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   Table of Contents - Current issue
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July-August 2019
Volume 23 | Issue 4
Page Nos. 387-502

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EDITORIAL  

Calcium supplementation: Why, which, and how? p. 387
MK Garg, Namita Mahalle
DOI:10.4103/2230-8210.268505  
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REVIEW ARTICLES Top

Secondary and tertiary hyperparathyroidism in chronic kidney disease: An endocrine and renal perspective p. 391
Manju Chandran, Jiunn Wong
DOI:10.4103/ijem.IJEM_292_19  
Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject.
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Biosimilar insulins – What a clinician needs to know? p. 400
Sujoy Ghosh, Saptarshi Bose, Sandeep Gowda, Pradip Mukhopadhyay
DOI:10.4103/ijem.IJEM_180_19  
As the first biologics produced by recombinant deoxyribonucleic acid (DNA) technology were approved in the late 1980s and consequently the exclusive marketing rights of most of these biological medicinal products have expired or will expire very shortly, it is quite evident that biosimilars are being developed and marketed in developed as well as developing countries in line with these expiries. Hence, there is an explosion of published papers and scientific programs on biological medicinal products and biosimilar insulins in the last decade or so. Each of these papers or scientific programs generated more questions than providing clinically useful answers. The specific aim of the medical literature or scientific programs were blurred due to lot of attention (created by the innovators) directed towards confusing terminologies, past mishaps with biosimilars (in the era with the absence of regulatory guidelines for biosimilars) diverting our attention from the matters relevant to clinicians and patients. One of the principle reason behind this phenomenon has been our poor understanding of the manufacturing process, regulatory pathways, and study endpoints involved in developing a biosimilar in the present era. This drawback resulted in a nonsystematic approach in analyzing the biosimilars and apparently resulting in confusion. This review attempts at demystifying certain facets of frequently encountered information on biosimilars and acquire a personal understanding on the same, rather than depending on conflicting versions floated at different continuing medical educations (CMEs) and Diabetes Congresses.
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ORIGINAL ARTICLES Top

Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in India using Eq 5D 5L p. 407
Paresh C Parik, Varsha Jitendra Patel
DOI:10.4103/ijem.IJEM_29_19  
Objective: To assess the health-related quality of life of Type 2 Diabetes mellitus patients attending outpatient departments of a tertiary hospital using EQ-5D-5L. Methods: The study was conducted at a tertiary care hospital in India. The quality of life of patients with type 2 Diabetes mellitus, age 18 years and older, attending outpatient departments of Medicine and Endocrinology was assessed with the help of EQ-5D-5L, a measure of self-reported health related quality of life. Data was analyzed to obtain EQ-5D-5L scores for the five dimensions and EQ VAS score. Correlation of EQ VAS score with different variables was analyzed. Results: Out of total 358 participants, 208 had comorbidities, hypertension being the most common. Mean age was 60.71 ± 11.41 years and 216 (58.9%) were female participants. Out of five dimensions, Mobility, Self-care, Usual activities, and Pain/discomfort were most affected in age group 71 years and above while anxiety/depression affected age group 18–30 years the most. Mean EQ VAS score was 78.83 ± 15.02. Female participants had significantly higher EQ VAS score (P = 0.00) than male participants. EQ VAS score showed significant negative correlation with uncontrolled state of diabetes (P = 0.000). There was significant difference in EQ VAS score between patients with and without comorbidities. (P =0.004) Cronbach alpha for EQ-5D-5L was 0.76. Conclusion: The results suggest that EQ-5D-5L is a reliable measure for assessing health related quality of life of patients with Type 2 Diabetes mellitus. Type 2 Diabetes adversely affects the quality of life of patients. Uncontrolled disease and comorbidities can further compromise the quality of life.
