OBJECTIVES:Although intravenous (IV) insulin remains the standard treatment for diabetic ketoacidosis (DKA), subcutaneous (SC) insulin has been suggested as an alternative for uncomplicated DKA. We compared treatment duration, hospital length of stay (LOS) and adverse events in children with mild DKA treated with a SC insulin protocol to those of children treated with an IV insulin protocol. METHODS:We reviewed medical records of children with mild DKA admitted to a children's hospital before and after introduction of a SC insulin protocol. Children treated with the SC protocol received daily basal insulin along with rapid-acting insulin every 4 h. We compared outcomes for children treated with SC insulin to those of children treated with IV insulin. RESULTS:Twenty two children were treated with SC insulin and 29 with IV insulin. In the SC group vs. the IV group, mean protocol duration (17.1 ± 8.6 vs. 13.5 ± 4.6 h) and LOS (34.9 ± 16.7 vs. 37.8 ± 23.6 h) were not significantly different (p=0.07 and p=0.63, respectively). There were no significant differences in adverse events frequency between groups. No child treated with SC insulin required a change to IV insulin treatment. CONCLUSIONS:Treatment of children with uncomplicated mild DKA with SC insulin is safe and effective without prolonging LOS.
INTRODUCTION:Sex development is precisely orchestrated by genetic and epigenetic mechanisms; disruption of this intricate process leads to differences in sex development (DSD). CONTENT:n this review, we systematically examine the role of epigenetic mechanisms in DSD, including DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling. Unlike previous reviews focused predominantly on animal models, we integrate available epigenetic evidence from human DSD patients and attempt to distinguish causative changes from secondary consequences. Endocrine-disrupting chemicals (EDCs) have been partially validated in animal models to affect gonadal and reproductive functions through epigenetic mechanisms, but human evidence remains limited. SUMMARY AND OUTLOOK:Finally, we cautiously propose a diagnostic workflow that integrates epigenetic testing and attempt to identify key gaps in current research and suggest testable directions for future studies.
OBJECTIVES:Pediatric thyroid cancers are rare, with papillary thyroid carcinoma (PTC) being the most common type. The diffuse sclerosing variant (DSV) is a rarer subtype associated with frequent recurrence and extensive lymphatic involvement. Among 51 pediatric patients treated for thyroid carcinoma at our tertiary center over a 20-year period, three were diagnosed with DSV-PTC. We present this retrospective case series to highlight its clinical course and diagnostic challenges. CASE PRESENTATION:Three patients (aged 8-17) presented with neck swelling; one also exhibited high fever and neck pain. While thyroid function tests were normal, serum thyroglobulin levels were significantly elevated. Imaging revealed diverse presentations: a solitary nodule, diffuse enlargement mimicking an abscess, and diffuse inflammation. Following fine-needle aspiration confirmation of PTC, all patients underwent total thyroidectomy and central and bilateral lymph node dissection. Histopathology confirmed DSV-PTC in all cases. Every patient presented with diffuse lymph node metastasis; two showed extrathyroidal extension, and one had distant pulmonary metastasis. Genetic analysis identified a BRAF V600E alteration in one case and RET translocations in the other two, confirmed by fluorescence in situ hybridization (FISH) after negative broad next-generation sequencing (NGS) panels. All patients required revision surgery for residual tissue followed by radioactive iodine (RAI) therapy. At follow-up (13-28 months), outcomes ranged from stable disease and additional RAI requirement to complete remission without relapse. CONCLUSIONS:Although based on a small case series, our findings suggest that DSV-PTC can behave aggressively in pediatric patients and can mimic benign inflammatory conditions, leading to potential diagnostic delays. Early recognition and a comprehensive multimodal approach, including extensive surgery and RAI, appear vital for managing this challenging variant.
