focus of I-131 MIBG concentration is seen in the right suprarenal region measuring about 6–7 cm, the left suprarenal (faint focus) measuring around 2–3 cm. We further evaluated the family members, and the patient's sister, mother, and maternal uncle were all found harboring pheochromocytomas and paragangliomas and were evaluated, and tumors were excised subsequently. Genetic Diagnosis: Whole-exome sequencing of the affected members was done, and they were found to have a mutation nonsynonymous SNV c.C499T, p.R167W of VHL gene. The further plan is to carry out Sanger sequencing in the nonaffected members of the family subsequently.

Keywords: Pheochromocytoma, next-generation sequencing, VHL

 Prevalence of endogenous Cushing syndrome in adults with diabetes mellitus



Venkatarakesh Chintala, T. Sunanda, H. A. Vijaya Sarathi, K. Dileep Kumar

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

E-mail: venkatarakeshchintala@gmail.com

Introduction: Endogenous Cushing syndrome (CS) is reported in 1%–2% of patients with diabetes mellitus. However, a large study (n = 1000) from the Western part of India reported 0% prevalence of subclinical CS, whereas similar data from other parts of India are lacking. Hence, we evaluated the prevalence of endogenous CS in adults with diabetes mellitus at a tertiary health-care center in South India. Materials and Methods: We screened 250 patients of apparent type 2 diabetes mellitus for Cushing syndrome with 1 mg overnight dexamethasone suppression test (ONDST) as a screening test and positive cases were further evaluated as per the standard protocol. Results: The mean age of the study population was 48.4 ± 4.3 years and 130 were male. Six patients had unsuppressed ONDST cortisol (≥1.8 μg/dl). Of these, only two patients had unsuppressed low-dose dexamethasone suppression test (LDDST) cortisol (≥1.8 μg/dl). The prevalence of endogenous CS among adults with diabetes mellitus was 0.8%. Both patients were females of middle age (44 years and 54 years) and had subclinical disease and borderline unsuppressed LDDST cortisol (2.35 and 1.87 μg/dl). One patient was diagnosed to have adrenocorticotropic hormone (ACTH)-independent CS (plasma ACTH at 8:00 am: 8 pg/ml) due to a cortisol-secreting left adrenal adenoma (2.7 cm × 2.5 cm × 1.8 cm), whereas the other female patient had Cushing disease (plasma ACTH at 8:00 am: 27 pg/ml) due to a pituitary microadenoma (6 mm × 3.4 mm × 3.2 mm). The patient with adrenal adenoma opted for conservative management whereas the patient with Cushing disease is planned for pituitary adenoma excision by an experienced neurosurgeon. Conclusion: The prevalence of endogenous CS in adults with diabetes mellitus is 0.8%. Screening of adults with diabetes mellitus for endogenous CS may be useful; however, larger studies are required before recommending routine screening.

Keywords: Cushing, diabetes, overnight dexamethasone suppression test

 Testing for cortisol insufficiency – A survey of practices among endocrinologists: Is it time to resolve the diagnostic dilemma



Nalini B. Wagmode, Nandhini Lakshmana Perumal1, Belinda George1, Ganapathi Bantwal1, Vageesh Ayyar1

Department of Endocrinology, ESI Medical College, PGIMSR,1Department of Endocrinology, St. John's Medical College, Bengaluru, Karnataka, India.

E-mail: naliniwb@gmail.com and naliniwagmode@gmail.com

Introduction: Testing for adrenal pathologies such as adrenal insufficiency and congenital adrenal hyperplasia (CAH) is commonly done in clinical practice. However, physicians encounter problems due to nonavailability of injection. Synacthen and the complexity of tests like the insulin tolerance test (ITT). Hence, most physicians adopt alternative testing strategies using injection Acton Prolongatum. Aims and Objectives: The aim of this study was to assess the current practices among endocrinologists in testing for adrenal pathologies such as adrenal insufficiency and CAH. Materials and Methods: A questionnaire covering the various procedures and protocols commonly used for testing the adrenal reserve and CAH was administered to endocrinologists. Results: The questionnaire was administered to 150 endocrinologists. Forty-nine of them participated in the survey. 24% of them practice in academic institutions. The most common indication for testing adrenal cortisol reserve was assessment of hypothalamic–pituitary–adrenal axis after exposure to exogenous steroids. Only 35% of participants performed ITT in their practice and it was done on rare occasions only. 69.38% of endocrinologists use injection Acton Prolongatum and 74.4% use injection Synacthen. 70.5% of endocrinologists used a dose of 24 units (range, 12–60 units) of Acton Prolongatum in adults. It was administered intramuscularly by 64.7% and subcutaneously by the rest. Peak serum cortisol level was measured at 60 min by 73.5% and 20.5% measured both 30 and 60 min values. 91.1% of respondents used a cutoff level of ≥18 μg/dl to define adequacy of cortisol status. 48.5% of respondents also reported using Acton Prolongatum to obtain stimulated 17-hydroxyprogesterone levels and 28.9% reported using it in children at varying dose. Nonavailability of injection Synacthen was most cited for its reduced usage. Conclusion: Acton Prolongatum is a popular alternative to injection Synacthen among endocrinologists in India. Nonavailability of Synacthen is commonly encountered.

Keywords: ACTH stimulation test, acton prolongatum, cortisol deficiency, synacthen

 Insulinoma: A rare cause of hypoglycemia in a young male



Sujata Devi, Pankaj Kumar1

Departments of General Medicine and1General Surgery, AIIMS, Bhubaneswar, Odisha, India.

E-mail: sujiankita@gmail.com

Introduction: Insulinoma is an uncommon pancreatic islet cell neuroendocrine tumor. It is more commonly found in females between the fourth and sixth decades of life. Case Report: A 33-year-old male presented with a history of recurrent hypoglycemic symptoms such as palpitations, nausea, vomiting, and severe sweating during prolonged fasting periods for 5 years. He also reported multiple episodes of loss of consciousness during this period. On evaluation, there was increased fasting insulin level (43.70 μU/ml) with C-peptide of 3.56 ng/ml and alpha hydroxybutyrate of 198 U/l, confirming endogenous hyperinsulinemia. He had a contrast-enhanced computed tomography of the abdomen which revealed a 28 mm × 25 mm intensely enhancing mass in the pancreatic head without any local invasion or metastases. Enucleation of the tumor was done. Histopathological examination confirmed it to be a pancreatic neuroendocrine tumor. He remained asymptomatic during follow-up. Conclusion: Insulinoma, though rare, should be one of the differential diagnoses in young patients with multiple events of hypoglycemia. Insulinomas are generally 90% benign tumors with excellent surgical result and have good long-term prognosis.

Keywords: Insulinoma, islet cell tumor, lethal hypoglycemia, neuroendocrine tumor, pancreas tumor

 Pheochromocytoma with extra-adrenal disease in familial p. arg82leu Von Hippel-Lindau gene mutation – A rare association



Behera Kishore Kumar, Prakash Kumar Sasmal1, Sahu Suchanda2

Departments of Endocrinology,1Biochemistery and2Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India.

E-mail: endocrin_kishore@aiimsbhubaneswar.edu.in

Introduction: p. Arg82Leu Von Hippel-Lindau (VHL) gene mutation, especially as VHL 2C although uncommon, presents with bilateral (b/l) pheochromocytoma (PCC) only. However, association with another neuroendocrine tumor (NET) with PCC in VHL 2C is not reported. We report two cases of VHL 2c from the same family presenting usually with PCC and other NET who has a more aggressive course. Method: A p. Arg82Leu VHL gene mutation as diagnosed by analyzing all the three exons ad flanking ironic region of the VHL were amplified by PCR and screened for mutation by directional sequencing on ABI 3130 sequencer. Case – 1: A 15-year-old girl presented to us with typical symptoms of headache, palpitation, and sweating and with appropriate investigation diagnosed with b/l PCC [Figure 1]a. She had laparoscopic b/l adrenalectomy done in August 2018. She was on regular follow-up for 1 year and completely off from any medication. Recently, she presented with severe abdominal pain; on evaluation, she was found to have a large ovarian [Figure 1]b mass with high alpha-fetoprotein. She underwent right salphingo-oopherectomy, and biopsy revealed mixed germ cell tumor of the ovary. Case 2: Her mother 35 years old had absence seizure 5 years back. A CT of the abdomen was done at that time which showed b/l adrenal mass [Figure 2]. In August 2018, she had a repeat CT abdomen which showed the same lesion at both the adrenal glands. In follow-up CT abdomen done in August 2019, abdomen which showed a pancreatic mass likely to be a NET in the pancreas and a paraganglioma [Figure 2]. However, she was totally asymptomatic over this year without any hypertension or sweating. Discussion: We report two cases of familial b/l PCC as a part of VHL with p. Arg82Leu germline mutation with variable penetrance. Both cases are indicative of aggressive disease. The same mutation reported earlier in India had milder form of the disease followed up for 30 years[1] which itself indicates of variable penetrance of same mutation. Conclusion: B/l PCC was not the sole presentation of germline mutation of p. Arg82Leu as reported earlier both in India and abroad[2] in VHL syndrome, but it can present with another tumor with variable phenotype. Therefore, it is advisable that regularly follow-up of VHL is warranted.{Figure 24}{Figure 25}

Keywords: Pheochromocytoma, Von Hippel-Lindau gene mutation

References

John AM, C GP, Ebenazer A, Seshadri MS, Nair A, Rajaratnam S, et al. P.Arg82Leu von Hippel-Lindau (VHL) gene mutation among three members of a family with familial bilateral pheochromocytoma in India: Molecular analysis and in silico characterization. PLoS One 2013;8:e61908.Nordstrom-O'Brien M, van der Luijt RB, van Rooijen E, van den Ouweland AM, Majoor-Krakauer DF, Lolkema MP, et al. Genetic analysis of von Hippel-Lindau disease. Hum Mutat 2010;31:521-37.

 A case series of bilateral adrenal masses in a tertiary care center in Eastern India



Soham Tarafdar, Jan Ahamed, Subhankar Chowdhury

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

E-mail: sohamtarafdar@gmail.com

Introduction: Bilateral adrenal masses are rare and have varied etiological diagnoses and treatment protocols. The Indian data published from Western India have suggested pheochromocytoma and tuberculosis as the most common two etiologies for bilateral adrenal masses. Other diagnoses include metastasis, histoplasmosis, lymphoma, and macronodular adrenal hyperplasia. Aims and Objectives: To analyze the clinical, biochemical, radiological, and microbiological features related to etiopathological diagnosis. Materials and Methods: Retrospective data for 11 patients admitted in 1 year (2018–2019) in a tertiary care center in Eastern India were collected for analysis. Results: Of 11 patients, 7 (63.6%) were diagnosed to have adrenal histoplasmosis. None of the patients had symptoms suggestive of histoplasmosis affecting another organ system. All patients of histoplasmosis were proven by computed tomography-guided fine needle aspiration cytology from adrenal glands and appropriate staining by periodic acid-Schiff and Grocott's methenamine silver staining. Of the 11 patients, 2 (18.2%) had disseminated tuberculosis with adrenal involvement and 2 (18.2%) patients had pheochromocytoma. Patients with pheochromocytoma had no evidence of adrenocortical insufficiency. Three out of nine patients with infective etiology (tuberculosis and histoplasmosis) presented with features of acute adrenal crisis, five patients had subclinical adrenal insufficiency, and one patient had biochemically adrenocorticotrophic hormone-dependent Cushing's syndrome without clinical features. Type 2 diabetes mellitus was the most common comorbidity associated found in five patients with infective etiology, while none of the patients in this case series were HIV positive. Discussion and Conclusion: This small case series suggests histoplasmosis as one of the leading causes of bilateral adrenal mass. This is contrary to data published from Western India where pheochromocytoma and tuberculosis were the two most common causes. This highlights the specific geographic distribution of histoplasmosis in India and warrants that proper staining techniques utilized to identify histoplasmosis in all cases of bilateral adrenal mass.{Figure 26}{Figure 27}{Figure 28}

Keywords: Bilateral adrenal mass, histoplasmosis, pheochromocytoma

 Intestinal pseudo-obstruction as initial presentation of pheochromocytoma



Devjit Majumder, Ajitesh Roy, Ashok Kumar1, Rana Bhattacharjee1, Partha Pratim Chakraborty2

Department of Endocrinology and Metabolism, Vivekananda Institute of Medical Sciences and Ramakrishna Mission Seva Pratishthan,1Department of Endocrinology and Metabolism, IPGMER/SSKM Hospital,2Department of Endocrinology and Metabolism, CMC, Kolkata, West Bengal, India. E-mail: dvjtmajumder2@gmail.com

Background: Intestinal pseudo-obstruction is a relatively uncommon complication of pheochromocytoma/paraganglioma. Clinically, this is manifested by chronic constipation or even acute intestinal pseudo-obstruction. We describe a 56-year-old female admitting with abdominal distension, pain, recurrent vomiting, and constipation in whom complete evaluation ultimately revealed unilateral adrenal pheochromocytoma. Case: A 56-year-old female with a history of diabetes and a long history of hypertension was admitted with abdominal distension, ill-defined pain, recurrent vomiting, and constipation for the past 2 weeks. Examination revealed a thin built female with pallor, low-normal blood pressure and tachycardia. Abdomen was distended with absent bowel sounds without any palpable mass. Baseline evaluation showed hypokalemia and poor glycemic status. The abdominal distension persisted despite achieving euglycemia and normokalemia. There had been intermittent hypertensive spells with a documented blood pressure up to 200/110 mm of Hg for the last several years without accompanying spell. Abdominal radiograph revealed large dilated loops of the colon. Contrast-enhanced computed tomography of the abdomen documented a lobulated, brightly enhancing mass (4.7 cm × 4.2 cm) in the left suprarenal region without calcification, necrosis, or hemorrhage. Plasma metanephrines were grossly elevated and thus, a diagnosis of adrenal pheochromocytoma was established. Discussion and Conclusion: This female presented with ileus and megacolon and had occasional hypertensive spells. In the absence of the typical triad such unusual presentation may deceive the attending physician and the diagnosis of pheochromocytoma, a potentially life-threatening condition may be overlooked. The underlying pathogenesis of intestinal pseudo-obstruction in pheochromocytoma is multifactorial. The incidence of pheochromocytoma is low and intestinal pseudo-obstruction is an uncommon complication in this setting, as reflected by a handful of such cases in the literature. If the tumor can be resected successfully, the chance of complete recovery is high. To conclude, the diagnosis of pheochromocytoma should be considered in a hypertensive patient presenting with intestinal pseudo-obstruction and megacolon.

Keywords: Megacolon, pheochromocytoma

 Diabetes mellitus in pheochromocytoma and paraganglioma: Prevalence, dynamics of insulin secretion and sensitivity, and predictors of remission



Saurav Khatiwada, Shifra Agarwal1, Rajeev Kumar2, Nandita Gupta3, Nikhil Tandon3, V. P. Jyotsna3

Departments of Endocrinology and Metabolism,1Pathology,2Urology, and3Endocrinology, AIIMS, New Delhi, India.

E-mail: ssauravkhatiwada@gmail.com

Introduction: Pheochromocytoma/paraganglioma (PPGL) is associated with secondary diabetes mellitus (DM). Most studies on prevalence are retrospective and have not reported remission rate with validated measures. In addition, although both insulin sensitivity and secretion are known to be impaired, their relative contribution to dysglycemia in PPGL is unknown.

Aims and Objectives:

To ascertain the pre and post-operative prevalence of DMTo evaluate the impact of insulin secretion parameters (ISPs) and insulin sensitivity index (ISI) on the prevalence of DMTo explore for predictors of DM preoperatively and remission postoperatively.

Materials and Methods: Thirty-four patients with PPGL underwent hemoglobin A1c (HbA1c) testing and oral glucose tolerance test with 75-g anhydrous glucose with samples for plasma glucose and serum insulin drawn at 0, 30, 60, 90, and 120 min preoperatively and at follow-up (n = 24), 3–15 months post surgery. Results: The pre- and postoperative prevalence of DM was 48% (18/37) and 17% (4/24), respectively, by American Diabetes Association criteria. Thirteen of the eighteen patients with DM required oral hypoglycemic agent and/or insulin pre surgery. Ten (77%) out of the 13 patients with DM who followed up went into remission. Comparison of patients with the highest (Q4) to the lowest (Q1) quartiles of ISI (1/fasting insulin) and insulinogenic index (IGI) (ISP) preoperatively revealed trends toward higher prevalence of DM with lower IGI (Q4 to Q1: 29% vs. 71%, n = 28, P = 0.24) and no association with 1/fasting insulin level (Q4 to Q1: 50% vs. 57%, n = 28, P = 1.00). DM for < 3 years preoperatively predicted postoperative remission. Discussion and Conclusion: There is high prevalence of DM in PPGL (48%), with remission rate of 77% in North India. Impaired insulin secretion appears to be its major driver. Duration of DM < 3 years and lower HbA1c are significantly associated with remission in DM. The study upholds screening and treatment of DM at priority in cases with PPGL.

Keywords: Diabetes mellitus, paraganglioma, pheochromocytoma, prevalence, remission

 Clinical spectrum of 21-OH deficiency congenital adrenal hyperplasia: A single-center retrospective study



Prudwiraj Sanamandra, Jugal Gada, Nikhil Bhagwat, Prema Varthkavi

Department of Endocrinology, BYL Nair Charitable Hospital, Mumbai, Maharashtra, India.

E-mail: prudraj@gmail.com

Introduction: 21-hydroxylase deficiency (21-OH deficiency) is the most common form of congenital adrenal hyperplasia (CAH). It is a single enzyme defect which is heterogeneous in terms of clinical manifestations. Aims and Objective: The objective was to assess the clinical profile and management of patients with 21-OH CAH presenting to a tertiary care hospital. Methods and Patients: The data of 16 patients of 21-OH deficiency CAH registered in the Endocrine Clinic of BYL Nair Charitable Hospital, Mumbai, between 2008 and 2019, and following up for a minimum of 2 years, were included in this retrospective study. Results: A total of 14/16 patients (87.5%) were genetically female (46XX). Nine (56.25%) patients presented in infancy. Ambiguous genitalia/clitoromegaly was the most common presentation (n = 9; 56.25%); one patient presented as failure to thrive. Hirsutism (n = 3) or masculinization (n = 1) was the presenting feature in the second decade. The male's patient in this series (46XY) presented as salt wasting and isosexual precocious puberty. Discussion and Conclusion: Salt wasting CAH is the most common phenotype of 21-OH deficiency worldwide. However, the simple virilizing phenotype was the most common in the present series, with ambiguous genitalia being the most common presentation. A high index of suspicion is required to diagnose CAH in males and patients with subtle adrenal insufficiency.

Keywords: Adrenal, congenital adrenal hyperplasia, disorder of sex development

 GONADS



 The role of urinary gonadotropins (luteinizing hormone and follicle-stimulating hormone) in the diagnosis of pubertal disorders



Manoranjan Tripathy, A. K. Choudhury, A. K. Baliarsinha

Department of Endocrinology, SCB MCH, Cuttack, Odisha, India.

E-mail: dr.manoranjan84@gmail.com

Introduction: The serum basal and gonadotropin-releasing hormone analog (GnRHa)-stimulated gonadotropins are invasive tests used for the diagnosis of pubertal disorders. The first morning void urinary gonadotropins may represent integrated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, so they can be used to differentiate between various pubertal disorders. Aim and Objective: We aimed to evaluate the role of urinary gonadotropins in the diagnosis of various pubertal disorders such as early and delayed puberty. Materials and Methods: This was a longitudinal cross-sectional study conducted between November 2017 and September 2019 in the Department of Endocrinology, SCB Medical College and Hospital. We had a total of 91 cases of pubertal disorders, out of which 30 cases were early puberty which included 13 cases of central precocious puberty (CPP), 7 cases of premature thelarche (PT), and 10 cases of peripheral precocious puberty (PPP). There were 61 cases of delayed puberty which included 19 cases of hypogonadotropic hypogonadism (HH), 24 cases of constitutional delay of growth and puberty (CDGP), and 18 cases of hypergonadotropic hypogonadism (Hyper-Hypo). The first morning void urinary LH and FSH evaluation was done in all these cases. Results: The urinary LH and FSH correlated statistically significantly with serum basal LH and FSH in both early and delayed puberty (Spearman's correlation coefficient >0.5 in all cases and P < 0.001). The Kruskal–Wallis test for both urinary LH and FSH to differentiate between various causes of early puberty such as CPP, PT, and PPP as well as delayed puberty such as HH, CDGP, and Hyper-Hypo was statistically significant (P < 0.001). Conclusion: Urinary gonadotropin is a useful noninvasive test to differentiate between various pubertal disorders and can be used in the place of invasive and cumbersome GnRHa-stimulated tests.

