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Background Thyroid dysfunctions are the most common endocrine abnormalities observed in trisomy 21 (T21). The prevalence of thyroid disorders in children with T21 varies between 4% and 40%. Dysregulation of thyroid function, which is specific to T21, is a possible etiology. Thyroid dysfunction can have a significant impact on cognitive development and growth. Transiently abnormal thyroid function tests (TFTs) are frequently observed in T21 and may cause diagnostic confusion. There is a lack of literature on several specific thyroid conditions (such as CH, transient abnormal TFT and thyroid dysfunction) in children with T21 in resource-limited settings. Methods Records of children followed up at the Child Development Clinic dedicated to children with T21 at the university unit of Lady Ridgeway Hospital (LRH), Sri Lanka, were reviewed retrospectively. The prevalence and characteristics of different thyroid dysfunctions were studied. Results Among the 88 children with T21 (Male: Female ratio of 1.5:1), 35 (39.7%) had thyroid dysfunction. Seventeen (20%) children were managed as congenital hypothyroidism (CH), nine (10.2%) had transiently abnormal TFTs. Acquired hypothyroidism was noted in 8 (9%) children, and two children (2.3%) had hyperthyroidism. Among the 17 children who were managed as CH, 12 (70.5%) were diagnosed during the neonatal period following newborn screening (NBS). The mean TSH level at diagnosis was 22.3 mIU/l (10.6–58). All 17 children had normal ultrasound scans of the thyroid. The average current thyroxine dose in the < 3-year-old group (n = 4) was 2.1 µg/kg/day, and in the ≥ 3-year-old group, it was 2.5 µg/kg/day. The interquartile range(IQR) for age at diagnosis of acquired hypothyroidism was between 7years 9months to 12years 8 months. In those managed as transiently abnormal TFTs, the time taken for TFTs to normalise (without any treatment) ranged widely between six weeks and eight months. Conclusion Thyroid dysfunction is a commonly encountered challenge in managing T21. Transiently abnormal TFTs are common and require close observation. Gland-in situ CH (GIS-CH) is increasingly being detected among this population. The cost-effectiveness of using genetic analysis in GIS-CH in resource-limited settings needs to be studied. Differentiating transient CH from permanent CH is quite challenging in clinical practice, although the low thyroxine dose requirement, especially after 3 years of age, may provide valuable information. Further longitudinal studies are needed to delineate the prevalence of transient vs. permanent CH.

46, XY disorders of sex development (DSD) are clinically and genetically heterogeneous congenital conditions caused by abnormal or incomplete gonadal, genital, or chromosomal development that results in discordant phenotypic sex. The pathophysiology of 46, XY DSD is influenced by genetic variations in sex development genes, including SNPs, indels, and CNVs. Twelve clinically confirmed children with 46, XY DSD and four healthy controls were selected for the current study. Direct sequencing was performed to detect potential genetic variants in exon 4 of NR5A1 (N = 12) and the single exon of the SRY (N = 10) genes. Additionally, nine patients (N = 9) were analysed for large deletions or duplications in the sex determination genes NR5A1, SRY, SOX9, NR0B1, and WNT4 using the multiple ligation probe amplification (MLPA) technique. One patient displayed ambiguous heterozygous duplications in exon 3 of WNT4 and in exons 4 and 6 of NR5A1, while another sample showed ambiguous heterozygous duplication within exon 3 of NR5A1. Two novel variants were detected during SNP analysis of the SRY gene: c.568A > C in 4 patients and c.(- 33 T > A) in 7 patients and all four healthy controls. According to in silico prediction, c.568A > C was classified as \"benign\", whereas the 5'UTR variant (c. - 33 T > A) appears non-pathogenic, given its presence in all healthy controls. In addition, previously reported silent variant c.393G > A was detected in exon 4 of NR5A1 in 5 patient samples. A missense variant, c.437G > C, was identified in exon 4 of the NR5A1 gene in one patient. As per in silico prediction, this variant was indicated as \"benign\", although previous studies have suggested it may act as a disease modifier and susceptibility factor for micropenis and cryptorchidism. This study contributes to defining the mutation spectrum of SRY and NR5A1 genes in 46, XY DSD in a cohort of patients in Sri Lanka. These findings may aid in developing genetic diagnostic tools for early diagnosis and improved clinical management. However, future research should focus on expanding the cohort size to improve the generalisability of these findings. Whole-exome sequencing can be used to identify genetic variants, which can be evaluated through functional studies to determine their biological impact.

