Purpose:The long-term impact of continuous glucose monitoring (CGM) initiation on glycemic trajectories in children and adolescents with type 1 diabetes (T1D) remains unclear. We assessed 5-year glycated hemoglobin (HbA1c) trajectories according to CGM initiation timing in Korean children and adolescents with T1D. Methods:We retrospectively analyzed patients diagnosed with T1D at ≤18 years between 2015 and 2024 at a single pediatric diabetes center. Patients were categorized by CGM initiation timing (<1 month, 1-<12 months, ≥12 months, or no-CGM use). HbA1c was assessed at prespecified intervals up to 60 months, and adjusted trajectories and rates of change were estimated with linear mixed-effects models accounting for repeated measurements within patients. Results:Among 216 patients (mean follow-up, 61.3 ± 34.8 months), 69.9% used CGM and 40.7% initiated within 1 month of diagnosis. Baseline HbA1c was higher in the early-CGM group than in the delayed/no-CGM group (12.5% [IQR, 11.0-13.9] vs 11.1% [IQR, 8.8-13.2]; p<0.001), but converged within 12 months. Median HbA1c at 60 months was 6.8%, 6.8%, 7.7%, and 7.3% in the <1-month, 1-<12-month, ≥12-month, and no-CGM groups; the proportion achieving HbA1c <7.0% fell from 86.4% at 9 months to 47.1% at 60 months in the no-CGM group, which alone showed a rising trajectory in mixed-effects models (+0.27% per year; p<0.001). Conclusion:Early CGM initiation after T1D diagnosis was associated with more favorable 5-year HbA1c trajectories compared with delayed initiation or no CGM use, supporting routine early CGM adoption in pediatric T1D management.
Intrathyroidal ectopic thymus (IET) is a benign condition caused by aberrant thymic migration during embryogenesis. Often detected incidentally on ultrasound (US), it can mimic malignant thyroid nodules, leading to unnecessary interventions. We aimed to define the imaging characteristics of IET and emphasize an accurate diagnosis to avoid unwarranted procedures. We describe 5 pediatric cases of IET diagnosed by cervical US and monitored through long-term serial imaging. All lesions appeared as intrathyroidal nodules with echogenicity and internal foci typical of thymic tissue. Follow-up imaging showed no significant changes. None of the patients had thyroid dysfunction or clinical symptoms. The distinctive sonographic features of IET can differentiate it from malignant nodules, preventing unnecessary biopsies or surgeries. US follow-up confirmed a benign course and supports conservative management strategies.
Pediatric obesity is a growing global concern because it leads to an increased prevalence of abnormal glucose metabolism, including dysglycemia, prediabetes, and type 2 diabetes. Those conditions are associated with significant cardiovascular risk factors such as dyslipidemia, hypertension, metabolic dysfunction-associated steatotic liver disease, and sleep disturbances. Insulin resistance is a key contributor to the pathophysiology of those conditions, and the physiological reduction in insulin sensitivity during puberty further contributes to their pathogenesis in youth. However, insulin sensitivity improves after puberty, leading to spontaneous normalization of glucose metabolism in most individuals and complicating the concept of prediabetes. Therefore, general population screening for diabetes in youth is not recommended except in certain populations with high prevalence. When prediabetes is identified, lifestyle modification remains the primary intervention because pharmacologic treatments have yet to show efficacy in youth. This review explores the definitions, risk factors, screening recommendations, and management strategies for prediabetes in children and adolescents and highlights the limitations of applying adult-based diagnostic criteria to the pediatric population.