OBJECTIVES:Familial nonautoimmune hyperthyroidism (FNAH) is a rare disorder caused by activating germline variants in the thyroid-stimulating hormone receptor gene (TSHR) and can mimic antibody-negative Graves' disease. We report a family with hyperthyroidism and the TSHR variant Gly413Ser and provide clinical, segregation, and functional evidence that this p10-region variant is a novel cause of FNAH. CASE PRESENTATION:The disorder was recognized after a 15-year-old boy presented with abdominal pain and diarrhea and was found to have suppressed thyrotropin, high-normal free thyroxine, and slightly elevated free triiodothyronine, without thyrotropin receptor antibodies (TRAb) or ophthalmopathy. Family review revealed multigenerational TRAb-negative hyperthyroidism. Genetic testing identified NM_000369.5(TSHR):c.1237G>A, p.(Gly413Ser), initially classified as a variant of uncertain significance. Twelve family members were investigated: nine affected individuals carried the variant, and three unaffected relatives tested negative. Age at diagnosis ranged from 10 to 73 years. Antithyroid drugs gave symptom relief, but relapse occurred after withdrawal; definitive (ablative) treatment was performed in all but one of the affected family members. Basal cyclic adenosine monophosphate (cAMP) production by the Gly413Ser variant was approximately threefold increased, with unchanged inositol 1-phosphate and thyrotropin-stimulated responses. CONCLUSIONS:TSHR Gly413Ser is a pathogenic activating variant causing FNAH. Persistent TRAb-negative hyperthyroidism, especially with familial clustering, should prompt TSHR genetic testing and cascade evaluation.
OBJECTIVES:Data on menstrual cycle-related metabolic variability in adolescents with type 1 diabetes (T1D) using automated insulin delivery (AID) systems are scarce. We aimed to quantify cycle-dependent differences in insulin requirements and glycemic outcomes in this population. METHODS:In this retrospective observational cohort study, adolescents with T1D aged 12.0-17.9 years who were at least 1 year postmenarche and had used AID for ≥6 months were included. Menstrual cycles were tracked using smartphone applications, and nine complete cycles per participant were analyzed. Insulin delivery and continuous glucose monitoring data were extracted from Glooko. Outcomes included total daily insulin dose (TDD), time in range (TIR), time above range (TAR), time below range (TBR), mean glucose, glucose coefficient of variation (CV), and recorded carbohydrate intake. Linear mixed-effects models were used. RESULTS:Fifty-one adolescents contributed 459 menstrual cycles. Mean age was 14.7 ± 1.8 years, and median HbA1c was 7.2 % (interquartile range 6.8-7.5 %). TDD was higher during the luteal than the follicular phase (1.05 vs. 0.95 U/kg/day; mean difference +0.10 U/kg/day, 95 % CI 0.05-0.15; p<0.001). The luteal phase was associated with reduced TIR (-6.3 %, p=0.001), increased TAR (+5.5 %, p=0.01), higher mean glucose (+12.5 mg/dL, p=0.03), and higher CV (39.4 vs. 35.0 %, p=0.03). TBR and carbohydrate intake did not differ significantly. CONCLUSIONS:In adolescents with T1D who menstruate and use AID systems, insulin requirements and glycemic control vary across the menstrual cycle, with increased insulin demand and hyperglycemia during the luteal phase. These findings highlight clinically relevant cycle-related metabolic variability despite the use of AID.
OBJECTIVES:Inactivating parathyroid hormone (PTH)/PTHrP Signalling Disorder Type 1 (iPPSD1) is a rare genetic condition caused by loss-of-function mutations in the PTH1R gene, presenting with PTH resistance and variable skeletal and dental manifestations. The gene is catalogued under OMIM *168468. Compound heterozygous variants are exceptionally rare and associated with severe phenotypes. CASE PRESENTATION:We report a 9-year-old female from the Indian subcontinent presenting with primary failure of tooth eruption, dental anomalies, valgus deformity, and PTH resistance with subclinical hypothyroidism. Whole exome sequencing identified novel compound heterozygous variants in exons 8 and 9 of the PTH1R gene (NM_002820.4: c.557G>A [p.Arg186His] and c.686delC [p.Phe230fs*6], confirmed in trans), confirmed by Sanger sequencing and absent from major population databases. CONCLUSIONS:This is the first reported case of a compound heterozygous PTH1R variant in the Indian population, expanding the known allelic spectrum of iPPSD1 and highlighting the importance of genetic diagnosis in guiding clinical management. Early molecular diagnosis enabled appropriate multidisciplinary management.