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Keywords: Pubertal disorders, urinary follicle-stimulating hormone, urinary gonadotropins, urinary luteinizing hormone

 Prevalence of hypogonadism and its relation with glycemic control, body mass index and age group in type 2 diabetes mellitus: Results of a cross sectional study



Abhishek Shrivastava

R and R Medicare Centre, Jabalpur, Madhya Pradesh, India. E-mail: abhishri2002@yahoo.com

Background and Aims: There is an increased prevalence of hypogonadotrophic hypogonadism in men with type 2 diabetes mellitus. Similarly, men with hypogonadism are at an increased risk for the development of type 2 diabetes mellitus and/or metabolic syndrome. This suggests a possible bidirectional relationship between insulin resistance and low levels of testosterone. The objective of this study was to estimate prevalence of hypogonadism and testosterone deficiency syndrome in adult patients with type 2 diabetes mellitus and examine the relation of glycosylated hemoglobin, age, and body mass index with hypogonadism in these patients. Materials and Methods: In this cross-sectional study, adult male patients (30–60 years of age) with type 2 diabetes on oral antidiabetics were included after their written informed consent of the participants. Patients on anabolic steroid or opioid drug use, primary or secondary gonadal failure, acute medical illness or history of hormonal treatment were excluded from the study. Detail medical and treatment history was taken to rule out other obvious underlying etiology for hypogonadism. After recording baseline demographic details, patients underwent laboratory investigations to find level of total testosterone and glycosylated hemoglobin. The prevalence of hypogonadism was evaluated based on the total testosterone level. Hypogonadism was defined as total testosterone level of less than 300 ng/dl. The Androgen Deficiency in Aging Males questionnaire was used to find the prevalence of TDS. After the estimation of laboratory values, patients were divided into two groups; those with hypogonadism and without hypogonadism. The level of glycosylated hemoglobin between two groups, i.e. those with hypogonadism and without hypogonadism was compared. Similarly, a comparison of glycosylated hemoglobin was done between patients with and without testosterone deficiency syndrome. A comparison of hypogonadism and testosterone deficiency syndrome was done in patients between 30 to 45 years of age and 46 to 60 years of age. Statistical Analysis: Categorical variables are reported as numbers and percentages. Continuous variables are presented as mean and standard deviation. Unpaired t-test was used to examine difference in the mean values between two groups. Chi-square test was used to calculate the difference in the frequencies. Results: In this study, a total of 50 male patients were included. The mean (+standard deviation [SD]) age of the patients in the study was 45.98 (+7.93) years. Of 50 patients, 23 (46%) patients were in the age group of 30 to 45 years, whereas 27 (54%) were in the age group of 46 to 60 years. Number (%) of patients with a history of hypertension, smoking, and alcohol consumption included 25 (50%), 7 (14%), and 42 (84%), respectively. The mean (+SD) glycosylated hemoglobin and total testosterone level of the entire study population was 8.31 (+1.70)% and 399.64 (+158.36) ng/dl, respectively. Hypogonadism and testosterone deficiency syndrome were present in 17 (34%) and 31 (62%) patients, respectively. The mean (+SD) level of glycosylated hemoglobin in patients with hypogonadism was 8.89 (+1.84)%, whereas in patients with normal total testosterone level the mean (+SD) level of glycosylated hemoglobin was 7.84 (+1.86)%. The difference in mean glycosylated hemoglobin between two groups was not statistically significant, but there was trend for higher levels of glycosylated hemoglobin in patients with hypogonadism (P = 0.0631). The mean (+SD) glycosylated hemoglobin in patients with testosterone deficiency syndrome was 8.80 (+1.83)%. The mean (+SD) glycosylated hemoglobin in patients without testosterone deficiency syndrome was 7.51 (+1.08)%. The difference in glycosylated hemoglobin between the two groups was statistically significant (P = 0.0028). The mean (+SD) body mass index of patients with hypogonadism was 26.35 (+1.87) kg/m2, whereas of the patients without hypogonadism was 26.09 (+2.53) kg/m2. There was no significant difference in the body mass index of patients with hypogonadism and those without hypogonadism (P = 0.68). The mean (+SD) body mass index of patients with testosterone deficiency syndrome was 26.48 (+2.28) kg/m2, whereas of the patients without testosterone deficiency syndrome was 25.68 (+2.33) kg/m2. There was no significant difference in the body mass index of patients with testosterone deficiency syndrome and those without testosterone deficiency syndrome (P = 0.24). A total of 11 (47.8%) and 6 (35.3%) patients in the age group of 30 to 45 years and 46 to 60 years had hypogonadism, respectively. This difference was statistically not significant (P = 0.057). Testosterone deficiency syndrome was present in 10 (43.5%) and 21 (77.8%) patients of 30 to 45 years of age and 46 to 60 years of age, respectively. The difference in the frequency of testosterone deficiency syndrome in two age groups was statistically significant (P = 0.013). Conclusion: Patients with type 2 diabetes mellitus showed a high prevalence of hypogonadism and testosterone deficiency syndrome. The level of glycosylated hemoglobin was significantly high in patients with testosterone deficiency syndrome as compared to those without testosterone deficiency syndrome. Testosterone deficiency syndrome was significantly higher in patients between 46 and 60 years of age than those in 30 to 45 years of age.

Keywords: Diabetes, hypogonadism, prevalance

 46, XX congenital adrenal hyperplasia reared as male



Akanksha Gautam, Rama Walia, Anil Bhansali

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

E-mail: akanksha.gautam1989@gmail.com

Introduction: Patients with 46, XX congenital adrenal hyperplasia (CAH) are mostly reared as females; however, in patients with greater degree of virilization, delayed diagnosis, or suboptimal treatment, male sex of rearing may have to be assigned. We present here clinical profile of four such patients. Aims and Objective: The aim was to study the clinical profile, management, and outcomes of patients with 46, XX CAH assigned male sex of rearing. Materials and Methods: This was a prospective study from the Endocrinology Department, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Results: From a cohort of 65 patients with CAH, four patients were identified with 46, XX karyotype and male sex of rearing. All had 21-hydroxylase deficiency: Two having salt wasting and 2 having simple virilizing form. The age at diagnosis ranged from 2 weeks to 3 years; however, because of poor compliance and suboptimal treatment, all were poorly controlled with mean 17-hydroxyprogesterone levels being 84.45 ng/mL at the time of presentation. Prader stage of genitalia was between 4 and 5. The mean age of undergoing genitoplasty was 11.2 years (range: 4–17 years). All patients also underwent oophorectomy with hysterectomy after psychological assessment and parental consent: done in view of development of gonadotropin-dependent precocious puberty (earliest at 4 years of age). All patients remain on hydrocortisone and fludrocortisone replacement, with one patient also receiving testosterone replacement. Discussion and Conclusion: Gender assignment in 46, XX CAH may be guided by multiple factors including gender identity, gender role, degree of virilization, and parents' preferences. Even with an early diagnosis, poorly compliant and undertreated patients end up with poorly controlled disease. Hence, male sex of rearing may have to be assigned in these patients, thus requiring multiple surgeries.

Keywords: 46, XX, congenital adrenal hyperplasia, male sex of rearing, virilization

 Partial gonadal dysgenesis – A rare presentation of 46, XY disorder of sex development: A focused review



M. Manasa, B. Vivekanand, A. Mythili, Jayanthy Ramesh, K. A. V. Subrahmanyam

Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India.

E-mail: manasaprasadmdr@gmail.com

Background: Partial gonadal dysgenesis (PGD) is an uncommon disorder characterized by sexual ambiguity due to variable degree of testicular dysgenesis. Here, we present a case report of a 17-year-old girl who presented with peripubertal virilization, which is rare in PGD. Case Report: A 17-year-old, reared as a female, presented with complaints of lack of breast development and failure to attain menarche. She noticed appearance of pubic hair at 11 years followed by increase in the size of phallus at 13 years. There was no history of breast development. She is first in birth order, born to nonconsanguineous parents, observed no genital ambiguity at birth, and assigned female sex. On examination, eunuchoid proportions were present, with temporal hair recession, and there was masculine habitus. Sexual Maturity Rating was A3P4B1. External genitalia examination showed a stretched phallic length of 5.5 cm; a phallic index of 384 mm2; ventral chordee and penoscrotal hypospadias; fused labioscrotal folds with pigmentation and rugosity and no palpable gonad in the right labioscrotal fold; and soft 2–3 ml soft-tissue palpable in the left labioscrotal fold. External masculinization score was 6.5/12. On evaluation, karyotype was 46, XY; basal testosterone was 92.05 ng/dl; human chorionic gonadotropin (HCG)-stimulated testosterone was 96.64 ng/dl; dihydrotestosterone (DHT) was 216.11 pg/ml; androstenedione (A) was <0.3 ng/ml; testosterone (T)/DHT was 4.47; T/A was 3.2; follicle-stimulating hormone was 65.01 mIU/ml; and luteinizing hormone was 19.22 mIU/ml. Magnetic resonance imaging pelvis showed rudimentary uterus and vagina, blind-ending short rudimentary vaginal pouch, and well-defined oval structures measuring 29 mm × 10 mm in the right inguinal canal and 15 mm × 11 mm in the left labioscrotal fold likely testes. Conclusion: PGD should be suspected in 46, XY disorder of sex development with genital ambiguity with peripubertal virilization. The presence of Mullerian remnants with dysgenetic gonads in such a setting suggests PGD.

Keywords: Partial gonadal dysgenesis 46, XY disorder of sex development

 Palpable abdominal lump in a young adult male: A rare presentation of 46, XY disorder of sex development



M. Manasa, B. Vivekananda, A. Mythili, Jayanthy Ramesh, K. A. V. Subrahmanyam

Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India.

E-mail: manasaprasadmdr@gmail.com

Background: Usual presentation of 46, XY disorder of sex development (DSD) is atypical external genitalia and hypogonadism. 46, XY DSD with cryptorchidism or dysgenetic testes can develop tumors which are often small. Here, we present a case report of a 21-year-old male with 46, XY DSD presenting with a large palpable abdominal mass. Case Report: A 21-year-old male presented with complaints of abdominal distension and weight loss. On examination, there was a palpable lump in the hypogastric and umbilical region, extending into both lumbar regions. He was second in birth order, born out of third-degree consanguineous parents, observed no genital ambiguity, and was reared as male. He noticed an increase in penile length and pubic and axillary hair at 13 years of age. On examination, he was well-androgenized SMR A3P5 with well-developed phallus and scrotum and no palpable gonads. Ultrasonography (USG) abdomen showed a very large, 30-cm mixed echogenic mass in the retroperitoneum below the bifurcation of the aorta. Computed tomography (CT) showed similar findings. USG scrotum showed right inguinoscrotal hernia and no testes in bilateral scrotal sacs. Fine-needle aspiration cytology of the mass was suggestive of germ cell tumor of the testis. The patient had grossly elevated lactate dehydrogenase (LDH) of 2143 U/l, mildly elevated beta-human chorionic gonadotropin, and normal alpha-fetoprotein levels. He underwent four cycles of chemotherapy with bleomycin, etoposide, and cisplatin. Postchemotherapy, his LDH value reduced to 230U/l. CT abdomen postchemotherapy showed bilateral undescended testicular tumors with left inguinal omentocele and hence planned for surgery. Intraoperatively, atrophied uterus with left gonad and mass with right gonad were visualized. Total abdominal hysterectomy with bilateral gonadectomy was done. On HPE, testicular tissue and atrophied uterine tissue and cervix were noted. Karyotype was 46, XY. Postoperative serum testosterone was 23 ng/dl, elevated follicle-stimulating hormone and luteinizing hormone. The patient was started on testosterone replacement therapy and is on regular follow-up. Conclusion: In 46, XY DSDs, the incidence of malignancy ranges from 7.5% to 30% depending on the etiology. Testicular malignancy as a presenting symptom is uncommon, especially in persistent Mullerian duct syndrome (PMDS) which usually presents with undescended testis and inguinal hernia. Our case describes such a rare presentation of PMDS.

Keywords: Abdominal lump adult 46XY disorder of sex development

 Study of efficacy of gonadotropin therapy and predictors of spermatogenesis in male congenital hypogonadotropic hypogonadism patients



Ravi Kumar Shah, Anurag Lila, Swati Ramteke Jadhav, Virendra Patil,

Sushil Sonawane, Brijesh Krishnappa, Nalini Shah, Tushar Bandgar

Department of Endocrinology, KEM Hospital, Mumbai, Maharashtra, India. E-mail: rk_shreeji@yahoo.com

Introduction: Therapeutic goals in males with congenital hypogonadotropic hypogonadism (CHH) include inducing virilization and gaining fertility. Testosterone replacement therapy (TRT) accomplishes all of these goals except for attainment of fertility. Literature regarding efficacy and predictors of response of gonadotropin therapy (GnT) in CHH cohort remains limited. Aims and Objectives: To study the efficacy of GnT in CHH for (i) pubertal induction in terms of achieving virilization, normal serum testosterone levels (>3.5 ng/ml), as well as initiation of spermatogenesis; (2) inducing spermatogenesis; and (3) identifying predictors of therapy specifically for achieving spermatogenesis. Materials and Methods: This was a retrospective analysis of case records of 40 patients on GnT with a minimum 12 months posttreatment follow-up. Patients were divided into two cohorts: Cohort 1 patients with minimal (<6 months) or no prior TRT and received GnT for inducing virilization and fertility, while Cohort 2 patients virilized with prior TRT (>6 months) and received GnT for fertility. Cohort 1 received gradually increasing hCG dosages with or without hMG pretreatment (n = 5), while Cohort 2 was on adult dosages of hCG from the beginning of therapy. Results: Cohort 1 had 22 patients (severe phenotype: 14 and partial phenotype: 8) while Cohort 2 had 18 patients (severe phenotype: 11 and partial phenotype: 7). In overall cohort, the mean age at starting GnT was 24.1 ± 6.1 years, baseline bi-testicular volume (BTV) was 6.7 ± 5.3 ml, and three patients had bilateral cryptorchidism. After 30.9 ± 13.1 months of GnT, last BTV achieved was 16.7 ± 10.8 ml showing a median of 145% (76%–391%) increment. 80% of patients achieved adult testosterone level. Spermatogenesis was achieved in 72.2% of patients, of which 52.2% patients had sperm concentration > 5 million/ml. Median highest sperm concentration was 5 (0–12) million/ml and median on treatment inhibin-B level was 81 (46–117) pg/ml. Overall, Cohort 1 responded significantly better than Cohort 2, with very stark difference of response between severe phenotypes of both cohorts. There was no difference of response between the partial phenotypes of two cohorts. hMG pretreatment patients had higher sperm counts than combined treatment group in Cohort 1. Duration of prior androgen therapy was significant negative predictor for patients with severe phenotype. Conclusion: GnT is effective in achieving spermatogenesis in CHH patients with severe and partial phenotype. Pubertal induction with GnT has rewarding results, especially for patients with severe phenotype. hMG pretreatment should be considered for patients with severe phenotype. Long-term prior androgen therapy may be detrimental in patients with severe phenotype.

Keywords: Congenital hypogonadotropic hypogonadism, gonadotropin therapy

 A spectrum of patients with isolated hypogonadotropic hypogonadism: A single-center experience



Saurav Shishir Agrawal, Chhavi Agrawal, Partha Pratim Chakraborty, Anirban Sinha, Animesh Maiti, Asish Kumar Basu

Department of Endocrinology, Medical College, Kolkata, West Bengal, India. E-mail: docssagrawal@gmail.com

Introduction: Congenital isolated hypogonadotropic hypogonadism (IHH) is caused due to defect in GnRH neuronal development, migration, and action. Materials and Methods: We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, and management of 13 patients with IHH who presented to our center between 2016 and 2019. Results: There were 11 males (84.6%) and 2 females (15.3%) in which IHH was diagnosed on the basis of the previously established criteria. Among the 13 patients, five patients (38.4%) were diagnosed with Kallman Syndrome, while eight patients (61.5%) were normosmic IHH [nIHH]). The prevalence of magnetic resonance imaging abnormalities was seen in 63.6% of the patients. Four out of 5 (80%) anosmic patients had hypoplastic olfactory bulbs, while three out of 13 (23%) patients had an incidentally diagnosed microadenoma. One patient out of 13 (7.6%) each had abnormalities in form of renal agenesis, hearing loss, and dental abnormality, while cryptorchidism was found in two of our patients. Complete absence of puberty was more common in Kallman syndrome group as compared to nIHH group. Relative distribution of nonreproductive features could not be compared due to small sample size. Of the 11 male patients, six have been started on gonadotropins therapy with HCG injection only in those with testicular volume >4 ml and a combination of HCG and FSH in patients with testicular volume <4 ml. Four patients were started on testosterone therapy. Both the females were started on estradiol therapy first with a plan for ovulation induction when desired. The patients are being followed up on 3 monthly basis clinically, level of sex hormones, and semen analysis as required. Conclusion: Although genetic etiology of IHH is increasingly being studied, Indian data on phenotypic spectrum and therapeutic outcomes for IHH are scarce.{Figure 29}{Figure 30}

Keywords: Anosmia, hypogonadism, hypogonadotropic

 A case series of three patients with ovotesticular disorder of sex development



Ajay Raj Mallela, Neelaveni Kudugunti, Rakesh Kumar Sahay

E-mail: ajayprakashdr@gmail.com

Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition with a molecular basis of disorder being not known. It can be subcategorized based on karyotype into 46 XX/46 XY chimeric variants, 46 XX and 46 XY. Case Series: We report three cases of OT-DSD. The age of presentation was newborn period, and the clinical presentation was ambiguous genitalia with phallus-like structure and hypospadias. Bilateral crytorchidism was noted in two of them while unilateral crytorchidism was noted in one of them. Karyotyping was 46 XX, 46 XY, and 46 XX/XY among three patients, respectively. Diagnosis of OT-DSD was made by histopathological examination (HPE) of the gonads. Case 1: A 46 XY child reared as male had biochemical evidence for the presence of testicular tissue; however, magnetic resonance imaging (MRI) pelvis did not identify the type and location of gonadal structures; hence, diagnostic laparotomy was performed which showed one gonad in the right inguinal canal and streak gonad, hemiuterus, and fallopian tube in the left pelvis, reported as testis and ovary on HPE, respectively. Case 2: A 46 XX/XY child reared as male at 10 months of age underwent inguinal surgery for right inguinal swelling which showed hemiuterus and HPE of the gonad showed ovotestis. At 13 years 4 months, he presented with gynecomastia with elevated serum estradiol levels and HPE was reported as ovotestis. Bilateral gonadectomy with testicular prosthesis implantation was done. Case 3: A46 XX child reared as female had biochemical evidence for the presence of testicular tissue. MRI showed uterus and bilateral gonads with follicles in the pelvis. Diagnostic laparotomy with left gonadal biopsy was suggestive of ovotestis. She was planned for gonadectomy. Conclusion: OT-DSD is a very rare disorder. Delay in diagnosis will take a toll on child's psychological well-being. The multidisciplinary approach to diagnose, evaluate, and plan the treatment is advocated in OT-DSD.

Keywords: 46 XX, 46 XY, karyotyping, ovotesticular disorders

 Case series of Mayer–Rokitansky–Kuster–Hauser syndrome



Apsia Ruhi, Vijay Sheker Reddy Danda, P. Srinivas Rao, D. Sandeep Reddy, Piyush Lodha, Chaitanya Konda

Department of Endocrinology, Gandhi Medical College/Hospital, Hyderabad, Telangana, India.