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A cross-sectional study of stretched penile length in boys from West Bengal, India p. 412
Ajitesh Roy, Rana Bhattacharjee, Partha P Chakraborty, Soumik Goswami, Kaushik Biswas, Pradip Mukhopadhyay, Subhankar Chowdhury
DOI:10.4103/ijem.IJEM_51_19  
Introduction: Short penile length is a commonly encountered problem in clinical practice. Detection of abnormal stretched penile length (SPL) warrants appropriate endocrine evaluation. Ethnicity-specific SPL data are required to detect these abnormalities. There is a dearth of such data in India. This study aims to establish normative values of SPL in boys from West Bengal. Materials and Methods: This is a cross-sectional study. SPL, testicular volume (TV), height/length, and weight were measured in 460 boys aged 1 to 13 years from the schools located at urban, suburban, and rural areas in the state of West Bengal, India. Similar data were collected from 36 healthy neonates within 1–3 days of full-term delivery at IPGME and R and SSKM Hospital, Kolkata, West Bengal, India. Results: The 5th percentile, median, and 95th percentile of SPL were 1.7, 2.0, and 2.7 cm for neonates; 3.5, 4.4, and 6.4 cm for the children aged 1 Y–2 Y 11 M; 4.0, 5.5, and 7.0 cm for the age group 3 Y–4 Y 11 M; 4.2, 6.0, and 7.2 cm for the age group 5 Y–6 Y 11 M; 4.3, 6.0, and 7.6 cm for the age group 7 Y–8 Y 11 M; 4.4, 6.5, and 9.0 cm for the age group 9 Y–10 Y 11 M; and 4.8, 7.0, and 11.0 cm for the age group 11 Y–12 Y 11 M, respectively. SPL showed significant positive correlation with TV [r = 0.365, P < 0.0005] and height of the children [r = 0.516, P < 0.0005], but not with BMI. Conclusion: Our study provides normative data of SPL in neonate and children aged 1 to 13 years from the eastern part of India. SPL value correlated positively with TV and height of children.
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Continuation of metformin till night before surgery and lactate levels in patients undergoing coronary artery bypass graft surgery p. 416
Tarannum Bano, Sunil Kumar Mishra, Mohammad Shafi Kuchay, Yatin Mehta, Naresh Trehan, Pooja Sharma, Manish Kumar Singh, Ambrish Mithal
DOI:10.4103/ijem.IJEM_114_19  
Background: Lactic acidosis is a rare but serious complication associated with metformin therapy in certain high-risk patients. NICE guidelines and the British National Formulary advise the discontinuation of metformin before surgery. The drug manufacturer's datasheet advises the withdrawal of metformin 48 h before surgery. However, the data regarding perioperative use of metformin is scarce. Aims: To evaluate the effect of continuation of metformin till night before surgery on lactate levels in patients undergoing coronary artery bypass graft (CABG) surgery. Materials and Methods: In this prospective cohort study, 1,800 consecutive patients who underwent CABG between 1st November 2015 and 31st October 2016 were enrolled. Following exclusion criteria, a total of 790 subjects were included for final analysis. Three-hundred and eight seven (48.9%) patients with diabetes received metformin till night before surgery (Met group), 239 (30.3%) patients with diabetes were non-metformin users (Non-Met group), and 164 (20.8%) patients were having no diabetes (Non-Diab group). Lactate levels and arterial pH were measured using arterial blood gas machine. Postoperative morbidity outcome data were obtained by collecting clinical data, routine biochemistry, and chest imaging. Results: The mean metformin dose was 1,124.6 mg/day (SD: 509.3; range: 500–2,500 mg/day). Mean postoperative lactate levels were 1.91 ± 0.7 in Met group, 2.04 ± 0.79 in Non-Met group, and 2.07 ± 0.78 in Non-Diab group. Lactic acidosis occurred in 41 patients and there was no difference among the groups [Met group = 18 (4.7%); Non-Met group = 14 (5.9%)]. Among secondary outcome measures, acute renal failure occurred more frequently in diabetic patients [Met group = 46 (11.9%) and Non-Met group = 32 (13.4%)] as compared with non-diabetic patients. There were no differences with regard to pneumonia, length of ICU stay, and duration of ventilatory support among the three groups. Conclusions: Continuation of metformin till night before surgery is not associated with significant changes in lactate levels in patients undergoing CABG.
