Indira Maisnam

Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: An open label randomized prospective study from Eastern India

Vitamin-D supplementation in vitamin-D insufficient/deficient prediabetes individuals is associated with significantly lower progression to diabetes (6/55 vs. 13/49; p=0.04) and higher reversal to normoglycemia (23/55 vs. 10/49; p=0.02), associated with decreased insulin resistance and systemic inflammation (TNFα and IL6). Baseline vitamin-D and 2h blood glucose independently predicted progression to diabetes.

Tumor necrosis factor alpha −238G/A (rs 361525) gene polymorphism predicts progression to type-2 diabetes in an Eastern Indian population with prediabetes

Prediabetes (IPD; n=122) and normoglycemic individuals (n=100) underwent assessment of polymorphisms of TNFα (-238, -308) and IL6 (-174). After 27.25±5.64 months, 16 IPD had reverted to normoglycemia and 18 progressed to diabetes. TNFα -238AA/GA genotypes were significantly more common in IPD, had higher TNFα, higher progression to diabetes and lower reversal.

Increased Soluble TNF Receptor-1 and Glutathione Peroxidase may Predict Carotid Intima Media Thickness in Females with Cushing Syndrome

OBJECTIVE Cardiovascular events are the most common cause of mortality in Cushing syndrome (CS). This study aimed to evaluate the impact of novel factors on atherosclerosis in endogenous CS. METHODS A total of 22 female patients with CS and 33 normal female controls underwent evaluation of fibrinogen, high-sensitivity C-reactive protein (hsCRP), inflammatory cytokines (interleukin [IL]-6, IL-1β, soluble tumor necrosis factor receptor [sTNFR]-1, and sTNFR2), glutathione peroxidase (GPx; measure of oxidative stress), carotid intima media thickness (CIMT; a measure of atherosclerosis), and percent change in flow-mediated vasodilation (%FMV) of the brachial artery, a measure of endothelial dysfunction. Stepwise multiple linear regressions were done after adjusting for variables in models 1 through 3 to evaluate their role in predicting CIMT and %FMV. Model 1 consisted of age and body mass index (BMI). Model 2 consisted of model 1 plus blood pressure (BP), fasting blood glucose (FBG), and 2-hour postglucose blood glucose (2hPGBG). Model 3 consisted of model 2 plus triglycerides and low- and high-density lipoprotein. RESULTS Females with CS had significantly higher BMI, BP, FBG, 2hPGBG, total cholesterol, triglycerides, fibrinogen, IL-6, IL-1β, sTNFR1, and GPx. CIMT and %FMV were significantly higher and lower, respectively, in CS patients. Regression analyses revealed sTNFR1 to be a consistent predictor of CIMT after adjusting for model 1 (β = 0.656; P = .004), model 2 (β = 0.571; P = .047), and model 3 (β = 0.683; P =.026). GPx was a predictor of CIMT after adjusting for model 1 (β = 0.565; P = .033) and model 3 (β = 0.756; P= .038). CONCLUSION This study highlights increased CIMT and endothelial dysfunction in CS, associated with an altered inflammatory milieu. sTNFR1 and GPx may predict CIMT in females with CS.

Syndrome of Extreme Insulin Resistance (Rabson-Mendenhall Phenotype) with Atrial Septal Defect: Clinical Presentation and Treatment Outcomes

Syndrome of extreme insulin resistance (SEIR) is a rare spectrum disorder with a primary defect in insulin receptor signalling, noted primarily in children, and is often difficult to diagnose due to the clinical heterogeneity. SEIR was diagnosed in an adolescent girl with facial dysmorphism, exuberant scalp and body hair, severe acanthosis, lipoatrophy, dental abnormalities, and short stature (Rabson-Mendenhall phenotype). She had elevated fasting (422.95 pmol/L) and post-glucose insulin levels (>2083 pmol/L). Total body fat was decreased (11%; dual-energy X-ray absorptiometry). Basal growth hormone (GH) was increased (7.9 μg/L) with normal insuline-like growth factor 1 (37.6 nmol/L) suggestive of GH resistance. She had fatty liver and polycystic ovaries. Echocardiography revealed ostium secundum type atrial septal defect (ASD). Blood glucose normalized with pioglitazone (30 mg/day). Delayed development, severe insulin resistance, mild hyperglycemia, absence of ketosis, and remarkable response of hyperinsulinemia and hyperglycemia to pioglitazone which persisted even after 1 year of diagnosis are some of the notable features of this patient. This is perhaps the first report of occurrence of congenital heart disease (ASD) in a patient of SEIR (Rabson-Mendenhall phenotype). This report highlights the clinical features of SEIR and the role of insulin sensitizers like pioglitazone in the management of such patients. Conflict of interest:None declared.