E-mail: apsia2k2omc@gmail.com

Background: Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina. It results from agenesis or hypoplasia of the Mullerian duct system. MRKH may be isolated (Type I) or can be associated with renal, vertebral, and to a lesser extent, auditory and cardiac defects (MRKH Type II). We report here four cases during the past 1 year. Two were 19-year-old women who presented with primary amenorrhea (MRKH Type I) and one was a 19-year-old who presented with primary amenorrhea and had polydactyly and renal anomaly (MRKH type 2) while the other is a 35-year-old woman presented with primary infertility. Case Presentation: All the four cases came to the Department of Endocrinology with complaints of primary amenorrhea and primary infertility. All were born to nonconsanguineous parentage, full-term normal vaginal delivery with normal birth weight. They noticed normal secondary sexual characteristics at 13–14 years of age. None had anosmia, unwanted facial hair, acne, or voice change. On examination, none had turner stigmata. One out of four had preaxial polydactyly. Height, weight, and body proportions were within normal range. All had SMR B5A3P5, normal female external genitalia. Systemic examination was normal. Hormonal study for follicle-stimulating hormone, luteinizing hormone, and estradiol was within normal limits. X-ray cervical spine was normal in all. On magnetic resonance imaging, all had hypoplastic uterus and normal ovaries. One had left renal agenesis. Karyotyping showed 46XX. Conclusion: Considering the varying presentation of MRKH and numerous treatment options, it is important that each case be individualized and management aspects be discussed and fertility options available to be explained. There is a need for more research in this field.

Keywords: Amenorrhea, Mayer–Rokitansky–Kuster–Hauser, Mullerian duct, vaginal agenesis

 Polycystic ovary syndrome in adolescents: Clinical and metabolic characterization



Ajay Kumar Shukla, Preeti Dabadghao, Vijayalakshmi Bhatia

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

E-mail: dr.ajayshukla@gmail.com

Introduction: Calculated prevalence of polycystic ovary syndrome (PCOS) was reported as 3.4% in 18–20 years age college students from our center. Clinical hyperandrogenism was uncommon. Majority of them were lean but had high waist-to-hip ratio and prehypertension. Glucose tolerance and beta-cell function can be abnormal in them because of obesity and/or PCOS per se. Aim: To study clinical, biochemical, and metabolic profile including beta-cell function in adolescents (12–20 years) with PCOS attending a tertiary care center. Materials and Methods: Seventy-five adolescents with PCOS diagnosed by the NIH criteria (age 17.6 ± 2 years) were compared with 25 healthy controls (18.1 ± 2 years). Beta-cell function indices were calculated on oral glucose tolerance test. Data were analyzed in SPSS 23 software. Results: PCOS adolescents were heavier and had significantly higher body mass index (25.56 ± 5.7 vs. 21.33 ± 3.15, P < 0.0001), waist circumference (81.54 ± 12.3 vs. 70.6 ± 6.44, P < 0.0001), systolic blood pressure (116.2 ± 10.5 vs. 110.7 ± 8.4, P = 0.02), and low-density lipoprotein-cholesterol (98, 80–121 vs. 81, P = 0.012). Forty-three percent PCOS had waist circumference > 0 cm and at least one metabolic abnormality as compared to just 4% in controls and 10% had metabolic syndrome compared none in controls. Twenty-two percent PCOS had glucose tolerance abnormality as compared to 9% in controls. HOMA-IR, disposition index, and area under the curve for glucose and insulin were comparable in both PCOS and controls, but PCOS adolescents had significantly higher fasting C peptide (3.09 ± 1.67 vs. 3.06 ± 1.12, P = 0.012). Glucose tolerance was maintained at the cost of higher C peptide signifying early beta-cell dysfunction. The prevalence of family history of diabetes was similar in both groups which could explain the comparable results of indices of insulin resistance. Conclusion: There is a trend toward higher prevalence of metabolic abnormalities and metabolic syndrome in adolescents with PCOS. However, most of the indices of insulin resistance and beta-cell dysfunction are similar to controls.

Keywords: Beta-cell function, hyperandrogenism, polycystic ovary syndrome in adolescents

 P-450 oxidoreductase deficiency with antley-bixler phenotype: A rare cause of 46XY disorders of sex development



Balram Sharma, Hardev Ram Nehra, Sandeep K. Mathur

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

E-mail: naincypurwar@yahoo.co.in

Introduction: We present the first case of 46 XY disorder of sex development from India due to P450 Oxidoreductase deficiency with novel variant (p.Ala541Thr). Case Discussion: Six-month-old boy presented with ambiguous genitalia since birth. No history of neonatal crisis, failure to thrive and pigmentation of skin, maternal virilization, or drug ingestion during pregnancy. On Examination: Weight 6.2 Kg (3rd centile), height 64 cm (3rd centile), MPH-170 (25th–50th centile), head circumference 38 cm (−2.7 SD), vitals stable, trigonocephaly with fused anterior and posterior fontanelle, prominent pointed forehead, midfacial hypoplasia, up slanting eyes, hypertelorism, and low set ears were present. Genitalia: 1.5 cm phallus-like structure with foreskin, chordee, single perineal opening in the form of penoscrotal hypospadias, bifid scrotum with poor rugosity, and poor pigmentation and both gonads (1 ml) were palpable in labioscrotal fold with external masculinization score (EMS), 6/12 and Prader stage 4. Investigations showed normal electrolytes and blood sugar, high basal ACTH, poststimulation cortisol 14 mcg/dl, basal 17-OHP was 8.6 ng/ml and poststimulation 12 ng/ml, with low DHEAS 36.4 mcg/dl and androstenedione 0.42 ng/ml, LH 16.09 mIU/ml (elevated), follicle stimulating hormone 2.97 mIU/ml (normal) and low testosterone for his age. T/dihydrotestosterone (DHT) 9.6 (normal <10) and testosterone/androstenedione ratio 0.95 (normal >0.8). Abdominal and pelvic imaging showed normal adrenal glands and absent female internal genitalia, bilateral testis in labioscrotal fold (right testis – 6 × 6.5 × 11 mm, left testis – 6.6 × 7× 10 mm), corpora cavernosa and bifid scrotum. NCCT head showed metopic craniosynostosis with trigonocephaly and hypotelorism. A skeletal survey showed bowing of femora. Twenty-cell karyotype of peripheral blood lymphocyte was 46 XY. The next-generation sequencing was done of the POR gene, which revealed a heterozygous missense variation in exon 13 of the POR gene variant (p.Ala541Thr), which has not been reported yet. The patient was initiated hydrocortisone, fludrocortisone, DHT gel and corrective surgery is planned.

Keywords: Antley bixler phenotype, 46 XY disorders of sex development, POR deficiency

 A study of clinical and hormonal profile of cases of 46, XY disorders of sex development



Sagar Barasara, Nikhil Bhagwat, Prema Varthkavi, Jugal Gada

Department of Endocrinology, B.Y.L. Nair Charitable Hospital, Mumbai, Maharashtra, India.

E-mail: sagar.barasara03@gmail.com

Introduction: 46, XY disorders of sex development (DSDs) result from disorders of gonadal development, androgen synthesis, or androgen action. Patients with 46, XY DSD present with myriad phenotypes ranging from unambiguous female genitalia to ambiguous male genitalia and could be raised either as males or females. Their management is a medical and social challenge. Aim: The aim is to study the clinical, hormonal profile, etiology, and management of patients with 46, XY DSD presenting to a tertiary care municipal hospital. Methods: We assessed forty patients registered with the Endocrine Clinic from 2014 to 2019. We classified patients as having 46, XY DSD on the basis of clinical, karyotyping, hormonal, and imaging studies. Results: Forty (age: neonate to 32 years) of 86 patients with DSD had 46, XY DSD. Fifteen patients were reared as female, 22 as male, and gender had not been assigned to 3 patients. Micropenis (17/22; 77.3%) was the most common presentation. Hypospadias was present in 59% (13/22). The mean EMS score at presentation was 7.167. In patients who were reared as female, the most common presentation was inguinal swelling, followed by virilization at puberty. Androgen insensitivity syndrome (AIS) (n = 11; 27.5%) was the most common diagnosis followed by 5-alpha reductase deficiency (n = 9; 22.5%). Gonadal dysgenesis (n = 8; 20%), 17-beta hydroxysteroid dehydrogenase type III deficiency (n = 4; 10%), vanishing testis syndrome (n = 1), and DSD with cloacal abnormality (n = 1) were the other etiologies. Six patients had an inconclusive biochemical profile. Five patients presenting with virilization at puberty were reassigned male gender as per their gender identity and role. Discussion and Conclusion: In our study, AIS was the most common etiology of XYDSD in accordance with published literature. 5-alpha reductase deficiency and gonadal dysgenesis were seen more frequently in our cohort compared to previously reported literature.

Keywords: 46, XY disorder of sex development, clinical profile, disorder of sex development, hormonal profile

 PEDIATRIC AND ADOLESCENT ENDOCRINOLOGY



 Interesting case of hypothalamic hamartoma with gelastic seizures and central precocious puberty



Ajay Raj Mallela, Neelaveni Kudugunti, Rakesh Kumar Sahay

Osmania Medical College, Hyderabad, Telangana, India.

E-mail: ajayprakashdr@gmail.com

Hypothalamic hamartomas (HHs) are rare, congenital, nonprogressive tumor-like malformations that originate from tuber cinereum and inferior hypothalamus. HH can manifest with diverse clinical manifestations. We report the case of a 7-year-old boy presented with a history suggestive of the classical triad of HH (gelastic seizures, severe neurocognitive delay, and precocious puberty). His episodes of laughter were typical of gelastic seizures from history and video review. He also had episodes of complex partial seizures with secondary generalization. Clinical examination and biochemical investigations were diagnostic of gonadotropin-dependent precocious puberty. His bone age was 15 years. His magnetic resonance imaging brain showed evidence of 22 mm × 14 mm × 19 mm of HH arising from the region of tubercinerum. Electroencephalogram showed generalized background slowing with intermittent spike and wave discharges. The child was managed with gonadotropin-releasing hormone receptor agonists for central precocious puberty and antiepileptics (carbamazepine and clobazam). The child continued to have seizures on maximum dose of both antiepileptics. The severity of HH-associated epilepsy necessitated surgery in this patient. Our case highlights the need for early diagnosis of underdiagnosed HH and unrecognized gelastic epilepsy which can significantly affect the growth and development in the pediatric population.

Keywords: Central precocious puberty, gelastic seizures, GnRH receptor agonists, hypothalamic hamartoma

 A rare case of craniopharyngioma presenting as central precocious puberty



Rukma Rajendra Narkar, Anoj Kumar Baliarsinha, Arun Kumar Chaudhary, Vaibhav Pathak

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

E-mail: ruksnarkar@gmail.com

Objectives: Craniopharyngioma is the most common tumor affecting pituitary function in childhood. Usual presentation is with nonspecific features of increased intracranial pressure, such as headache. Most patients present with growth and puberty delay. However, they rarely may present with features of endocrine hyperfunction. We report a case of craniopharyngioma presenting as central precocious puberty. Materials and Methods: A 6-year-old male child presented with a history of noticing development of pubic hair for the past 4 months. There was no history of noticing growth spurt. On examination, his vital parameters were found to be stable, height was above the 97th centile, weight was above the 97th centile, and pubertal staging was found to be as axillary hair Stage 1, pubic hair Stage 3, and a stretched penile length of 7.5 cm. Bilateral testicular volume was found to be 8 cc. Results: Basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were found to be in low-normal male adult range. One-hour postgonadotropin-releasing hormone analog LH and FSH were compatible with a diagnosis of central precocious puberty. Magnetic resonance imaging brain was suggestive of a 3.2 cm × 3.1 cm × 2.8 cm suprasellar mass with features consistent with the diagnosis of a craniopharyngioma [Figure 1]. The patient planned for surgery followed by radiotherapy. Conclusions: Although it is a rare finding, a possibility of craniopharyngioma must be considered during evaluation of a patient presenting with gonadotropin-dependent sexual precocity.{Figure 31}

Keywords: Craniopharyngioma, gonadotropin-dependent sexual precocity, precocious puberty

 A case of Turner syndrome with 46, X del (Xq)



Asha Ranjan, N. K. Agrawal, S. K. Singh, M. S. Dhananjaya, Rujul Jain, Vahid Bharmal

Department of Endocrinology, IMS, BHU, Varanasi, Uttar Pradesh, India. E-mail: asharjn. 85@gmail.com

Introduction: Turner syndrome (TS) is the most frequent chromosomal anomaly in human involving ~ 1% to 2% conceptuses. The most common abnormality is monosomy X (45, X), followed by mosaic forms such as 45, X/46, XX, 45, X/47XXX, and 45, X/46, XY. Structural abnormality with complete deletion of Xq with typical turner phenotypic stigmata is rare. Case Report: An 18-year-old female presented with primary amenorrhea and nondevelopment of secondary sexual characteristics. She was born to the unrelated parents with no significant birth history and normal developmental miles stones. She had no cyclic pain abdomen or anosmia and did not suffer from recurrent ear infections. On examination, her height was 143 cm (<3rd centile, Indian Academy of Pediatrics), weight 42 kg, SMR A1P3B1. She had short and webbed neck, low posterior hair line, cubitus valgus deformity, short 4th and 5th metatarsals, scoliosis, high-arched palate, low set ears, and pigmented nevi. The systemic examination was normal including audiometry. Her hormonal profile was as follows: follicle-stimulating hormone, 42 IU; luteinizing hormone, 46 IU; and T3/T4/thyroid-stimulating hormone, 119 ng/dL/8.4 μg/dL/13.88 μIU/ml with positive anti-thyroid peroxidase antibody. Abdominal and pelvic imaging showed hypoplastic uterus and ovaries with no renal abnormalities. The typical clinical features of short stature, primary amenorrhea, and stigmata were suggestive of TS. The karyotyping showed 46, X del (Xq), which is an uncommon chromosomal abnormality in TS. The patient was started on levothyroxine (62.5 μg/day) and estrogen (0.312 mg/day) and was followed up. Discussion: Here, we present a case of TS with typical stigmata with uncommon karyotype. 45, X usually manifests the full Turner's phenotype and mosaic forms present with milder phenotypes. Complete X (p) deletion phenotype is similar to 45, X. Region Xp22.33-Xp22.12 contains SHOX gene, which is responsible for short stature and skeletal abnormalities. Phenotype in X (q) deletion is variable depending on the site and amount of deletion. Most frequent presentation is primary ovarian failure due to deletions of CR2 (critical region 2) at Xq23-q28. The height can be short due to loss of interstitial or terminal X (q) with variable skeletal and skin manifestations. No obvious candidate genes for short stature have been assigned to this region so far. Conclusion: TS with 46, X del (Xq) is uncommon structural abnormality. Complete 46, X del (Xq) patients may present with complete gonadal dysgenesis, short stature, and typical Turner's stigmata.

Keywords: Short stature, Turner syndrome

 Unusual cause of precocious puberty: Two case reports



Dhananjaya Melkunte Shanthaiah, Neeraj Kumar Agrawal, Sourabh Arora, Rujul Jain, Asha Ranjan, Vahid Bharmal

Department of Endocrinology, IMS BHU, Varanasi, Uttar Pradesh, India. E-mail: djmsbmc@gmail.com

Onset of pubertal changes before 8 years in girls and 9 years in boys is defined as precocious puberty. We did a retrospective analysis of patients admitted in the endocrinology ward in previous 4 years, and two interesting cases of precocious puberty were identified. Case 1: A male child aged 7 years had presented with a history of development of pubic hair and enlargement of testes and penis. Testicular volume was 20 ml bilaterally with a stretched penile length of 8 cm. Basal LH, FSH, and total testosterone were 3.02 IU/L, 5.2 mIU/ml, and 340 ng/dl, respectively. Magnetic resonance imaging showed a suprasellar mass measuring 22 mm × 10 mm with hypothalamus thickening. The child developed diminution of vision in the left eye and underwent bifrontal craniotomy decompression of tumor at a private hospital. The tissue biopsy showed pilocytic astrocytoma. Case 2: A girl child aged 6 years presented with increased hair growth all over body acne, voice change, and clitoral enlargement. Basal 17-hydroxyprogesterone, testosterone, and cortisol level were 0.8 ng/ml, 408 ng/dl, 12.83 mcg/dl, respectively. Basal LH was 0.04 IU/L. Contrast-enhance computed tomography abdomen showed a heterogeneously enhancing mass lesion in right adrenal measuring 5 cm × 3 cm showing necrosis, calcifications and with absolute washout of <60%, and extension of tumor thrombosis into suprarenal inferior vena cava, suggestive of adrenocortical carcinoma (ACC). Diagnosis of heterosexual precocious puberty due to androgen secreting ACC was made. Conclusion: Pilocytic astrocytoma and androgen-secreting ACC are rare causes of precocious puberty. The case reports emphasize that the knowledge about various causes of precocious puberty is required for proper management of patients with precocious puberty.

Keywords: Adrenocortical carcinoma, pilocytic astrocytoma, precocious puberty

 Simple virilizing congenital adrenal hyperplasia presenting with sexual precocity: A retrospective data analysis of 23 cases



M. Madhu Babu, B. Vivekanand, A. Mythili, K. A. V. Subrahmanyam, Jayanthy Ramesh

Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India.

E-mail: drjayanthyramesh@gmail.com

Background: Causes of precocious puberty may range from normal variants to pathological conditions with significant risk of morbidity. Data on the clinical correlates for progression to central precocious puberty (CPP) are sparse, especially in the Indian population. Aim: The aim was to study the clinical profile of 23 children with simple virilizing congenital adrenal hyperplasia (CAH) who presented with peripheral precocity and determine the factors associated with the likelihood of progression to central precocity in these group of patients. Materials and Methods: We retrospectively analyzed the case records of 23 children who presented to King George Hospital, Visakhapatnam, between 2008 and 2019, with a diagnosis of simple virilizing CAH, with the mode of presentation being precocious puberty. Detailed history, anthropometry, Sexual Maturity Rating, and bone age were recorded. 17-hydroxyprogesterone (17-OHP), serum testosterone, serum estradiol, and serum luteinizing hormone were done as required. The time of progression to CPP was recorded. Results: The mean age of presentation of the 23 children with simple virilizing CAH was 4.8 years. The male-to-female ratio was 1:3.6. Seven children (30.4%) progressed to CPP over a mean period of 2.4 years. The height standard deviation score (SDS) at baseline of those progressed to CPP was 1.72 versus 1.37 in those who have not progressed. The mean bone age advancement of those who progressed to CPP was 4 years, 5 months versus 2 years, 2 months in those who have not progressed. The mean baseline stimulated 17-OHP between these two groups was 220 ng/ml versus 174.7 ng/ml. Conclusion: These findings suggest that significant percentage of children with simple virilizing CAH progress to CPP. Those with higher baseline stimulated 17-OHP, height SDS, and bone age advancement were more likely to progress to CPP. This highlights the importance of early and effective hypothalamic–pituitary–adrenal axis and androgen suppression in these group of patients, based on frequent clinical, biochemical, and radiological monitoring.{Figure 32}{Figure 33}{Figure 34}{Figure 35}{Figure 36}{Figure 37}

Keywords: Bone age, congenital adrenal hyperplasia, central precocity, height standard deviation score, precocity

 Rarest of the rare – A case of primordial dwarf



Mandeep Sharma, Naresh Bansal, K. S Brar, Rakhi Malhotra

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

E-mail: rakhi.malhotra@gmail.com

Introduction: Children with severe intrauterine growth restriction (IUGR) who continue to be severely stunted throughout life without apparent chromosomal or hormonal aberration are known as primordial dwarfs. It is a rare and clinically heterogeneous entity. Defining its subtype and causal mutation can save patients from unnecessary and sometimes harmful diagnostic and therapeutic interventions. We describe a rare case of primordial dwarf due to Schimke immunoosseous dysplasia (SIOD). Aim and Objectives: The objective of the study is to discuss the approach to a case of Primordial dwarfism and to discuss in detail the clinical manifestations of this rare entity of SIOD. Case Description: A 5 years and 3 months old child, a product of nonconsanguineous marriage, fourth in birth order was born by full-term normal vertex delivery. His birth weight was 1.5 kg. There was a history of GDM in mother and a previous history of two spontaneous first-trimester abortions and one full-term IUD. He was brought by parents in view of the inability to gain adequate height since the past 3 years. His height was the same as that of his 10-month-old younger sister. He was otherwise playful and active with normal scholastic performance. On examination, he was 80 cm tall (Ht SDS – 5.07), weighed 10 kg (Wt SDS – 2.21), upper segment: lower segment –1.05, and head circumference – 45 cm (less for age). He had dysmorphic facies in the form of triangular face, prominent forehead, megalocornea, microdontia, micrognathism, and short neck. He was also noted to have acanthosis nigricans, abdominal protuberance, temporal wasting, and coffee-colored spots on the abdomen. Investigations revealed dyslipidemia, hypoalbuminemia, nephrotic range proteinuria, low insulin-like growth factor-1, and low serum Vitamin D levels. X-ray Spine showed platyspondyly and osteopenia. Bone age was the same as chronological age. Keeping the clinical profile in mind, he was diagnosed as a case of microcephalic primordial dwarf. However, in view of nephrotic range proteinuria, the presence of multiple lentigines and skeletal dysplasia (platyspondyly), whole-exome sequencing was done with the differential of SIOD. Homozygous deletion of SMARCAL1 gene was detected. On further testing, he was also detected to have abnormal immunoglobulin profile (low IgG) and low CD4 count, which are known to be associated with this condition. He is now under the treatment of pediatric nephrologist and is planned for renal biopsy. GH therapy for short stature has been tried but is ineffective and may aggravate the metabolic complications. Discussion and Conclusions: SIOD is a rare cause of syndromic short stature due to homozygous or compound heterozygous deletion of SMARCAL 1 gene. It is characterized by progressive proteinuric glomerulopathy, spondyloepiphyseal dysplasia, growth retardation, dysmorphic features, defective cellular immunity, and multiple lentigines. Growth failure is seen in 100% of cases (96% also have IUGR). Management is mainly symptomatic, and most children progress to end-stage renal disease within 6 years of diagnosis.