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Inverse relationship between 25 hydroxy Vitamin D and parathormone: Are there two inflection points? p. 422
Pradip Mukhopadhyay, Sujoy Ghosh, Kingshuk Bhattacharjee, Subhankar Chowdhury
DOI:10.4103/ijem.IJEM_322_19  
Context: There is no consensus about the inflection point for 25 hydroxy vitamin D below which the intact PTH level increases. Objective: Determine the relationship/inflection point between 25 hydroxy vitamin D and parathormone levels. Materials and Methods: We performed a population-based analysis on a nonobese cohort (n = 405). Results: Prevalence of vitamin D deficiency was 58.76% (n = 228). Vitamin D insufficiency was found in 34.56% (n = 140). An inverse relationship between 25 hydroxy vitamin D (25(OH)D) and intact PTH exist, but strength of such relationship is weak (r = −0.16, P = 0.018). With respect to the 25(OH)D cut-off of 16 ng/mL by IOM (EAR linked), proportion of persons with high intact PTH was higher in the group with lower 25(OH)D compared with higher 25(OH)D group (P = 0.005) and it was similar for RDA linked cut-off of 20 ng/mL also (P = 0.017). LOWESS method revealed two inflection points at which PTH levels change. A less conspicuous inflection point was found at 32 ng/mL (95% CI, 27–36), which reasonably corroborates with the current cutoff of definition of vitamin D sufficiency, and the second, steeper inflection point was found at 16.5 ng/ml (95% CI, 14.9–18.8) which corroborates with the IOM supported EAR linked value of 25(OH)D level in general population and possible definition of vitamin D deficiency. Conclusions: There are possibly two inflection points at which PTH levels change in relation to 25(OH)D levels
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Prevalence of childhood obesity in an affluent school in Telangana using the recent IAP growth chart: A pilot study p. 428
Naval Chandra, Beatrice Anne, K Venkatesh, G Dharma Teja, Shiva Krishna Katkam
DOI:10.4103/ijem.IJEM_151_19  
Aims and Objectives: To study the prevalence of obesity in children in an affluent school in Hyderabad, Telangana, using the recent Indian Academy of Paediatrics (IAP) growth charts and to compare the same with the Centre for Disease Control and Prevention (CDC) charts. Methods: A cross-sectional study was conducted in an affluent school of Hyderabad in January 2018. After getting appropriate permission, anthropometry measurements of the school children were done. The data were collected from students of Classes 4–10. Each class had three sections. Each section had around 25–30 students. Body mass index (BMI), calculated as weight (kg)/height2 (m2) was used to classify the participants using age- and gender-specific cut-points as per CDC growth charts and the recent IAP charts. Results: A total of 544 students were studied. About 52% were boys (n = 288) and 48% were girls (n = 256). Using the IAP charts, 24.6% were obese and 35.8% were overweight. Using the CDC criteria, the prevalence of obesity and overweight was 15.4% and 26.1%, respectively. The mean BMI in the obese group was 25.6 ± 3.5 kg/m2 and in the overweight group was 21.1 ± 1.9 kg/m2. The prevalence of obesity and overweight was more in girls (obesity 32.8% versus 17.3% and overweight 44.5% versus 28.1%, respectively). The highest prevalence of childhood obesity was seen in the 8–10 years age group. Conclusions: Our study reflects the increased prevalence of obesity and overweight in the adolescent age group, using the recent IAP criteria.
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Presentation, morbidity and treatment outcome of acromegaly patients at a single centre p. 433
Rayees Ul Hamid Wani, Raiz Ahmad Misgar, Moomin Hussain Bhat, Javaid Ahmad Bhat, Shariq Rashid Masoodi, Mir Iftikhar Bashir, Arshad Iqbal Wani
DOI:10.4103/ijem.IJEM_132_19  
Introduction: The management of acromegaly, a rare and potentially curable disease, has undergone a paradigm shift in the past few decades. Many of the treatment modalities recommended for acromegaly are either too expensive or not available in many parts of India. There is a dearth of treatment and outcome data in Indian patients. Aim: Our aim was to study the clinical presentation, hormonal profile, radiology, management, and outcome of the disease at our center. Materials and Methods: Fifty one patients with acromegaly who attended the Department of Endocrinology, SKIMS, Srinagar, between October 2015 and April 2017, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, and outcome were evaluated. Results: The gender distribution was equal with the mean age of 42.3 ± 10.9 years at diagnosis. The majority (41) of the patients had macroadenoma. The most common presenting manifestations were acral enlargement and headache. Hypertension was present in 23, musculoskeletal manifestations in 19, and diabetes mellitus in 11 patients. Surgery was the most common method of treatment. Preoperatively only one patient with micro-adenoma had hypocortisolism, which was persistent in postoperative period, while no patient had preoperative or postoperative hypothyroidism or hypogonadism. As per the present consensus criteria, 23.7% patients achieved disease control (40% with microadenoma and only 19.5% with macroadenoma). The surgical complications occurred in 5 patients–CSF leak in 3 meningitis in 2 patients all except one having macroadenoma. Conclusions: The presentation of disease was generally comparable to that reported in literature. Cure rates were significantly lower than those reported from many large centers.
