Aug 2026· Frontiers in Endocrinology· Vol 17· 0 citations· 42 references
Medicine
TL;DR
Adrenal androgen activity, reflected by DHEA-S, represents a significant endocrine pathway linking obesity to accelerated skeletal maturation, highlighting developmentally specific windows of endocrine-metabolic interaction in growing children.
Abstract
Background Childhood obesity is associated with advanced bone age (BA), but the underlying endocrine mechanisms remain unclear. We investigated the mediating role of dehydroepiandrosterone sulfate (DHEA-S) in the relationship between adiposity and skeletal maturation. Methods This retrospective study included 1,252 children aged 4–12 years from a single center. Skeletal maturation was assessed using the BA-to-chronological age (CA) ratio. Advanced maturation was defined as BA/CA > 1.1. Mediation analysis was performed to evaluate whether DHEA-S explains the association between BMI SDS and skeletal maturation. Results Body mass index standard deviation score (BMI SDS) and DHEA-S were independently associated with the BA/CA ratio (p < 0.05). In boys younger than 9 years, DHEA-S demonstrated good discriminative performance for advanced maturation (Area under the curve = 0.817). Mediation analysis showed that DHEA-S significantly mediated the association between BMI and BA/CA in boys < 9 years (β = 0.512, p = 0.024) and in girls ≥ 8 years (β = 0.377, p = 0.003). In young boys, the direct effect of BMI became non-significant after inclusion of DHEA-S, consistent with substantial mediation by adrenal androgens. Conclusions Adrenal androgen activity, reflected by DHEA-S, represents a significant endocrine pathway linking obesity to accelerated skeletal maturation. The magnitude of this mediation varies by age and sex, highlighting developmentally specific windows of endocrine-metabolic interaction in growing children.
A sex-specific protective effect of puberty on MASLD risk in children, with advancing puberty associated with significantly lower odds of MASLD in boys, but not in girls.
Background Elevated insulin-like growth factor-1 (IGF-1) levels are associated with earlier pubertal onset and accelerated bone maturation. However, the effect of IGF-1 increases during growth hormone (GH) therapy on bone age (BA) advancement across different etiologies of short stature remains unclear. Methods This multicenter observational study included 1,944 children with idiopathic growth hormone deficiency (IGHD), idiopathic short stature (ISS), or small for gestational age (SGA) enrolled in the LG Growth Study registry between 2020 and 2024. IGF-1 standard deviation score (SDS), auxological parameters, GH dose, and BA were assessed during GH therapy. BA advancement was defined as the first occurrence of a BA-to-chronological age ratio (BA/CA) >1 during follow-up. Cox proportional hazards regression models were used to evaluate the association between IGF-1 SDS and BA advancement, with additional multivariable adjustment for potential clinical confounders. Additional subgroup analyses according to age, sex, diagnosis, and GHD severity were performed. A sensitivity analysis using BA/CA >1.2 was also conducted. Results Each 1-unit increase in IGF-1 SDS was associated with a higher risk of BA advancement in the overall cohort (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.15–1.33, p<0.001), with consistent associations in males and females. Compared with IGHD, children with ISS (HR 1.63, 95% CI 1.26–2.11) and SGA (HR 2.15, 95% CI 1.82–2.55) showed significantly increased risks of BA advancement. Additional analyses stratified by age, GHD severity, and pubertal initiation showed consistent findings. Sensitivity analysis using BA/CA >1.2 confirmed the association between IGF-1 SDS elevation and significant BA advancement. Conclusion Increases in IGF-1 SDS during GH therapy are independently associated with accelerated bone maturation in children with short stature, particularly in those born SGA. These findings remained consistent across multiple subgroups and sensitivity analyses, supporting the importance of individualized GH dosing with careful monitoring of IGF-1 levels and skeletal maturation.
J. Ahn, Hwalrim Jeong, Junghwan Suh et al.· Frontiers in Endocrinology· 0 citations
Whether pubertal timing across the ages of 8–15.5 years was associated with diurnal cortisol slope, the cortisol awakening response, total morning cortisol, and total daily cortisol output at the age of 15.5 years was sought.
Background: Hormonal alterations, may complicate the metabolic consequences linked to childhood obesity. To study the relation between pediatric obesity and hormonal abnormalities, along with the correlation between body mass index (BMI) and other metabolic and endocrine markers.
Methods: A prospective observational study including 325 children aged 6 to 14 years was conducted at a tertiary care teaching hospital in north India over 30 months (January 2024 to July 2026). Individuals were classified into three categories based on their BMI percentiles for age and gender as normal weight, overweight, and obese. In addition to blood pressure and anthropometric data, fasting biochemical markers such as cortisol, free thyroxine (free T4), glucose, insulin, and thyroid-stimulating hormone (TSH) were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to determine insulin resistance. One-way analysis of variance and multivariate linear regression with age and gender adjustments were used for statistical analysis.