Purpose: Polyethylene glycol-recombinant human growth hormone (PEG-rhGH) is the first commercial long-acting rhGH preparation approved in China. This study was designed to assess the efficacy and safety of PEG-rhGH in treating growth hormone deficiency (GHD) during the transition period. Methods: A prospective, multicenter and single-arm study was performed. The entire study duration spanned 66 weeks, comprising a 2-week trial screening phase, a 12week dose-adjustment period, and a 52-week PEG-rhGH treatment phase. A total of 10 interviews were conducted over the course of the study. The primary endpoint was change in body composition; secondary endpoints were changes in lumbar bone mineral density (BMD, L1-4) and lean body mass (LBM). Sex- and age-specific equations were developed to adjust body composition z-scores. Results: : A total of 31 subjects were included in this study. Throughout the 64-week therapy with PEG-rhGH, the insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) demonstrated progressive elevation from baseline (-3.07 to -1.38; P<0.001). Significant alterations in body composition parameters were observed throughout the study. Body weight increased 3.96 kg (P<0.001), and the body weight SDS exhibited significant elevation from baseline (0.67) to 64 weeks (1.14; P=0.005). LBM significantly increased (4.54 kg; P<0.001), but there was a statistically significant reduction in fat percentage (Fat%) from 37.40% to 33.94% (P=0.008) and Fat% SDS from 1.91 to 1.47 (P= 0.009). The lumbar BMDz-score improved from-1.54 at baseline to-1.12 postintervention, but did not reach statistical significance (P>0.05). The triglyceride (TG) levels of the subjects decreased significantly at week 64 (P=0.018). There was no statistically significant difference in the changes of other lipid profile indicators. In this study, no adverse events attributable to direct drug-related causes were identified. Conclusion: Based on our study, PEG-rhGH can improve IGF-1 levels and alter body composition parameters by increasing LBM and decreasing body fat and TG levels in patients with GHD during the transition period, and it has a comparable safety profile and helps improve therapeutic adherence.
Differentiated thyroid cancer (DTC) is the most common form of pediatric thyroid cancer, yet its management has been largely based on evidence from adults. Recent advances in science and clinical studies of pediatric DTC, particularly in papillary thyroid carcinoma, the predominant subtype, now form the basis of emerging paradigms and revised guidelines. The potential of malignancy in thyroid nodules, as defined by current ultrasound risk stratification systems, has been evaluated in pediatric patients, enabling evidence-based indication for fine-needle aspiration biopsy. Observational studies comparing the effect of different interventions on prognosis, complications, and quality of life, challenge traditional surgical approaches in favor of potentially less extensive initial resection. Recognition of distinct underlying oncogenic drivers has not only paved the way for discoveries in the biology of pediatric thyroid cancer but has also advanced the era of targeted systemic therapy for progressive and metastatic pediatric DTC. Certain genome alterations, particularly oncogenic gene fusions that are more common in pediatric DTC, can now be targeted with small-molecule inhibitors, offering more effective therapy for metastatic disease with fewer and less severe adverse effects. This review offers an evidence-based summary of these data and the evolving trends in the diagnosis and management of pediatric DTC.
Blau syndrome, a granulomatous autoinflammatory disease, is a rare condition that is typically characterized by a triad of polyarthritis, uveitis, and dermatitis. It is caused by either an autosomal dominantly inherited or a de novo pathogenic variant in the NOD2 gene. In this report, we present a case of an 11-month-old male with Blau syndrome who presented with calcitriol-mediated hypercalcemia at an early stage. Severe hypercalcemia was controlled by intravenous fluid therapy, diuretics, calcitonin and a short course of corticosteroids. Following resolution of the hypercalcemic episode, the patient gradually developed the full clinical spectrum of Blau syndrome, including symptoms of the classic triad, along with hepatosplenomegaly, lymphadenopathy, and bone marrow involvement. Trio-genome sequencing reported a de novo pathogenic heterozygous variant in the NOD2. Following the genetic testing result, corticosteroids and methotrexate were introduced to control the disease. This is the first reported case of Blau syndrome presenting with hypercalcemia as an initial manifestation, preceding the development of the classic triad of symptoms. This case underscores the importance of considering Blau syndrome in the differential diagnosis of early-onset hypercalcemia of unknown etiology. Molecular genetic testing should be pursued in such cases to facilitate accurate and timely diagnosis, enabling appropriate management.