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Prevalence of end-organ damage, beta cell reserve, and exocrine pancreas defect in fibrocalculous pancreatic diabetes: An Eastern India perspective p. 438
Beatrice Anne, Sujoy Ghosh, Ipsita Ghosh, Sayantan Ray, Subhankar Chowdhury, Deep Dutta
DOI:10.4103/ijem.IJEM_214_19  
Background: Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India. Materials and Methods: Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM). Results: Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD. Conclusion: CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation.
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Long-term response to recombinant human growth hormone therapy in Indian children with growth hormone deficiency p. 446
Monita Gahlot, Alpesh Goyal, Arun K C. Singh, Viveka P Jyotsna, Nandita Gupta, Rajesh Khadgawat
DOI:10.4103/ijem.IJEM_300_19  
Background: Growth hormone deficiency (GHD) remains the most common indication for use of recombinant human growth hormone (rhGH) therapy in clinical practice. However, there is a paucity of studies focusing on long-term response to rhGH therapy in the Indian context. Aim: To determine the response to rhGH therapy and its predictors in children with GHD followed up at a tertiary care center in North India. Materials and Methods: We performed a retrospective review of the records of children with GHD who received rhGH therapy for at least 1 year. The relevant anthropometric, biochemical and radiological data at baseline and follow-up were recorded. Results: A total of 99 children (64 boys, 35 girls; 61 isolated GHD, 38 multiple pituitary hormone deficiency) were studied. The mean (±SD) age and height SDS at treatment initiation were 12.4 (±3.0) years and −4.0 (±1.1) respectively, while median (IQR) serum insulin-like growth factor 1 (IGF-1) and peak growth hormone level on clonidine stimulation were 73 (25-167) ng/ml and 1.1 (0.4-3.6) ng/ml respectively. The height velocity was highest during the first year of treatment (10.6 ± 3.0 cm/year), declining to 8.7 ± 2.7 and 7.9 ± 2.2 cm/year during second and third year, respectively. Over the subsequent years, there was further graded fall in height velocity, declining to 4.8 ± 3.6 cm/year (n = 2) during the seventh year. The height gain during first year was negatively correlated with age at initiation of treatment, baseline height SDS, baseline serum IGF-1 and peak serum GH level on GH stimulation test, while it showed a positive correlation with bone age delay at baseline. Only baseline height SDS was found to have a significant negative correlation with height gain during the second year. Conclusions: This study provides data on long-term response to rhGH therapy and its predictors in Indian children with GHD.
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Is 3–4 weeks required for TSH to rise post thyroidectomy? A prospective study and discussion of its implications on patient care p. 452
Subramanian Kannan, Shriraam Mahadevan, Dhalapathy Sadacharan, K Thirumurthi
DOI:10.4103/ijem.IJEM_166_19  
Context: In patients with differentiated thyroid cancer (DTC), for the purpose of radioiodine (131I) whole-body scan and treatment of remnant, or residual tumor, or metastatic disease, thyroid hormone withdrawal remains the standard approach for raising thyroid-stimulating hormone (TSH) levels to ensure adequate radioiodine uptake. Thyroid hormone is withdrawn 3–4 weeks prior radioiodine therapy (RAIT) to allow the serum-TSH concentration to rise to above 25–30 mU/L. Aims: We studied the time taken for TSH to rise in 40 patients after total thyroidectomy operated for DTC. Settings and Design: Prospective observational study. Methods and Materials: 40 patients with proven differentiated thyroid cancer attending a tertiary care center were studied. Statistical Analysis Used: Data was analyzed by using SPPSS software for windows (version 15, SPSS Inc., Chicago, USA). Results: After performing preoperative TSH in all patients excluding preoperative TSH elevation, it was planned to collect weekly postoperative samples till TSH ≥30. The mean (standard deviation, SD) age of the cohort was 40 (13) years with 35 females (88%) and their mean (SD) preoperative TSH was 3.6 (1.35) mIU/L. At the end of the first week postoperatively, the mean TSH of the cohort was 24.25 (6) with 8 patients (20%) achieving the cut-off of TSH ≥30 mIU/L and 30 patients (75%) achieving TSH level ≥20 mIU/L. At the end of the second week, the mean TSH was 53 (17) with all patients (100%) achieving a TSH level >30 mIU/ml. Conclusions: An iodine whole-body scan can be performed in 10–14 days after total thyroidectomy instead of the usual wait time of 4 weeks. This could improve patient QOL and avoid complications related to prolonged hypothyroidism.
