The Impact of Body Mass Index, Residual Beta Cell Function and Estimated Glucose Disposal Rate on the Development of Double Diabetes and Microvascular Complications in Patients With Type 1 Diabetes Mellitus.

Background The clinical impact of body mass index (BMI), residual beta cell function and estimated glucose disposal rate (eGDR) in the development of double diabetes (DD) and microvascular complications are largely unknown. We aimed to assess whether BMI, residual beta cell function measured by plasma "C" peptide and insulin resistance measured by eGDR have any impact on the development of DD and microvascular complications in patients with type 1 diabetes mellitus (T1DM). Methods It is a cross-sectional observational study involving 113 T1DM patients of more than five years duration who were classified into two groups: normal BMI (18.5-22.9 kg/m2) and overweight/obese group (≥ 23kg/m2) based on Asian BMI classification. Based on their eGDR values, they were grouped into four categories: ≥ 8, 6-7.99, 4-5.99, and < 4 mg/kg/min. The prevalence of DD based on eGDR values was determined. Their BMI and different eGDR categories were compared with the prevalence of diabetic retinopathy and nephropathy and their odds ratio (OR) was calculated. Results The median and interquartile range (IQR) of the eGDR of the overweight/obese group was significantly lower than the normal BMI group (5.3 [3.96-8.15] vs 8.72 [6.50-9.77 mg/kg/min], p < 0.001). The prevalence of DD in the overweight/obese T1DM group and normal BMI group was 75% and 33.3% respectively. The OR of retinopathy and nephropathy in the overweight/obese group was 3.28 (p = 0.007) and 3.01 (p = 0.015) respectively when compared to the normal BMI group. The OR of retinopathy and nephropathy in T1DM patients with eGDR < 4 mg/kg/min was 17.13 (p = 0.001) and 18.5 (p = 0.001) respectively. The lower the eGDR values, the higher the prevalence of retinopathy and nephropathy regardless of HbA1c levels. Conclusion As overweight and obesity are increasingly becoming more prevalent in T1DM, the eGDR will better predict the development of DD and microvascular complications irrespective of HbA1c levels. It is more useful as a variable and easily inducted into routine clinical practice. However, residual beta cell function was not useful in predicting the development of microvascular complications.

Comparison of Novel Biomarkers of Insulin Resistance With Homeostasis Model Assessment of Insulin Resistance, Its Correlation to Metabolic Syndrome in South Indian Population and Proposition of Population Specific Cutoffs for These Indices.

Background The clustering of risk factors of cardiovascular disease (CVD) in individuals has been defined as Metabolic Syndrome (MetS). The major forerunner of all the components of MetS is Insulin Resistance (IR) which is measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and requires the measurement of fasting plasma insulin levels. We attempted to study the performance of lipid-based biochemical markers of IR for the diagnosis of MetS and postulate a population-specific cutoff for these indices in the South Indian population. In this study, we analyzed three lipid-based indices, Triglyceride Glucose index (TyG index), triglyceride: high-Density Lipoprotein (TG:HDL) ratio, and lipid accumulation product (LAP).  Methods This was a cross-sectional study and included apparently healthy individuals presenting to our hospital for routine Master Health Checkup assessment and apparently healthy population residing in Kallindhiri, a village near Madurai. Based on the anthropometric measurements and blood investigations, Body Mass Index (BMI), Waist hip ratio, Waist height ratio, HOMA-IR, TyG index, TG:HDL ratio, and LAP were calculated. The diagnostic efficacy of these indices was compared against the presence of MetS based on the NCEP ATP III criteria. The receiver operating characteristic (ROC) Curve was performed to discriminate decision levels (cutoffs) of serum markers in early diagnosis of metabolic syndrome. The results were considered significant with a p-value less than 0.05. Results We included a total of 192 patients in our study, consisting of 36% (n=70) males and 63% (n=122) females. All the baseline characteristics except height, weight, and HDL cholesterol were comparable between the male and female groups. The values of HOMA-IR, TyG index, TG:HDL ratio, and LAP showed an increasing trend with the BMI. The mean values of HOMA-IR, TyG index, TG:HDL ratio and LAP was significantly higher in patients with MetS than in patients without MetS. Based on the ROC curve plotted for the data, a population-specific cutoff for these indices was computed. Our proposed cutoff for the South Indian population for HOMA-IR is 1.23, for TyG index is 4.65, for TG:HDL ratio is 3.44 in males and 2.6 in females and for LAP is 43.81 Conclusion The cutoffs for the novel indices of insulin resistance which have been previously studied in Caucasian populations cannot be applied to Indian populations due to distinct ethnic characteristics. The diagnostic accuracy of these novel lipid-based biomarkers of Insulin Resistance is better than the biochemical gold standard of HOMA-IR based on the ROC curve. We propose the usage of these population-specific cutoffs in routine clinical practice for early diagnosis of metabolic syndrome.

