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Objective: Thyrotoxic periodic paralysis is a rare manifestation of thyrotoxicosis. Here, we describe the clinical and biochemical features and treatment outcomes of this disorder., Methods: This retrospective study was conducted at a tertiary care centre in southern India. The clinical and biochemical features, treatment received, and therapeutic outcomes of all patients with thyrotoxicosis and acute flaccid paralysis without any other identifiable causes (cases for the study) were compared with an equal number of consecutively selected patients who presented with thyrotoxicosis but without features paralysis (controls for the study) during the same period., Results: A total of 41 cases and controls were included in this study. The proportion of males was 92.6 % and 43.9 % among the cases and controls, respectively. The mean age was 32.8 (±7.6) years [cases] and 39.7 (±11.3) years [controls]. Among cases, 20 % of patients presented without clinical thyrotoxic features. Graves' disease was the most common aetiology of thyrotoxicosis in both groups (92.6% of cases and 87.8% of controls). The prevalence of goitre was significantly higher among controls (90.2 %) than among cases (53.7 %). The mean serum potassium, free T4 and Total T3 levels were significantly lower in the cases, than in the controls. Among these cases, two patients had an additional aetiology for persistent hypokalaemia, likely Gitelman's syndrome., Conclusion: This is one of the largest series of thyrotoxic periodic paralysis cases in India. Among subjects with thyrotoxicosis, serum potassium, free T4, and total T3 levels were significantly lower in those with periodic paralysis than in those without.

Abstract: Medullary nephrocalcinosis is an uncommon manifestation of primary hyperaldosteronism (PHA) and the exact etiology of this association is still debated. Here we report three cases of PHA with medullary nephrocalcinosis and how medullary nephrocalcinosis in one patient led to misdiagnosis as renal tubular acidosis (RTA). Although PHA and RTA can share overlapping symptoms, careful evaluation of clinical presentation, biochemical tests, and imaging studies are essential to differentiate between the two conditions and ensure appropriate management. Also, awareness of this uncommon manifestation of PHA is essential to avoid misdiagnosis as tubulopathy, as this may delay the treatment., (Copyright © 2024 Copyright: © 2024 Journal of Postgraduate Medicine.)

Introduction: Thyroid storm is an uncommon but life-threatening presentation of thyrotoxicosis with a mortality rate of 10%. Our objective was to study the demographics, clinical and biochemical characteristics, and outcomes of inpatients diagnosed with thyroid storm in the Indian context., Methods: This retrospective study was conducted by analysing the institutional electronic medical records (EMR) of all patients admitted with thyroid storm from 2004 to 2020 with a Burch-Wartofsky score (BWS) of ≥45., Results: Thirty-five patients with a BWS ≥45 were included, of whom 71.4% were women, with a mean age of 44.9 ± 10.2 years. 43% did not have any prior history of thyrotoxicosis. Graves' disease was the most common underlying aetiology (71.4%), followed by toxic multinodular goitre (14.3%). Cardiovascular (94.3%) and gastrointestinal-hepatic dysfunction (88.6%) were the most common clinical manifestations. Features of Central nervous system (CNS) dysfunction were seen in only 42.3% of patients diagnosed with a thyroid storm. The Japanese Thyroid Association (JTA) criteria diagnosed only 26 patients (74.3%) with "definite" thyroid storm. The mortality rate was 8.6%, and all three patients expired within 48 hours of admission., Conclusion: Nearly one in every two patients with thyroid storm had previously undiagnosed thyrotoxicosis. Toxic multinodular goitre is a notable aetiology in Indians. Features of CNS dysfunction, considered relatively specific for thyroid storm, were less prominent in our series. The JTA criteria might alter the classification of some patients diagnosed with a thyroid storm, when compared to the BWS score due to fewer CNS features among Indian patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Endocrinology and Metabolism.)

Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India., Methods: The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived., Results: Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m 2 , women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy., Conclusions: Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality., Isrctn Registration Number: 13432279., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Vasan, Alex, Roy, Gowri, Sinha, Suresh, Philip, Kochumon, Jaiswal, Arulappan, Ramakrishnan, Sachdev, Tandon, Thomas, Jebasingh, Osmond, Karpe, Bhargava, Antonisamy, Prabhakaran, Fall and Thomson.)