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Demystifying “steroid withdrawal” during remission in Cushing's disease: Is mineralocorticoid replacement the answer? p. 456
Nimisha Jain, K Mahesh Kumar, Naresh Sachdeva, Anil Bhansali, Rama Walia
DOI:10.4103/ijem.IJEM_260_19  
Objective: To study renin-angiotensin-aldosterone axis status (RAAS) in patients of Cushing's disease (CD) at baseline and 6 weeks after curative trans-sphenoidal surgery and evaluate the role of mineralocorticoid replacement in the resolution of “steroid withdrawal syndrome” (SWS). Postoperative RAAS status had not been evaluated in previous studies, although aldosterone levels have been shown to be suppressed during medical therapy with pasireotide and cabergoline. Materials and Methods: This was a prospective, single-center study. Patients with CD, aged between 15–75 years, undergoing curative pituitary surgery were recruited. An 8 am and 11 pm cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline. An 8 am cortisol was measured 6 weeks after surgery to demonstrate remission. Plasma-renin activity and plasma-aldosterone concentration were measured at baseline and 6 weeks after curative surgery. Results: A total of 14 patients (11 female, 3 male) were recruited initially, of these 8 patients completed the study. The plasma-renin activity was not suppressed at baseline and did not rise significantly after surgery (P = 0.717). However, plasma-aldosterone concentration was in the low-normal range at baseline and had risen significantly 6 weeks after surgery (P = 0.013). No difference was noted in subgroups with or without hypertension. Conclusion: Curative pituitary surgery leads to normalization of plasma-aldosterone concentration in patients with CD just 6 weeks after surgery. Hence, mineralocorticoid replacement may not prove beneficial in alleviating the “SWS” in postsurgical CD patients who have achieved remission.
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Role of metformin, Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) receptor agonists, and orlistat based multidrug therapy in glycemic control, weight loss, and euglycemia in diabesity: A real-world experience Highly accessed article p. 460
Deep Dutta, Ritu Jaisani, Deepak Khandelwal, Soumitra Ghosh, Rajiv Malhotra, Sanjay Kalra
DOI:10.4103/ijem.IJEM_185_19  
Background: This study evaluated the real-world weight loss and glycemic outcomes of multidrug therapy (MDT) according to various combinations of metformin, sodium-glucose cotransporter -2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor analogs (GLP1a), and orlistat in diabesity. Methods: Data retrospectively captured from medical records of 2 different centers in New Delhi for patients >35 years-age having prediabetes/diabetes and on at least any one of the 4 above medications with >6-months follow-up was analyzed. Results: In total, 5,336 patient records were screened; 2,442 with prediabetes/diabetes were considered; 1,509 patients who fulfilled all criteria were analyzed. Use of metformin, SGLT2i, sulfonylureas, DPP4i, pioglitazone, orlistat, and GLP1a was 85.35%, 74.95%, 68.32%, 60%, 39.16%, 9.08%, and 4.17%, respectively. However, 365, 970, and 104 patients were on one of 4 concerned medications (Group-1; 24.18%), dual MDT (Group-2; 64.28%), and triple/quadruple MDT (Group-3; 6.89%). Metformin with SGLT2i was most commonly used dual MDT (94.12%). Analysis according to weight-loss quartiles from 558 patients showed 6.9 kg weight-loss in the highest quartile. People losing maximum weight were significantly younger; had higher use of metformin, SGLT2i, GLP1, orlistat, and lower pioglitazone use; greatest HbA1c reduction (–1.3 vs. –0.3; quartile-1 vs. quartile –4; P < 0.001); and significantly higher occurrence of HbA1c<5.7% (16.8% vs. 6.29%; quartile-1 vs. 4; P < 0.001). Patients in Group-3 had the highest baseline BMI and maximum weight loss with highest number of patients with HbA1c<5.7% (19.44% vs. 10.34%; Group-3 vs. Group-1; P < 0.001). Conclusion: Greater weight loss with HbA1c reduction along with a greater number of patients attaining HbA1c <5.7% highlights that MDT is the way forward to tackle diabesity in India.