Fahr's Disease and Hypoparathyroidism - A Missing Link.

Fahr's disease is an idiopathic basal ganglia calcification with autosomal dominant inheritance. Prior to diagnosing Fahr's disease based on computed tomography (CT) and/or magnetic resonance imaging (MRI) of the brain, one should rule out hypoparathyroidism (HP), and pseudohypoparathyroidism (PHP). Treatments of these conditions are entirely different. HP- and PHP-related hypocalcemia requires calcium, calcitriol, and vitamin D therapy in a long run to avoid recurrent seizures whereas Fahr's disease is treated with an antiepileptic alone.

"Congruency the ART of Being Real" - 46XY DSD Due to 5 α Reductase Deficiency - Challenges in Decision Making.

Disorders of sexual development (DSDs) are heterogenous group of disorders characterized by discrepancy in chromosomal, gonadal, and phenotypic sex. DSD is a Medico-Social Emergency. 5 α reductase type 2 deficiency is one of the rare causes of 46 XY DSD. The degree of under virilization varies from clinically female to a near male phenotype. Müllerian structures were absent. At puberty, there might be features of virilization. Gender incongruence or dysphoria occurs frequently during puberty. An important marker for diagnosis is an elevated testosterone to dihydrotestosterone ratio in the basal state or following HCG stimulation. All 46 XY DSD require an appropriate molecular diagnosis prior to gender assignment and gender reassignment surgery. Gender reassignment surgery and/or Gonadectomy should be performed only after 18 years if there are compelling indications like suspicion of malignancy or presence of gender dysphoria or gender incongruence.

Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study.

PURPOSE: Endocrinal insufficiency caused by vasculotoxic snake envenomation is under-recognized and is mostly confined to a specific geographic area. We conducted a prospective study to determine the prevalence and pattern of pituitary-target gland insufficiencies caused by snake envenomation. MATERIALS AND METHODS: The hormonal evaluation of patients who had suffered from vasculotoxic snake envenomation was done at baseline and at 6 months of follow-up. Those patients with a documented hormonal insufficiency underwent magnetic resonance imaging (MRI) of the hypothalamo-pituitary area. The severity of envenomation was assessed by the acute physiology and chronic health evaluation II (APACHE-II) score, the sepsis-related organ failure assessment (SOFA) score, and the snake bite severity score (SBSS) for all patients. RESULTS: Seventy-six patients were seen during the study period, of which 60 were available for a repeat hormonal evaluation at 6 months, with the majority of patients belonging to the middle age group (mean age, 37.6 ± 14.9 years). The mean lag period at presentation was 32 ± 20 h. Thirty-five patients (46.1%) had coagulopathy, 20 patients (26.3%) had acute kidney injury (AKI), and 8 of 76 patients (10.5%) needed renal replacement therapy (RRT) in the form of hemodialysis. Six patients (out of 41 with vasculotoxic bites) developed chronic hypopituitarism, which was in continuation with the acute hypopituitarism that they developed. Growth hormone and glucocorticoid deficiencies were the most common endocrinopathies observed. The occurrence of hypopituitarism was observed only in patients with a vasculotoxic snake bite (due to Russell's viper); coagulopathy, renal insufficiency, or any of the scoring tools did not predict the occurrence of hypopituitarism. CONCLUSION: Acute asymptomatic and chronic symptomatic or asymptomatic hypopituitarism are important sequelae of viper bite in a small proportion of patients and can occur in the presence of normal pituitary imaging. Routine prospective pituitary hormone screening should be done in all patients within the first 6 months of envenomation by the vasculotoxic snakebite as chronic pituitary dysfunction can often occur in these patients.

