Rakesh Sahay

Objective: PCOS is a complex endocrine disorder associated with metabolic and hormonal dysregulation. The visceral adiposity index (VAI) and free androgen index (FAI) have emerged as predictive markers for PCOS. This study aims to evaluate the role of VAI and FAI from the aspect of metabolic and hormonal imbalance in PCOS women from urban and rural areas of India. Study Design and Subjects: Women within the reproductive age of 18–40 years from both rural and urban areas of India were recruited in the study between November 2018 and July 2022 for this cross‐sectional study. 12,100 women were approached to participate in the study, of whom 8993 subjects were enroled. After clinical examination and all investigations according to the protocol, 795 were PCOS cases, while 2475 were non‐PCOS cases as per Rotterdam criteria. The PCOS group was segregated according to obesity. Measurements: Hormonal profile and ovarian morphology were evaluated along with anthropometric parameters. VAI, FAI, and Lipid Accumulation Product (LAP) were calculated based on biochemical parameters. Results: VAI and FAI were significantly elevated in PCOS compared to non‐PCOS. VAI, FAI, and LAP were significantly increased in obese PCOS. VAI, independent of BMI, was significantly associated with the Ferriman Gallaway (FG) score, FBG, fasting insulin, and LAP, whereas FAI was associated with BMI and LAP. Conclusion: The study underscores that VAI may serve as the surrogate marker of PCOS, independent of obesity.

Introduction: Congenital hypothyroidism (CH) is among the most common preventable causes of intellectual disability worldwide. In India, the absence of universal neonatal screening leads to delayed diagnosis and consequent neurocognitive morbidity. This study aimed to assess intelligence quotient (IQ) and behavioral profiles in children with CH in relation to the timing of levothyroxine (LT4) initiation and serum T4 levels at diagnosis. Methods: A cross-sectional study of 30 children with CH aged ≥3 years attending the endocrinology outpatient clinic at Osmania General Hospital, Hyderabad, was conducted between January 2017 and December 2018. IQ was assessed using the Binet Kamat Scale of Intelligence. Behavioral profiling was performed using the Achenbach Child Behavior Checklist (CBCL). Patients were stratified by age of LT4 initiation (6 months). Analysis included ANOVA, box plot analysis, and one-sample t tests using SPSS version 20. Statistical significance was set at p < 0.05. Results: Of 30 patients (17 girls, 13 boys), 46.6% were initiated on LT4 after 6 months of age. Mean IQ was 79, 59.5, and 61.12 in those initiated on treatment within 1 month, 1–6 months, and after 6 months, respectively. Males had significantly lower serum T4 at diagnosis (0.45 ± 0.25 vs. 2.25 ± 1.48 μg/dL; p = 0.0002) and lower IQ (46.08 ± 22.59 vs. 76.6 ± 26.89; p = 0.003). Behavioral scores were within normal limits; however, withdrawn/anxiety/social/thought (WAST) composite score showed a trend toward elevation. Height SDS did not differ significantly between treatment initiation groups (p = 0.172). Conclusion: Children with CH in this Indian cohort demonstrated substantially lower IQ compared to internationally reported values, attributable to delayed diagnosis and suboptimal therapy adherence. Males exhibited more severe biochemical disease at diagnosis and greater neurocognitive impairment. Routine behavioral assessment and cognitive behavioral therapy should be incorporated into standard CH follow-up in resource-limited settings.

Hypertension in infancy is rare and usually secondary to renal, cardiovascular, or endocrine disorders. PASNA syndrome (primary aldosteronism, seizures, and neurological abnormalities) (OMIM #615474) caused by activating CACNA1D mutations, has been increasingly recognized with wider availability of genetic testing. We report a 5-month-old male infant with incidentally detected severe hypertension (>99th percentile), neonatal jitteriness, and global developmental delay. Laboratory evaluation showed markedly elevated aldosterone (824 ng/dL) (SI: 22.9 nmol/L) (reference range, 5-150 ng/dL [SI: 0.14-4.2 nmol/L]) with low-normal renin and normal renal and cardiac imaging. Genetic analysis revealed a heterozygous CACNA1D missense variant (c.2241C > G; p.Phe747Leu) likely pathogenic and a heterozygous MED12L variant, classified as variants of unknown significance. The mother was an asymptomatic carrier of the CACNA1D variant. Blood pressure improved with nifedipine followed by spironolactone (2.5 mg/kg/day). Neurological symptoms partially improved, though motor delay persisted. This case expands the phenotypic spectrum of PASNA syndrome and highlights the need for early genetic evaluation in infants with unexplained hypertension and neurological abnormalities. The concurrent MED12L variant may contribute to the neurodevelopmental phenotype, underscoring the complexity of dual-gene involvement.