Growth hormone deficiency (GHD), idiopathic short stature (ISS), and persistent short stature after birth small for gestational age (SGA) are major pediatric indications for recombinant human growth hormone (rhGH) therapy, but direct pooled comparisons of GH-IGF-1 axis profiles and treatment outcomes remain limited. We performed a systematic PubMed/MEDLINE search covering January 2005 to December 2024 and identified 47 studies including 18,642 children: 9,214 with GHD, 6,807 with ISS, and 2,621 with SGA. Study quality was assessed using the Newcastle-Ottawa Scale, Cochrane RoB 2.0, and AMSTAR-2. Random-effects meta-analyses were used to calculate pooled mean differences, standardized mean differences, and 95 % confidence intervals. Baseline IGF-1 SDS was lowest in GHD (-2.9 ± 1.1) compared with ISS (-1.5 ± 1.2) and SGA (-1.3 ± 1.1; p<0.001). Complete GHD showed greater first-year height velocity (HV) than ISS (MD +0.80 cm/year; 95 % CI 0.52-1.08) and SGA (MD + 0.62; 95 % CI 0.28-0.96). One-year ΔHeight SDS was also greater in GHD than ISS (SMD +0.24; 95 % CI 0.17-0.31) and SGA (SMD +0.19; 95 % CI 0.09-0.29). ΔIGF-1 SDS and near-adult height gain similarly favored GHD. Younger age at treatment initiation and lower baseline IGF-1 SDS significantly predicted more robust response. Overall, rhGH improves growth and IGF-1 outcomes across GHD, ISS, and SGA, with the strongest response in complete GHD, supporting early treatment and IGF-1-guided therapeutic strategies.
OBJECTIVES:Pheochromocytoma is a rare but potentially life-threatening tumor in children, and its diagnosis may be challenging due to variable clinical presentations. We aimed to describe the diagnostic process and clinical outcomes of a child with a giant pheochromocytoma presenting with severe hypertension and metabolic abnormalities. CASE PRESENTATION:A 16-year-old female with a three-year history of hypertension and hyperglycemia, previously diagnosed with essential hypertension and type 2 diabetes mellitus, was found to have a 12.4 cm adrenal mass weighing 280 g. Congenital total hemihypertrophy provided an additional clinical clue. Biochemical evaluation demonstrated marked catecholamine excess, impaired glucose regulation (HbA1c: 6.4 %), low HOMA-IR (2.39), and markedly elevated plasma renin activity (60.8 ng/mL/h), consistent with secondary hyperaldosteronism. Following open total adrenalectomy, biochemical normalization and favorable radiological follow-up were achieved. Despite the large tumor size and multifocal lymphovascular invasion, preserved succinate dehydrogenase subunit B (SDNB) expression and a low Ki-67 proliferation index (2-3 %) were observed. CONCLUSIONS:This case highlights the importance of considering pheochromocytoma in children with persistent hypertension and atypical metabolic findings. Tumor size and individual histological features may not fully reflect biological behavior; integrated assessment incorporating molecular markers may improve risk stratification and clinical management.
OBJECTIVES:Tirzepatide has demonstrated efficacy for adults and youth with type 2 diabetes (T2D) and adults with obesity, but real-world pediatric data remain limited. We evaluated clinical outcomes among youth prescribed tirzepatide across three academic centers. METHODS:We conducted a multicenter retrospective study of patients aged ≤21 years with T2D and/or obesity who initiated tirzepatide and had at least one follow-up visit. Primary outcomes were changes in hemoglobin A1c (A1C), body mass index (BMI), BMI z-score, and weight at first and second follow-up. RESULTS:The cohort included 74 patients. Median age was 18.4 years, 45.9 % were female, 86.5 % had T2D, and 78.4 % had prior GLP-1 RA exposure. At first follow-up (median 102 days [IQR 74, 133]), BMI decreased from 42.7 to 42.0 kg/m2 (n=69; p=0.003), BMI z-score from 2.9 to 2.8 (n=69; p<0.001), weight from 126.2 to 123.9 kg (n=69; p=0.001). In those with T2D, A1C decreased from 8.0 % to 7.2 % (n=58; p<0.001) and basal insulin dose declined from 59.7 to 43.9 units/day (n=24; p=0.008). At second follow-up, A1C, BMI, BMI z-score, and weight remained significantly lower than baseline. In multivariable regression analysis among patients with T2D, prior GLP-1 RA use and partial nonadherence were associated with smaller A1C reductions, while higher baseline A1C and higher tirzepatide dose were associated with greater A1C reductions. CONCLUSIONS:In this multicenter real-world cohort, tirzepatide use among youth with T2D and/or obesity was associated with reductions in BMI and, in those with T2D, reductions in A1C despite prior GLP-1 RA exposure.