Isolated Cushing’s Syndrome in Early Infancy Due to Left Adrenal Adenoma: An Unusual Aetiology

Bilateral macronodular adrenocortical disease as a part of McCune Albright Syndrome (MAS) is the most common cause of endogenous Cushing’s syndrome (CS) in infancy. Adrenocortical tumors causing CS in infancy are extremely rare. We report the case of a girl with CS who presented at age 4 months with obesity and growth retardation. Her 8 am paired cortisol and adrenocorticotropic hormone levels were 49.3 μg/dL and <1 pg/mL, respectively with non-suppressed serum cortisol (41 μg/dL) on high-dose dexamethasone suppression test. Abdominal computed tomography scan demonstrated a 5.3x4.8x3.7 cm homogenous left adrenal mass with distinct borders. Laparotomy following pre-operative stabilization with ketoconazole 200 mg/day, revealed a 7.5x5x4 cm lobulated left adrenal mass with intact capsule and weighing 115 grams. Histopathology showed small round adrenal tumor cells with increased nucleo-cytoplasmic ratio and prominent nucleoli. The cells were separated by fibrous septae without any evidence of vascular or capsular invasion– findings consistent with adrenal adenoma. On the 8th post-operative day, after withholding hydrocortisone supplementation, the 8 am cortisol level was <1 μg/dL, suggestive of biochemical remission of CS. The patient improved clinically with a 7.5 kg weight loss over the next 3.5 months. This is perhaps the youngest ever reported infant with CS due to adrenal adenoma. Lack of clinical and biochemical evidence of hyperandrogenism as well as the benign histology in spite of the large tumor size (>7 cm diameter; 115 g) are some of the unique features of our patient. Conflict of interest:None declared.

Panhypopituitarism with empty sella a sequel of pituitary hyperplasia due to chronic primary hypothyroidism

Asymptomatic reversible pituitary hyperplasia is common in patients with untreated primary hypothyroidism. Occurrence of empty sella (ES) in this scenario is extremely rare (only three reports till the date) and panhypopituitarism has not been reported in such patients. We report a 27 year man with severe short stature (height-133 cm; standard deviation score-7.36) and delayed puberty who had symptoms suggestive of hypothyroidism along with chronic persistent headache since 6 years of age. Pituitary imaging done for headache at 11 years age showed pituitary hyperplasia. He was diagnosed of primary hypothyroidism for the 1st time at 21 year age, a diagnosis which was likely missed for 15 years. Levothyroxine therapy leads to resolution of all symptoms and a height gain of 28 cm over last 6 years. Evaluation for lack of progression of puberty along with chronic nausea, vomiting, fatigue and weight loss for the last 1 year revealed secondary hypocortisolism (9 am cortisol-4.8 mcg/dl; ACTH-3.2 pg/ml), growth hormone deficiency (IGF-1: 65 ng/ml; normal: 117-325 ng/ml) and hypogonadotrophic hypogonadism (9 am testosterone: 98 ng/dl; [280-1500] LH-0.01 mIU/L [1.14-5.75]) with ES on magnetic resonance imaging (MRI) brain. Uncontrolled thyrotroph hyperplasia due to chronic untreated primary hypothyroidism for 15 years may have been damaging the adjacent corticotrophs, somatotrophs and gonadotrophs resulting in panhypopituitarism and empty sella. This is perhaps the first report of panhypopituitarism with empty sella syndrome developing in a patient with pituitary hyperplasia, a sequel of chronic untreated primary hypothyroidism.

Lean mass is the strongest predictor of bone mineral content in type-2 diabetes and normal individuals: an eastern India perspective

BackgroundImpact of body fat distribution on bone mineral content (BMC) and density (BMD) at different sites has not been studied in type-2 diabetes (T2DM). This study aimed to compare BMC and BMD in normal (BMI < 25 kg/m2) and increased BMI (BMI ≥ 25 kg/m2) T2DM patients with age and BMI matched normal controls, and evaluate the impact of lean mass and body fat distribution parameters on them.MethodsSeventy-six T2DM patients and 56 normal controls underwent anthropometric assessment, blood sampling and estimation of BMC, BMD, body fat and lean mass distribution by dual energy X-ray absorptiometry (DXA).ResultsIncreased BMI individuals (n = 63) had significantly higher BMD, BMC, fat mass and significantly lower 25-hydroxy-vitamin-D (25OHD), as compared to normal BMI individuals (n = 69). Lean mass had stronger positive correlation with BMC and BMD, compared to fat mass. BMI, sagittal abdominal diameter (SAD) and Android/Gynoid (A/G) ratio had positive correlation with BMC and BMD. Percent body fat had negative correlation with BMC and BMD. T2DM patients had higher central obesity (A/G ratio). WC was the best predictor of A/G ratio. Regression analysis revealed lean mass to be the strongest predictor of BMC after adjusting for age, sex, BMI and 25OHD, in normal individuals and patients with diabetes, followed by fat mass. BMD right femur, BMC, lean mass and A/G ratios were significantly higher in males (n = 74). Fat mass and percent body fat were significantly higher in females (n = 58). Fat mass was the best predictor of BMC in males where as lean mass was the best predictor of BMC in females.ConclusionIncreased BMI and T2DM are associated with increased BMC and BMD at different sites, with lean mass having the strongest impact on BMC in normal individuals and patients with diabetes. Males have higher BMC and BMD as compared to females, likely due to a greater lean mass, A/G ratio, along with lesser fat mass and percent body fat.