Keywords: Immuno osseous dysplasia, primordial dwarf, Schimke's, short stature, SMARCAL

 A rare case of neonatal hypoglycemia



Sandeep K. Mathur, Balram Sharma, Hardev Nehara1,Naincy Purwar2, Anshul Kumar2, Himanshu Sharma2

Department of Endocrinology, SMS,1SMS,2SMS Medical College, Jaipur, Rajasthan, India.

E-mail: drhimanshu89.mamc@gmail.com

Introduction: Neonatal hypoglycemia due to hyperinsulinemic hypoglycemia (HH) is clinically, genetically, and morphologically heterogeneous groups of disorders characterized by dysregulated insulin secretion by pancreatic β-cells. It is the most common cause of both transient and persistent hypoglycemia. Case History: We report a case of a boy presenting at the age of 10 weeks with convulsion and altered sensorium due to hypoglycemia. On evaluation, a diagnosis of HH was made, and the patient managed on increased feeding but had recurrent hypoglycemic episodes and so started on tablet diazoxide and injection octreotide but to no avail. Genetic analysis for ABCC8 and KCNJ11 gene by Sanger sequencing was done showing heterozygosity for previously reported ABCC8 missense mutation with father having the same mutation but asymptomatic. Whole-body Ga-68 DOTA-NOC-PET-CT was done, which showed a bulky pancreas and diffusely increased DOTA-NOC uptake in entire pancreas, suggestive of diffuse subtype. Following this, total pancreatectomy was done; the patient has maintained euglycemia on insulin therapy. Discussion: In our case, the genetic analysis showed a paternally inherited heterozygous mutation, having diffuse subtype on imaging. HeterozygousABCC8 mutations have been reported to have focal disease; however, to the best of our knowledge, this is the first case in India, having diffuse subtype on imaging with a paternally inherited heterozygous mutation.{Figure 38}{Figure 39}

Keywords: ABCC8, congenital hyperinsulinemic hypolglycemia, diffuse lesion

 Neonatal thyrotoxicosis with maternal Hashimoto's disease: Rare clinical case



Rashi Agrawal, M. P. Silveira, Ankush Desai1

Departments of Paediatrics and1Endocrinology, Goa Medical College, Bambolim, Goa, India.

E-mail: rashi91@gmail.com

Introduction: Neonatal thyrotoxicosis is a rare clinical entity usually encountered in the setting of maternal Graves' disease due to transplacentally acquired TSH receptor antibodies (TRAbs). The occurrence of neonatal thyrotoxicosis with maternal autoimmune hypothyroidism is extremely rare. Aims and Objective: To report a case of neonatal thyrotoxicosis born to a mother with autoimmune hypothyroidism. Materials and Methods: Clinical history, examination, relevant investigations, and management of the case were observed. Results: A 15-day-old female neonate born to a hypothyroid mother on levothyroxine replacement during pregnancy was referred with neonatal thyroid screen, suggestive of thyrotoxicosis. On clinical evaluation, the baby had tachycardia, irritability, and craniosynostosis. Thyroid function tests were suggestive of primary overt thyrotoxicosis. Technetium-99 thyroid scan revealed diffuse increased uptake pattern of both lobes. TRAbs were positive in baby as well as mother. Based on the diagnosis of neonatal thyrotoxicosis, baby was treated with oral carbimazole resulting in clinical and biochemical improvement. TRAb titers were negative at 9 weeks and the baby became biochemically euthyroid at 12 weeks of treatment. Discussion and Conclusion: Neonatal thyrotoxicosis is a life-threatening condition requiring high index of suspicion of the neonatologist. The condition is transient when accompanied with maternal Graves' disease. Occurrence of neonatal thyrotoxicosis with maternal autoimmune hypothyroidism is unexpected and extremely rare. The possible mechanism is new development of TRAbs in hypothyroid mother during pregnancy which are transplacentally transmitted to fetus. This case reflects the importance of surveillance in babies born to mothers with autoimmune hypothyroidism.

Keywords: Hashimoto's disease, neonatal thyrotoxicosis, TSH receptor antibodies

 Thyroid dysfunction in diabetes of young at tertiary care hospital



Rashi Agrawal, M. P. Silveira, Ankush Desai1

Departments of Paediatrics and1Endocrinology, Goa Medical College, Bambolim, Goa, India.

E-mail: rashi91@gmail.com

Introduction: Type 1 diabetes, the most common form of diabetes in the young, is associated with other autoimmune conditions, including autoimmune thyroid disease. Syndromic forms of diabetes are also associated with thyroid dysfunction (TD). TD adversely affects the physical growth, neurocognitive development, and glycemic control of the affected children. Thus, adequate screening programs of TD in young diabetics need to be established. Aims and Objective: To determine the spectrum of TD and thyroid autoimmunity in young diabetics attending pediatric endocrine clinic at the medical college. Materials and Methods: Demographic and clinical details, physical examination, serum thyroid function tests, and anti-TPO antibody titers and thyroid ultrasonography were recorded in the subjects. Results: Eighty-three young diabetics were enrolled for the study, of which 59 had Type 1 diabetes mellitus (DM). TD was noted among 22 patients, of which 13 had Type 1 DM. There was no statistically significant difference based on gender, age of onset of diabetes, glucose levels at presentation, treatment modalities, and present glycemic status. Anti-TPO antibodies were positive in 21 subjects, all being Type 1 DM. Discussion and Conclusion: The prevalence of TD and thyroid autoimmunity was 26.5% and 25.3%, respectively, which is in line with studies conducted worldwide. Higher proportion of patients with TD was females. Presence of anti-TPO antibodies was highly predictive of TD. Since thyroid function affects glucose homeostasis through various mechanisms and both thyroid disease and diabetes affect the overall growth and development of children adversely, it is imperative to have routine screening protocols in place which are carried out at outpatient follow-up of young diabetics.

Keywords: Anti-TPO antibodies, autoimmunity, diabetes of young, thyroid dysfunction

 An oncocytic adrenocortical tumor presenting with precocious puberty



Niya Narayanan, Ayan Roy, Chandhana Merugu, Sadishkumar Kamalanathan, Dukhabandhu Naik, Jayaprakash Sahoo

Department of Endocrinology, JIPMER, Puducherry, India. E-mail: drniya87@gmail.com

Introduction: Oncocytic adrenocortical tumors (OATs) are extremely rare tumors of the adrenal gland and are usually benign and nonfunctional. So far, in the pediatric age group, only nine cases have been reported. We describe the case of a functional oncocytic adrenocortical adenoma in a 4-year-old boy who presented with precocious puberty and Cushing syndrome. Case Report: A 4-year-old boy presented with penile enlargement, voice change, abnormal body odor, excessive body hair growth, and behavioral changes for the past 6 months. His parents had noticed recent rapid weight gain with no growth spurt. On physical examination, he had hypertrichosis and Cushingoid facies and was prehypertensive. Examination of genitalia showed a stretched penile length of 10 cm with a girth of 8.2 cm, prepubertal testes, and Tanner stage III pubic hair. The abdominal examination was normal. Hormonal assessment showed a basal cortisol level of 19.8 μg/dL, adrenocorticotropic hormone level < 10 pg/mL with disruption of diurnal rhythm (12 AM midnight sleeping cortisol: 21.3μg/dL), and an overnight 1-mg dexamethasone suppression cortisol of 19μg/dL. Serum testosterone and dehydroepiandrosterone sulfate were elevated (231 ng/dL and 1261μg/dL, respectively). A contrast-enhanced computed tomography abdomen showed a 3.3 cm × 3 cm × 3.7 cm heterogeneously enhancing mass lesion (110 HU) of the right adrenal gland. A right adrenalectomy was done and histopathology was suggestive of adrenocortical adenoma-oncocytic variant. Postoperatively, the patient was started on hydrocortisone replacement, which was gradually tapered to replacement dose. Serum testosterone level done 2 weeks postsurgery was suppressed (<7 ng/dL). Conclusion: OATs are uncommon tumors, most of which are detected incidentally. Only 17% are functional and rarely present in the pediatric age group.

Keywords: Oncocytic adrenocortical tumor, pediatric Cushing, precocious puberty

 Patterns of clinical practices of endocrinologists in the management of congenital adrenal hyperplasia in children: A survey



Nandhini Lakshmana Perumal, Nalini B. Wagmode, Belinda George, Ganapati Bantwal, Vageesh Ayyar

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

E-mail: lp.nandhini@gmail.com

Introduction: Congenital adrenal hyperplasia (CAH) is a rare genetic disorder with serious morbidity and mortality. The diagnosis and management of this condition presents several challenges. Although there are established clinical guidelines to manage such patients, there is a significant disparity in the practices among treating physicians. Aims and Objective: The aim of this survey was to assess the management practices of endocrinologists in the management of children with CAH in comparison with the Endocrine Society guidelines. Methods: A questionnaire addressing various aspects of management of CAH in children including diagnosis, treatment, and monitoring of therapy was administered to practicing endocrinologists. Results: The questionnaire was administered to 150 practicing endocrinologists. The response rate was 33%. 26% of the participants were physicians practicing in academic institutions. 63% of respondents were treating children with CAH independently and 15% in collaboration with a pediatrician or a pediatric endocrinologist. 46% of patients were reviewed 3 monthly and 28% 6 monthly. The dose of hydrocortisone used in infants varied from 10 to 30 mg/m2/day. 84% of physicians were using the recommended dose of 10–15 mg/m2/day. 71% of respondents used a fludrocortisone dose of 100–200 μg/day in infants. Regarding salt supplementation, 44% of respondents advised 1–2 g of extra salt, 44% recommended 3–5 g, and 10.3% used more than 5 g/day. The frequency of monitoring for various parameters was 17-hydroxyprogesterone (6 monthly, 82% and annually, 13.3%), plasma renin activity (27.9% 6 monthly and 32% annually), serum testosterone (68.18% 6 monthly and 22.7% annually), and bone age (26% 6 monthly and 64.4% annually). 81% of respondents shared written instructions regarding the stress dosing of steroids. Only 16.2% of respondents had used adjuvant therapy to augment linear growth. Conclusion: Our survey indicates that despite the diversity in the management of CAH among endocrinologists, most follow the recommendation of the Endocrine Society.

Keywords: Children, congenital adrenal hyperplasia, practices

 A study of response to growth hormone in children with growth hormone deficiency



Charushila Dhole, Nikhil Bhagwat, Jugal Gada, Prema Varthkavi

Department of Endocrinology, B.Y.L. Nair Charitable Hospital, Mumbai, Maharashtra, India.

E-mail: adeshcharu@gmail.com

Introduction: Growth hormone (GH) therapy is now increasingly available to patients across all strata of society. One of the factors which impact response to GH is the age at which therapy is initiated. Aims and Objectives: The aim of this study is to assess the response to GH replacement therapy in patients with GH deficiency (GHD) attending the growth clinic of a tertiary care center. Methods: We included thirty patients with GHD who were on GH for at least 1 year. The population comprised twenty patients with isolated GHD and 10 with combined pituitary hormone deficiency (CPHD). Anthropometry, mid-parental height, systemic examination, and bone age (Tanner-Whitehouse 3) were recorded basally. Patients underwent estimation of insulin-like growth factor-1, peak GH, appropriate laboratory investigation, and pituitary magnetic resonance imaging (MRI). Patients with CPHD received adequate hormone replacement before diagnosis and treatment. Patients received GH at a dose of 0.18 mg/kg/week daily subcutaneously and were re-evaluated posttherapy. Results: CPHD patients had two (n = 1), three (n = 4), or four (n = 5) hormone deficiencies. MRI revealed anterior pituitary hypoplasia (APH; n = 18), APH with ectopic posterior pituitary and stalk abnormality (n = 4), and craniopharyngioma (n = 3) and was normal in 5 patients [Table 1]. Conclusion: GH therapy (0.18 mg/kg/week) initiated before 10 years of age induced greater height velocity, whereas after 10 years, it induced a greater advancement in bone age – which could compromise the final adult height – leading to the question “Should older patients be initiated with a larger dose of GH?{Table 8}

Keywords: Effect on height and bone age, growth hormone deficiency in children

 Arrested puberty due to suprasellar germinoma: A case report



Chandan Kumar Mishra, Rahin Mahata, Partha Pratim Chakraborty, Anirban Sinha, Animesh Maiti

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

E-mail: mishra.chandan86@gmail.com

Introduction: Germinomas and other germ cell tumors of the central nervous system are the most common extrasellar tumors that arise in the suprasellar and pineal regions that commonly cause sexual infantilism. These are more common in males with a peak incidence in the second decade and during infancy. Here, we report a case of a 17-year-old girl presenting with arrested puberty with panhypopituitarism and diagnosed as a case of germinoma. Case Report: This 17-year-old girl presented with secondary amenorrhea (for the past 1 year) and short stature. She attained spontaneous thelarche at around 12 years. There is a history of the use of OCPs around 15 months back for 2–3 months during which she menstruated. Birth and developmental history were normal. There is no history of recurrent ear discharge, easy fatigueability, and constipation. There is no history suggestive of features of raised ICT or chronic systemic illness. There is, however, a history of increased frequency of micturition and thirst for the past 6 months. On examination, she was found to have proportionate short stature with a height of 141.4 cm (<3rd %tile) with height age of 11 years, SMR: B3P1, no goiter. No other turner stigmata were found. Fundus examination and confrontation perimetry were normal. Work-up of the patient showed evidence of panhypopituitarism (free thyroxine: 0.72 ng/dl, thyroid-stimulating hormone: 1.59, cortisol: 5.12 mcg/dl, follicle-stimulating hormone: 0.6 mIU/ml, luteinizing hormone: 0.02 mIU/ml, insulin-like growth factor-1: 18.4 ng/ml, and prolactin: 35.04 ng/ml). The tests were also done for polyuria which confirmed central DI. Magnetic resonance imaging pituitary was done which showed heterogeneously enhancing mass in the suprasellar and pineal regions. Subsequently, lumbar puncture revealed high cerebrospinal fluid beta-human chorionic gonadotropin (with elevated serum levels). Conclusion: Germinomas can cause arrested puberty. Germinoma being a radio- and chemosensitive tumor can usually be managed without surgery. Hence, this case highlights the need to diagnose germinomas early which can be treated nonsurgically.{Figure 40}{Figure 41}{Figure 42}{Figure 43}

Keywords: Arrested puberty, central diabetes insipidus, panhypopituitarism

 BONE AND MINERALS AND PARATHYROIDS



 Awareness of diabetic retinopathy among patients with type 2 diabetes mellitus, attending a tertiary care center



Anulekha Mary John, Ancy George, Anju K. Francis

Department of Endocrinology and Metabolism, Believers Church Medical College Hospital, Pathanamthitta, Kerala, India.

E-mail: anulekhageorge@gmail.com

Introduction: Diabetic retinopathy (DR) is a serious cause of irreversible blindness and is the most common microvascular complication of diabetes. Although various modalities of treatment are available, patients often present late in the course of the disease when treatment is more difficult. Aims and Objective: This study aimed to assess the level of awareness and current knowledge about DR. Materials and Methods: This study was conducted among patients with type 2 diabetes mellitus, attending a tertiary healthcare center in South India. A structured questionnaire was used to collect information. Data obtained was analyzed using Microsoft Excel 2007. Results: A total of 120 participants (62 [51.6%] males and 58 [48.3%] females) with type 2 diabetes were interviewed. The mean age ± standard deviation for the study population was 59.9 ± 12.18% years. Of the study population, 38% were aware that diabetes can affect the eyes and only a few patients were aware that DR could lead to blindness. Patients' compliance with routine retinal assessment was poor, with only a total of 39% of participants having had an eye examination in the previous year. Discussion and Conclusion: Only 38% of the study population was aware of diabetic retinopathy. More awareness-building initiatives to increase the effectiveness of DR screening program are warranted. Annual fundus examination in all diabetic patients aids in the prevention of blindness and allows early intervention.

Keywords: Blindness prevention, diabetic retinopathy, microvascular complication

 A study of trabecular bone score and bone density in subjects with hyperthyroidism



Sandeep Kumar Agarwal, Kripa Elizabeth Cherian, Nitin Kapoor, Felix Jebasingh, H. S. Asha, Nihal Thomas, T. V. Paul

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

E-mail: drskagarwal2k9@gmail.com

Objectives: Hyperthyroidism may have a deleterious effect on bone and thus increases the risk of fractures. Trabecular bone score (TBS), a noninvasive indicator of bone microarchitecture, has not been studied in the Indian population with hyperthyroidism. The aim of this study was to look at the TBS and bone mineral density (BMD) in women diagnosed to have Graves' disease compared with age- and body mass index (BMI)-matched controls. Materials and Methods: This was a cross-sectional study conducted over a period of 6 months. The study population 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, lumbar spine, and hip was done using a dual-energy X-ray absorptiometry scan. Thyroid function tests and parameters of bone health including calcium, phosphorus, parathormone, 25(OH) vitamin D, CTX, and P1NP were measured. Results: The mean (standard deviation [SD]) age of our study participants (cases vs. controls) was 34.5 (9.0) and 35.7 (5.0) years, and the mean (SD) BMI (cases vs. controls) was 23.2 (4.8) and 24.3 (4.8) kg/m2, respectively. The mean (SD) TBS was statistically significantly lower in cases when compared to controls (1.299 [0.111] vs. 1.346 [0.089]; P = 0.035). The BMD (g/cm2) in the study participants, when compared with controls, was statistically 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). There was a significant negative correlation between the duration of hyperthyroidism and TBS (r = −0.325; P = 0.050). Conclusion: Hyperthyroidism was associated with a significant reduction in TBS (an indicator of bone microarchitecture) and bone density at the femoral neck and lumbar spine when compared to healthy, age- and BMI-matched controls.

