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

Childhood epilepsy is often linked to endocrine and metabolic disturbances, partly from prolonged antiseizure treatment. While thyroid dysfunction is known in this population, routine tests may miss subtle changes in hormone sensitivity or peripheral metabolism. This study seeks to thoroughly assess central and peripheral thyroid hormone regulation in pediatric epilepsy and explore its connection to metabolic health. In this cross-sectional study, 152 children and adolescents with epilepsy and 116 age- and sex-matched controls underwent assessment of thyroid function (TSH, FT4, FT3), central thyroid hormone sensitivity indices (TFQI, PTFQI, TSHI, TT3RI, TT4RI), peripheral thyroid hormone metabolism (FT3/FT4 ratio), and metabolic parameters (fasting glucose, insulin, and lipid profile). Stratified and multivariable regression analyses were performed to identify independent associations, and correlation analyses were used to explore thyroid–metabolic relationships. Children with epilepsy had higher fasting insulin and a worse lipid profile than controls. Thyroid function markers (TSH, FT4) and central thyroid sensitivity indices were similar between groups, but FT3 and the FT3/FT4 ratio were elevated, suggesting altered peripheral thyroid metabolism despite preserved central regulation. Multivariable analyses identified BMI z-score as a major independent determinant of metabolic alterations and thyroid hormone sensitivity, while antiepileptic drug exposure and disease duration showed variable and modest associations. Conclusions: Pediatric epilepsy is characterized by preserved central thyroid regulation but altered peripheral thyroid hormone metabolism, as reflected by an increased FT3/FT4 ratio. These findings suggest a multifactorial and potentially adaptive endocrine–metabolic remodeling influenced by adiposity and treatment exposure, warranting further investigation in longitudinal studies.