Delayed hyponatraemia(DH) is a common complication following trans-sphenoidal surgery(TSS) for pituitary tumour. We evaluated the prevalence of DH following TSS, and assessed the factors associated with DH, including early post-operative diabetes insipidus(EPDI). This retrospective study included 100 TSS for pituitary tumours in 98 patients, over a period of 26 months. Subjects were divided into two groups: those who developed hyponatraemia and those who did not develop hyponatraemia, during post-operative days 4 to 14. The clinical characteristics and peri-operative parameters were compared between the two groups, to identify factors predicting DH. The mean age of the patients was 42.0±13.6 years, 58 (59%) were females and 61 (61%) had functional tumours. Thirty-six patients(36%) developed DH following TSS of whom majority(58%) were diagnosed on post-operative days 7 and 8; only 8/36 (22%) were symptomatic. Syndrome of inappropriate antidiuretic hormone secretion(SIADH) was found to be the most common aetiology of DH. On logistic regression analysis, intra-operative cerebrospinal fluid(CSF) leak (OR 5.0; 95% CI 1.9-13.8; p=0.002), EPDI (OR 3.4; 95% CI 1.3-9.2; p=0.015) and peri-operative steroid use (OR 3.6; 95% CI 1.3-9.8; p=0.014) were found to be significantly associated with DH. In conclusion, EPDI, intra-operative CSF leak and peri-operative steroid use were significant predictors of DH. EPDI predicts moderate to severe hyponatraemia with 80% specificity but has low sensitivity(47%). As most patients have asymptomatic hyponatraemia, serum sodium measurement on POD 7 to 10 would be helpful to identify DH in patients at increased risk., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: DPM is supported as a fellow of the Wingara Mura Leadership Program, University of Sydney and received a grant from The University of Sydney, Charles Perkins Centre Aboriginal and Torres Strait Islander Wingara Mura Leadership Academy Early to Mid-Career Research Seeding Grant; associated manuscript processing charges will be costed to these funds. LM-B received a NHMRC Australia grant to their university for salary and research projects, including Global Alliance for Chronic Diseases (GACD), and was a board member for the Australian Diabetes Society 2014–2021. GSG received consulting fees from the Australian Department of Health and NSW Health for their role on a national advisory panel review about medications for smoking cessation and clinical work in refugee health; had unpaid leadership roles for the Global Alliance for Chronic Disease and Global Implementation Society; and received grants to their institution for research into Indigenous smoking cessation from the Australian Department of Health, NHMRC, GACD and Cancer Australia and Cure Cancer Australia. AGT received grants from NHMRC Australia (grant numbers 1143155, 1171966, and 1182071) and a Medical Research Future Fund (Australian Government; grant number 2015976) while writing the grant; funds were made to their institution. JAA received a NHMRC Australia, GACD grant for the Breathe Easy, Walk Easy, Lungs for Life (BE WELL) project and grant funds used to attend annual GACD scientific meetings. KSL received NHMRC Centre of Research Excellence (application number 1117198) and Ideas grant (application number 1183744). MC received a GACD/Canadian Institute of Health Research (CIHR) grant to their institution. MA received a CIHR grant for a research programme with Indigenous communities (commercial tobacco harm reduction) and is a Pallium Canada board member. FGo-Sm received Global Alliance for Chronic Diseases-Health Research Council funding to their institution in 2017 (reference: 17/705). DM received a postgraduate scholarship from the National Health and Medical Research Council (NHMRC), Australia while preparing this manuscript; was an unpaid member of Australian Diabetes Association's Clinical Advisory Sub-Committee and the Northern Territory Maternal and Neonatal Network. These institutions had no role or influence on the content of the manuscript. All other authors declare no competing interests. We acknowledge all members of the GACD Indigenous Population Working Group for their advice, guidance and support preparing this statement. This statement reflects the perspectives of the contributing authors of the GACD Indigenous Populations Working Group, but it does not necessarily reflect the perspective of GACD and the funding agencies.

Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research., (© 2022. The Author(s).)