PURPOSE:Psychiatric conditions are common in children and adolescents with diabetes and can hinder disease management. In this study, we examined whether mental health status at diagnosis predicts glycemic control at 1 year. METHODS:We included 57 patients aged 6-18 years diagnosed with type 1 or type 2 diabetes between 2019 and 2023 at Seoul National University Bundang Hospital. Mental health was assessed within 3 months of diagnosis using the Eating Disorder Inventory-2, Children's Depression Inventory, and Child Behavior Checklist (CBCL) for ages 6-18. Poor glycemic control was defined as glycated hemoglobin >6.5% at 1 year. Associations between screening results and glycemic control were analyzed using Fisher exact test and multivariate logistic regression. RESULTS:Of the 57 patients, 32 (56.1%) had type 1 diabetes, and the mean age at diagnosis was 12.9±3.1 years; 31 (54.4%) were male. Poor glycemic control at 1 year was observed in 16 patients (28.1%). Although individual subscale positivity was not significantly associated with glycemic control, borderline somatic complaints on the CBCL were significantly associated with poor control (p=0.022). In multivariate analysis, having 2 or more positive CBCL subscales showed a trend toward association with poor glycemic control (adjusted odds ratio=21.47, p=0.054). CONCLUSION:Early psychological screening, especially for somatic symptoms or multiple psychological problems, may help identify those at risk for poor glycemic control in pediatric diabetes. These findings underscore the importance of early detection and intervention in optimizing diabetes management.
Childhood and adolescent obesity are growing global health concerns, with genetic factors playing an important role. Despite the increasing prevalence of obesity in India, monogenic obesity remains underdiagnosed. We report 2 cases of early-onset morbid obesity due to melanocortin-4 receptor (MC4R) gene mutation. Case 1 was a 5-year-old boy who presented with severe hyperphagia and rapid weight gain since infancy. Case 2 was a 12-year-old girl who presented with progressive obesity, hyperphagia, and bilateral genu varum. Both patients exhibited severe insulin resistance with no syndromic stigmata. Genetic analysis confirmed a homozygous MC4R mutation in both cases. They were managed with a multidisciplinary approach that included dietary modification, structured physical activity, and pharmacotherapy using the glucagon-like peptide-1 analog liraglutide and metformin. Both cases showed a satisfactory response to liraglutide. These case reports highlight the point at which monogenic obesity can be clinically suspected and distinguished from syndromic obesity. Moreover, they underscore the role of genetic testing for monogenic obesity and the targeted therapies in its management.
Stunting remains a major public health concern in Southeast Asia, and is shaped by a complex interplay of genetic, inflammatory, and nutritional factors. This scoping review sought to map genetic polymorphisms associated with stunting in Southeast Asian children and to identify candidate biomarkers for early diagnosis and biologically targeted interventions. Following the Arksey and O'Malley framework and the PCC (Population, Concept, Context) model, a systematic search was conducted across 7 databases. Eligible studies were peer-reviewed, published in English from 2015–2024, involved children under 18 years of age, and investigated gene variants in relation to stunting. A total of 902 records were screened independently by 3 reviewers using predefined criteria, with consensus procedures to resolve any discrepancies. Eleven studies met the final inclusion criteria. Thematic analysis and protein-protein interaction mapping revealed that 5 key polymorphisms—IGF1R, GHSR, MTRR, CASP1, and CARD17—were significant contributors to growth impairment. IGF1R polymorphisms were associated with a 2.46-fold increase in stunting risk (odds ratio [OR], 2.46; 95% confidence interval [CI], 1.60–3.78), while MTRR variants yielded an OR of 1.93 (95% CI, 1.22–3.05). Similarly, GHSR and CASP1 polymorphisms were linked to increased odds of stunting (OR, 2.15; 95% CI, 1.38–3.34 and OR, 1.67; 95% CI, 1.10–2.54, respectively). These polymorphisms were consistently associated with disrupted growth hormone signaling, chronic inflammation, and nutrient-sensitive pathways. The biological network underlying stunting in this population points to a converging mechanism of impaired endocrine function and inflammatory dysregulation. However, this review’s scope is limited by underrepresentation of some Southeast Asian nations and exclusion of non-English literature. Early genetic screening for high-risk biomarkers and precision-driven nutritional interventions may offer more effective strategies to reduce the burden of stunting in Southeast Asian children.
