Objective: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. Design: This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. Methods: Data were collected from 461 patients aged 0–18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits. Results: The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0–14.5) mg/m²/day at age 1–8 years and the highest dose of 14.0 (11.6–17.4) mg/m²/day at age 12–18 years. Glucocorticoid doses decreased after 2010 in patients 0–8 years (P < 0.001) and remained unchanged in patients aged 8–18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. Conclusions: Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.

It is known that obesity is associated with vitamin D deficiency and observational studies have shown vitamin D deficiency to be linked with the development of type 2 diabetes. There are no comprehensive data regarding vitamin D deficiency in children with obesity in Sri Lanka and the objective of the study was to assess the prevalence of Vitamin D deficiency and its association with metabolic derangements among children with obesity. Two hundred and two children between 5 and 15 years of age attending the obesity clinic Lady Ridgeway Hospital (LRH) were recruited excluding those having possible secondary causes for obesity. Blood was drawn after 12-h overnight fast for fasting blood glucose(FBG), lipid profile, serum insulin, alanine aminotransferase (ALT),aspartate aminotransferase(AST), Vitamin D, parathyroid hormone(PTH),high sensitivity C reactive protein(hs-CRP). Oral glucose tolerance test (OGTT) was done with 2 h random blood glucose. Anthropometry, blood pressure were measured, and body fat mass was assessed using bio-impedance. Vitamin D deficiency (< 20 ng/ml) was seen in 152(75.2%) children and 43(21.3%) had insufficient (20-30 ng/ml) levels. Skin fold thickness, fasting and post-glucose insulin, HOMA-IR, PTH, LDL, Serum cholesterol and hs-CRP showed statistically significant negative correlations with Vitamin D levels. Vitamin D deficiency was significantly high in Sri Lankan children with obesity and showed significant negative correlations with indicators of insulin resistance and adiposity.

Background: Micronutrient deficiencies are identified among obese individuals. Vitamin D deficiency (VDD) is prevalent in obese children, and is hypothesized to cause insulin resistance and metabolic abnormalities. This study aimed to determine the effect of vitamin D supplementation on obesity and related metabolic abnormalities among obese Sri Lankan children with VDD.Methods: A triple-blind randomized controlled trial was conducted among vitamin D deficient (< 20 ng/ml), obese children (n = 96), randomly allocated to three intervention arms - treatment arm receiving weekly vitamin D₂50,000 IU; supplementation arm receiving 2500 IU weekly and control arm, receiving placebo. Anthropometry, percentage fat mass (%FM) and blood pressure were assessed and fasting blood glucose, fasting insulin, lipid profile, aspartate transaminase (ALT), alanine transaminase (AST), vitamin D, parathyroid hormone (PTH) and hs-CRP and OGTT with 2-h random blood glucose and insulin was performed at baseline and after 24 weeks of treatment. Ethics Review Committee of Faculty of Medicine, University of Colombo approved the protocol.Results: Waist circumference Z-score, %FM and serum calcium significantly improved across all three arms, ALT significantly improved in treatment and supplementation arms while, BMI Z-score, PTH and vitamin D significantly improved in the treatment arm. Biceps (p = 0.035) and subscapular (0.048) skin fold thickness, vitamin D (p = 0.004) and ALT (p = 0.012) significantly improved in the treatment arm.Conclusions: A strict dietary and physical activity regimen could improve some of the anthropometric, body composition and metabolic profiles, but high dose vitamin D, enhances those improvements. Therefore high dose vitamin D seems to potentiate management outcomes of obese children with vitamin D deficiency.Trial registration: The study was registered at the Sri Lanka Clinical Trials Registry (SLCTR/2015/017) on 12th September 2015 athttps://slctr.lk/trials/slctr-2015-017.

Context Congenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion despite low blood glucose. Persistent HI is often monogenic, with the majority of cases diagnosed in infancy. Less is known about the contribution of monogenic forms of disease in those presenting in childhood. Objective We investigated the likelihood of finding a genetic cause in childhood-onset HI and explored potential factors leading to later age at presentation of disease. Methods We screened known disease-causing genes in 1848 individuals with HI, referred for genetic testing as part of routine clinical care. Individuals were classified as infancy-onset (diagnosed with HI < 12 months of age) or childhood-onset (diagnosed at age 1-16 years). We assessed clinical characteristics and the genotypes of individuals with monogenic HI diagnosed in childhood to gain insights into the later age at diagnosis of HI in these children. Results We identified the monogenic cause in 24% (n = 42/173) of the childhood-onset HI cohort; this was significantly lower than the proportion of genetic diagnoses in infancy-onset cases (74.5% [n = 1248/1675], P < 0.00001). Most (75%) individuals with genetically confirmed childhood-onset HI were diagnosed before 2.7 years, suggesting these cases represent the tail end of the normal distribution in age at diagnosis. This is supported by the finding that 81% of the variants identified in the childhood-onset cohort were detected in those diagnosed in infancy. Conclusion We have shown that monogenic HI is an important cause of hyperinsulinism presenting outside of infancy. Genetic testing should be considered in children with persistent hyperinsulinism, regardless of age at diagnosis.

Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim: Study temporal trends of AI related AE in the I-CAH Registry. Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019. Results: In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02). Conclusion: The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.

Introduction: Resistant starch (RS) has beneficial effects on postprandial glucose metabolism in both animals and adults. Hitherto, there have been no studies in children of the acute metabolic and hormonal effects of RS-containing meals.Objectives: We aimed to compare serial plasma glucose, insulin, gut hormone, leptin profiles and satiety scores in obese children after meals containing variable amounts of RS.Methods: This was a single blind, non-randomised, crossover study of 20 obese children aged 10–14 years old without comorbidities. Three test meals containing rice (M1), rice cooked with coconut oil (M2), rice cooked in coconut oil with lentils (M3) were given in sequence after a 12-hour fast . Blood samples were analysed for glucose (PG), insulin, leptin, glucagon-like polypeptide (GLP) 1, ghrelin and peptide YY (PYY) at appropriate times between 0 and 180 min.Results: Meal M2 resulted in significantly lower postprandial glucose values compared with meal M1 (maximal incremental glucose, ∆C_max, p<0.05; area under the curve, ∆AUC_0–3, p<0.01) and meal M3 (maximal concentration, C_max, p<0.01; ∆C_max, p<0.001, and ∆AUC_0–3p<0.01). M2 also produced lower insulin values compared with M1 (p<0.05). Postprandial ghrelin was significantly higher after M1 compared with M3 (p<0.05). PYY, GLP1 and median satiety scores were not significantly different between the three meals.Conclusion: This study shows that M2, the meal containing RS alone, induced beneficial effects on acute postprandial glucose, insulin and ghrelin concentrations in obese children without diabetes. Acute postprandial satiety scores were not significantly affected by the three meals.Trial registration number: SLCTR/2020/007.