Introduction Obesity being a global epidemic, currently has several adverse health outcomes. Weight stigma is a significant barrier to delivering quality services and also impairs clinical progress. We intended to study the association of stigma with demographic and clinical variables in obese patients to identify the obstacles in treatment-seeking, so stigma could be adequately addressed to improve clinical outcomes. Methods This study was a retrospective chart review in a Bariatric clinic in a tertiary care hospital. The weight self-stigma questionnaire (WSSQ) was routinely used in the clinic. Demographic and clinical data were collected for 146 obese patients.  Results Female patients (73%) had higher stigma scores. The mean total stigma score was 41.6(SD 3.83), the total self-devaluation score was 21.88(SD 2.10), total fear of enacted stigma was 21.26(SD 2.33). Multivariate analysis revealed an association between stigma with multiple dysfunctional eating patterns like bingeing, overeating, and grazing (Adjusted aOR 3.86, 95% CI- 1.66-8.96) and psychiatric diagnosis (adjusted aOR 3.00, CI- 1.25-7.17). Conclusion This study found an association between stigma and certain clinical variables that maintain and worsen obesity and comorbid psychiatric diagnoses. This highlights the importance of an assessment of mental health and stigma in general practice when dealing with patients with obesity. Treating the underlying psychiatric comorbidities and addressing unhealthy eating behaviors can help reduce self-stigma. Stigma is a barrier to treatment-seeking that needs to be addressed in the community., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jiwanmall et al.)

Background Dapsone treatment may reduce HbA1c levels in patients with diabetes. Aims To assess the prevalence and characteristics of dapsone associated reduction of HbA1c in patients with Hansen's disease. Methods A retrospective data review of outpatient and inpatient charts of consecutive patients with Hansen's disease and type 2 diabetes mellitus was conducted over two years from January 2014 to January 2016 at the Department of Dermatology, CMC Vellore, India. Results Of the 245 patients with a confirmed diagnosis of Hansen's disease who were on oral dapsone 100 mg/day as part of their treatment regimen, 49 patients had diabetes and were eligible for the study as per predetermined inclusion criteria. Of these, 35 subjects (71%) had an HbA1c discordantly lower than the corresponding mean plasma glucose levels. Patients with discordant HbA1c levels were more likely to be male and to have a higher RBC mean corpuscular volume (MCV). A greater reduction in HbA1c levels was seen during the initial 3 months of therapy of dapsone treatment. Limitations The small sample size and retrospective design were limitations of this study. Also, we did not analyze the role of methemoglobinemia or the utility of alternative measures of glycemic control in these patients. Conclusion We describe a high prevalence of dapsone associated inappropriate HbA1c lowering in type 2 diabetes mellitus patients. This may have serious implications for the management of diabetes in patients on therapy with dapsone.

Background: Most of the patients suffering from diabetes develop Sensory neuropathy which proceeds with development of painful neuropathy. This can lead to formation of ulcers in later stages. Currently, available Quantitative Sensory Testing (QST) devices take more time to perform and are expensive. NEURO TOUCH is such device which combines four parameters of QST in one unit. Its portable, battery operated and handy device with real time display of results along with data storage and data transfer facility. It can perform tactile sensation threshold, vibration and thermal testing threshold along with skin temperature measurement. This study was undertaken to establish the diagnostic validity, reproducibility and repeatability for early detection of peripheral neuropathy., Methods: A total of 317 subjects were recruited for QST assessment with NEURO TOUCH; Tactile threshold sensation, vibration perception and thermal threshold testing along with skin temperature. A subset of 30 subjects in each group were considered for repeatability and reproducibility test., Results: The mean difference for vibration perception threshold was 0.6 when compared with gold standard device. Regarding the cold and warm perception threshold the mean difference was 1.1 and 2 °C respectively when compared with gold standard device. For skin temperature measures there was a mean difference of 1.2 °C with respect to standard device., Conclusions: The NEURO TOUCH device was easy-to-use, compact and provided an efficient multimodality approach which can help for screening of peripheral neuropathy patients with type 2 diabetes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Context: Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge., Objective: With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes., Methods: This case series of 11 patients who were positive for WFS1 variants were identified with next-generation sequencing (NGS)-based screening of 17 genemonogenic diabetes panel. These results were further confirmed with Sanger sequencing., Results: 9 out of 11 patients were homozygous for pathogenic/likely pathogenic variants in the WFS1 gene. Interestingly, 3 of these probands were positive for the novel WFS1 (NM_006005.3): c.1107_1108insA (p.Ala370Serfs*173) variant, and haplotype analysis suggested a founder effect in 3 families from Southern India. Additionally, we identified 2 patients with young-onset diabetes who were heterozygous for a likely pathogenic variant or a variant of uncertain significance in the WFS1 gene., Conclusion: These results project the need for NGS-based parallel multigene testing as a tool for early diagnosis of WFS and identify heterozygous WFS1 variants implicated in young-onset diabetes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Early onset hypertension is one of many major medical disorders that have evolved over the current millennium across both the developing as well as the developed world. Though various mechanisms have been postulated for the evolution of hypertension in these individuals, one of the most relevant ones is that of low birth weight and its association with hypertension. Barker from historical evidence has postulated the foetal onset adult disease (FOAD) or Thrifty phenotype on Low Birth Weight (LBW) associated hypertension. Later, Brenner highlighted the importance of low nephron mass and future implications. In this review we elaborate the mechanisms that were postulated for LBW-related hypertension as well the potential antihypertensive therapy that may be used in these individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jebasingh and Thomas.)