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Surgical management of primary hyperparathyroidism in the era of focused parathyroidectomy: A study in tertiary referral centre of North India p. 468
Sanjay K Yadav, Saroj K Mishra, Anjali Mishra, Sabaretnam Mayilvagnan, Gyan Chand, Gaurav Agarwal, Amit Agarwal, Ashok K Verma
DOI:10.4103/ijem.IJEM_255_19  
Background: Despite the benefits of focused parathyroidectomy (FPTx), few studies have questioned its durability with lower long-term cure rates than bilateral or conventional parathyroidectomy (CPTx). The objective of this study is to bring out the information on the type of surgical management versus cure rate, recurrence, and role of intra-operative parathyroid hormone (IOPTH) level monitoring of PHPT patients. Material and Methods: This was a retrospective study of all PHPT patients treated at our center based on operative approach (CPTx vs FPTx) or use of IOPTH. Treatment failure was divided into persistent or recurrent disease, based on documentation of hypercalcemia in combination with an inappropriate PTH within 6 months or more of surgery, respectively. Results: Overall, 50.78% patients underwent CPTx and 49.32% FPTx. 29 FPTx were converted to CPTx. Intention to treat analysis between CPTx and FPTx showed that the persistence rate was not statistically different at 2.54% and 4%, respectively (P = 0.98). Furthermore, when the persistence rate was scrutinized by a treatment received (TR) instead of ITT analysis, the persistence rate was higher for the patients who underwent TR-CPTX than for the patients subjected to TR-FPTX (3.22% vs 1.08%) but not significant statistically. We further analyzed the outcome of FPTx with IOPTH (n = 213) and FPTx without IOPTH (n = 28). The outcome did not differ between two groups statistically. Conclusion: FPTx yields a similar success rate as compared to CPTx even in symptomatic PHPT patients and can be performed safely even without intra-opeartive adjunct IOPTH in selected patients.
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Assessment of anthropometric and physical health indicators before and after pituitary surgery in patients with nonfunctioning pituitary adenomas, acromegaly, and Cushing disease p. 473
Cyro G S. Leães, Matheus V Fernandes, Luiza Alves, Bruna Araújo, Carolina G. S L. Rech, Nelson P Ferreira, Luis H T. Rosa, Júlia F S. Pereira-Lima, Miriam C Oliveira
DOI:10.4103/ijem.IJEM_301_19  
Introduction: Individuals with pituitary adenomas may have organic consequences of their disease or therapy, and psychological changes can compromise their quality of life (QoL). This study aimed to determine the anthropometric profile and health indicators of patients with pituitary adenoma before and after pituitary surgery. Methods: Forty-four patients were included in this study. Out of these, 22 patients had nonfunctioning adenomas (50%), 17 acromegaly (38.6%), and 5 patients with Cushing's disease (11.4%). Anthropometric measurements included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Health indicators included body fat percentage (BF%), basal metabolic rate (BMR), maximal oxygen uptake (VO2max), and hand grip strength. Physical activity level (the International Physical Activity Questionnaire [IPAQ]), subjective perception of health, body image (Body Shape Questionnaire), body satisfaction (Stunkard Figure Rating Scale) were used. Results: The mean patient age was 47.2 ± 14.6 years; of which 25 were women (56.8%). Before surgery, 75.0% were overweight or obese, 84.1% had WC with risk of metabolic complications, and 90.0% had WHR with cardiovascular risk. There was a high BF% in 56.4% of cases, low BMR in 65.1%, lower VO2max in 16.2%, and below-average grip strength in 88.6%. Hypopituitary patients had poorer cardiorespiratory fitness. The IPAQ showed reduction in physical activity, and 79.5% of patients were dissatisfied with their body image. Patients with nonfunctioning adenomas had better perception of their health while those with Cushing's disease had more distorted body image. Postoperatively, patients with acromegaly showed improvement in WHR and physical activity level, and patients with Cushing's disease showed improvement in anthropometric variables. Conclusions: These findings emphasize the need for continuous monitoring of this population for anthropometric indicators associated with metabolic and cardiovascular comorbidities as well as body satisfaction.