A Rare Association of Obesity, Diabetes Mellitus and Bilateral Cryptorchidism: Prader - Willi Syndrome.

Prader-Willi syndrome is a genomic imprinting disorder, characterized by obesity, hyperphagia, mental retardation, short stature and hypogonadism. The presenting signs and symptoms depend upon the age at which the patient is seen. Here we report a case of Prader-Willi syndrome, who presented at 16 years of age with diabetes mellitus and cryptorchidism.

Heterosexual precocity: rare manifestation of virilizing adrenocortical oncocytoma.

Adrenocortical oncocytomas are extremely rare, and most of the tumors are benign and nonfunctioning. To our knowledge, only 30 cases have been reported in English published studies, and most patients are 40 to 60 years of age. So far, in the pediatric age group, only three cases of functioning adrenocortical oncocytoma have been reported. We report a case of functioning adrenocortical oncocytoma in a 3 1/2-year-old female child who presented with premature pubarche, clitoromegaly, and increased serum dehydroepiandrosterone sulfate and testosterone. She was managed successfully with right adrenalectomy, and the tumor histology was consistent with adrenal oncocytoma.

Acrogigantism and facial asymmetry: McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies. Association of MAS with GH excess is rare, and in most of the instances somatotropinoma has not been documented. Treatment of patients of MAS with acromegaly is difficult because of thickened calvarium and dysplastic skull bone. We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia, café-au-lait macules and also had acromegaly due to pituitary macroadenoma, and treated with gamma knife radiosurgery.

Spectrum of neurological manifestations of idiopathic hypoparathyroidism and pseudohypoparathyroidism.

We describe clinical, biochemical, radiological profile, and treatment outcome in 97 patients with idiopathic hypoparathyroidism seen over a period of 18 years. Of the 97 patients, 78 (80%) had idiopathic hypoparathyroidism and 19 (20%) had pseudohypoparathyroidism. The mean age±standard deviation (SD) at presentation was 28.7±14.1 years. There were 52 males, the mean lag time from first reported symptom to diagnosis was 5.9±5.2 years and the mean (±SD) follow-up was 1.8±0.4 years. The most common presenting manifestation was carpopedal spasm in 68 (70%) patients, followed by paresthesia and seizures in 52 (54%) patients. The mean (±SD) serum calcium and inorganic phosphate concentrations were 6.1±1.5 mg/dl and 6.3±1.5 mg/dl, respectively. The most common imaging abnormality noted was basal ganglia calcification followed by cerebral cortex and cerebellum calcification. More than one-third of patients were on various antiepileptic drugs including phenytoin. In addition to oral calcium and active vitamin D (calcitriol), twenty-six patients (27%) also required hydrochlorothiazide. The important finding in our study was long lag time from the first reported symptom to diagnosis. Phenytoin was the drug in almost one- third of our patients with seizures. Practicing clinicians should have high index of suspicion of diagnosis hypoparathyroidism in the appropriate clinical states to avoid the morbidity associated with hypoparathyroidism. Phenytoin should be avoided in patients with hypoparathyroidism and seizures.

An unusual cause of gynaecomastia.

Gynaecomastia in adolescents and young adults is a common endocrine disorder with usually benign aetiology. However, gynaecomastia in middle-aged men is uncommon and warrants intensive search to unravel its aetiology. The authors report a 42-year-old male who presented with gynaecomastia due to feminising adrenocortical carcinoma.