Introduction: There is dearth of data on prevalent vertebral fractures in perimenopausal women in India and limited literature on the utility of FSH, AMH and estradiol in evaluating bone health them. The objective was to study the prevalence of vertebral fractures (VF) and to assess the utility of FSH, estradiol and AMH in predicting them in Indian perimenopausal women MATERIALS AND METHODS: It was a cross-sectional study. Perimenopausal women aged 40-49 years underwent assessment for prevalent vertebral fractures, bone mineral density (BMD) and trabecular bone score (TBS). Utility of serum FSH, estradiol and AMH in predicting prevalent vertebral fractures was also assessed., Results: A total of 300 perimenopausal women with mean (SD) age of 43.2 (2.8) years was recruited and 18% had moderate-severe VF. Mean (SD) serum AMH was lower in perimenopausal women with VF as compared to those without fractures [0.752 (0.594) vs 1.023 (0.704) P = 0.006]. AMH showed significant positive correlation with TBS (r = 0.3; P < 0.001) and BMD at the femoral neck (r = 0.2; P < 0.001) and lumbar spine (r = 0.3; P < 0.001).On ROC analysis, AMH demonstrated good performance in predicting prevalent VF with an AUC of 0.800 (95% CI 0.705-0.880) and a sensitivity of 85% and specificity of 60% at a cut-off of 1.12 ng/mL. On an exploratory multivariate logistic regression analysis, AMH significantly predicted prevalent fractures with an adjusted OR (OR) of 1.85 (95% CI: 1.03-3.00; P = 0.04). The performance of FSH and estradiol in predicting prevalent fractures was sub-optimal., Conclusion: About one-fifth of the study subjects had prevalent vertebral fractures. AMH may be a menstrual cycle independent biomarker and may reflect bone loss in perimenopausal women. Further prospective studies are needed to validate these findings., (© 2021. The Japanese Society Bone and Mineral Research.)

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Aims: The measuring tools used for assessment of neuropathy include various questionnaires, monofilament testing, Biothesiometry and the gold standard test, nerve conduction studies (NCS). This study aims to evaluate the diagnostic accuracies of Michigan Neuropathy Screening Instrument (MNSI), Biothesiometry, Semmes Weinstein Monofilament (SWMF), Sural Radial Amplitude Ratio (SRAR) and minimal F wave latency as compared to conventional NCS and arrive at a simple diagnostic algorithm for early detection of Diabetic Peripheral Neuropathy (DPN)., Methods: In a cross-sectional observational study on 48 Type 2 diabetes mellitus patients, MNSI, Biothesiometry, SWMF and NCS including F waves and SRAR were done and diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) calculated taking NCS as gold standard., Results: MNSI, Biothesiometry, SWMF, SRAR and minimal F wave latency had a sensitivity of 64.3%, 78.6%, 14.3%, 100% and 78.6% and specificity of 67.7%, 52.9%, 94.1%, 23.53% and 76.47% respectively, with reference to NCS. Based on combined sensitivities and specificities, we arrived at a simple algorithm for early diagnosis of DPN, which showed that DPN could either be diagnosed or ruled out in 75% of the patients by a combination of the Biothesiometry, SRAR and left lower limb minimal F wave latency results., Conclusions: In the setting of an outpatient, multidisciplinary diabetic clinic, simple tests such as questionnaires, monofilament testing and biosthesiometer could be performed with greater ease while considering NCS as the gold standard. This algorithm, combining Biothesiometry, SRAR and left lower limb minimal F wave latency would be less time consuming and help in early diagnosis of DPN., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Endocrinology and Metabolism.)