OBJECTIVES:Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder characterized by congenital and progressive microcephaly, severe developmental delay, epilepsy, and progressive cerebral atrophy. Therapeutic experience with L-asparagine supplementation remains limited and heterogeneous. CASE PRESENTATION:We report a preterm female infant born to consanguineous parents who presented with congenital microcephaly and early-onset myoclonic epilepsy. During follow-up, diaphragmatic eventration was identified and contributed to recurrent episodes of respiratory failure. Metabolic screening studies were unremarkable; however, cerebrospinal fluid asparagine concentration was markedly reduced (4.42 μmol/L; reference range 8-34 μmol/L). Brain magnetic resonance imaging demonstrated cerebral atrophy with white matter involvement. Whole-exome sequencing identified a homozygous splice-site variant in the ASNS gene. Oral L-asparagine supplementation was initiated at 5 months of age (50 mg/kg/day and increased to 100 mg/kg/day after one week). A reduction in seizure frequency was observed following treatment initiation; however, this finding should be interpreted cautiously because it coincided with changes in antiepileptic therapy. No meaningful neurodevelopmental progress was observed during follow-up. CONCLUSIONS:ASNSD should be suspected in patients with progressive microcephaly and early-onset epilepsy despite normal metabolic screening, and CSF amino acid analysis is valuable for diagnosis. Although a reduction in seizure frequency was observed following L-asparagine supplementation in our patient, this finding should be interpreted cautiously because phenobarbital was discontinued and topiramate therapy was initiated during the same period. Therefore, the therapeutic efficacy of L-asparagine supplementation remains uncertain, and its impact on neurodevelopment appears limited.
OBJECTIVES:Environmental endocrine disruptors (EDCs), particularly prevalent pesticide residues, are suspected contributors to the increasing incidence of central precocious puberty (CPP). This study explored the associations of urinary neonicotinoid insecticides (NNs) with sex hormones and pelvic ultrasound indicators in girls with CPP. METHODS:Girls were divided into three subgroups: CPP, non-CPP pubertal and prepubertal groups. Urinary levels of nine pesticides were screened via Kruskal-Wallis H test with Dunn's test; only nitenpyram (NIT) with intergroup differences was further analyzed. Stratified correlation and adjusted linear regression assessed links between NIT and sexual development markers, while quartile-based logistic regression examined the dose-response association between NIT and CPP risk. RESULTS:Thiamethoxam (THI), clothianidin (CLO), flupyradifurone (FPF), and sulfoxaflor (SUL) showed a 100 % detection rate, while thiacloprid (THIA) was the least detected (85.8 %). The NIT concentration was significantly higher in the CPP group (p<0.05). Stratified multivariate linear regression adjusted for age and BMI-SDS demonstrated that elevated NIT was independently positively associated with ovarian volume (OV) (B=0.73, 95 % CI: 0.15-1.31, p=0.014, β=0.294) and estradiol (E2) (B=116.64, 95 % CI: 49.58-183.70, p=0.002, β=0.682) only in CPP group, while no significant correlations were detected in non-CPP pubertal or prepubertal groups. Logistic regression revealed a significant ascending dose-response trend between elevated NIT quartiles and CPP risk (p for trend=0.048). CONCLUSIONS:NIT exposure acts as an independent environmental risk factor for CPP in girls, and aggravates sex hormone disturbance and abnormal ovarian development only in children with CPP. Restricting daily children's exposure to NNs is clinically and public health meaningful.
