Dysregulation of Thyroid, Growth, and Appetite Hormones in Children and Adolescents With Neurodevelopmental Disorders: A Meta-analysis.

Abstract

Background: Neurodevelopmental disorders [NDDs, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and tic disorder] usually arise during childhood or adolescence, but impact quality of life throughout the whole life cycle. Therefore, early diagnosis of NDDs is necessary; however, its etiology remains unclear. This study aimed to evaluate levels of thyroid, growth, and appetite hormones between children and adolescents with NDDs and healthy controls (HCs) by a meta-analysis of all evidence that demonstrated the importance of these indicators, but yielded controversial results.

Methods: Five online databases were searched to retrieve relevant articles published before March 1, 2025. Mean and standard deviation data were collected and pooled using Stata 15.0 software to generate standardized mean difference (SMD) with 95% confidence intervals (CIs) as the effect size (ES) measure.

Results: Fifty-four studies were included. The overall meta-analysis, subgroup, and trim-and-fill adjusting revealed that compared with HCs, levels of thyroid hormone free triiodothyronine (FT3) (SMD = 0.22; 95% CI = 0.04 to 0.40; p_ES = 0.015), total triiodothyronine (TT3) (SMD = 0.82; 95% CI = 0.36 to 1.28; p_ES < 0.001), and thyroid peroxidase antibody (TPO-Ab) (SMD = 0.37; 95% CI = 0.08 to 0.67; p_ES = 0.014) were significantly increased, while free thyroxine (FT4) (SMD = -0.67; 95% CI = -0.69 to -0.64; p_ES < 0.001), total thyroxine (TT4) (SMD = -0.35; 95% CI = -0.50 to -0.20; p_ES < 0.001), and thyroid stimulating hormone (TSH) (SMD = -0.22; 95% CI = -0.41 to -0.03; p_ES = 0.026) were significantly decreased in children and adolescents with NDDs. These changes were mainly observed in ADHD patients, with TPO-Ab increased only in ASD patients. Levels of the appetite hormone leptin were significantly elevated in male NDDs (SMD = 0.74; 95% CI = 0.10 to 1.38; p_ES = 0.023) and ASD patients (SMD = 0.46; 95% CI = 0.17 to 0.74; p_ES = 0.002) relative to HCs, but not in ADHD cases. Growth factor IGF-1 (insulin-like growth factor-1) was only significantly lower in the cerebrospinal fluids of ASD patients when compared with HCs (SMD = -0.89; 95% CI = -1.42 to -0.36; p_ES = 0.001).

Conclusions: Thyroid hormones and IGF-1/leptin may respectively represent promising biomarkers for predicting ADHD and ASD in children and adolescents.