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Background Late dinner (LD) can worsen the glucose profile in type 2 diabetes (T2D). We assessed the short-term effect of early dinner (ED) on glycemic control in habitual late eaters with uncontrolled T2D. Methodology This interventional, single-arm, within-group trial recruited 10 habitual late eaters with uncontrolled T2D (glycosylated hemoglobin: 7-9% and either fasting plasma glucose (FPG): ≥140 mg/dl or post-prandial plasma glucose: ≥200 mg/dl). They had their usual LD (beyond 22:00 hours) on Days 0-3 and ED (before 20:00 hours) on Days 4-10. Continuous glucose monitoring system (CGMS) parameters, two-hour post-dinner, and fasting (10-hour post-dinner) investigations were analyzed. Bedtime hunger was assessed using a Labeled Magnitude Satiety Scale. Results The mean dinner time was reduced from 22:28 hours to 19:29 hours. CGMS revealed that ED lowered the 10-hour post-dinner incremental area under the curve (22,587.9 ± 5,168.3 mg/dl×mins vs. 15,886.3 ± 4,288.7 mg/dl×mins, P < 0.002), 10-hour post-dinner average blood glucose (ABG) (137.5 ± 9.3 mg/dl vs. 125 ± 7.9 mg/dl, P < 0.002), 24-hour ABG (132.2 ± 7.5 mg/dl vs. 124.8 ± 5.4 mg/dl, P = 0.037), and night mean amplitude of glucose excursion (83.7 ± 5.8 mg/dl vs. 69.3 ± 7.5 mg/dl, P = 0.027). ED also reduced FPG (119.8 ± 7.3 mg/dl vs. 105.2 ± 5.7 mg/dl, P = 0.015), fasting insulin (15.0 ± 4.3 µIU/ml vs. 9.7 ± 2.7 µIU/ml, P < 0.002), and HOMA-IR (4.36 ± 1.2 vs. 2.56 ± 0.79, P < 0.002). Post-dinner glucose, insulin, and inflammatory markers were unchanged. Bedtime hunger increased significantly on Days 4 and 5 but returned to baseline by Day 10. Conclusions A simple modification of dinner time in habitual late eaters with uncontrolled T2D improves FPG, glycemic control, and insulin resistance in the short term., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Chauhan et al.)

Objective: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia)., Results: We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A., Conclusions: We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH., (© 2024 John Wiley & Sons Ltd.)

Pheochromocytoma is a chromaffin cell-derived adrenal medullary tumour and usually presents with paroxysms of hypertension, palpitations, sweating and headache due to excessive catecholamine release. These tumours can also secrete a variety of bioactive neuropeptides and hormones other than catecholamines, resulting in unusual clinical manifestations. We report a female in her mid-30s who presented with fever, anaemia, thrombocytosis and markedly elevated inflammatory markers. The fever profile, including cultures, was negative. Contrast-enhanced CT of abdomen showed a large solid-cystic right adrenal lesion with elevated plasma-free normetanephrine levels suggestive of pheochromocytoma. The fever persisted despite empirical antibiotics and antipyretics. Interleukin-6 (IL-6) levels were elevated (41.2 pg/mL (3-4 pg/mL)). She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: It is postulated that 25(OH)D deficiency is associated with a worse prognosis of COVID-19., Aims: We aimed to find out whether baseline serum 25-hydroxy vitamin D levels were correlated with COVID-19 disease severity or not in Indian population., Settings and Design: It is a prospective observational study., Methods and Material: We prospectively recruited 200 COVID-19-positive adult patients and measured their baseline vitamin D levels on admission and prospectively followed their clinical course for their outcome and correlated the association., Statistical Analysis Used: The continuous data were represented as mean (±SD) or median (IQR), while the categorical data were represented as proportions. Parametric data were analysed using unpaired T -test and ANOVA for two and more than two groups, and for categorical, nonparametric data, Chi-square test were applied. A two-sided P value of <0.05 was considered as statistically significant with 95% confidence interval., Results: Eighty-six per cent (172/200) of patients had hypovitaminosis D (<30 ng/mL). The prevalence of 25(OH) severe deficiency, deficiency and vitamin D insufficiency was 23%, 41% and 22%, respectively. Clinical severity was graded as asymptomatic (11%), mild (14%), moderate (14.5%), severe (37.5%) and critical (22%). Sixty per cent of patients had clinically severe or critical disease requiring oxygen support with eleven per cent ( n = 22) mortality overall. Age ( P : 0.001), HTN ( P : 0.049) and DM ( P : 0.018) were negatively associated with clinical severity. No linear association was found between vitamin D levels and clinical severity. Low vitamin D levels had a significant inverse association with inflammatory markers like neutrophil-lymphocyte ratio (NLR, P : 0.012) and IL-6 ( P : 0.002)., Conclusions: Vitamin D deficiency was not associated with worse outcomes of COVID-19 infection in Indian population., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Context: Glycemic variability plays a major role in the development as well as the progression of cardiovascular disease in diabetes., Aims: We compared the mean plasma glucose and glycemic variability (GV) parameters on and off hemodialysis (HD) in patients with End-Stage Diabetic Nephropathy (ESDN) and End-Stage Renal Disease (ESRD)., Settings and Design: Cross-sectional study., Methods and Material: We included 23 ESDN and 6 ESRD patients who underwent continuous glucose monitoring (CGM) (iPro2) for 6 days and a glucose-free dialysate for 4 hours thrice weekly. EasyGV software was used to calculate the variability parameters {mean glucose, Time in range (TIR), Time above and below range (TAR/TBR), CV (Coefficient of Variation) and MAGE}., Statistical Analysis Used: The quantitative data variables were expressed by using mean and SD. Unpaired t -test was used to compare the two groups. P value <0.05 was considered significant., Results: In the ESDN group, TIR was significantly lower whereas TAR and TBR were significantly higher on HD day. MAGE (101.88 ± 40.5 v/s 89.46 ± 30.0, P < 0.007) and CV (29.41% v/s 21.67%) were higher on HD day. Subjects with pre-HD glucose values ≥180 mg/dl (Group B, n = 24) had a rapid drop with a delayed higher rise in glucose values than those with pre-HD glucose values <180 mg/dl (Group A, n = 27). Ten patients had 13 episodes of hypoglycemia. The CGM parameters were not different in the ESRD group., Conclusions: Targeting a pre- HD glucose value <180 mg/dl could be a good strategy to prevent larger fluctuation during and post HD., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Endocrinology and Metabolism.)