OBJECTIVES:The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor that regulates energy homeostasis. Pathogenic MC4R variants represent the most common cause of monogenic obesity and are frequently associated with increased linear growth. However, the mechanisms linking MC4R signaling to somatic growth remain incompletely understood. We report a child with severe growth hormone deficiency (GHD) carrying a heterozygous MC4R variant (c.496G>A; p.V166I), in whom recombinant human growth hormone (rhGH) therapy triggered an unexpectedly exaggerated clinical and biochemical response, suggesting a potential pharmacogenetic interaction between MC4R signaling and the GH/IGF-1 axis. CASE PRESENTATION:The male patient was first evaluated at 1 month of age due to micropenis and diagnosed with multiple pituitary hormone deficiencies. At 57 months of age, his height was 97.3 cm (-2.56 SDS) and annual growth velocity was 4.1 cm/year (<-2 SDS); rhGH (somatropin) therapy was initiated. Despite severe biochemically confirmed GHD, rhGH at 0.03 mg/kg/day triggered an exaggerated response: IGF-1 levels increased from -3.35 SDS to +8.00 SDS. Concurrently, his height velocity accelerated to 16 cm/year, and his bone age rapidly advanced by approximately 4 years over a 23-month period, culminating in mandibular prognathism. CONCLUSIONS:The coexistence of severe GHD and an MC4R variant is rarely described, and such a pronounced response to rhGH has not previously been reported. These findings suggest that MC4R p.V166I may modulate peripheral GH/IGF-1 signaling and act as a pharmacogenetic modifier of GH responsiveness. Careful rhGH dose titration with close IGF-1 monitoring may be considered in patients carrying the MC4R p.V166I variant.
INTRODUCTION:Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessive disorders and is a leading cause of primary adrenal insufficiency in children. Most cases are due to classic 21-hydroxylase deficiency. Earlier diagnosis has been made possible with newborn screening, which has also reduced the risk of adrenal crises. This review is based on a search of PubMed, Embase, Scopus, and Medline for articles published from 2000 to 2025, using the terms "congenital adrenal hyperplasia", "21-hydroxylase deficiency", "primary adrenal insufficiency", and "steroidogenesis" with a focus on paediatric studies, clinical trials, systematic reviews, and consensus guidelines. CONTENT:The aims of clinical management are appropriate glucocorticoid and mineralocorticoid replacement, prevention of adrenal crises, monitoring of growth, puberty, and metabolic health. The main challenges include balancing androgen suppression with minimising glucocorticoid overexposure and monitoring for long-term complications such as early bone maturation and testicular adrenal rest tumours. Diagnostic accuracy and genotype-phenotype correlations have improved through advances in biochemical testing and molecular genetics. Newer and adjunctive therapies, including modified-release hydrocortisone, CRF1 receptor antagonists, adrenal-targeted drugs, and experimental gene therapies, may further improve disease management and simplify treatment. SUMMARY AND OUTLOOK:Effective management of CAH in children requires balancing optimal hormonal control with minimising treatment-related adverse effects. Newer and future therapies are expected to improve physiological management and long-term outcomes. Further research is needed to enhance individualised care and support transition to adult services.
OBJECTIVES:Despite routine vaccination recommendations, concerns remain about vaccine-induced immune responses in some patients with inborn errors of metabolism (IEM). Therefore, antibody levels against vaccine antigens should be monitored to detect possible immune dysfunction. The aim of this study is to evaluate the vaccine antibody responses among children with IEM who have to follow protein restricted diet, and to compare with those in healthy children, and also to identify the factors affecting vaccine antibody responses in these patients. METHODS:Anti-HBs and measles immunoglobulin G results of 25 patients diagnosed with amino acid metabolism disorder; phenylketonuria, organic acidemia, homocystinuria and urea cycle disorder, and 58 healthy children of the same age and gender were recorded. Seropositivity rates and titers were compared between two groups, and also with age, daily protein intake, diet duration, total protein, albumin and hemoglobin levels. RESULTS:Seropositivity against hepatitis B was 64 %, and against measles was 80 % in the patient group, and these seropositivity rates were lower than those in the control group. These results show that the trend of the findings was maintained even after adjustment for age. No significant differences in vaccine antibody responses was found among disease subgroups. CONCLUSIONS:As children receiving long-term protein-restricted diets may demonstrate reduced vaccine antibody responses, these findings warrant confirmation in larger prospective studies. We believe that vaccine antibody responses should also be reviewed during metabolic follow-up in these patients.