IntroductionResistant 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.ObjectivesWe aimed to compare serial plasma glucose, insulin, gut hormone, leptin profiles and satiety scores in obese children after meals containing variable amounts of RS.MethodsThis 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.ResultsMeal M2 resulted in significantly lower postprandial glucose values compared with meal M1 (maximal incremental glucose, ∆Cmax, p<0.05; area under the curve, ∆AUC0–3, p<0.01) and meal M3 (maximal concentration, Cmax, p<0.01; ∆Cmax, p<0.001, and ∆AUC0–3p<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.ConclusionThis 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 numberSLCTR/2020/007.

Neonatal diabetes mellitus (NDM) is a disorder characterized by persistent, severe hyperglycemia presenting during the first six months of life. These disorders are rare and the incidence is approximately 1 in 90,000 live births. The aim was to describe the clinical presentation, molecular genetics and outcome of patients with NDM from a single paediatric endocrine center from a low-middle income country, Sri Lanka. A retrospective study was conducted on patients diagnosed with NDM. Medical records were reviewed for demographic data and data on clinical, biochemical and genetic analysis. The majority (96%) who underwent mutation analysis had pathogenic genetic mutations on Sanger sequencing. Permanent NDM (PNDM) was diagnosed in 19 patients with three having a syndromic diagnosis. The most common mutation was in . The majority of patients with PNDM (63%) presented with severe diabetic ketoacidosis. All patients with Transient NDM remitted by six months of age. Nearly half (47%) with PNDM were switched to sulfonylurea therapy with good glycemic control (glycosylated haemoglobin A1c ranged 6-7.5%). Data from the Sri Lankan cohort is comparable with other populations. The majority of cases are due to mutations resulting in PNDM.

Background Pediatric adrenocortical tumors include both benign adenomas and highly virulent malignant tumors. However, they are very rare among children. The aim of this study is to evaluate the clinicopathological data of children presenting with adrenocortical tumors and assess their survival in a South Asian population. Case presentation This is a retrospective cohort study that includes patients diagnosed with adrenocortical tumors from August 2020 to August 2022 followed-up at Lady Ridgeway Hospital. Seven children were diagnosed with adrenal cortical tumors. Their ages ranged from 10 months to 6.5 years. Five of them were boys. All displayed signs of peripheral precocious puberty. One boy phenotypically had features of Beckwith–Wiedemann syndrome. The median time for diagnosis after the onset of symptoms was 4.4 months. The preoperative diagnosis was based on clinical manifestations, elevated dehydroepiandrosterone sulfate levels, and suprarenal masses on computed tomography. All five boys had right-sided suprarenal masses, while the two girls had them on the left side. All underwent surgery for tumor resection. The diagnosis was confirmed based on the histopathology of the adrenal specimens. Four children had a Wieneke score of 4 or more, suggesting the possibility of adrenocortical carcinoma; however, only two of them behaved as malignant tumors. To date, two children have developed local recurrences within a very short period. Conclusion Adrenocortical tumors are uncommon in children, and treatment options are limited. To identify early recurrences, routine clinical, radiological, and biochemical examinations at least once every 6–8 weeks is important.

Diabetes is a major non‐communicable disease with long‐term complications. Over one million children and adolescents are affected with type 1 diabetes in the world. The number of children and adolescents with type 2 diabetes is also on the rise due to the increase incidence of childhood diabetes. South East Asian (SEA) contributes 184 100 children and adolescents with type 1 diabetes under the age of 20 years for this global health issue as at 2019. Countries of SEA region share same socio demographic, cultural, and economic challenges when it comes to holistic care of affected children. It is timely to discuss common concerns of these countries to give the best possible care for children affected with diabetes to minimize the burden of diabetes related complications, which would potentially affect the socioeconomic development of the respective countries.