Keywords: Bone mineral density, bone turnover marker, hyperthyroidism, trabecular bone score

 A rare cause of fragility fracture



Rimesh Pal, Sanjay Kumar Bhadada, Vandana Dhiman

Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

E-mail: rimesh.ben@gmail.com

Introduction: Hypophosphatasia is an inheritable disorder characterized by defective mineralization of bones and teeth, due to inactivating mutations of the alkaline phosphatase (ALPL) gene. It is a rare and probably underrecognized cause of fragility fracture. Aims and Objectives: This is a case of adult hypophosphatasia presenting with fragility fracture. Materials and Methods: Sanger sequencing of the ALPL gene was performed at the University of Edinburg. Results: A 47-year-old female presented with pain in the right thigh and difficulty in walking for the last 3 months. She was eumenorrheic. On examination, there was tenderness over the right thigh; physical examination was otherwise noncontributory. Radiographs of the pelvis and bilateral thighs revealed transverse fractures at the junction of the upper and middle-third of both the femora. Biochemical investigations revealed normocalcemia (serum calcium 9.4 mg/dl), normophosphatemia (serum phosphorous 4.5 mg/dl), and normal renal function. She was Vitamin D sufficient (serum 25-hydroxyvitamin D 52.9 ng/ml) with serum intact parathyroid hormone of 23.6 pg/ml. However, her serum total ALP levels were persistently low ranging from 19.6 to 34 IU/l (range: 42–128 IU/l). Screening of the family members revealed low ALP levels in five individuals. Genetic analysis revealed a novel heterozygous missense mutation in exon 5 (c.311a>g; p.104 Asn>Ser) of ALPL gene in the proband and two siblings. In-silico analysis predicted it to be pathogenic. On inquiry, the siblings had a history of premature loss of deciduous teeth, although they had never sustained a fracture. Our patient underwent intramedullary nailing of bilateral femurs. She is presently on calcium and Vitamin D supplements, and all measures for procuring asfotase alfa are underway. Discussion and Conclusion: Hypophosphatasia in adults can present with osteomalacia, pseudo-fractures, and fragility fractures. Normal serum ALP levels measured post fracture do not rule out hypophosphatasia. Family screening and genetic analysis will confirm the diagnosis.

Keywords: Alkaline phosphatase, fragility fracture, hypophosphatasia

 Utility of anthropometric indicators in predicting osteoporosis in ambulant postmenopausal women from South India



Kalyani Sridharan, Kripa Elizabeth Cherian, Nitin Kapoor, Thomas V. Paul

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

E-mail: sridharan.kalyani22@gmail.com

Background: Use of dual-energy X-ray absorptiometry (DXA) is limited by availability and cost in resource-limited settings. Ethnicity-derived anthropometric cutoffs are good surrogate markers in predicting osteoporosis. Aims: The aim of this study is to assess the correlation between bone mineral density (BMD) measured by DXA scan and anthropometric variables such as body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and neck circumference (NC) and derive receiver operating characteristic (ROC) curves for these variables. Methods: This is a cross-sectional observational study which recruited postmenopausal South Indian women from the community. Anthropometric variables such as weight, BMI, WC, HC, and NC were measured. BMD was assessed by means of DXA scan. Correlation between the anthropometric variables and DXA BMD at the neck of femur (NOF) and lumbar spine (LS) was assessed. ROC cutoffs were derived for the individual anthropometric measures. Results: A total of 308 postmenopausal women were included in the study. All the anthropometric variables showed significant independent positive correlation with DXA BMD at both the skeletal sites, whereas age showed a significant negative correlation. Weight showed the best correlation (r = 0.48; P < 0.01) and at a cutoff of 49.5 kg had a sensitivity of 95.4% and a specificity of 33% and an area under the curve (AUC) (95% confidence interval) of 0.757 (0.695–0.818) for the derived ROC with NOF osteoporosis. The cutoffs at which other anthropometric measures predicted NOF osteoporosis are as follows: NC – 20.25 cm (85.3% sensitivity, 31.9% specificity; AUC: 0.668 [0.602–0.734]; WC – 82.5 cm (89.4% sensitivity, 28.6% specificity; AUC: 0.651 [0.580–0.722]; and HC – 90.5 cm (89.9% sensitivity, 34.1% specificity; AUC: 0.690 [0.622–0.757]). Conclusion: We derived cutoffs for various anthropometric variables from the ROCs and the sensitivity and specificity at these cutoffs. Given the ease of measurement of these anthropometric variables and the cost and unavailability of DXA scanners at all places, these could be used to screen for osteoporosis.

Keywords: Anthropometry, bone mineral density, osteoporosis, postmenopausal

 Persistent bone disease: A challenge after surgery in a case of primary hyperparathyroidism with parathyroid adenoma



Geeta Aurangabadkar, Vaibhavi Modi1, K. D. Modi

Department of Endocrinology, Care Hospital,1V R K Medical College, Hyderabad, Telangana, India.

E-mail: vrgeeta@yahoo.com

Background: Osteoporosis is relatively uncommon in men and remains underresearched, especially in the Indian population. It can occur in the setting of old age, hypogonadism, hyperparathyroidism, and other causes. Patients with mild primary hyperparathyroidism (PHPT) can have varied misleading presentation, and hypogonadism must be considered as an important cause for persistent bone disease. Case Presentation: We present an interesting case of a 54-year-old gentleman who was investigated for recurrent bladder calcification seen on ultrasound scan. In view of the biopsy showing dysplasia/malignancy, he was initially treated with radiotherapy and chemotherapy. As his bladder calcification continued to recur, he was referred to the endocrinology department for further investigations. The biochemical findings and imaging reports were consistent with PHPT. However, even a year after parathyroidectomy for an adenoma, he had evidence of persistent osteoporosis (dual-energy X-ray absorptiometry scan showing a T score of − 2.5 in the lumbar spine). Further investigations revealed primary hypogonadism with high gonadotropins possibly secondary to local radiotherapy. This patient was advised androgen replacement therapy and Vitamin D and calcium supplements. He had no subsequent recurrence of bladder calcification. Conclusion: Patients with mild PHPT often have nonspecific symptoms that may be superimposed with those of hypogonadism. Hypogonadism is an important cause to consider in case of persistent osteoporosis. This case report highlights the importance of active screening in such patients for the underlying hypogonadism.

Keywords: Hypogonadism, persistent osteoporosis, primary hyperparathyroidism

 Parkinson's disease and osteoporosis in elderly men (POEM study) – A cross-sectional study to look for bone health in Parkinson's disease



S. G. Basavaraj, Nitin Kapoor, Nihal Thomas, Thomas V. Paul

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

E-mail: thomasvpaul@yahoo.com

Introduction: Osteoporosis is an important nonmotor component of Parkinson's disease and Parkinsonism (PD) and coupled with disability, postural imbalances, and increase chance of falls, lead to a higher number of fractures and its associated adverse outcomes. Although there are studies showing the impact of PD on bone mineral density (BMD) in PD patients, most of these studies are from the Western countries, and there is a paucity of data from the Asian countries, including India. Aims and Objective: The aim is to study the BMD and bone health parameters in male patients with Parkinsonism and compare them with age-matched controls from the community. Materials and Methods: We performed a cross-sectional study of 49 patients with Parkinsonism and 33 patients from community which were age-matched to Parkinsonism groups as control group. We assessed BMD, bone biochemistry, and bone turnover markers in the study participants. Results: The baseline characters were similar in both the groups, with mean age of 61.2 years. The PD group had significantly lower 25OH-Vitamin D levels and higher bone resorption marker (CTx C terminal telopeptide of Type 1 collagen) levels. The BMD was not statistically different among three groups at any site. However, in patients with Parkinsonism and postural instability (severe disease), there was significantly lower BMD at femoral neck, hip, and lumbar spine, even after adjusting for confounding factors like BMI. In patients with Parkinsonism, there was significant negative correlation of duration and severity (according to modified Hoehn and Yahr scale) of the disease with BMD. Conclusion: Higher prevalence of Vitamin D deficiency in the disease groups needs to be treated adequately. Lower BMD values in patients with Parkinsonism and postural instability need periodic bone health assessment and appropriate management for osteoporosis.

Keywords: Bone mineral density, c-terminal telopeptide of type 1 collagen, osteoporosis, Parkinson's disease

 Postrenal transplant hypercalcemia: A case report



K. D. Modi, Geeta Aurangabadkar1, Vaibhavi Modi2, Ashvinikumar Aiyanger

Consultant, CARE Hospital,1Department of Endocrinology, CARE Hospital,2VRK Medical College, Hyderabad, Telangana, India.

E-mail: drkdmodi@yahoo.co.in

Postrenal transplant hypercalcemia is reported in 5%–58% of cases in various studies. It is detrimental for grafted kidney and has negative correlation with graft outcome. Parathyroidectomy or calcimimetic drugs are the main line of treatment. Response to calcimimetic drug suggests intact negative feedback between serum calcium and parathyroid hormone and indirectly negates the need for parathyroid surgery due to autonomously functioning parathyroid glands. We report one such case of postrenal transplant hypercalcemia who was successfully managed with calcimimetic drug. Case: A 59-year-old nondiabetic male, 1 year 7 months postrenal transplant was referred to us for persistent postrenal transplant hypercalcemia. His serum calcium, phosphorus, creatinine, and urea were 11.8, 2.1, 0.7, and 20 mg/dl, respectively. Serum parathyroid hormone (PTH) was 701 pg/ml and Vitamin D level was 27.4 ng/ml. Pretransplant PTH (6 months before renal transplant) was 956 pg/ml. Computed tomography scan abdomen showed evidence of speck calcification in transplanted kidney. Technetium 99m-methyl diphosphonate scan showed physiological tracer uptake in appendicular and axial skeleton without any evidence of focal increased uptake or evidence of super scan. Sestamibi scan for parathyroid gland showed parathyroid gland hyperplasia without evidence of isolated increased uptake in any of the parathyroid gland. He was advised tablet cinacalcet 30 mg twice daily. After 2 weeks of cinacalcet, his serum calcium and phosphorus were 9.5 and 2.6 mg/dl, respectively. His cinacalcet dosage was reduced to 30 mg/day and is maintaining normal serum calcium and phosphorus on the same dosage, 6 months after cinacalcet therapy.

Keywords: Calcimimetic drug, hypercalcemia, renal transplant

 Change in bone mineral density and its predictors after curative surgery in symptomatic primary hyperparathyroidism



Rimesh Pal, Priyanka Singh, Ashwani Sood1, Tulika Singh2, Ashutosh Kumar Arya, Divya Dahiya3, Sanjay Kumar Bhadada

Departments of Endocrinology,1Nuclear Medicine,2Radiodiagnosis and Imaging and3General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

E-mail: rimesh.ben@gmail.com

Introduction: Patients with primary hyperparathyroidism (PHPT) have reduced bone mineral density (BMD) that predisposes them to an increased risk of fragility fractures. Objectives: We sought to determine improvement in BMD after successful surgery in symptomatic PHPT and factors associated with it. Methods: We conducted a prospective observational study wherein symptomatic PHPT patients underwent dual-energy X-ray absorptiometry (DEXA) pre and postcurative surgery (duration varying from 12 to 36 months). DEXA was performed using HOLOGIC Discovery A by a well-trained and dedicated technician. Results: Forty-one patients of symptomatic PHPT were included in the study (M:F = 8:33, mean age 45.5 ± 13.3 years). The median percentage change in BMD (ΔBMD) at lumbar spine (L1–L4), total hip (TH), neck of femur (NOF), and distal radius (DR) was 8.56 (interquartile range: 3.68–15.97), 7.24 (2.60–15.02), 8.92 (1.39–15.97), and 6.14 (0.00–13.96), respectively, at a median duration of 17 months (12–26.5) postsurgery. On analyzing individual cases, increase in BMD at spine, TH, NOF, and DR was observed in 93%, 92%, 91%, and 80% patients, respectively. There was no difference in ΔBMD between males and females; however, premenopausal females had a greater rise in BMD at spine (P = 0.001), TH (P = 0.033), and DR (P = 0.11) as compared to their postmenopausal counterparts. Age at surgery was negatively correlated with ΔBMD. Preoperative serum calcium level was positively correlated with ΔBMD at TH (rs = 0.465, P = 0.002) and NOF (rs = 0.371, P = 0.017) as was preoperative serum iPTH with ΔBMD at NOF (rs = 0.481, P = 0.001). Finally, change in body mass index (BMI) was positively correlated with ΔBMD at lumbar spine (rs = 0.369, P = 0.018), TH (rs = 0.473, P = 0.002), and DR (rs = 0.315, P = 0.045). Discussion and Conclusion: Curative surgery in PHPT causes rise in BMD in about 90% of patients with maximum rise noted at lumbar spine and least at DR. Premenopausal status, younger age, higher preoperative serum calcium/PTH, and BMI rise postsurgery positively correlate with increase in BMD.

Keywords: Bone mineral density, hypercalcemia, primary hyperparathyroidism

 Evaluation of bone mineral density in subjects with Type 1 diabetes



U. Vinod, Pradip Mukhopadhyay1, Sujoy Ghosh1

IPGME and R, SSKM Hospital,1Department of Endocrinology and Metabolism, IPGME and R, SSKM Hospital, Kolkata, West Bengal, India. E-mail: vinu56@yahoo.com

Introduction: (1) Diabetes mellitus is a metabolic disorder that increases fracture risk and interferes with bone formation and impairs fracture healing (2) Patients with Type 1 diabetes have low bone mineral density and increased risk of fractures, which is one of the least studied complications in them. Aims and Objectives: (1) To measure bone mineral density in patients with Type 1 diabetes (2) To measure bone turnover markers (BTMs) in Type 1 diabetes and their association with bone mineral density in these patients. Materials and Methods: This cross-sectional observational study was conducted in Type 1 diabetes clinic of IPGME and R and SSKM Hospital with 45 cases and 11 controls (siblings or first-degree relatives) with measurement of biochemical parameters (serum calcium, serum phosphorus, Vitamin D, and intact parathyroid hormone), BTM (osteocalcin, CTX, and PINP), and baseline dual-energy X-ray absorptiometry (GE lunar prodigy) measuring Total Body less Head and anteroposterior (AP) spine. Inclusion Criteria: All consecutive patients attending Type 1 diabetic clinic of Department of Endocrinology with age < 21 years were included in the study. Exclusion Criteria: Known case of systemic disorders involving bone and patients taking medication affecting bone were excluded from the study. Results and Discussion: (1) Significant alteration of BTM (osteocalcin and CTX) in control and diabetic groups (2) Z score of AP spine showed positive correlation with osteocalcin (r = 0.520) and PINP (r = 0.577) and negative correlation with CTX (−0.362) in patients with diabetes with low bone mineral density. Conclusion: (1) The study shows that patients with Type 1 diabetes have increased bone turnover which may have impact on bone mineral density (2) Further studies are required to elucidate these results.

Keywords: Bone mineral density, bone, Dual energy X-ray absorptiometry

 Persistent Hypercalcemia Following Parathyroidectomy: A Case-Based Approach



C. N. Antonypillai, D. Jegavanthan1, C. G. K. Amiyangoda1, P. A. D. M. Kumarathunga1, R. S. Mohomed1, H. Mahendran1, F. Kiyamudeen2

Departments of Endocrinology,1Diabetes and Endocrinology,2Chemical Pathology, Teaching Hospital, Kandy, Sri Lanka.

E-mail: dhulashi22@gmail.com

Introduction: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in ambulatory patients. Parathyroidectomy is the treatment of choice for symptomatic patients. Although it provide cure in majority, re-do parathyroidectomy is required in a subset of patients due to persistent disease. The management challenges and the approach of a failed parathyroidectomy are discussed here. Case Report: A 23-year-old male who presented with acute pancreatitis was found to have hypercalcemia, and evaluation confirmed PHPT. Initial investigations failed to localize the adenoma. Parathyroid exploration was done, and two and half glands were removed as only three glands could be visualized intraoperatively. Histology revealed normal glands. As he had persistently elevated parathyroid hormone (PTH) levels postoperatively, he was re-evaluated. Repeat sestamibi scan revealed 0.5-cm nodule within the right lobe of the thyroid. Further confirmation with parathyroid venous sampling revealed very high levels of PTH in the middle thyroid vein. The patient was offered with re-do parathyroidectomy, and the culprit parathyroid adenoma was dissected which was histologically confirmed later. The patient was improved clinically and biochemically. Discussion: Parathyroidectomy is the definitive treatment of PHPT. The traditional surgical approach was bilateral neck exploration. However, advances in the imaging techniques, along with intraoperative PTH monitoring, have led to preoperative localization and focused parathyroidectomy. Management of persistent hyperparathyroidism following parathyroidectomy is challenging. If re-operations are required, it should be done by experienced surgeons after proper localization. It includes repeating noninvasive and, if necessary, invasive investigations such as guided fine-needle aspiration cytology and selective venous sampling. If culprit parathyroid is not still identified, other options include partial or complete thyroidectomy, partial or complete median sternotomy, and ligation of the blood supply to the missing parathyroid gland. Conclusion: Re-do parathyroidectomy is required in a subset of patients with persistent hyperparathyroidism, and more invasive strategies are helpful in localizing suspected lesion.

Keywords: Hypercalcemia, parathyroid venous sampling, primary hyperparathyroidism, sestamibi scan

 Primary hyperparathyroidism masquerading as rickets in children: Two case reports



Saurabh Arora, S. K. Singh, N. K. Agrawal, M. S. Dhananjaya, Rujul Jain, Asha Ranjan, Vahid Bharmal

Department of Endocrinology, IMS, BHU, Varanasi, Uttar Pradesh, India. E-mail: saurabharora3084@gmail.com

Introduction: Primary hyperparathyroidism (PHPT), typically a disease of middle aged and elderly, is an uncommon condition in children and adolescents. In children, the disease has bimodal age distribution with calcium-sensing receptor mutation presenting in infancy as hypercalcemic emergency and parathyroid adenoma or hyperplasia presenting later in childhood with bony lesions. The childhood parathyroid adenomas are often familial with multiglandular involvement and present with severe bone involvement, unlike adults. Rickets as the presenting feature of PHPT is extremely rare. Case Report: We report two cases of primary hyperparathyroidism masquerading as rickets in children. Both patients presented with genu valgum and short stature. The first patient was a 16-year-old girl who had hypercalcemia with normal Vitamin D levels at the time of presentation and sustained pathological fracture of the left tibia during hospital stay. The second patient had normal calcium with low Vitamin D levels and was treated on the lines of Vitamin D deficiency rickets. Reevaluation due to lack of clinical improvement following Vitamin D and calcium supplementation in the latter patient revealed hypercalcemia with normal 25 hydroxyvitamin D levels and persistently elevated PTH levels. Ultrasonography showed parathyroid gland adenoma in both patients. Both of them underwent resection of parathyroid adenomas confirmed on histopathology. Postsurgery, both patients had hypocalcemia followed by normocalcemia. Conclusion: We conclude that parathyroid adenoma, although uncommon in children, is an important cause of skeletal disease that may initially be confused with Vitamin D deficiency.

Keywords: Hyperparathyroidism, parathyroidectomy, rickets

 Osteocalcin prototype for screening and assessing women with low bone mass



Sonam Suresh Hatkar, Hetal Bhadricha, Meena Desai

ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India.

E-mail: mends153@gmail.com

Introduction: Osteocalcin (OC), one of the key players in bone endocrinology, is a γ-carboxyglutamic acid protein expressed and secreted solely by osteoblasts. Initially, OC was hypothesized to act in extracellular matrix mineralization and used as a serum marker of osteoblastic bone formation. OC levels were used to evaluate the bone remodeling and metabolic bone disease conditions like osteoporosis. Aims and Objective: One of the major goals was translating basic research into a diagnostic kit with a view to bring these findings to the clinicians. The objective of the study was to develop an indigenous ELISA for human OC, to document its utility in diagnosis and management of osteoporosis, and to evaluate with a commercial ELISA kit. Materials and Methods: A Sandwich ELISA for OC was developed using immune reagents prepared indigenously and validated for sensitivity, specificity, and accuracy. The assay was compared with commercial ELISA kit using Bland–Altman and Deming linear regression analysis (n = 257 samples), and utility was assessed using receiver operating characteristic (ROC) curve analysis (n = 359 samples) correlating with bone mass density (BMD) measurements. Results: Developed ELISA was precise, accurate, matrix-free, and cost-effective. The OC levels were significantly different in women with osteopenia and osteoporosis compared to women with normal bone mass. The prevalence of osteopenia was high (56%) while osteoporosis was observed in (13%) of Indian women (21–65 years). ROC analysis demonstrated a cutoff value of OC >11.9 ng/mL for osteopenia with area under the curve (AUC) 0.831 and OC >14.9 ng/mL for osteoporosis with AUC 0.932. A good correlation (P < 0.0001) was observed in the OC levels by the two assays. The cutoff values were similar (>13.2 ng/mL for osteopenia and >16.4 ng/mL for osteoporosis) with the commercial kit. Discussion and Conclusion: The diagnostic sensitivity, specificity, and accuracy was >85%. The OC prototype has a great potential for routine screening and management of osteopenia and osteoporosis in Indian women.

