Thyroid-metabolic interactions in pediatric epilepsy: insights from central sensitivity indices and peripheral hormone markers

Introduction: Pediatric epilepsy is frequently associated with endocrine and metabolic alterations, partly related to long-term antiseizure therapy. Although thyroid dysfunction has been described in this group, conventional laboratory tests may not detect more subtle changes in hormone sensitivity or peripheral thyroid metabolism. The present study aimed to provide a comprehensive evaluation of central and peripheral thyroid hormone regulation in children with epilepsy and to examine its relationship with metabolic status. Methods: This cross-sectional study included 152 children and adolescents with epilepsy and 116 healthy peers matched for age and sex. All participants underwent measurement of thyroid function parameters (TSH, FT4, FT3), indices of central thyroid hormone sensitivity (TFQI, PTFQI, TSHI, TT3RI, TT4RI), markers of peripheral thyroid hormone metabolism (FT3/FT4 ratio), and metabolic variables (fasting glucose, insulin, and lipid profile). Stratified analyses and multivariable regression models were used to determine independent associations, while correlation analyses explored links between thyroid-related indices and metabolic measures. Results: Compared with controls, patients with epilepsy showed higher fasting insulin levels and a less favorable lipid profile. Standard thyroid function tests (TSH and FT4) and indices of central thyroid sensitivity did not differ between groups. However, FT3 concentrations and the FT3/FT4 ratio were increased in the epilepsy cohort, indicating changes in peripheral thyroid hormone metabolism despite preserved central regulation. Multivariable models identified BMI z-score as the main independent factor associated with both metabolic alterations and thyroid hormone sensitivity indices, whereas exposure to antiseizure medications and disease duration showed weaker and less consistent relationships. Conclusions: Children and adolescents with epilepsy appear to maintain normal central thyroid regulation but exhibit modifications in peripheral thyroid hormone metabolism, reflected by a higher FT3/FT4 ratio. These results point to a complex and possibly adaptive endocrine–metabolic adjustment influenced by body composition and treatment factors, highlighting the need for confirmation in prospective longitudinal studies.