PURPOSE:Multiple protocols exist for the dosing and duration of human chorionic gonadotropin (hCG) and the sampling schedule of the hCG stimulation test. This study analyzes the testosterone response following a single-dose hCG test. METHODS:This observational study analyzes 103 prepubertal undervirilized males who underwent a single-dose hCG test. A dosage of 1,500 IU was used for those under 2 years of age and 5,000 IU for those over. Testosterone levels were measured before and 72 hours after the hCG injection, and the fold of increase was analyzed. As part of the unit protocol, those with a suboptimal response to a single-dose test (n=19) underwent a 3-day hCG test. RESULTS:A significant 23.65-fold increment of testosterone, with a poststimulated value of 167.26 (interquartile range [IQR], 62.30-279.15) ng/dL, was observed following a single dose of hCG. Of the 103 subjects, 19 (18.4%) had a subnormal response with testosterone levels of 8.20 (IQR, 3.48-29.70) ng/dL. A 3-day test on these 19 subjects showed a testosterone level of 18.4 (IQR, 10.6-64.2) ng/dL, which is statistically significant. However, the 3-day hCG test revealed an adequate response in only 3 patients. The remaining 16 did not achieve the expected outcome, and 15 of these patients had laboratory evidence of hypogonadism either genetically or biochemically. CONCLUSION:A single-dose hCG stimulation test could serve as an alternative to a 3-day hCG test in the initial assessment of Leydig cell function, thereby avoiding repeated injections, hospital visits, and school absenteeism.
PURPOSE:In this study, the neural communication patterns between hypothalamic structures and cortical areas in girls diagnosed with central precocious puberty (CPP) were explored. Endocrine profiles were incorporated to clarify the pathophysiological interactions between cerebral networks and hormonal regulation. The hypothalamus was designated as the key focus area for connectivity analysis. METHODS:Fifty-seven girls (37 CPP, 20 non-CPP) were recruited from the Pediatric Development Clinic at the Second Affiliated Hospital of Anhui Medical University. The collected data included demographic information, gonadotropin-releasing hormone stimulation tests, and magnetic resonance imaging scans. Hypothalamic functional connectivity (FC) was analyzed using predefined region of interest coordinates, and correlations between hormone levels and FC values were assessed. RESULTS:Compared to the non-CPP group, the CPP group exhibited elevated baseline follicle-stimulating hormone (FSH), baseline luteinizing hormone (LH), peak FSH, peak LH, and peak LH/FSH ratios. Patients with CPP exhibited enhanced neural synchronization linking the right lateral hypothalamic effector zone to the right superior frontal gyrus (displaying a borderline significant correlation with peak LH concentrations), concurrent with diminished functional coupling of the right lateral hypothalamic efferent to the right fusiform/supramarginal gyri. The left lateral hypothalamic projections demonstrated amplified connectivity with the right cuneus. No FC differences were observed in the medial hypothalamus. CONCLUSION:Abnormal lateral hypothalamus FC patterns were identified in CPP girls and were particularly linked to peak LH levels. The findings offer novel insights into the neuroendocrine mechanisms underlying CPP.
PURPOSE:Down syndrome (DS) is associated with metabolic dysregulation, obesity, and increased risk of chronic inflammation. This study aimed to assess subclinical inflammation in children with DS by evaluating inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), and their association with metabolic parameters including ghrelin, lipid profiles, and vitamin D levels. METHODS:A total of 49 children with DS (aged 1-18 years) and 22 age-matched healthy controls were enrolled. Anthropometric data, body fat percentage, and metabolic parameters were assessed. Inflammatory markers (hs-CRP, apolipoprotein-B [Apo B], adiponectin), metabolic hormones (ghrelin, insulin), and lipid profiles were determined from venous blood samples. Statistical analyses included bivariate correlation, analysis of variance, and multiple linear regression to identify predictors of inflammation. RESULTS:Children with DS exhibited significantly higher hs-CRP levels than controls (p=0.03), indicative of increased systemic inflammation. Higher hs-CRP levels were associated with older age (r=0.33, p=0.006), greater obesity (body mass index: r=0.32, p=0.011), and elevated serum insulin and low-density lipoprotein levels. Ghrelin levels correlated negatively with Apo B (r=-0.41, p<0.001) and positively with hs-CRP (r=0.30, p=0.012). Predictors of inflammation (based on hs-CRP) included older age, male sex, higher gamma-glutamyl transferase level, and a diagnosis of DS (adjusted R²=0.276). CONCLUSION:Children with DS are prone to metabolic inflammation, with increasing age and obesity exacerbating inflammatory responses. Clinicians should monitor and manage weight, dyslipidemia, and inflammation in this population to prevent long-term complications such as cardiovascular diseases and insulin resistance.