Neuroendocrine carcinoma of the thyroid causing adrenocorticotrophic hormone-dependent Cushing's syndrome.

BACKGROUND Cushings syndrome (CS) due to ectopic adrenocorticotrophic hormone (ACTH) and/or ectopic corticotropic releasing hormone (CRH) secretion accounts for <10% of all CS. Neuroendocrine carcinomas rarely cause CS. These carcinomas have been found to secrete either ACTH or rarely CRH. Herein we report a case of neuroendocrine carcinoma originating from the thyroid as the source of ACTH-dependent CS. SUMMARY A 30-year-old woman with features of CS presented with severe respiratory distress. Six months before that, she was diagnosed with primary hypothyroidism and started on levothyroxine (LT4) therapy. Biochemical evaluation was done, and nonsuppressed serum cortisol levels following dexamethasone with high ACTH confirmed a diagnosis of ACTH-dependent CS. Magnetic resonance imaging of the brain showed a bulky pituitary gland. Adrenal imaging showed bilateral adrenal hyperplasia. A computerized tomography scan showed a large anterior mediastinal mass arising from the neck and extending behind the transverse aortic arch. She underwent emergency thoracotomy due to rapidly progressive superior mediastinal syndrome and left vocal cord palsy. At surgery, the mass was seen originating from the thyroid and the thymus was compressed posteriorly. Near total thyroidectomy and thymectomy with removal of pericardial seedlings were done. Histopathology revealed sheets, cords, and nests of round or oval tumor cells with hyperchromatic nuclei and scant cytoplasm with local invasion and lymphovascular embolization suggestive of a neuroendocrine carcinoma arising from thyroid, staining positive for cytokeratin, synaptophysin, and chromogranin-A, and negative for calcitonin and carcinoembryonic antigen. CONCLUSIONS Here we report a case of a neuroendocrine tumor of the thyroid causing ACTH-dependent CS. The tumor was negative for calcitonin staining, indicating that this was not a medullary carcinoma of the thyroid. Neuroendocrine carcinomas originating from the thyroid gland are very rare. A thyroid tumor of neuroendocrine origin causing ACTH-dependent CS has not been reported previously.

Thyroid associated orbitopathy with ocular myasthenia in primary hypothyroidism: Keep those eyes open

Thyroid associated orbitopathy, although seen most commonly with thyrotoxicosis, is also known to occur in primary hypothyroidism. Myasthenia gravis is an autoimmune condition with an established association with autoimmune thyroid disease. We report the case of a patient who presented with recent onset unilateral ptosis that was fatigable with a history of proptosis since a year. On examination, she had a goiter, bilateral proptosis, restriction of upward gaze and adduction both eyes and normal pupils. Investigations revealed primary hypothyroidism with anti-thyroid peroxidase positive and anti-acetylcholine receptor antibody positive. Computerized tomography orbit showed thickening of medial and inferior rectus characteristic of thyroid orbitopathy. A diagnosis of primary hypothyroidism with thyroid orbitopathy with ocular myasthenia gravis was made. Patient is on Levothyroxine and anticholinesterase medications and is on follow-up. We present this case to highlight that the presence of ptosis in a patient with thyroid orbitopathy should alert the clinician to the possible coexistence of myasthenia gravis.

Tetany due to hypoparathyroidism as the initial manifestation of autoimmune polyendocrine syndrome type-2: A case report.

Hypoparathyroidism is most commonly isolated and idiopathic. Hypoparathyroidism in autoimmune polyendocrine syndrome type-2 (APS-2) is extremely rare with few isolated reports and usually presents late. We present perhaps for the first time, hypoparathyroidism being the initial manifestation of APS-2 which was diagnosed in a 32 year lady with tingling of the extremities along with hypocalcemic tetany for 15 years. She also had generalized acral and mucosal hyperpigmentation of 2 years duration. Investigations were significant for low calcium (7.1mg/dl), elevated phosphorus (4.8mg/dl), vitamin-D insufficiency (27.4ng/ml), low intact parathyroid hormone (2.3pg/ml), low basal (4.7mcg/dl) and stimulated serum cortisol (9.2mcg/dl at half hour, 11.4mcg/dl at 1 hour post synacthen), elevated triiodothyronine (2.1ng/ml) and free tetraiodothyronine (2.4ng/dl) along with suppressed TSH (<0.005 U/L). Imaging relevaled mild cerebellar calcification, normal adrenals with diffuse uptake of Tc99- pertechnate. A diagnosis of hypoparathyroidism with Addisons and Graves’ disease as a part of APS-2 was made. This report intends to highlight the clinical heterogeneity and varied presentation of APS-2. Routine screening of other hormonal function (especially adrenal function, thyroid function and blood glucose) in a patient with diagnosed hypoparathyroidism is advisable to decrease the chances of missing APS-2.