Background: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers., Methods: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots., Results: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry., Conclusion: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Lower serum 25-hydroxyvitamin D [25(OH)D] is associated with greater adiposity and adverse cardiometabolic risk profile. The evidence is inconsistent among South Asian Indians. We aimed to examine associations between 25(OH)D and cardiovascular (CVD) risk markers in a rural and urban cohort from South India., Subjects/methods: In this cross sectional study, 373 individuals (men, n = 205) underwent detailed CVD risk marker assessment including anthropometry [body mass index (BMI), waist, (WC) and hip circumferences (HC)], body composition analysis using dual energy x-ray absorptiometry (DXA), blood pressure and biochemical analysis (glucose, insulin and lipids). The distribution of CVD risk factors were compared across serum 25(OH)D levels, stratified as deficiency (<20 ng/ml), insufficiency (20 to 29 ng/ml) and normal (≥30 ng/ml) levels. Multiple regression analysis, adjusting for potential confounders, was used to study associations of 25(OH)D with adiposity and cardiometabolic traits., Results: The mean and standard deviation (SD) of age, BMI and 25(OH)D levels were 41.4 (1.1) years, 25.5 (4.8) kg/m2 and 23.4 (10.4) ng/ml respectively. The prevalence of 25(OH)D deficiency was 39.9% in this cohort. Individuals in the 25(OH)D deficiency category had significantly higher mean (SD) BMI [26.6 (5.1) kg/m2], waist circumference [89.9 (12.5) cm] and total fat mass [20.6 (7.9) kg] compared with the Vitamin D sufficient group [BMI: 24.0 (4.4); WC 84.7 (12.0); total fat mass: 15.2 (6.8)]. Significantly inverse associations were observed with DXA measured total and regional fat depots with 25(OH)D levels, while anthropometric indices of adiposity showed significant inverse association only in women. After adjusting for total fat mass, no significant associations were observed between 25(OH)D and the cardiometabolic traits., Conclusions: Our results confirm that lower 25(OH)D is independently associated with both total and regional adiposity, but not with cardiometabolic traits, in this population., Competing Interests: The authors have declared that no competing interests exist.

Objective: Graves disease (GD) and the toxic phase of subacute thyroiditis (SAT) have similar clinical and biochemical presentations, and differentiating them requires sophisticated investigations. Since thyroid hormones have been noted to affect all hematologic cell lines, we have used the platelet lymphocyte ratio (PLR)-an index usually utilized in inflammatory or malignant disorders-to compare patients with and without thyrotoxicosis and to analyze its use in distinguishing between patients with GD and SAT prior to therapy., Methods: This was a cross-sectional study conducted in the Department of Endocrinology, Christian Medical College, Vellore, India. During the study period, 800 patients with features of thyrotoxicosis visited the outpatient clinic. Those who had thyroid radioiodine ( 131 I) uptake (RAIU) study and complete blood count (CBC) at diagnosis were included (N = 500). Based on the RAIU values, these were divided as GD (n = 354) and SAT (n = 146). Baseline characteristics, thyroid function tests, and components of the CBC and PLR were obtained. The data were compared with a group of 250 matched euthyroid controls. Analyses were performed using SPSS version 21.0 software., Results: PLR showed significant reductions in both GD and SAT patients when compared to euthyroid controls (P = .01), with greater reductions seen in GD than SAT (74.5 ± 19 vs. 84.4 ± 26; P = .01). Using receiver operating characteristic analysis of PLR, an optimal PLR cut-off of 70.4 was found to differentiate GD from SAT with a sensitivity of 86% and specificity of 74%., Conclusion: PLR can be used as a novel surrogate marker to differentiate between patients with GD and SAT prior to therapy, especially in resource-limited settings., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