Keywords: Bone turnover, Indian women, osteocalcin, osteopenia, osteoporosis

 A case of transient osteoporosis of hip



Mandeep Sharma, Rakhi Malhotra, K. S. Brar, Naresh Bansal

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

E-mail: nareshbansal2310@gmail.com

Introduction: Transient osteoporosis of the hip (TOH) is a poorly understood and forgotten clinical entity. An early and accurate diagnosis of TOH can lead to complete resolution of symptoms and avoid unnecessary investigations and treatment for other mimicking conditions. Aim and Objectives: The objective of the study is to present clinical presentation and management of a case of TOH. Case Description: A 34-year-old male presented with 4 months' history of sudden onset, severe, mechanical type of the right hip pain, accompanied by a disproportionate functional disability necessitating use of a walking stick. There was no antecedent history of trauma, inflammatory arthritis, urinary complaints, fever, or steroid use. On clinical examination, he had antalgic gait with restriction of movements, especially abduction and rotation, although no external signs of inflammation are present. The initial radiographs are normal, but marked osteoporosis of the femoral head with preserved joint space was seen on radiographs obtained several weeks after the onset of symptoms. Magnetic resonance imaging hip showed evidence of bone marrow edema in addition to moderate joint effusion besides ruling out other pathologies such as avascular necrosis, insufficiency fractures, infection, and neoplasm mimicking TOH. The bone scan showed intense uptake in the femoral head and neck suggesting TOH. He was managed conservatively with nonsteroidal anti-inflammatory drugs and rest with complete recovery of pain and resolution of osteoporosis. Discussion and Conclusions: The transient osteoporosis of the hip is a nondestructive and self-limiting condition of the hip, which responds well to the conservative treatment. Awareness of this entity is important to the clinicians for an early diagnosis and to avoid unnecessary treatment for other mimicking conditions.{Figure 44}{Figure 45}{Figure 46}

Keywords: Avascular necrosis hip, bone marrow edema syndrome, transient osteoporosis hip

 Paget's disease of bone: A case series of 66 patients with long-term follow-up from south India



S. Geethalakshmi, Shriraam Mahadevan, Karthik Balachandran, Adlyne Reena Aasirvatham

Department of Endocrinology, Sri Ramachandra Medical College Hospital, Chennai, Tamil Nadu, India.

E-mail: drgeethalakshmi86@gmail.com

Introduction: Paget's disease is a disorder of the skeleton characterized by increased osteoclastic activity. While the prevalence in the Western population is 1%–2%, the prevalence in India is not known. Aims and Objectives: The aim is to study the clinical, biochemical, and radiological profile, therapeutic details, and follow-up data of patients with Paget's disease of the bone. Materials and Methods: Retrospective data were collected from the follow-up of private endocrine clinics of two hospitals over the past 12 years. The data were analyzed using SPSS 21.0 software package. Results: There were a total of 66 patients (47 male). The mean age at presentation was 67.26 ± 8.18 years. Polyostotic involvement was seen in 89.4% of the patients. The symptoms at presentation were bone pain in 51.55%, headache in 4.5%, skeletal deformities in 18.2%, pathological fractures in 3%, and deafness in 63.6% of individuals. Patients (16.7%) were asymptomatic and were incidentally diagnosed during the evaluation of an elevated alkaline phosphatase. The temporal artery sign was positive in 21.2% of patients. PET-

Keywords: Familial pagets, osteosarcoma, pagets disease, polyostotic

 Multiple endocrine neoplasia type 1: Experience from a tertiary care center in South India



S. Soumya, T. Ajeesh, Ramesh Gomez, Abilash Nair, Darvin V. Das, Puthiyaveetil Khader Jabbar

Department of Endocrinology and Metabolism, Government Medical College, Thiruvananthapuram, Kerala, India.

E-mail: rameshgomez@yahoo.com

Introduction: Multiple endocrine neoplasia type 1 (MEN1, also called Werner syndrome) is a rare autosomal dominant inherited syndrome caused by mutations in MEN1 tumor suppressor gene, presenting with tumors of two of following three cell types: parathyroid, duodenopancreatic endocrine, and pituitary. Aims and Objectives: (1) To describe clinical profile of MEN1 patients managed from a tertiary care center in South India over 3 years. (2) To compare MEN1-associated primary hyperparathyroidism (PHPT) with the clinical profile of the apparent sporadic PHPT patients (n = 36) presented to the same center over this period. Materials and Methods: data were collected from patient records. Results: Eight MEN1 patients included were two males and six females. The mean age at diagnosis was 49.75 years (59 years for males and 46.6 years for females). Presence of PHPT, gastroenteropancreatic neuroendocrine tumor (GEP-NET), and pituitary tumors was in 8 (100%), 4 (50%), and 2 (25%), respectively. PHPT was the most common presenting lesion (50%), followed by GEP-NET (37.5%) and pituitary tumor (12.5%). Among the four cases with GEP-NET, two were metastatic gastrinoma, one was insulinoma, and one had nonfunctioning pancreatic NET. Two pituitary tumors were one ACTH-secreting macroadenoma and one nonfunctioning microadenoma. Other features of MEN1 present were collagenoma in 5 (62.5%) and adrenal adenoma in 3 (37.5%), of which two were nonfunctioning and one aldosterone secreting. Adrenal adenoma was bilateral in one patient. Genetic analysis was done in five cases and mutation in MEN1 gene was identified in all five cases. Discussion and Conclusion: The clinical profile of our MEN1 cases was similar to other cohorts reported. Peculiar features of our cohort are the occurrence of rare tumors such as ACTH-secreting pituitary macroadenoma and aldosterone-secreting adrenal tumor. On comparing the mean of highest serum calcium, parathyroid hormone levels, 24-h urinary calcium per kg body weight, pattern of glandular involvement, and histopathology, MEN1-associated PHPT cases were found to be less severe than sporadic PHPT cases.

Keywords: Collagenoma, Cushing's syndrome, gastroenteropancreatic neuroendocrine tumor, multiple endocrine neoplasia type 1, primary hyperparathyroidism

 A study of bone mineral density in individuals with gender dysphoria on gender-affirming therapy



Rakesh Bobba, Pramila Kalra, Mala Dharmalingam

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

E-mail: kalrapramila@gmail.com

Introduction: Bone health is an essential consideration in transgender patients on long-term hormones. Objective of this Study: To study the bone mineral density in individuals with gender dysphoria (GD) who were on gender-affirming hormonal therapy for at least 6 months. Materials and Methods: It was a hospital-based, cross-sectional study of bone mineral density in individuals with GD on gender-affirming therapy measured at two sites – hip and spine compared with their genetic sex. Serum calcium, serum albumin, serum phosphorous, 25 hydroxy-Vitamin D levels were measured. Results: The mean age of individuals with GD was found to be 27.25 ± 6.26 years. Out of the 20 individuals, transgender males and females were 11 and 9, respectively. The mean corrected calcium was 9.2 ± 0.427 mg/dl, phosphorous was 3.84 ± 0.547 mg/dl, and Vitamin D levels were 23.2 ± 6.99 ng/ml. In transgender males, the mean T scores of hip and spine were 0.44 ± 1.175 and 0.13 ± 0.946 and mean Z scores of hip and spine were 0.77 ± 1.027 and 0.23 ± 0.961. In transgender females, the mean T scores of hip and spine were −0.83 ± 0.663 and −1.97 ± 1.111, respectively, and the mean Z scores of hip and spine were −0.54 ± 0.464 and −1.97 ± 1.111. In transgender females, the mean T scores of hip and spine in individuals who underwent orchidectomy were −0.32 ± 0.843 and −2.06 ± 0.541 and mean Z scores of hip and spine were 0.0 ± 0.469 and −2.26 ± 0.676. Conclusion: In this study, we observed that the transgender females who underwent orchidectomy had a lower mean T score and Z score of hip and spine compared to individuals who did not undergo the procedure. This could be attributed to beneficial effect of estrogen on bone metabolism in GD individuals.

Keywords: Bone health, bone mineral density, gender-affirming therapy, gender dysphoria

 Effect of zoledronate in hepatic osteodystrophy: A double-blinded placebo-controlled trial



Henith Raj, Sadishkumar Kamalanathan, Jayaprakash Sahoo, Pazhanivel Mohan1, K. Nagarajan2, Vijaya Bhaskar Reddy3, Harsh Durgia, Ayan Roy

Departments of Endocrinology,1Medical Gastroenterology and2Radiodiagnosis, JIPMER,3Vijay Diabetes, Thyroid and Endocrine Clinic, Puducherry, India. E-mail: rafaelmathes@gmail.com

Introduction: Alterations in bone metabolism that occur in chronic liver disease are defined as hepatic osteodystrophy.[1] Currently, general treatment measures and timing of treatment in hepatic osteodystrophy are based on the literature on postmenopausal osteoporosis.[2] Hence, we undertook this randomized trial to study the effect of zoledronate in hepatic osteodystrophy. Materials and Methods: This study was a randomized double-blinded placebo-controlled trial with an allocation ratio of 1:1. We randomized 36 male cirrhosis patients (Child A and B) into two arms, 19 in zoledronate arm and 17 in placebo arm. Patients in the zoledronate arm received 1 g calcium PO/day and 500 IU Vitamin D PO/day for 12 months and a single infusion of 4 mg zoledronic acid at baseline, whereas patients in the placebo arm received similar calcium and Vitamin D doses and a single infusion of 100 ml normal saline at baseline. The primary outcome of the study was to assess the change in bone mineral density (BMD) at lumbar spine between the two arms at 12 months. Results: Of 36 patients, 28 patients completed the study (15 in zoledronate arm and 13 in placebo arm). The mean percentage increase in the lumbar spine BMD (g/cm2) in the zoledronate and placebo arms was 5.11 (3.5) and 0.72 (4.63) (P = 0.008), respectively. Six patients (31.6%) in the zoledronate arm experienced adverse effects such as fever and myalgia. Conclusion: Zoledronate was effective in improving the lumbar spine BMD in male hepatic osteodystrophy patients.

Keywords: Bone mineral density, hepatic osteodystrophy, zoledronate

References

Barbu EC, Chiţu-Tişu CE, Lazăr M, Olariu C, Bojincă M, Ionescu RA, et al. Hepatic osteodystrophy: A Global (Re) View of the problem. Acta Clin Croat 2017;56:512-25.Danford CJ, Trivedi HD, Bonder A. Bone health in patients with liver diseases. J Clin Densitom 2019. pii: S1094-6950(18)30253-1.

 FRAX-based osteoporosis treatment thresholds for resource-poor settings in India



Lakshmi Nagendra, Nisha Bhavani, Praveen V. Pavithran, Arun S. Menon, Harish Kumar, Usha V. Menon, Vasantha Nair, Prem Narayanan, Nithya Abraham

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

E-mail: drlakshminagendra@gmail.com

Introduction: Many current guidelines for the assessment of osteoporosis, including those in India, are based on DXA-derived T-score thresholds. This may deny many patients of treatment in resource-poor settings in India, where DXA is not available freely. Aims and Objectives: Our aim was to develop risk stratification system and treatment thresholds for osteoporosis using the FRAX model for India without bone mineral density (BMD) testing. Materials and Methods: The intervention threshold was set at the age-dependent 10-year probability of a major osteoporotic fracture that was equivalent to a patient with a prior fragility fracture. The lower assessment threshold was set at the age-specific probabilities in patients with no clinical risk factors. We validated the derived intervention thresholds prospectively in a cohort of 222 women and subsequently measured BMD. Results: We formulated graphs based on region-specific body mass index data and FRAX Indian model which allow for risk stratification of patients into low, medium, and high risk for fractures. The 10-year major osteoporotic fracture probability rose progressively with age from 2.1% at the age of 40 years to 18% at the age of 90 years. With advancing years, the difference in probability between women with a T-score of − 2.5 standard deviation and women of the same age without any risk factors decreased. BMD criterion for intervention using a fixed T-score became less and less appropriate with advancing age. Applying the interventional thresholds in our cohort, BMD could have been avoided in 122/222 (54.9%) patients and treatment could be offered in 33/122 (27%) patients without BMD testing. Discussion and Conclusion: Based on this risk stratification, the patients with high risk for fracture can be offered treatment even in the absence of facilities for BMD testing. Individuals with probabilities of a major osteoporotic fracture below the lower assessment threshold can be reassured. Individuals with probabilities of a major osteoporotic fracture within the limits of the assessment thresholds should have a BMD test and probabilities recomputed.

Keywords: India, osteoporosis treatment thresholds

 A Vitamin D prescription pattern survey across India



D. M. Ajay Aggarwal, D. N. B. Roopak Wadhwa, D. M. Dheeraj Kapoor1, D. M. Ajay Ajmani2, D. M. Arun Pande3, D. M. Rajeev Khanna4, M. D. Alok Joshi5, D. M. Alok Sachan6, D. M. Prem Patidar7, M. D. Shivam Srivastava8, D. M. Sandeep Julka9, Raju Vyas Mch10

Departments of Endocrinology and10Cardiothoracic and Vascular Surgery, Fortis Hospital, Delhi,1Department of Endocrinology, Artemis Hospital, Gurugram, Haryana,2Department of Endocrinology, BLK Memorial Hospital, New Delhi,3Department of Endocrinology, Sahara Hospital, Lucknow, Uttar Pradesh,4Dr. Khanna's Endocrinology Clinic, Amritsar, Punjab,5Department of Internal Medicine, Max Hospital, Delhi,6Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh,7Department of Endocrinology and Bariatric Medicine, Jeevan Rekha Superspeciality Hospital, Jaipur, Rajasthan,8Boehringer Ingelheim-Diabetes Care, Bengaluru, Karnataka,9Department of Endocrinology, Radiance Clinic and CHL Hospital, Indore, Madhya Pradesh, India.

E-mail: ajay.ajmani1957@gmail.com

Vitamin D is important for development, growth, and maintenance of health. Vitamin D deficiency (VDD) is highly prevalent in India. Vitamin D is commonly prescribed to reduce morbidities and achieve better health. The information regarding Vitamin D prescription pattern from our country is limited. We conducted a survey to assess the prescription pattern of Vitamin D, alone and in combination with calcium among prescribers across India (New Delhi, Amritsar, Gurugram, Lucknow, Bengaluru, Indore, Jaipur, and Tirupati). Overall, 621 prescribers took part. Majority were internists (44.2%), followed by orthopedicians (17.2%), obstetricians (14.3%), family physicians (11.7%), endocrinologists (4.8%), and others, including rheumatologists (7.8%). Majority (88.8%) prescribers preferred fixed-dose calcium/Vitamin D combinations. Combinations of calcium with cholecalciferol, calcitriol, and alfacalcidol were a choice of 73.2%, 23.1%, and 3.5% prescribers, respectively. Calcium/cholecalciferol combination was most prescribed by family physicians (87.3%), endocrinologists (83.3%), and obstetricians (80.9%) and least by nephrologists (45.4%); they preferred calcium/alfacalcidol (27.2%) and calcium/calcitriol (54.5%). To treat VDD, cholecalciferol and calcitriol were preferred by 56.3% and 37.2% prescribers, respectively, calcitriol was the choice of obstetricians (55%), orthopedicians (49.5%), internists (36%), and few endocrinologists (16.6%). For severe VDD, oral and injectable cholecalciferol was a choice of 57.6% and 37% prescribers, respectively, whereas 5.32% preferred both forms. For severe VDD, oral cholecalciferol was the treatment of choice of nephrologists (72.7%), internists (65.8%), and endocrinologists (60%), whereas injectable form was preferred by gynecologists (53%), orthopedicians (44.8%), and endocrinologists (36.6%). This survey shows that calcitriol with/without calcium and injectable Vitamin D is quite popular among prescribers. Calcitriol may increase the risk of hypercalcemia/hypercalciuria, aortic stenosis in the fetus, whereas injectable Vitamin D may cause toxicity. We conclude that the oral cholecalciferol is a natural choice for VDD. In view of the potential side effects, calcitriol should be used for specific indications, and injectable Vitamin D should be avoided as far as possible.

Keywords: Calcitriol, cholecaciferol, Vitamin D

 Endocrine adverse effects of atypical antipsychotics: A snapshot view



Sweta Mandal, Subhankar Chowdhury, Pradeep Kumar Saha1

Department of Endocrinology, IPGME and R and SSKM Hospital,1Institute of Psychiatry, IPGME and R and SSKM Hospital, Kolkata, West Bengal, India. E-mail: swetamou@gmail.com

Introduction: Atypical antipsychotics, being 5HT2A/D2 antagonists, can cause hyperprolactinemia-induced hypogonadism leading to lower BMD. Other possible reasons of altered BMD are Insulin resistance and low Vitamin D-associated hypocalcemia. Antipsychotics may also lead to hypothyroidism by increasing TRH, producing autoimmunity, or by inhibiting thyroid peroxidase. Aims and Objective: The aim is to assess hormonal, metabolic, and body composition changes in patients requiring atypical antipsychotics. Materials and Methods: We conducted a prospective study between two cohorts of drug naive patients (18–45 years) who were treated with olanzapine or risperidone. Baseline hormonal (Prolactin, TSH, FT4, T3, iPTH), anti-TPO, metabolic parameters (fasting lipid profile, HbA1C, HOMA-IR, calcium, phosphate, magnesium, and 25-hydroxy Vitamin D), and body composition by bioelectrical impedance analysis were evaluated. These were repeated at 1 month and 3 months after the initiation of drugs. Exclusion criteria: Patients with CLD/CKD/T2DM/hyperthyroidism/hypogonadism, patients on lithium/SSRI/TCA/corticosteroid, and pregnant/lactating woman. Results: Prolactin level was raised in risperidone group at 1st follow-up but came down in 2nd follow-up, whereas in olanzapine group, hyperprolactinemia was present in 2nd follow-up, but the level was lower than that of risperidone group. In risperidone group, statistically significant decrease of Vitamin D (r = −3.159, P = 0.0391) and increment of iPTH (r = 0.3744, P = 0.0074) are evident with time. In olanzapine group, statistically significant increment of TSH (r = 0.2981, P = 0.0045), anti-TPO (r = 0.2938, P = 0.0060), insulin resistance (r = 0.232, P = 0.082), and HbA1C (r = 0.3465, P = 0.0096) in serial follow-up are obtained. Conclusion: Hyperprolactinemia is short-lived with risperidone but higher than olanzapine group. Hypocalcemia, low Vitamin D, hyperparathyroidism are seen in the risperidone group. However, autoimmune hypothyroidism, insulin resistance, and visceral fat are common in the olanzapine group.

Keywords: Atypical antipsychotics, hyperparathyroidism, hypocalcemia, thyroid autoimmunity, Vitamin D deficiency

 Effect of 2 mg versus 4 mg of intravenous zoledronic acid on bone mineral density at lumbar spine in Indian postmenopausal women with osteoporosis: A double-blind, parallel-arm, randomized control trial



Harsh Durgia, Ayan Roy, Jayaprakash Sahoo, Sadishkumar Kamalanathan, Sonali Sarkar1, G. Ramkumar2

Departments of Endocrinology,1Community Medicine and2Radiodiagnosis, JIPMER, Puducherry, India.