OBJECTIVES:This study aimed to evaluate serum apelin levels in obese adolescents and to investigate their association with hepatic steatosis and metabolic risk parameters. METHODS:This prospective case-control study included 75 obese adolescents and 68 age- and sex-matched healthy controls. Anthropometric measurements, biochemical parameters, and serum apelin levels were assessed. Hepatic steatosis was evaluated using ultrasonography. Multivariable logistic regression analysis including age, sex, waist circumference, and serum apelin levels was performed. RESULTS:Serum apelin levels were significantly lower in obese adolescents compared with controls. Although apelin levels tended to be lower in participants with hepatic steatosis, the difference did not reach statistical significance. No significant correlations were observed between apelin levels and insulin resistance, lipid parameters, or liver enzymes. Multivariable analysis did not demonstrate an independent association between apelin levels and hepatic steatosis. CONCLUSIONS:Serum apelin levels were significantly lower in obese adolescents than in healthy controls. Although apelin levels tended to be lower in participants with hepatic steatosis, no independent association was demonstrated in this cohort. Larger prospective studies are needed to clarify the potential relationship between apelin and hepatic steatosis in pediatric obesity.
OBJECTIVES:Hyperchloremia is common in diabetic ketoacidosis (DKA), with prevalence reaching 90 %. However, its clinical impact in pediatric DKA remains unclear. This study aimed to assess the association between hyperchloremia and DKA recovery time, bicarbonate rise rate, and Pediatric Intensive Care Unit (PICU) stay, and to identify predictors of hyperchloremia. METHODS:This is a retrospective cohort study that included children under 13 years admitted to the PICU with DKA between 2018 and 2024. Patients with other acute acid-base disorders were excluded. Mann-Whitney test and Chi-square test were used as appropriate. Predictors of hyperchloremia were identified using binary logistic regression. Spearman correlation was used to assess associations between chloride levels and clinical outcomes. RESULTS:Among 162 patients, 132 (81.5 %) had hyperchloremia and 30 (18.5 %) had normochloremia. Hyperchloremic patients had longer DKA resolution time (16 vs. 8.25 h, p<0.001), slower bicarbonate rise (0.66 vs. 0.88 mmol/L/h, p=0.004), and longer PICU stay (26 vs. 18 h, p<0.001). Chloride levels significantly correlated with DKA resolution time, bicarbonate rise, and time to reach bicarbonate ≥15 mmol/L. Hyperchloremia was independently predicted by lower body weight (aOR: 0.9, 95 % CI: 0.83-0.98, p<0.001) and use of 0.9 % NaCl as intravenous fluid (aOR: 4.94, 95 % CI: 1.41-17.4, p<0.001). CONCLUSIONS:Hyperchloremia in children with DKA is associated with delayed recovery and prolonged PICU stay. Lower body weight and 0.9 % NaCl use increase hyperchloremia risk. More prospective studies are needed to assess alternative fluids containing different chloride concentrations.
OBJECTIVES:Children with multiple food allergies (MFA) often follow elimination diets that restrict major dietary sources of iodine, thereby increasing the risk of iodine deficiency. This study aimed to evaluate urinary iodine concentration (UIC) and thyroid function parameters in children with MFA and to compare these findings with those of age- and sex-matched healthy controls. METHODS:In this prospective cross-sectional study, 47 children aged 0-13 years with IgE-mediated MFA on elimination diets were compared with 52 age- and sex-matched healthy controls between October 2022 and March 2024. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were measured using electrochemiluminescence immunoassay, and UIC was determined by inductively coupled plasma mass spectrometry (ICP-MS). Anthropometric parameters were also assessed. RESULTS:Serum TSH, fT3, and fT4 levels did not differ significantly between the MFA and control groups (p>0.05). However, median UIC was significantly lower in the MFA group [86 μg/L (IQR: 50-115)] compared with controls [126 μg/L (IQR: 105-134)] (p=0.001), indicating mild iodine deficiency in the MFA group. No cases of overt hypothyroidism were detected. CONCLUSIONS:Children with multiple food allergies receiving elimination diets are at increased risk of mild iodine deficiency, even in iodine-sufficient regions, although overt thyroid dysfunction may not yet be evident. These findings highlight the importance of routine monitoring of iodine status and early nutritional interventions in this vulnerable population.