Aims The aim of the study was to evaluate the prevalence and predictors of abnormal glucose tolerance (Diabetes + Prediabetes) and its resolution in Acromegaly., Settings and Design: Retrospective observational study., Methods and Material: Ninety patients with acromegaly and followed up post operatively for 1 year were included. The study cohort was divided into two groups: Group A: abnormal glucose tolerance [AGT: Diabetes + prediabetes (n = 40)] and Group B: normal glucose tolerance (NGT) (n = 50).The impact of the following parameters: age, sex, Waist Circumference(WC), Body Mass Index (BMI), duration of acromegaly, Growth Hormone (GH) levels, Insulin like Growth Factor 1 (IGF1) levels, pituitary tumour size, hypertension, and family history of diabetes as predictors for diabetes were studied pre surgery and post-surgery at 3 months and 1 year affecting glycaemia. Unpaired t-test, chi-square test and binary logistic regression analysis were used for statistical analysis., Results: The prevalence of AGT in our cohort was 44.44% (Diabetes 37.77%, prediabetes 6.66%).Patients with AGT were older (44.2 ± 12.21 years vs. 34.92 ± 11.62 years; p = 0.00040) and had higher WC (in cm) (91.35 ± 7.87 vs.87.12 ± 6.07; p = 0.005) than NGT. Hypertension and family history of diabetes were significantly more frequent in patients with AGT. GH and IGF1 levels were not significantly different between the groups. On binary logistic regression, Sex (p = 0.0105) (OR = 6.0985), waist circumference (p = 0.0023) (OR = 1.2276) and hypertension (p = 0.0236) (OR = 1.632) were found to be significant predictors of AGT in acromegaly. After surgery 42.5% and 62.5% patients became normoglycemic at 3 months and 1 year respectively. On binary logistic regression there were no predictors for achieving normoglycemia at 3 months or 1 year, however the delta change in GH, BMI and tumour size were significant., Conclusions: The prevalence of AGT was 44.44%. Female sex, WC and hypertension were found to be significant predictors of AGT in acromegaly. Post-surgery normoglycemia was achieved in 42.5% at 3 months and 62.5% at 1 year with no predictors for normalisation of AGT., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Obstructive sleep apnea syndrome (OSAS) in association with Type 2 Diabetes Mellitus (DM) may result in increased glycemic variability affecting the glycemic control and hence increasing the risk of complications associated with diabetes. We decided to assess the Glycemic Variability (GV) in patients with type 2 diabetes with OSAS and in controls. We also correlated the respiratory disturbance indices with glycemic variability indices., Methods: After fulfilling the inclusion and exclusion criteria patients from the Endocrinology and Pulmonology clinics underwent modified Sleep Apnea Clinical Score (SACS) followed by polysomnography (PSG). Patients were then divided into 4 groups: Group A (DM with OSAS, n  = 20), Group B (DM without OSAS, n  = 20), Group C (Non DM with OSAS, n  = 10) and Group D (Non DM without OSAS, n  = 10). Patients in these groups were subjected to continuous glucose monitoring using the Medtronic iPro2 and repeat PSG. Parameters of GV: i.e. mean glucose, SD (standard Deviation), CV (Coefficient of Variation), Night SD, Night CV, MAGE and NMAGE were calculated using the Easy GV software. GV parameters and the respiratory indices were correlated statistically. Quantitative data was expressed as mean, standard deviation and median. The comparison of GV indices between different groups was performed by one-way analysis of variance (ANOVA) or Kruskal Wallis (for data that failed normality). Correlation analysis of AHI with GV parameters was done by Pearson correlation., Results: All the four groups were adequately matched for age, sex, Body Mass Index (BMI), waist circumference (WC) and blood pressure (BP). We found that the GV parameters Night CV, MAGE and NMAGE were significantly higher in Group A as compared to Group B (p values < 0.05). Similarly Night CV, MAGE and NMAGE were also significantly higher in Group C as compared to Group D ( p value < 0.05). Apnea-hypopnea index (AHI) correlated positively with Glucose SD, MAGE and NMAGE in both diabetes (Group A plus Group B) and non- diabetes groups (Group C plus Group D)., Conclusions: OSAS has a significant impact on the glycemic variability irrespective of glycemic status. AHI has moderate positive correlation with the glycemic variability., Competing Interests: Competing interestsThe authors declare that they have no competing interests. No conflict of interest., (© The Author(s) 2020.)