Aim: This study aimed to assess efficacy and safety of evogliptin versus sitagliptin, when added to background metformin therapy in Indian patients with uncontrolled type 2 diabetes., Method: Overall, 184 patients with uncontrolled type 2 diabetes (7% ≤ HbA 1c  < 10%) receiving ≥8 weeks of stable metformin monotherapy (≥1 g/day), were randomized to receive add-on treatment (evogliptin 5 mg or sitagliptin 100 mg) for 24 weeks. Primary endpoint was change in HbA 1c from baseline to 12 weeks (non-inferiority margin: <0.35)., Results: Mean reductions in HbA1c at 12 weeks in evogliptin- and sitagliptin-treated patients were -0.37 (1.06) and -0.32 (1.14), respectively. The adjusted mean difference between treatment groups was -0.022 (95% CI: -0.374, 0.330; P = 0.901), that demonstrated non-inferiority. Reductions in FPG and PPG were similar between evogliptin and sitagliptin at 12 and 24 weeks. Changes in body weight were comparable between the treatment groups. Patients achieving target HbA 1c  < 7.0% (evogliptin, 26.7% vs. sitagliptin, 20%) was almost equal in both groups. Treatment-emergent adverse events occured in 52 patients (evogliptin, 25% and sitagliptin, 31.5%) and were generally mild., Conclusions: Evogliptin was non-inferior to sitagliptin in HbA 1c reduction. It effectively improved glycemic control and was well tolerated in type 2 diabetes patients inadequately controlled by metformin alone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Stage 0 Acute Charcot's Neuroarthropathy (ACN)in Type 2 Diabetes patients is a challenging diagnosis with subtle clinical features and normal appearing plain radiographs of the affected foot. Delay in diagnosis can lead to progression of disease and irreversible deformities. There is a paucity of data on Stage 0 ACN from India. The aim of this study was to assess clinical and radiological characteristics and treatment outcomes in Indian Type 2 Diabetes patients with Stage 0 ACN., Materials and Methods: A comparative, case-control study was carried out amongst patients attending the Integrated Diabetes Foot Clinic at a tertiary care South Indian hospital. During the 3-year study period, a total of 1811 patients with Type 2 Diabetes Mellitus were screened. Of these, n = 10 patients with stage 0 ACN Charcot's arthropathy were identified based on clinical features and MRI imaging of the foot for confirmation of diagnosis. These were compared with an age and duration of diabetes-matched group of n = 50 patients without ACN as controls., Results: Our study identified 10 patients (0.5%) with Stage 0 Acute charcot neuroarthropathy (ACN) in the study population. Those with ACN had higher BMI, poorer glycaemic control and greater degree of peripheral neuropathy (p < 0.05). Clinically relative lack of pain and infrared thermometric temperature difference >2 °C in the affected foot were the most significant findings, while MRI foot was useful in early detection of active and severe stage 0 disease. Total contact cast was the preferred initial offloading modality, with delay in initiating complete immobilization leading to worse outcomes., Conclusions: This is the first study to highlight the characteristic features of Stage 0 ACN in Indian Type 2 Diabetes patients. Thorough clinical evaluation, infrared thermometry and radiological findigs on MRI foot leads to early disease detection. Complete offloading, preferably with total contact casts can prevent disease progression and chronic deformities., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Context: The size and morphology of the adrenal glands are affected by several physiological and pathological conditions. Radiologists need to be aware of the normal thickness of adrenal gland to accurately assess patients with suspected adrenal pathology. However, there is limited data on the normal size of the adrenal glands. Moreover, this has not been studied in our population., Aims: To study the normal thickness of adrenal gland on computerized tomography (CT) in Indian adult population., Settings and Design: Retrospective study in a tertiary care hospital in Southern India., Subjects and Methods: Our study included 586 adults who underwent a CT abdominal angiogram over 15 months, and excluding patients with clinical or imaging evidence of adrenal disease. The measurements made included: the maximum thickness of the body, medial and lateral limbs, measured perpendicular to the long axis., Results: The median age was 51 (range: 18-85) years. The mean maximum thickness of the adrenal body, medial, and lateral limbs were 7.2 ± 1.8, 4.1 ± 1.1, and 4.3 ± 1.1 mm on the right side and 8.8 ± 1.9, 4.7 ± 1.1, and 4.9 ± 1.3 mm on the left. The cumulative thickness of the body and the limbs were 15.6 ± 3.7 mm and 18.4 ± 3.8 mm on the right and left sides, respectively. There was a statistically significant difference in all the measurements between the right and left adrenal glands (all P values = 0.000) and between men and women, being larger in men ( P value <0.05). Among our patients 27% had at least one adrenal gland body measuring ≥10 mm in thickness., Conclusions: Our study has defined the normal range of adrenal gland thickness in an Asian Indian adult population, which may be used as a baseline reference for future research and as a reference for radiological reporting., Competing Interests: There are no conflicts of interest.

A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature.

Introduction: Symptomatic skeletal disease in primary hyperparathyroidism is over 30 times more common in India compared to the west. The classical "brown tumour" is commonly seen with the major sites being ends of long bones, the pelvis and ribs. Facial involvement is rare and, when present, usually involves the mandible., Case Report: We report a 68-year-old gentleman with a rare initial presentation of primary hyperparathyroidism with bilateral maxillary brown tumours., Discussion and Conclusion: Successful parathyroid surgery resulted in a regression in the tumours. The report highlights the need to consider primary hyperparathyroidism in the initial differential diagnosis of bony lesions of the jaw.