E-mail: harshdurgia@ymail.com

Introduction: Recommended dose of zoledronic acid for the treatment of osteoporosis is 4–5 mg annually. However, effects of lower doses of zoledronic acid have not been studied in patients with osteoporosis. Aims and Objective: The primary objective of this study was to analyze the effect of single dose of 2 mg versus 4 mg of intravenous zoledronic acid on change in bone mineral density (BMD) at lumbar spine in postmenopausal women with osteoporosis after 12 months of treatment. Materials and Methods: In this study, a total of 70 patients of postmenopausal osteoporosis were randomized to receive either 2 mg (Group I) or 4 mg (Group II) of zoledronic acid once at baseline. The primary endpoint of our study was change in lumbar spine BMD at 12 months. Secondary endpoints included change in BMD at femoral neck and total hip and change in bone turnover markers (BTMs) over 12 months. Results: A total of 64 patients (31 in Group I and 33 in Group II) completed follow-up. The mean percentage increase in lumbar spine BMD at the end of 12 months was 4.86 ± 3.05 and 5.35 ± 3.73 in 2 mg and 4 mg groups, respectively. In noninferiority analysis, 2 mg proved to be inferior to 4 mg with noninferiority margin of 0.5% (P for noninferiority = 0.49). There was no difference in secondary endpoints between both the groups at the end of 12 months. Acute-phase reactions were the most common side effects (43%) noted in both the groups without any between group difference (P = 0.649). Discussion and Conclusion: Both the doses of zoledronic acid led to a significant rise in BMD at lumbar spine with reduction in BTMs at the end of 12 months. The dose of 2 mg zoledronic acid was inferior to 4 mg zoledronic acid with respect to change in lumbar spine BMD at 12 months.

Keywords: Bone turn over markers, dexa, fracture

 Retrospective study of the clinical presentation, imaging modalities, and surgical outcomes in patients with primary hyperparathyroidism presenting to a tertiary health-care center from 2014 to 2019



Sukirti Misra, Nikhil Bhagwat, Prema Varthkavi, Jugal Gada

Department of Endocrinology, B.Y.L Nair Charitable Hospital, Mumbai, Maharashtra, India.

E-mail: sukirtimisra09@gmail.com

Introduction: Primary hyperparathyroidism (PHPT) is a common endocrine disorder which may present as a debilitating disease in developing countries or a relatively asymptomatic one in developed countries. Aims and Objectives: To study the clinical presentation, imaging modalities, and surgical outcomes in patients with PHPT. Materials and Methodology: This retrospective study includes all the histopathologically proven patients of PHPT who presented from 2014 to 2019. Clinical, laboratory, imaging, and pathology data were recorded in an Excel sheet, and frequency tables were made for qualitative data. Correlation between various data parameters was done using Chi-square test. Results: There were 49 patients with proven PHPT (female: 32 and males: 17) in this study. The most common age of presentation was 20–39 years (range, 9–61 years). The most common presentation was bone pains (65.30%), followed by fracture (40%), proximal myopathy (35%), gastrointestinal symptoms (30%), nephrolithiasis (20%), and pancreatitis (16%). The mean levels of calcium were 11.65 mg/dl, phosphorus 2.405 mg/dl, alkaline phosphate 1231 IU/l, Vitamin D 32.5 ng/ml, and parathyroid hormone (PTH) 1117.9 pg/ml. Hypercalciuria was seen in 79% and pancytopenia in 2/49 patients. MIBI (95%) was more sensitive than four-dimensional computed tomography neck (89%) and ultrasound (80%) for tumor localization. Intraoperative PTH levels and frozen section were used to confirm adequacy of surgery. Histopathologically multiple adenomas (n = 5), hyperplasia with pseudoadenomatous changes (n = 2), malignant features (n = 2), and solitary adenoma in 40 patients. Tumor weight varied from 0.3 to 20 g and did not correlate significantly with Vitamin D levels. Postoperatively, severe hypocalcemia (8/49) and hypophosphatemia (2/49) occurred despite prophylaxis for hungry bone. Postoperatively, sepsis (n = 1), pancreatitis (n = 1), and dilated cardiomyopathy (n = 1) caused mortality. Discussion and Conclusions: Symptomatic hyperparathyroidism is still prevalent in our setup. Pancreatitis was an important presenting feature. MIBI was seen to be the most sensitive localization technique. Preoperative Vitamin D deficiency probably led to hungry bone as a common complication.

Keywords: Clinical profile, imaging modalities, primary hyperparathyroidism, surgical outcome

 Intraoperative parathyroid estimation in the surgical treatment of parathyroid adenoma - Experience of a single tertiary care center



Pallavi Pitale, Padmaja Achanta1, Madan Kapre2, Shailesh Pitale1

GMC,1Dew Medicare and Trinity Hospital,2Neeti Clinics, Nagpur, Maharashtra, India.

E-mail: achantapadmaja@yahoo.com

Introduction: Parathyroid adenomas are benign neoplasms of the parathyroid gland that constitute single most common cause of primary hyperparathyroidism, accounting for 85% of the cases. Imaging techniques help to localize the parathyroid adenoma preoperatively. Intraoperative parathyroid hormone (IOPTH) assay can reliably confirm or refute the presurgical localization techniques. We at a tertiary care center present our experience of IOPTH of 6 cases for 4 years. Aims and Objectives: (1) The aim of this study is to evaluate the effectiveness of IOPTH assay in minimally invasive surgery of parathyroid adenomas. (2) To confirm the preoperative localization site of parthyroid adenomas. Materials and Methods: (1) Preoperative sample-baseline value estimation of PTH was done by chemiluminiscence method.(2) The surgically removed adenoma was washed in normal saline and run as the sample. Then, 5-min and 10-min postoperative sample estimation of PTH was done. (3) The turnaround time of the assay was 20 min. (4) The value of PTH should decline by >50% of the initial baseline value, which marks the completion of the surgery. Results: In all the 6 cases, the saline wash sample of the adenoma showed very high values (>1900 pg/ml) and serum levels of 10-min postoperative samples declined by >50%. Of the 6 cases reported, 5 cases were operated for the first time. One case was a redo surgery in which PTH levels were high post operatively. Discussion and Conclusion: IOPTH assay is extremely helpful in a minimally invasive approach. In our case series, we have confirmed the successful removal of the pathological tissue by very high values of PTH in saline wash samples of the surgical specimen and postoperative decrease in serum levels by >50%. This novel method (saline wash estimation of PTH in surgical specimen) has not been reported earlier. The IOPTH assay helps to confirm preoperative localization and successful removal of parathyroid adenoma.

Keywords: Intraoperative parathyroid hormone, parathyroid adenoma, parathyroid hormone estimation

 Vitamin D levels estimated by liquid chromatography–tandem mass spectrometry in southern coastal Andhra Pradesh



Anudeep Reddy, Chaithanya, Sunanda Tirupati, Vijaya Sarathi, K. Dileep Kumar

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

E-mail: drvijayasarathi@gmail.com

Introduction: Serum 25-OH Vitamin D (25OHD) includes both 25-OH Vitamin D2 (25OHD2) and 25-OH Vitamin D3 (25OHD3). Most of the Vitamin D is synthesized in the skin and is in D3 form, whereas D2 form is derived from plant sources. Serum 25OHD2 contribution to serum 25OHD levels is low. However, there are no studies that report serum 25OHD2 among Indians. Aims and Objective: The aim of this study is to estimate Vitamin D status in healthy adult volunteers from southern coastal Andhra Pradesh using liquid chromatography–tandem mass spectrometry (LC-MS/MS) method. Materials and Methods: This is a community-based cross-sectional study conducted between January 2019 and July 2019. Apparently healthy adults were randomly selected. Pregnant and lactating women, individuals on calcium, Vitamin D, or multivitamin supplements, and those with acute illness were excluded from the study. A fasting blood sample was collected from all the participants, and serum total Vitamin D, Vitamin D3, and Vitamin D2 levels are estimated by LC-MS/MS method. Vitamin D status was classified according to the guidelines by the Endocrine Society of the US. Results: The study included 82 participants including 47 females. The mean age of the study population was 34.3 ± 7.9 years. Serum total Vitamin D level was 17.9 ± 7.35 ng/ml. Only two individuals had Vitamin D sufficiency (serum 25OHD: >30 ng/ml), 31 patients had Vitamin D insufficiency (serum 25OHD: 20–30 ng/ml), and 48 patients had Vitamin D deficiency (serum Vitamin D: <20 ng/ml). Serum Vitamin D2 level of the study population was 0.60 ± 0.62 ng/ml accounting for 4.31 ± 5.59% of total Vitamin D levels. Serum 25OHD, 25OHD2, and 25OHD3 levels were not significantly different between males and females, whereas percentage serum 25OHD2 level tended to be higher among females than males (5.24 ± 6.89 vs. 2.74 ± 0.46, P = 0.053). Percentage serum 25OHD2 level inversely correlated with age (r = −0.263, P = 0.017) and serum 25OHD level (r = −0.406, P < 0.001). Discussion and Conclusion: Most of the adults from coastal southern Andhra Pradesh are Vitamin D insufficient or deficient. Serum 25OHD2 levels were negligible and accounted for less than 5% of serum 25OHD level.

Keywords: Liquid chromatography–tandem mass spectrometry, Vitamin D

 Use of intraoperative parathyroid hormone levels as a guide to parathyroid surgery



Sphoorti P. Pai, Vageesh Ayyar, Ganapathi Bantwal, Senthil Rajan1, Himagirish1, Belinda George, L. P. Nandhini

Departments of Endocrinology and1Surgery, St. John's Medical College, Bengaluru, Karnataka, India. E-mail: sphoortipai@gmail.com

Introduction: Parathyroidectomy has been conventionally performed through bilateral neck exploration (BNE), however, with IOPTH and focused parathyroidectomy, morbidity is lesser. IOPTH monitoring has been used to guide in predicting cure postoperatively. IOPTH predicts normocalcemia in the postoperative period. Here, we describe our experience from a tertiary care center with facility for IOPTH monitoring. Aims and Objectives: The aim of this study is to determine the sensitivity and specificity of intraoperative parathormone levels (IOPTH) in predicting postoperative normocalcemia. To compare the sensitivity and specificity of a single value of PTH – preincision or pre excision in IOPTH with the current standard of IOPTH monitoring (>50% fall from the highest of preincision or preexcision PTH). Materials and Methods: This study was conducted at a tertiary care center. All patients who underwent parathyroid surgery with IOPTH monitoring between January 2017 and August 2019 were included in this study. Patients were diagnosed with having hyperparathyroidism based on the following criteria - Elevated serum calcium level of >10.5 mg/dl, and an inappropriately low phosphorus level, with inappropriately high intact parathyroid hormone – iPTH measured by Electrochemiluminescence (ECLIA) sandwich assay with the sensitivity of 1.2 pg/ml. Intraoperative PTH levels were measured preincision, preexcision, and 10-min post excision. The percentage of fall in the IOPTH was calculated by taking the highest of the preincision and preexcision values. The fall in PTH was also calculated from preincision and preexcision PTH separately. The sensitivity and specificity were determined for each of the above in our institute in predicting postoperative normocalcemia. Results: Our study population had 31 patients, and it was female predominant. Most of the patients were symptomatic. The mean age of our population was 47 ± 14 years. Our average preoperative calcium levels were 11.99 ± 1.82 mg/dl. The mean postoperative day 1 serum calcium levels were 9.11 ± 1.02 mg/dl. The mean fall in IOPTH level in our patients was 80.93% ± 25.02% from the highest of the preincision and preexcision levels. All except one patient achieved postoperative normocalcemia. When we took highest of pre incision and preexcision value to calculate the fall in IOPTH, the sensitivity was 96.55% with a specificity of 50%. On taking a single value of preincision to determine IOPTH fall, the sensitivity was 96.3% with specificity of 50%. On taking a single value of preexcision, the sensitivity was only 69. 23% with a specificity of 100%.

Conclusion:

The fall of IOPTH > 50% from the highest of the preincision and preexcision to predict postoperative normocalcemia had the highest sensitivityHowever, if a single value of preexcision is taken to determine the IOPTH fall, a fall of > 50% ensured normocalcemia (100% specificity and 100% positive predictive value), but the sensitivity and negative predictive value was lowHence, a combination of preincision and preexcision values to determine the IOPTH value is the best approach, which is the current standard being practiced.

Keywords: Intraoperative parathyroid hormone, parathyroidectomy

 All that is bent is not rickets



S. Vishwanath, Ayyar Vageesh, Bantwal Ganapathi, George Belinda, L. P. Nandhini, Appaiah Sonali, Pai P. Sphoorti

Department of Endocrinology and Metabolism, St. John's Medical College Hospital, Bengaluru, Karnataka, India.

E-mail: dr.vishu.sp@gmail.com

We hereby report the case of a 20-year-old gentleman with short-limbed dwarfism, bowing of limbs, and alopecia universalis. He had a history of recurrent chest infections in the childhood; however, none were life threatening. A diagnosis of Vitamin D-resistant rickets type II was made, and he was treated with calcium and Vitamin D supplementation. During the subsequent visit, it was found that he had stopped medications for a period of 1 year and had no progression in the deformity since childhood. The patient's history was reviewed; on examination, he was found to have mesomelic short-limbed dwarfism. Biochemical findings showed normal calcium and Vitamin D levels. Skeletal imaging was suggestive of metaphyseal chrondrodysplasia. The primary diagnosis was reconsidered, and a genetic profile was conducted which was positive for recessive mutation of RMRP gene on chromosome 9p. A diagnosis of cartilage hair hypoplasia-McKusick type metaphyseal chrondrodysplasia was made.

Keywords: Cartilage hair hypoplasia, McKusick, metaphyseal chrondrodysplasia, RMRP gene

 OBESITY AND LIPIDS



 A cross-sectional study of body composition and metabolic parameters in men with chronic traumatic paraplegia



Kalyani Sridharan, Shipra Singh1, Judy A. John1, Kripa Elizabeth Cherian, Nitin Kapoor, Thomas V. Paul

Departments of Endocrinology, Diabetes and Metabolism and1Physical Medicine and Rehabilitation, Christian Medical College, Vellore, Tamil Nadu, India.

E-mail: sridharan.kalyani22@gmail.com

Background: Traumatic paraplegia due to road traffic accidents predominantly affects young men. Sarcopenia and metabolic parameters are less-studied aspects in these individuals. Aims: We aimed to examine body composition and measures of insulin resistance in paraplegic men and compare these parameters with age-, sex-, and body mass index (BMI)-matched controls. Methods: Men aged 18–45 years with traumatic paraplegia, 1–3 years post injury with T2–L1 neurological level, belonging to American Spinal Cord Injury Association (ASIA) impairment scale A or B, were recruited between 2016 and 2018 and compared to age-, sex-, and BMI-matched controls. Patients on drugs affecting bone metabolism, renal failure, severe infections, and malabsorption were excluded from the study. Body composition was measured by dual-energy X-ray absorptiometry scan. Fasting glucose and insulin were measured, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Results: Compared to controls (n = 36), cases (n = 43) had higher total body fat (%) (25.5 [21.2–28.9] vs. 20.2 [15.9–22.2]; P < 0.01) and lower appendicular lean mass/ height2 (5.81 ± 1.26 vs. 8.17 ± 1.12; P < 0.01). HOMA-IR was higher in cases (1.33 [1.03–2.12] vs. 0.94 [0.52–1.78]; P = 0.02), whereas QUICKI was lower (0.36 ± 0.04 vs. 0.38 ± 0.05; P = 0.02) when compared to controls. When subcategorized by ASIA category, ASIA A (complete neurological injury) had lower trunk to leg fat (0.61 ± 0.16 vs. 0.73 ± 0.10; P = 0.03), higher HOMA-IR (1.64 [1.14–3.33] vs. 1.0 [0.83–1.32]; P = 0.016) and lower QUICKI (0.34 ± 0.03 vs. 0.38 ± 0.02; P = 0.016) compared to ASIA B (incomplete neurological injury). Conclusion: Measures of body composition and insulin indices indicate sarcopenia and insulin resistance in men with traumatic paraplegia which is more profound in the subcategory with complete neurological injury. Well-designed longitudinal studies are needed to confirm the findings.

Keywords: Body composition, insulin resistance, paraplegia, sarcopenia

 Lipid accumulation product: A simple tool for prediction of insulin resistance in overweight and obese male individuals



Rahul Valsaraj, Nilanjan Sengupta, Arjun Baidya, Pranab Kumar Sahana, Soumik Goswami, R. S. Riyas

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

E-mail: rahulvals@gmail.com

Introduction: Overweight and obesity is a public health issue of the 21st century. Lipid accumulation product (LAP), a novel index of central lipid accumulation, is a cheap and effective tool in predicting insulin resistance, especially in the Indian population who are more prone for abdominal obesity. Aims and Objectives: The aim is to study the correlation of LAP with body mass index (BMI), fasting glucose, HOMA-IR, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) in overweight and obese (OVOB) males. Materials and Methods: This was an institutional-based cross-sectional study done from January 2018 to June 2019. The patients were studied in two groups as follows: (a) OVOB adolescents (n = 22) and (b) OVOB adults (n = 25). All results were compared to volunteers with normal BMI. They underwent a detailed clinical examination and anthropometric assessment. LAP = (waist circumference [cm] −65) × (triglyceride concentration [mmol/l]). Investigations included: fasting plasma glucose (FPG), fasting lipid profile, HOMA-IR, serum adiponectin, and hs-CRP. Females and patients with type 2 diabetes mellitus were excluded. Results: The mean age was in adolescent OVOB, and adult OVOB group was 14.13 ± 1.75 and 36.72 ± 11.6 years, respectively. The mean LAP in OVOB adolescent versus normal BMI adolescent was 62 ± 47.4 versus 15.2 ± 9.0 (P ≤ 0.0001), and OVOB adults versus normal BMI adults was 85.7 ± 54.8 versus 20.9 ± 36.5 (P ≤ 0.0001). In the OVOB adolescent group, LAP had a strong positive correlation with BMI (r = 0.878, P≤ 0.0001), FPG (r = 0.734, P≤ 0.0001), HOMA IR (r = 0.822, P≤ 0.0001), hs-CRP (r = 0.542, P = 0.009), and a negative correlation with adiponectin (r = −0.597, P = 0.003). Similar results were seen in the OVOB adults with LAP positively correlating with BMI (r = 0.932, P≤ 0.0001), FPG (r = 0.747, P≤ 0.0001), HOMA IR (r = 0.831, P≤ 0.0001), hs-CRP (r = 0.732, P = 0.0001), and negatively correlated with adiponectin (r = −0.675, P≤ 0.0001).Conclusion: In a resource-limited setting like India, LAP is a simple, inexpensive, and quick tool to predict visceral obesity and insulin resistance.

Keywords: Insulin resistance, lipid accumulation product, obesity

 Congenital generalized lipodystrophy presenting with cirrhosis



Y. P. Ganavi, Pramila Kalra

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

E-mail: ganavipattabhi@gmail.com

Introduction: Congenital and acquired are the types of generalized lipodystrophy, which is a rare condition of lipid and carbohydrate metabolism. These are divided based on the age at presentation and pattern of inheritance. Congenital generalized lipodystrophy (CGL) or Lawrence–Seip syndrome presents in the first 2 years of life and is inherited in an autosomal recessive pattern. The usual clinical features are loss of body fat, muscular hypertrophy, acanthosis, hirsutism, hepatomegaly with fatty liver, dyslipidemia, and hyperglycemia with insulin resistance. A 14-year-old girl with the clinical features of Lawrence–Seip syndrome is reported with nonalcoholic steatohepatitis progressing to cirrhosis. Case Report: A 14-year-old girl born out of second-degree consanguineous marriage with uneventful birth history and good scholastic performance presented with diabetes at 8 years without ketonuria. She is on a basal-bolus regime of insulin since then with a requirement of 3.17 units/kg. Physical examination revealed a height of 136.7 cm (<3rd centile) and weight of 31.5 kg (<3rd centile) with generalized loss of fat from the face, trunk, and extremities. She had coarse, acromegaloid features, hypertrichosis, marked acanthosis, and prominent muscles with normal genitalia. Her pubertal status revealed Tanner B1, P2 with sparse axillary hair. She had ascites secondary to portal hypertension due to cirrhosis and splenomegaly. She had recurrent pancreatitis secondary to hypertriglyceridemia. Laboratory values revealed triglycerides of 884 mg/dl and total cholesterol of 177 mg/dl with aspartate transaminase and alanine aminotransferase levels being 43 IU/L and 62 IU/L, respectively, and viral markers were negative. Her triglycerides reduced with dietary approach and fenofibrate. The patient's brother also has phenotypic features suggestive of CGL, but is biochemically normal. Discussion: The treatment of CGL is not well established. The strict dietary regimen is primordial in the management of CGL with the use of fenofibrate for hypertriglyceridemia. Recent studies have proposed replacement with recombinant leptin which has yielded promising results.