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Genetic alterations in anaplastic thyroid carcinoma p. 480
M Rashid, Amit Agarwal, Roma Pradhan, Nelson George, Niraj Kumari, M Sabaretnam, Gyan Chand, Anjali Mishra, Gaurav Agarwal, Saroj Kanta Mishra
DOI:10.4103/ijem.IJEM_321_19  
Introduction: Anaplastic thyroid cancer (ATC) is rare but fatal thyroid cancer responsible for majority of thyroid cancer related mortality. ATC may originate de novo or from preexisting differentiated thyroid cancer. Complex interaction between different gene mutation has been suggested to be the main causative factor for origin of ATC in both pathways. Mostly affected pathways are MAP kinase and PI3CA kinase. Hence, we decided to study the frequent alterations in both the pathways in ATC patients. Methodology: Clinico-pathological data of 34 ATC patients were collected retrospectively and Formalin Fixed Paraffin Embedded (FFPE) blocks were taken out for genetic analysis. DNA and RANA were isolated from FFPE tissues. BRAF V600E mutations were screened by RFLP PCR method and confirmed by sequencing. RAS, PI3CA and p53 mutations were checked by sequencing. RET/PTC translocations were screened by Real Time PCR. Results: A total of 34 patients were studied: Mean age 58.6+ 11.6 years with F:M- 1.8:1, 60% had history of goiter. Most common presenting symptom was rapidly growing thyroid mass followed by dyspnea, dysphasia and hoarseness of voice. Extent of disease was local, locoregional and metastatic in 32%, 35% and 33% respectively. 57.6% were euthyroid, 20.5 % were hyperthyroid while functional status were not available in 11.7%. FNAC was suggestive of ATC only in 52.9% cases. 15 (44%) were operated. BRAF V600E mutations were observed in 10/34 (29.4%). Interestingly, all three ATC patients with DTC components had previous history of goiter with rapid increase in size and BRAF V600E mutation, while BRAF was positive only in 7/31 (22.5%) of patients with no DTC component. Mean survival of 3.5 months in BRAF positive cases in comparison to 5.5 months in BRAF negative ATC. RAS mutations were found to be positive in 5.8%, and none had RET-PTC/PI3CA mutations. P53 mutation was positive in 7 patients. 3 patients presented with history of rapid increase in size of previous goiter while rest 4 patients presented with rapidly increasing thyroid swelling of 1 to 3 months. At presentation 2 patients has disease localized to thyroid, 4 has loco-regional disease and one patient presented with metastasis. 5 out of these 7 patients were operated (Total thyroidectomy:3, thyroidectomy with neck dissection:2). Mean survival was 4 months (1-6 months). Conclusion: BRAF V600E was the commonest mutation followed by p53 of the 5 genes tested and BRAF was more common in patients with previous history of longstanding goiter or differentiated thyroid cancer. This provides an indirect evidence of neoplastic transformation of PTC to ATC.