OBJECTIVES:The Tanner-Whitehouse 3 (TW3) method recognized globally for assessing skeletal maturity are based primarily on Western and East Asian populations, limiting their accuracy when applied to Indian children. The objective of present study was to develop population-specific reference values for Skeletal Maturity Scores (SMS) in Indian children aged 1-18 years using the TW radius-ulna-short bones (RUS-13) system, and to validate these data against the in vogue TW3 system. METHODS:This retrospective study analysed 3,549 left-hand radiographs (1,741 boys; 1,808 girls) from healthy Indian children obtained from previously approved bone age studies conducted between 2021 and 2024. Radiographs were scored using the TW3 RUS-13 method by two trained observers. Age- and sex-specific median SMS values were computed and smoothed using Gaussian curve fitting. The Indian SMS was validated prospectively in 50 children (20 healthy, 30 with endocrine disorders) and retrospectively for adult height prediction by substituting Indian bone ages into TW3 adult height prediction equations. RESULTS:SMS values increased progressively with age, showing earlier skeletal maturation in girls than boys. Indian children reached full skeletal maturity (SMS=1,000) at ∼16.5 years in girls and ∼17.5 years in boys. Comparison with TW2 and TW3 references indicated that Indian maturation patterns lie between these datasets. Validation demonstrated strong agreement between Indian and TW3 bone ages (ICC>0.95) and improved accuracy in adult height prediction using Indian SMS (mean absolute error = -0.1 cm for Indian vs. -0.9 cm for TW3). CONCLUSIONS:This study provides the first comprehensive Indian reference for skeletal maturity assessment. The Indian SMS enhances clinical accuracy for growth evaluation, endocrine diagnosis, and height prediction, supporting region-specific references for pediatric skeletal maturity.
OBJECTIVES:Changes in thyroid volume (TV) during the course of treatment of primary congenital hypothyroidism (CH) have not been fully elucidated. This study aimed to evaluate changes in TV according to etiology and their impact on treatment withdrawal rates. METHODS:Clinical features and thyroid ultrasonography (US) findings at diagnosis and at 3 years of age were evaluated in 178 patients with gland in situ CH. RESULTS:At diagnosis, thyroid ultrasound showed normal volume (64.3 %, n=133), hyperplastic (16.9 %, n=35), and hypoplastic (4.8 %, n=10) glands. In hyperplastic cases, median TV decreased significantly from 4.08 SDS (2.00-22.63) to 0.55 SDS (-1.68-8.52) over 3 years (p<0.0001), while hypoplastic glands showed an increase from -2.25 SDS (-2.75-2.00) to -1.05 SDS (-2.50-0.70) (p=0.005). No significant change was observed in normal volume patients [-0.42 SDS (-1.93-1.87) vs. -0.23 SDS (-2.36-5.16), p=0.305]. Transient CH rates differed by morphology (60.9 , 48.6, and 20 %, respectively; p=0.025). At 3 years, 70 % (n=7) of initially hypoplastic glands reached normal volume, with a treatment withdrawal rate of 28.6 %. CONCLUSIONS:In this study, which is the first to evaluate TV changes during the course of CH treatment, a significant decrease in TV SDS was found in patients with hyperplasia, whereas a significant increase was observed in those with hypoplasia. Despite initial hyperplasia or hypoplasia, TV could normalize over time, and treatment withdrawal was possible even in these groups.
OBJECTIVES:Overweight and obesity are highly prevalent in the general population but remain understudied in pediatric type 1 diabetes (T1D). We aimed to estimate the incidence and identify associated factors for developing elevated BMI in a contemporary, real-world cohort of racially diverse lean youth with new-onset T1D. METHODS:We reviewed medical records from 1,394 youth who were lean (BMI <85th percentile) at the onset of T1D between 2012 and 2024 (excluding those with thyroid or celiac diseases at any time), used BMI trajectory to stratify into mutually exclusive categories (stayed lean, developed overweight, or developed obesity), compared these for baseline characteristics, and estimated relative risk of becoming overweight or obese. RESULTS:Over a median of 29.2 months, 64.8 % of youth remained lean, 26.7 % developed overweight, and 8.5 % obesity. We identified significant baseline factors associated with the development of overweight (female, p<0.001; having multiple positive islet autoantibodies, p=0.026; and having lower hemoglobin A1c, p<0.001) and obesity (female, p=0.003). There were no statistically significant associations with age at T1D diagnosis, health insurance type, or positivity for thyroid or celiac antibodies. CONCLUSIONS:In sum, over 33 % of lean youth developed elevated BMI within a median of 2.4 years after T1D onset. Early identification of characteristics associated with incident overweight and obesity in youth with T1D may inform targeted weight-management interventions following diagnosis.