Functioning pituitary tumors contribute to significant morbidity and mortality. Proper diagnostic approach and management is essential for optimal outcomes. Prolactinomas, the commonest of these, are the only tumors which can be managed medically. Acromegaly, apart from acral enlargement, can have multiple comorbidities like diabetes, hypertension, and obstructive sleep apnea. The primary treatment is surgical and it can be supplemented by radiotherapy and medications such as somatostatin analogs, growth hormone receptor blockers, or cabergoline. Thyrotropin-secreting tumors are rare and present with hyperthyroidism. Optimal preoperative management followed by surgical resection often leads to cure., Competing Interests: None

A female child with deafness was diagnosed to have neonatal diabetes mellitus at the age of 6 months, on routine evaluation prior to cochlear implant surgery. She presented to us at 11 months of age with diabetic ketoacidosis due to an intercurrent febrile illness. Her haematological parameters showed megaloblastic anaemia and thrombocytopenia. Therefore a possibility of Thiamine Responsive Megaloblastic Anaemia (TRMA) syndrome was considered. She was empirically treated with parenteral thiamine hydrochloride (Hcl). Subsequently, due to the unavailability of pharmacological preparation of oral thiamine Hcl in a recommended dose she was treated with benfotiamine. She had a sustained improvement in all her haematological parameters on oral benfotiamine. The insulin requirement progressively reduced and she is currently in remission for last 2 years. The genetic analysis confirmed the diagnosis of TRMA syndrome. Thus benfotiamine can be considered a new treatment option in management of TRMA syndrome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: To find a single time point during clonidine stimulation test (CST), with highest diagnostic value to rule out growth hormone deficiency (GHD)., Settings and Design: This is a retrospective study of 79 CSTs carried out in a tertiary care center in India., Materials and Methods: A cohort of 79 children with unexplained short stature was divided into two groups: GHD and non-GHD. Any one stimulated growth hormone (GH) level >10 ng/mL was used to rule out GHD. Diagnostic accuracy of not only single time points but also time points in pairs was calculated., Statistical Analysis: The data were analyzed using SPSS statistical software 22.0. Descriptive statistics were used for analyzing demographic data. Mode for time to peak GH was calculated in each group. The specificity and false positive rates at each time point as well as combined time points were determined., Results: Assaying a single sample at 60 min after clonidine resulted in 20.5% false positive tests with specificity of 79.5%. Addition of the 90 min sample increased specificity to 92.3%., Conclusion: The 60 min sample after clonidine stimulation was the best single sample to rule out GH deficiency. Combined sampling at 60 min + 90 min is economical and less cumbersome, with minimal compromise on the specificity., Competing Interests: There are no conflicts of interest.

Competing Interests: Competing interests: None declared.