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Genetic profile of Indian pheochromocytoma and paraganglioma patients – A single institutional study p. 486
Gaurav Agarwal, Sendhil Rajan, Ramya C Valiveru, Sonam Tulsyan, Vinita Agrawal, Balraj Mittal, Ghazala Zaidi, Sabaretnam Mayilvaganan, Anjali Mishra, Amit Agarwal, Saroj Kanta Mishra, Eesh Bhatia
DOI:10.4103/ijem.IJEM_163_19  
Background and Aims: Pheochromocytomas (PCCs) and Paragangliomas (PGL) are rare catecholamine producing tumors that may present in sporadic or familial settings. Despite vast strides in understanding of PCC/PGL genetics in the last two decades, there is a dearth of information from India. The aim here is to study the prevalence of genetic mutations in Indian PCC/PGL patients. Settings and Design: Tertiary care academic hospital; prospective study. Methods: 50 histopathologically diagnosed PCC/PGL patients formed the study group. Clinical, biochemical, pathological attributes and outcomes were documented and the phenotype was compared to the genotype. Succinyl dehydrogenase (SDH), Re-Arranged during Transfection (RET), Von-Hippel-Lindau (VHL) and NeuroFibromatosis-1 (NF1) mutations were studied. Additionally, immunohistochemisty for SDHB was also done, and the results compared to mutational analysis of SDH by MLPA (Multiplex Ligation-dependent Probe Activation). Statistical Analysis: Independent samples t-test and Fisher's exact test were used as appropriate. P values ≤0.05 were considered statistically significant. Results: The mean age was 34.3 years. Of the 50 patients, 27 were males and 23 females. 10 patients (20%) in all were detected to have a genetic mutation. 6 patients possessed a RET mutation, while two had VHL mutations. No patient presented with a NF1 mutation. 2 patients had a SDH mutation, and Immunohistochemistry for SDHB correlated with mutational analysis for these patients. Conclusions: The proportion of patients with a familial variant of PCC/PGL is more than what the historic “Rule of Ten” suggests. Our study found that one in five patients have a genetic mutation. PCC/PGL patients with genetic mutations not only require more stringent follow-up, but also screening of family members.
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BRIEF COMMUNICATIONS Top

Slipped capital femoral epiphysis in primary hyperparathyroidism - Case report with literature review p. 491
Geena Susan George, Nishant Raizada, Puthiyaveettil Khadar Jabbar, Jayakumari Chellamma, Abilash Nair
DOI:10.4103/ijem.IJEM_306_19  
Primary hyperparathyroidism is not common in children and adolescents. Association of slipped capital femoral epiphysis and hyperparathyroidism is rare. We report the case of a 15-year-old boy who presented with pain in both hips and limping. He was diagnosed to have bilateral slipped capital femoral epiphysis (SCFE) and underwent cancellous screw fixation of both hips. He had proximal myopathy and pain at multiple points over the chest. Examination revealed an emaciated patient with genu valgum, rachitic rosary, Harrison's sulcus, and bony tenderness over the ribs. Investigations showed PTH-dependent hypercalcemia with serum calcium levels reaching >17 mg/dL and electrocardiography showing QTc shortening. Imaging revealed parathyroid adenoma. The work up for multiple endocrine neoplasia syndromes (MEN) was negative. Serum calcium was controlled by medical management and patient underwent expedited surgery. Postoperatively serum calcium levels normalized and patient became better biochemically and clinically including resolution of skeletal changes on follow-up. Only 12 cases of SCFE associated with primary hyperparathyroidism have been reported worldwide till date including the current case. The literature has been reviewed and it indicates that SCFE is associated with late adolescent age and severe hyperparathyroidism (severe bone disease, higher parathormone, serum calcium, and alkaline phosphatase levels).
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Artificial intelligence/machine learning in diabetes care p. 495
Rajiv Singla, Ankush Singla, Yashdeep Gupta, Sanjay Kalra
DOI:10.4103/ijem.IJEM_228_19  
Artificial intelligence/Machine learning (AI/ML) is transforming all spheres of our life, including the healthcare system. Application of AI/ML has a potential to vastly enhance the reach of diabetes care thereby making it more efficient. The huge burden of diabetes cases in India represents a unique set of problems, and provides us with a unique opportunity in terms of potential availability of data. Harnessing this data using electronic medical records, by all physicians, can put India at the forefront of research in this area. Application of AI/ML would provide insights to our problems as well as may help us to devise tailor-made solutions for the same.
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LETTERS TO THE EDITOR Top

Pituitary adenoma with granulomatous hypophysitis: A rare coexistence p. 498
Sumitra Sivakoti, BN Nandeesh, Anusha S Bhatt, BN Chandramouli
DOI:10.4103/ijem.IJEM_259_19  
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A case of euglycemic diabetic keto acidosis p. 500
MS Aneesh Ghosh
DOI:10.4103/ijem.IJEM_303_19  
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Clinical patterns and linear growth in children with congenital adrenal hyperplasia, a 11 year experience p. 501
Mahmood D Al-Mendalawi
DOI:10.4103/ijem.IJEM_303_19  
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