Universal salt iodisation (USI) plays an essential role in the provision of iodine (I) to populations worldwide. Countries adopting USI programmes, adhering to strict criteria laid down by expert organisations such as the Iodine Global Network, are estimated to have reduced the prevalence of I deficiency by 75% (protecting 720 million individuals worldwide). Despite this success, doubts have been raised as to the desirability of continuing such programmes because of (a) the need to reduce salt intake for cardiovascular prevention and (b) the induction of thyroid autoimmunity. We present current evidence from cross-sectional studies in several disparate populations of the possible short-term modulation of thyroid autoimmune markers, thyroid peroxidase (TPOAb) and thyroglobulin antibodies (TgAb), with minimal disruption of biochemical thyroid function. We also present evidence from longer term, mainly cross-sectional studies, that indicate a reduction in the prevalence of TPOAb and TgAb, and the persistence of normal biochemical thyroid function over as long as two decades of USI. We believe these studies indicate that USI is safe, and that long-term salt iodisation does not cause an increase in autoimmune thyroid disease in the populations studied and should not be a safety concern based on current evidence. More long-term and better-designed studies are required.

Abstract 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.

Hereditaryhypophosphatemic rickets with hypercalciuria ( HHRH) is a rare genetic condition with Autosomal recessive inheritance with a prevalence of 1 in 250000. It is due to mutation in SLC4A3 gene. Correct diagnosis of this condition is important as treatment with active vitamin D metabolites are contraindicated. Evolution of the disease despite initial completely normal bio chemistry has ben observed causing diagnostic confusion. First child presented at the age of 5.5 year with features of rickets. He had abnormal bone profile with normal vitamin D levels. urinary phosphate studies were compatible with HHRH. He was treated with phosphate supplementation and Potassium citrate. He has well responded to the treatment. Second child initially presented at 1.5 years of age with bowing and family history of hypercalciuria. All investigation findings including urinary phosphate studies were within normal limits. At the age of 2.5 year, he again presented with worsening of bowing. Bio chemical and urinary investigations were repeated. Laboratory findings were compatible with HHRH. It highlights the importance of repeated investigations despite initial normal parameters if the initial clinical suspicion is strong and clinical and investigation based diagnosis of this rare genetic disease in resource limited setting.

Abstract Background Although congenital adrenal hyperplasia (CAH) is known to be associated with adrenal crises (AC), its association with patient- or clinician-reported sick day episodes (SDE) is less clear. Methods Data on children with classic 21-hydroxylase deficiency CAH from 34 centers in 18 countries, of which 7 were Low or Middle Income Countries (LMIC) and 11 were High Income (HIC), were collected from the International CAH Registry and analyzed to examine the clinical factors associated with SDE and AC. Results A total of 518 children—with a median of 11 children (range 1, 53) per center—had 5388 visits evaluated over a total of 2300 patient-years. The median number of AC and SDE per patient-year per center was 0 (0, 3) and 0.4 (0.0, 13.3), respectively. Of the 1544 SDE, an AC was reported in 62 (4%), with no fatalities. Infectious illness was the most frequent precipitating event, reported in 1105 (72%) and 29 (47%) of SDE and AC, respectively. On comparing cases from LMIC and HIC, the median SDE per patient-year was 0.75 (0, 13.3) vs 0.11 (0, 12.0) (P < 0.001), respectively, and the median AC per patient-year was 0 (0, 2.2) vs 0 (0, 3.0) (P = 0.43), respectively. Conclusions The real-world data that are collected within the I-CAH Registry show wide variability in the reported occurrence of adrenal insufficiency–related adverse events. As these data become increasingly used as a clinical benchmark in CAH care, there is a need for further research to improve and standardize the definition of SDE.