Objective: To characterize genetic heterogeneity, clinical spectrum, and management outcomes of neonatal diabetes mellitus (NDM) in a tertiary care center in a resource-limited region, with emphasis on emerging genetic etiologies and simplified insulin regimens. Design: Observational case series with systematic prospective data collection at defined intervals. Methods: Seven consecutive infants with insulin-dependent hyperglycemia diagnosed within 6 months of life were enrolled and followed from presentation through 3-month outpatient follow-up. Clinical features, biochemical parameters, genetic testing results, and treatment responses were documented daily during hospitalization and at scheduled follow-up visits. Time to glycemic control (defined as blood glucose 100-180 mg/dL for ≥24 hours on stable therapy) and prognostic factors were analyzed. Results: Three of 7 cases (42.9%) had identified genetic mutations: two GCK mutations and one homozygous NARS2 variant (c.583T>C; p.Phe195Leu; VUS). Four cases (57.1%) remained genetically unsolved; three of these initially received glibenclamide following a provisional ARMS PCR report suggestive of ABCC8 variant, which was subsequently reclassified as benign on whole exome sequencing, prompting discontinuation of sulfonylurea therapy. GCK and NARS2-mutated cases required insulin-only therapy. A novel NARS2 case with severe intrauterine growth restriction (birth weight 1.5 kg) and marked hyperglycemia (640 mg/dL) achieved glycemic control in 7 days using simplified NPH (Neutral Protamine Hagedorn) insulin monotherapy without mealtime boluses, enabling exclusive breastfeeding. Severe malnutrition combined with metabolic acidosis was the strongest independent predictor of delayed control (40 days versus 5-7 days). All cases achieved glycemic control. Conclusions: Genetic testing provides essential precision-medicine guidance for NDM management despite a 42.9% diagnostic yield limited by current gene panels. This series expands the NARS2-associated NDM phenotypic spectrum and demonstrates that simplified basal-only NPH insulin regimens achieve excellent outcomes in IUGR neonates while enabling exclusive breastfeeding. Pragmatic strategies optimized for resource-limited settings enable equitable, high-quality NDM care.

Background: Genetic risk scores (GRS) for type 1 diabetes (T1D) have been developed primarily in European populations, limiting their generalisability across ancestries. Indians differ from Europeans in clinical characteristics of T1D and overall genetic architecture, yet systematic evaluation of T1D GRS performance in multi-regional Indian cohorts is lacking.Methods: The study included 597 T1D patients and 3347 non-diabetic controls from different regions in India. Genotyping, imputation, quality control analysis, and construction of the 67-SNPs T1D GRS were performed using standardised pipelines. Discriminative performance was assessed using Receiver Operative Curve-Area under Curve (ROC-AUC) analysis, and optimal thresholds were derived using Youden’s index. HLA-DQ diplotype frequencies were compared, and association analysis was conducted using multivariable logistic regression.Findings: T1D GRS showed consistent discriminative performance across Indian cohorts [ROC-AUC=0.84 (range=0·78-0·87)], supporting its comprehensive use for T1D classification in India. Notably, its performance was lower in islet cell autoantibody (IA) negative compared with IA positive T1D patients (ROC-AUC, 0·75 vs 0·85) and in adult-onset than in childhood-onset patients (0·74 vs 0·84). We observed a lower frequency of protective HLA-DQ diplotypes and a strong association of HLA-DQ81 containing diplotypes in childhood-onset T1D. Application of an India-specific T1D GRS score improved the sensitivity than the European cut-off.Interpretation: T1D GRS is a valuable unified diagnostic tool in Indians, but its performance varies by islet cell autoantibody status and age at onset, likely reflecting population-specific HLA architecture. European-derived T1D GRS thresholds under-classify the genetic risk, highlighting the importance of ancestry-aware optimisation in Indians.

To assess the efficacy and safety of a fixed-dose combination (FDC) of dapagliflozin and pioglitazone versus a loose combination (LC) as an add-on therapy