Context: Primary hypothyroidism has been thought of as an inflammatory condition characterized by raised levels of cytokines such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Depression is also well known to occur in hypothyroidism. Depression is also characterized by elevated inflammatory cytokines. We planned to study whether cytokines play an important part in linking these two conditions., Objectives: (1) To know the prevalence of depression in overt hypothyroidism due to autoimmune thyroid disease. (2) To correlate the levels of inflammatory markers with the occurrence of depression. (3) To study the effect of levothyroxine on inflammatory markers and depression., Materials and Methods: In this longitudinal, case-controlled study, 33 patients with autoimmune hypothyroidism (thyroid-stimulating hormone >10 uIU/ml) were included with 33 age-, sex-, and body max index-matched healthy controls. Individuals were tested for Serum TNF-α, IL-6, high-sensitivity-CRP (hs-CRP). They were assessed for depression using Montgomery Asberg Depression Rating Scale (MADRS) and World Health Organization Quality of Life (QOL) Scale. Patients received L Thyroxine titrated to achieve euthyroidism and were reassessed for inflammatory markers and cognitive dysfunction., Results: Nineteen patients (57%) had mild to moderate depression (MADRS >11). After 6 months of treatment, eight patients (42%) had remission of depression with significant improvement in QOL scores ( P < 0.05). TNF-α, IL-6, and hs-CRP were significantly elevated in patients compared with controls and reduced with therapy but did not reach baseline as controls. The change in inflammatory markers correlated with improvement in QOL scores in social and environmental domains ( P < 0.01)., Conclusions: Primary autoimmune hypothyroidism is an inflammatory state characterized by elevated cytokines which decline with LT4 therapy. It is associated with depression and poor quality of life. Treatment of hypothyroidism results in alleviation of depression in the majority of patients. Similarly, patients with mild to moderate depression should be tested for hypothyroidism as simple treatment may ameliorate their depression and improves MADRS score and QOL., Competing Interests: There are no conflicts of interest.

Introduction: Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population., Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality., Subjects and Methods: Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission., Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality., Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening., Competing Interests: There are no conflicts of interest.

Introduction: The prevalence of autoimmune thyroid disease (AITD) is 10-12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD) with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD) in this cohort helps reduce medication doses., Aim: To screen patients with AITD for the presence of celiac autoimmunity (CA)., Materials and Methods: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase). Those with a positive titer (but < 10 times the upper limit of normal) underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases., Results: Of a total of 280 (182 females and 98 males) patients with AITD screened, 24 (8.6%) turned out to be positive for CA. Of 24 (8.6%), 15 (8.24%) females and 9 (9.18%) males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients., Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD.

Introduction: We present a case of Mikulicz's Disease with hypophysitis. This is a rare clinical association as part of the group of IgG4- related diseases, a group of disorders which can have multiorgan involvement., Methods: A 55-year-old male patient was diagnosed with Mikulicz's disease. He was treated with oral steroids for six months with complete resolution. After two years the patient presented with fatigue, generalised weakness, and weight loss of 11 kg over six months. On evaluation he was found to have panhypopituitarism. MRI pituitary revealed homogeneously enlarged, well enhancing pituitary with thickening of the stalk. Serum IgG4 levels were significantly elevated. The patient was treated with methyl prednisolone pulse therapy followed by oral steroids for three months. He developed diabetes insipidus after starting steroid therapy. There was a significant resolution in the enlargement of the pituitary and stalk thickening at three months., Results: The clinical, biochemical, and radiological findings of hypophysitis associated with Mikulicz's disease are presented with a brief review of literature., Conclusions: IgG4-related diseases are rare and have recently been recognised as a cause of hypophysitis. They can have multiorgan involvement. A high index of suspicion is required for clinching this rare diagnosis, which can be confirmed by measurement of serum levels of IgG4. Steroid therapy can reverse the inflammatory changes in IgG4 hypophysitis. (Endokrynol Pol 2016; 67 (6): 622-626).

The article is one in the series of articles related to glycaemic management in festivals across all religions in India. The article discusses issues in glycaemic management among Parsi culture, which represent a small but ever important group of Indian population.

Background: Van Wyk-Grumbach syndrome is a rare complication of prolonged untreated primary hypothyroidism characterized by precocious puberty and enlarged multicystic ovaries. High index of suspicion and timely diagnosis can prevent unnecessary surgical procedures because this condition can be reversed with thyroid hormone supplementation., Case: A 12-year-old girl underwent abdominal ultrasonography for recurrent abdominal pain, which showed bilateral asymmetrical enlargement of ovaries. Ovarian tumor markers were negative. Subsequent evaluation revealed severe hypothyroidism. Patient was started on levothyroxine and both ovaries showed regression to normal volume within 1 year of normalizing thyroid function tests., Summary and Conclusion: Prompt and adequate medical management with levothyroxine can completely reverse ovarian enlargement associated with hypothyroidism., (Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)