Purpose:Continuous glucose monitoring (CGM) is being increasingly utilized in inpatient pediatric diabetes care; however, data on its real-world accuracy remain limited. Methods:We retrospectively assessed the clinical accuracy of factory-calibrated Dexcom G6 and G7 CGM systems in 69 pediatric patients with type 1 diabetes at a Korean tertiary hospital between 2019 and 2025. A total of 1838 CGM readings were temporally paired with point-of-care (POC) capillary glucose measurements. Accuracy was evaluated using the mean absolute relative difference (MARD), mean absolute difference (MAD), Bland-Altman analysis, and Clarke error grid classification. Subgroup analyses were performed according to the sensor day, glucose range, care setting, and CGM type. Results:The overall MARD was 10.6±10.1% and MAD was 15.4±16.2 mg/dL. Accuracy improved over time, with MARD declining from 13.8% (G6) and 11.0% (G7) on Day 1 to <10% on Days 6 and 4, respectively. Bland-Altman limits narrowed from ±60 to ±39 mg/dL. During Days 6-11, 86% of CGM-POC pairs were within Clarke Zone A and 97% in Zones A+B. The MAD increased with higher glucose levels, whereas the MARD was highest during hypoglycemia (15.2%) and lowest during hyperglycemia (8.5%). ICU admission significantly increased the MAD (p=0.001) without affecting the MARD. G7 demonstrated superior accuracy to G6 (pooled MARD: 9.8% vs. 11.2%, p=0.003). Mixed-effects modeling confirmed that sensor day was an independent predictor of accuracy improvement (-0.34% MARD/d, p<0.001). Conclusion:The Dexcom G6 and G7 CGMs met the ISO 15197:2013 and FDA integrated-CGM criteria after a short inpatient stabilization period.
Purpose: This study aims to examine the prevalence of overweight and obesity in children with type 1 diabetes mellitus (T1DM) in Hong Kong and to evaluate the association between obesity, glycemic control, and metabolic comorbidities. Methods: A retrospective cross-sectional study was conducted from 2022-2023 at the Hong Kong Children's Hospital, enrolling all children with T1DM. Anthropometric measurements and biochemical data were extracted from medical records, and prevalence rates of metabolic complications were compared. Results: One hundred twenty-six children (41% male, 89% Asian) with a median age of 12.8 years were included. Of these, 17.5% were either overweight or obese. There were no significant differences in hemoglobin A1c values between the normal-weight and overweight/obesity groups, though the latter group required higher total daily insulin doses. Children with overweight/obesity had higher prevalence rates of hypertension (28.6% vs. 2.9%) and dyslipidemia (90.5% vs. 71.9%). They were also more likely to have hypertension (adjusted odds ratio [aOR], 18.48; 95% confidence interval [CI], 3.42- 99.94) and hypertriglyceridemia (aOR, 7.71; 95% CI, 1.66-35.76). The overweight/obese group also exhibited significantly higher alanine aminotransferase levels (median, 18 IU/L vs. 14 IU/L), non-high-density lipoprotein cholesterol (HDL-C) levels (median, 3.3 mmol/L vs. 2.9 mmol/L), and triglyceride/HDL-C ratios (median, 1.09 vs. 0.52) and lower HDL-C levels (median, 1.4 mmol/L vs. 1.6 mmol/L). Among those with dyslipidemia, only 8% were started on lipid-lowering agents, while none of those with hypertension were started on antihypertensive agents. Conclusion: Despite a lower prevalence of overweight/obesity in Asian children with T1DM compared to Western populations, metabolic comorbidities occur at an exceptionally high rate. Early interventions to tackle these modifiable cardiovascular risk factors are crucial to prevent long-term complications.
