Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement.

Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (- 21.0%, confidence interval [CI] - 34.1 to - 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p < 0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

Clinical assessment of obesity and insulin resistance in type 1 diabetes subjects seen at a center in Kolkata.

OBJECTIVES: Type 1 diabetes mellitus (T1DM) is characterized by a selective destruction of pancreatic beta cells. Recent data suggest a role of insulin resistance (IR) along with the deficient insulin reserve. METHODS: Fifty-eight consecutive patients of T1DM, with low C-peptide levels were included. Patients with an obvious secondary cause like steroid therapy, fibrocalculous pancreatic disease, chronic infections or comorbid illness were excluded. A clinical assessment for the presence of obesity was made based on anthropometric data. Clinical markers of IR and the insulin dose required to achieve a stable glycemic control calculated in terms of body weight were also studied. RESULTS: There were 30 males and 28 females with a mean age of 16.5 +/- 2.3 (5-39) years. The mean body mass index (BMI) was 19.21 +/- 3.7 and the waist circumference was 67 +/- 5.2 cms. Nineteen ( 32.75%) and six (10.34%) patients were overweight (BMI > 23) and obese (BMI > 27) respectively while 16 (27.58%) had abdominal obesity. The body fat percentage was high (> 25%) in 34 (58.62%), mean 28.33 +/- 11.4%. Acanthosis nigricans was found in 14 (24.13%) cases, hypertension in two (3.4%) but none of the girls had clinical polycystic ovarian syndrome (PCOS). The insulin dose required was 1.11 +/- 0.41 u/kg (0.3-2.9) at an glycated haemoglobin A1C (A1C) of 7.56 +/- 1.04% (4.9-9.3), it was more than 0.6 u/kg/day in 38 (65.51%) patients. CONCLUSIONS: The study concludes that IR is present in a large number of Indian T1DM patients along with a high body fat percentage.

Profile of hypopituitarism in a tertiary care hospital of eastern India--is quality of life different in patients with growth hormone deficiency?

Hypopituitarism is of diverse aetiology. Apart from pituitary adenoma and Sheehan's syndrome, snakebite is a common aetiology of hypopituitarism. A total of 82 patients of hypopituitarism were studied. Biochemical and radiological investigations were done in all the cases. A quality of life questionnaire was put among the patients. Scores were calculated from the answers of the questionnaire and they were assessed about quality of life. Though growth hormone deficiency is associated with poor quality of life there were no significant differences with patients with hypopituitarism without any growth hormone deficiency.