Results: Obese children demonstrated markedly elevated levels of cortisol, TSH, HOMA-IR, and fasting insulin compared to their normal-weight counterparts, along with reduced levels of free T4 (p<0.05). A multivariate regression analysis, after controlling for age and gender, indicated that BMI was significantly associated with indicators of insulin resistance and thyroid hormone levels.
Conclusions: Childhood obesity is associated with significant hormonal and metabolic alterations, suggesting early endocrine adaptations that may have metabolic implications. While these changes (particularly thyroid-related shifts) represent reversible, adaptive responses rather than primary pathology, findings highlight need for early identification and intervention to prevent potential long-term cardiometabolic risks associated with pediatric-onset obesity.
Rakhi Jain, P. Upadhyay· International Journal of Con...· 0 citations
Early-life nutrition is a critical predictor of long-term health, yet the association between rapid early-childhood growth and adolescent obesity, particularly in relation to the “double burden of malnutrition,” remains under-researched in Indonesia. This study aimed to analyze the association between rapid growth and adolescent obesity. Data were obtained from the 1997, 2000, and 2014 waves of the Indonesian Family Life Survey (IFLS). This study included 641 children (aged 0–23 months at baseline) with complete anthropometric measurements across all three waves. Rapid growth was defined as an increase in z-scores of >0.67 in weight-for-age (WAZ), height-for-age (HAZ), or weight-for-height (WHZ) between 1997 and 2000. Multivariable logistic regression, stratified by baseline nutritional status, was used to estimate adjusted risk ratios (aRRs). The adolescent obesity prevalence was 4.5%. Rapid WAZ growth was significantly associated with adolescent obesity (aRR = 4.49; 95% CI: 1.32–15.25), whereas rapid WHZ growth showed a borderline association (aRR = 2.90; 95% CI: 0.87–9.47). Stratified analysis showed that the association between rapid weight gain and adolescent obesity was markedly stronger among children with a history of undernutrition (aRR = 14.99 for WAZ; aRR = 9.52 for WHZ) than among those without. Rapid weight gain during early childhood, particularly in children with a history of undernutrition, is a strong predictor of adolescent obesity. These findings emphasize the importance of integrating longitudinal growth-trajectory monitoring into routine child health assessments to promote healthy growth while minimizing future metabolic risks.
Background The classic paradigm of somatotropic-gonadal axis synergy in pubertal bone acquisition lacks validation in central precocious puberty (CPP), and the driver of the significant bone turnover marker (BTM) heterogeneity in this population is unknown. Objective To investigate the independent and potential synergistic associations of insulin-like growth factor-1 (IGF-1) and peak luteinizing hormone (LH) with BTMs in girls with CPP. Methods This retrospective cohort included 190 treatment-naïve girls with CPP. Participants were stratified into Low, Medium, and High bone turnover groups based on tertiles of a bone age-standardized composite Z-score of bone gla protein (BGP) and β-C-terminal telopeptide (β-CTX). We used multiple linear regression adjusted for chronological age, supplemented by E-value analysis. Results Marked BTM heterogeneity was confirmed (p for trend < 0.001). IGF-1 and peak LH levels exhibited significant graded increases across groups (p for trend = 0.003 and 0.030). After age-adjustment, IGF-1 independently correlated with both BGP (β = 0.069, p = 0.005) and β-CTX (β = 0.001, p = 0.030), while peak LH associated only with BGP (β = 0.411, p = 0.026). Critically, the IGF-1 × LH peak interaction was non-significant (p = 0.655 and 0.791 for BGP and β-CTX, respectively). In contrast, glucolipid metabolic parameters showed no differences, arguing against their major role and highlighting neuroendocrine specificity. Conclusion In this cross-sectional study of girls with CPP, heterogeneity in bone turnover was more strongly and consistently associated with the somatotropic axis (IGF-1) than with gonadotropin activity, and no significant synergy was observed. These findings suggest a potential shift toward a somatotropic-dominant mechanism in the context of pathological pubertal acceleration, highlight IGF-1 as a pivotal biomarker for skeletal metabolism assessment, and challenge the classical paradigm of somatotropic-gonadal axis collaboration. The proposed mechanism requires validation in longitudinal studies.
Fuhui Liu, Hai-Qin Jiang, Zhen-Zhen Li et al.· Frontiers in Endocrinology· 0 citations
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