Keywords: Diabetes, hypertriglyceridemia, lipodystrophy, nonalcoholic steatohepatitis, pancreatitis

References

Ferraria N, Pedrosa C, Amaral D, Lopes L. Berardinelli-seip syndrome: Highlight of treatment challenge. BMJ Case Rep 2013;2013. pii: bcr2012007734.Rashed AA, Mulla SA, Farooqib GA. Case report: Berardinelli-seip congenital generalized lipodystrophy – A case report and literature review. Curr Pediatr Res 2006;10:41-4.Khandpur S, Kumar A, Khadgawat R. Congenital generalized lipodystrophy of Berardinelli-Seip type: A rare case. Indian J Dermatol Venereol Leprol 2011;77:402.

 Evaluation of cardiometabolic and vascular risk factors in Turner syndrome



Dipti Sarma, Manjari Dwivedi

Department of Endocrinology, Gauhati Medical College, Guwahati, Assam, India. E-mail: manjari.dwivedi. 29@gmail.com

Introduction: Turner syndrome (TS) is the most common chromosomal abnormality in females and has a well-established association with structural heart diseases which is present in 30% of TS patients. Increasingly, it is being recognized that these patients also have adverse cardiometabolic profile which also contributes to increased cardiovascular mortality. Hypertension, glucose intolerance, and dyslipidemia have been reported to be more common in TS patients than the normal population. Aims and Objective: The aim and objective was to assess cardiometabolic and vascular risk factors in patients with TS and compare them with an age- and gender-matched healthy population. Materials and Methods: Data from 17 patients with TS and same number of healthy controls (13 ± 3.4 vs. 12.4 ± 2.69 years of age, respectively, P = 0.478) were compared with respect to anthropometry, blood pressure, and biochemistry including fasting lipid profile, fasting plasma glucose, fasting insulin, and high-sensitivity C-reactive protein (hs-CRP). Carotid intima media thickness (CIMT), as a marker of vascular risk, was measured by high-resolution B-mode ultrasonography. Means and standard deviations were calculated with conventional methods. Differences in means were tested using both parametric and nonparametric tests depending on the distribution of variables. Simple correlation was calculated with Pearson's method. Results: Among patients with TS, one had Type 2 diabetes mellitus, one was hypertensive, and three patients had structural heart defects. Body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, low-density lipoprotein, non-high-density lipoprotein cholesterol, fasting insulin, and Homeostatic Model Assessment of Insulin Resistance were found to be statistically significantly higher (P < 0.05) in patients with TS as compared to controls. CIMT and hs-CRP values were not different between the groups. Discussion and Conclusion: TS girls exhibit more cardiometabolic risk factors compared with age-matched girls. Higher fasting insulin levels, atherogenic lipid profile, blood pressure, and higher BMI and waist circumference suggest clustering of metabolic risk factors in TS patients, which contributes to increased mortality from cardiovascular cause.

Keywords: Cardiometabolic, cardiovascular mortality, Turner syndrome

 Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome



Sandeep Sahu, Anoj Kumar Baliarsinha

Department of Endocrinology, SCB Medical College and Hospital, Cuttack, Odisha, India.

E-mail: docsandy.rihan@gmail.com

Background: Insulin resistance has been implicated in the pathogenesis of both nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). We hypothesized that NAFLD would be common in women with PCOS. The aim of this study was to estimate the prevalence of and identify associated factors for hepatic steatosis in women with PCOS. Methods: This is a cross-sectional study conducted on 57 consecutive premenopausal women with PCOS. Clinical history, height, weight, and laboratory values were obtained. Fasting measurements of serum glucose and insulin were used to calculate Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Abdominal ultrasonography was used to determine the presence and severity of hepatic steatosis. Results: Of the 57 women (median age, 31 years), 32 (56%) had steatosis. The presence of steatosis was associated with a greater body mass index (BMI) and HOMA-IR, a lower fasting high-density lipoprotein, and a greater prevalence of impaired fasting glucose and impaired glucose tolerance. Conclusions: Fatty liver was identified in 56% of patients with PCOS. High BMI and insulin resistance appeared to be important associated factors. Early recognition of NAFLD in this group of young patients is warranted, and further investigation including liver biopsy might be indicated.

Keywords: Hepatic steatosis, insulin resistance, nonalcoholic fatty liver

 A Cross-sectional Study on the Correlation of Melatonin, Leptin, and Adiponectin Levels with Body Mass Index and Glycemic Indices among Shift Workers



Ganesh Namani, Rakesh Kumar Sahay, Neelaveni Kudunati, Naveen Charantimat

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

E-mail: drn.nganesh@gmail.com

Introduction: The prevalence of obesity, diabetes, and metabolic syndrome is on the rise across the globe, especially in developing countries such as India. Apart from traditional risk factors, shift work has been emerging as a major risk factor for the rising prevalence of obesity and diabetes. A large number of younger population are working at night shifts in India and they are at very high risk of obesity and metabolic syndrome due to circadian misalignment and sedentary nature of their job. Materials and Methods: It is a cross-sectional study involving apparently healthy 50 young people working in night shifts and 50 age- and body mass index (BMI)-matched people working in day shift in software/IT companies. They were assessed for sleep quality, physical activity, diet and fasting plasma sample for glucose, lipids, insulin, leptin, and adiponectin, urine for melatonin were taken, and 1 h glucose tolerance test (GTT) was done. Results: The mean age was 28.5 years in night shift workers and 29.2 years among day workers. The prevalence of metabolic syndrome was 46% among night shift workers and 24% among day workers. Night shift workers had significantly lower melatonin levels and higher insulin and leptin levels. Adiponectin levels were not significantly different. Melatonin has a negative correlation with BMI, 1 h GTT, and leptin levels and positive correlation with adiponectin, while leptin showed a positive correlation with BMI and insulin levels. Discussion and Conclusion: The prevalence of obesity and metabolic syndrome is very high among night shift workers. Shift workers have lower melatonin and higher insulin and leptin levels, suggesting higher levels of insulin resistance and leptin resistance. Lower melatonin levels might contribute to the high prevalence of obesity, insulin resistance, and metabolic syndrome among shift workers. Further studies are needed to establish the role of melatonin and its therapeutic potential for the prevention of these metabolic complications among shift workers.

Keywords: 1 h glucose tolerance test, adiponectin, leptin, melatonin, metabolic syndrome, shift work

 Persistent hypercalcemia following parathyroidectomy: A case-based approach



C. N. Antonypillai, D. Jegavanthan1, C. G. K. Amiyangoda1, P. A. D. M. Kumarathunga1, R. S. Mohomed1, H. Mahendran1, F. Kiyamudeen2

Departments of Endocrinology,1Diabetes and Endocrinology,2Chemical Pathology, Teaching Hospital, Kandy, Sri Lanka.

Introduction: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in ambulatory patients. Parathyroidectomy is the treatment of choice for symptomatic patients. Although it provide cure in majority, re-do parathyroidectomy is required in a subset of patients due to persistent disease. The management challenges and the approach of a failed parathyroidectomy are discussed here. Case Report: A 23-year-old male who presented with acute pancreatitis was found to have hypercalcemia, and evaluation confirmed PHPT. Initial investigations failed to localize the adenoma. Parathyroid exploration was done, and two and half glands were removed as only three glands could be visualized intraoperatively. Histology revealed normal glands. As he had persistently elevated parathyroid hormone (PTH) levels postoperatively, he was re-evaluated. Repeat sestamibi scan revealed 0.5-cm nodule within the right lobe of the thyroid. Further confirmation with parathyroid venous sampling revealed very high levels of PTH in the middle thyroid vein. The patient was offered with re-do parathyroidectomy, and the culprit parathyroid adenoma was dissected which was histologically confirmed later. The patient was improved clinically and biochemically. Discussion: Parathyroidectomy is the definitive treatment of PHPT. The traditional surgical approach was bilateral neck exploration. However, advances in the imaging techniques, along with intraoperative PTH monitoring, have led to preoperative localization and focused parathyroidectomy. Management of persistent hyperparathyroidism following parathyroidectomy is challenging. If re-operations are required, it should be done by experienced surgeons after proper localization. It includes repeating noninvasive and, if necessary, invasive investigations such as guided fine-needle aspiration cytology and selective venous sampling. If culprit parathyroid is not still identified, other options include partial or complete thyroidectomy, partial or complete median sternotomy, and ligation of the blood supply to the missing parathyroid gland. Conclusion: Re-do parathyroidectomy is required in a subset of patients with persistent hyperparathyroidism, and more invasive strategies are helpful in localizing suspected lesion.

Keywords: Hypercalcemia, parathyroid venous sampling, primary hyperparathyroidism, sestamibi scan

References

Pallan S, Rahman MO, Khan AA. Diagnosis and management of primary hyperparathyroidism. BMJ 2012;344:e1013.Wilhelm SM, Wang TS, Ruan DT, Lee JA, Asa SL, Duh QY, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg 2016;151:959-68.

 Prolactinoma presenting with precocious puberty



Subramanian Kannan, Kranti Khadilkar, K. S. Shivaprasad

Department of Endocrinology, Diabetes and Metabolism, Narayana Health City, Bengaluru, Karnataka, India.

Email: drkrantimd@gmail.com

Introduction: Prolactinomas usually present with symptoms of hypogonadism. We describe a case of prolactinoma presenting as precocious puberty instead of hypogonadism. Case: A 10-year-male child presented with increased testicular size and growth of phallus clinically diagnosed as gonadotropin-dependent precocious puberty (testicular volume: 14 cc and bone age: 13 years). Investigations showed testosterone: 440 ng/dl, follicle-stimulating hormone: 5.3 IU/L, luteinizing hormone: 4.13 IU, and prolactin in dilution: 1035 ng/ml. Magnetic resonance imaging (MRI) showed a 16 mm × 18 mm × 17 mm solid-cystic pituitary macroadenoma with quadrantanopia on perimetry. Other pituitary hormone axes and calcium levels were normal. Diagnosis and Management: We gave a trial of cabergoline 0.5 mg twice a week starting with a low dose and increasing every week. Follow-up: After 2 months of therapy, we found the prolactin levels decreased to 32 ng/ml, and the MRI showed a considerable reduction in size. This is a rare presentation of prolactinoma as precocious puberty probable reason could be an increased gonadal responsiveness to gonadotropins due to excess prolactin or a co-secreting pituitary adenoma (co-secreting prolactin and gonadotropins).

 Achieving higher levels of efficiency in a diabetes outpatient clinic with improved patient care quality through the use of digital clinical assistant software application



Subramanian Kannan, K. S. Shivaprasad, Kranti Khadilkar, Shalini Rajesh, Alben Sigamani1, Vellaichamy M. Annapandian2, Deviprasad Shetty3

Department of Endocrinology, Diabetes and Metabolism, Narayana Health City,1Department of Clinical Research, Mazumdar Shaw Medical Center, Narayana Health City,2Department of Academic Research, Narayana Hrudayalaya Foundations,3Department of Cardiothoracic Surgery, Narayana Institute of Cardiac Sciences, Narayana Health City, Bengaluru, Karnataka, India. E-mail: drkrantimd@gmail.com

Introduction: Electronic health records (EHRs) have shown to improve quality metrics in diabetes clinics however in most cases take away too much “doctors' time.” Aims and Objectives: We determined the impact of implementing a new physician workflow tool called “Cura Digital Assistant” in our diabetes outpatient department. Materials and Methods: We reviewed patients (>18 years) data of the clinic obtained from the Cura digital clinical assistant between January 2017 and December 2018. Patient records were reviewed for the trend of diabetes control (glycated hemoglobin [HbA1c], fasting blood sugars) and follow-up visits. Results: A total of 42,095 patients (males-24,491; 58.2%) records were reviewed (mean age: 50.65 ± 15.4 years; mean duration of diabetes: 8.3 ± 6.5 years, 89.2% already diagnosed with type-2 diabetes and 5.9% of patients newly diagnosed). A 49% increase in new clinic visits and three-fold increase in repeat visits was observed. There was a significant reduction in fasting blood glucose values (147.99 ± 58.64 vs. 137.67 ± 44.53 mmHg; P < 0.05) and HbA1c values (8.04 ± 1.87 vs. 7.72 ± 1.5; P < 0.05) in the latest visits comparing to initial visit of patients who have completed 6 months of follow-up. The number of patients with HbA1c <8% was 54% at initial clinical visit increased to 63% (P < 0.01) at their latest clinic visit, while the number of patients with low-density lipoprotein-cholesterol <100 mg/dL improved from 38.2% to 61.8% in 2018 (P < 0.01) and patients with blood pressure <140/90 mmHg was increased from 28.4% to 30.3% (P = 0.876). Discussion and Conclusion: This EHR technology helped us in streamlining our diabetes clinic workflow, thus increasing the new and follow-up visits. Better documentation and observation of parameters helped in achieving significant HbA1c reduction. Despite the adoption of new technology with the same clinical staffing and resources, we were able to improve the clinic throughput and patient care.

Keywords: Cura, diabetes care, digital clinical assistant, electronic health records

 An unusual case of dilated cardiomyopathy



Shubhayu Dey, Ajitesh Roy

Department of Endocrinology and Metabolism, Vivekananda Institute of Medical Sciences and Ramakrishna Mission Seva Pratishthan, Kolkata, West Bengal, India. E-mail: dey.shubhayu@gmail.com

Introduction: Calcium plays a central role in the sequence of myocardial excitation–contraction coupling. Hypocalcemia manifests with a number of clinical manifestations; however, heart failure is rare. Seizure may be the first manifestation of hypocalcemia. Although hypocalcemic seizures are widely documented in the medical literature, they are commonly missed. Here, we report a case presented with hypocalcemia-induced reversible cardiomyopathy and seizure. Case Presentation: A 42-year-old aged female from rural Bengal presented with shortness of breath for 7 days. At emergency room, we found her severely dyspneic. Oxygen saturation was 88%. There were features suggestive of heart failure. She was treated with ionotropes and diuretics at the intensive care unit. Routine electrolytes and renal function test were normal. She had mild anemia. Echocardiography (Echo) showed global hypokinesia (ejection fraction [EF] 31%). The patient improved and shifted to the ward. However, suddenly, she developed generalized tonic-clonic seizure. Then, we did noncontrast computed tomography brain and electrolytes including calcium. Neuroimaging revealed bilateral symmetrical calcification in the basal ganglia and caudate nuclei. Electrolytes were found normal except calcium which was found to be low (5.4 mg/100 ml). We treated the patient with intravenous calcium and evaluated for hypocalcemia. Primary hypoparathyroidism was diagnosed. We again took detailed history. She visited many doctors for the evaluation of generalized weakness and tingling and numbness of extremities. There was also a history of cataract surgery 4 years back. Screening for other autoimmune diseases was negative. The patient was discharged with oral calcium and calcitriol. We repeated echo after 3 months. Contractility was markedly improved; EF was 51%. Conclusion: Although rare, hypocalcemia is a potent cause of reversible cardiomyopathy. In all cases of dilated cardiomyopathy, measurement of serum calcium is mandatory. Prolonged history of generalized weakness with tingling sensation is not always somatoform disorder; one must exclude organic diseases. Serum calcium level should be checked in patients presenting with seizure.

 Adrenocorticotropin resistance syndrome – Rare cause of congenital primary hypoadrenocorticism



Shivani, R. A. Misgar, M. H. Bhat

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

Introduction: Adrenocorticotropin (ACTH) resistance syndrome, also known as familial glucocorticoid deficiency, is a rare autosomal recessive inherited cause of hypocortisolism despite raised ACTH and a preserved renin–aldosterone axis. It most commonly presents in the second decade of life with seizures, hypoglycemia, and increasing pigmentation, often associated with enhanced growth velocity. If not diagnosed and treated properly, it poses patients at risk for hypoglycemia precipitated by stress. Cases: We report two cases of ACTH resistance syndrome. One was a 2-year 5-month-old female child born of consanguineous marriage with progressive increase in pigmentation and recurrent episodes of hypoglycemic seizures: 8 am serum cortisol = 0.76 μg/dl, ACTH = 4550 pg/ml, sodium = 139 mmol/l, potassium = 4.6 mmol/l, normotensive, no genital ambiguity, normal 17(OH) progesterone, and adrenal imaging. Our second case was a 2-year 11-month-old female child, born of consanguineous marriage, with no history of salt crisis, who presented with progressive increase in generalized hyperpigmentation. Examination revealed no genital ambiguity. Investigations revealed normal electrolytes, 8 am cortisol = 0.27 μg/dl, ACTH = >1250 pg/ml, normal plasma aldosterone concentration, and normal 17(OH) progesterone levels. Both the patients were managed with oral hydrocortisone, leading to resolution of hypoglycemic seizures in the first case; however, there was a significant improvement in skin pigmentation in both the cases. Conclusion: ACTH resistance syndrome should be kept in mind in patients presenting with generalized increased pigmentation, childhood hypoglycemia without salt crisis, low serum cortisol, increased ACTH, and normal mineralocorticoid axis, especially with a history of consanguinity in parents.

 Identifying the burden of diabetes distress and assessing its impact on patients with Type 2 diabetes



Ratnesh Sinha, K. S. Shivaprasad, Kranti Khadilkar1, Subramanian Kannan

Department of Endocrinology, Diabetes and Metabolism, Narayana Health City,1Mazumdar Shaw Medical Center, Narayana Health City, Bengaluru, Karnataka, India. E-mail: drkrantimd@gmail.com

Introduction: Diabetes distress (DD) refers to the unique, often hidden emotional burdens and worries that patients experience when managing diabetes. It is associated with increased glycated hemoglobin (HbA1C) levels, comorbidities, and morbidity. Aims and Objectives: The purpose of the study is to find the magnitude of DD in Type 2 diabetes (T2DM) patients and its effect on glycemic status. Materials and Methods: The study included 250 patients with T2DM who attended the endocrine outpatient department from February to April 2019. DD was measured by using the Diabetes Distress Scale. Results: The prevalence of DD was 19.6%. The risk of DD was 4.25 times more in age ≤45 years as compared to age >45 years. Patients with HbA1c >8% had 8.8 times more DD. A positive moderate correlation was found (r(248) = 0.707, P < 0.001), indicating a statistically significant linear relationship between DD and HbA1c levels. Patients on insulin had more DD (5.4 times) as compared to patients who were on oral drugs. Patients with a history of treatment interruption had 11 times more risk of DD as compared to patients who did not have any treatment interruption. Discussion and Conclusion: DD was found to be high among patients aged ≤45 years, illiterates, patients on insulin, and patients with a history of treatment interruption and HbA1c > 8%. Patients with high DD were found to have higher HbA1c levels.

 Ambulatory blood pressure profile in patients with primary hyperparathyroidism before and after curative parathyroidectomy



Soham Mukherjee, Rimesh Pal, P. Jayaprakash, Anil Bhansali, Arunanshu Behera1, Sanjay Kumar Bhadada

Departments of Endocrinology and1General Surgery, PGIMER, Chandigarh, India.

E-mail: drsoham.mukherjee@gmail.com

Introduction: Primary hyperparathyroidism (PHPT) is found to have an association with the development of hypertension. Literature on the effect of curative parathyroidectomy on 24-h ambulatory blood pressure (AMBP) monitoring in PHPT patients is sparse. Aims and Objective: We aimed to study the effect of curative parathyroidectomy on 24-h AMBP in patients with symptomatic PHPT. Materials and Methods: In this prospective follow-up study of 17 patients with symptomatic PHPT, serum calcium, phosphorus, parathyroid hormone, and 25 hydroxyvitamin D were assessed. The 24-h AMBP parameters (mean 24-h systolic and diastolic blood pressure (BP), day time and night-time systolic and diastolic BP, mean arterial pressure, and nocturnal dipping status) were recorded pre- and postcurative parathyroidectomy. Results: Hypertension was observed in four (23.5%) patients. The mean 24-h systolic and diastolic BP did not differ pre- and postoperatively. However, there was significant reduction in the night-time systolic (P = 0.007) and diastolic BP (P = 0.034) after parathyroidectomy. Postoperatively, the prevalence of dipping status improved from 36% to 50%, which however did not achieve statistical significance. None of the biochemical parameters significantly correlated with BP. Discussion and Conclusion: Curative parathyroidectomy in patients with PHPT reduces the nocturnal BP and possibly improves the nocturnal dipping status.