Isolated increased free-triiodothyronine in medication-naïve children and adolescents with ADHD: a retrospective...

Thyroid hormones, free triiodothyronine (free-T3) in particular, are crucial for fetal development and child growth and may influence neurodevelopmental disorders including Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. Yet data are scarce and inconsistent, often relying on adult rather than pediatric reference intervals or on incomplete thyroid panels, and the value of free-T3 as a biomarker across development remains unclear.

In this retrospective observational study, we characterized thyroid function in medication-naïve patients aged 6 to 17 years with ADHD, using community laboratory results collected between March 2004 and December 2022 in a university pediatric department. Thyroid testing was prescribed prior to methylphenidate initiation. We determined the percentage of patients with free-T3, free-T4, and TSH levels below, within, or above age- and sex-adjusted reference intervals. In the largest immunoassay subgroup (ADVIA Centaur; n = 404), individual free-T3 values were converted to z-scores using published pediatric normative data. A longitudinal ancillary analysis assessed temporal stability in patients with repeat measurements. No non-ADHD comparison group was available.

Among 715 medication-naïve patients with ADHD (570 boys, 145 girls) with normal TSH, approximately one-third presented with isolated increased free-T3 concentrations (2IfT3 profile) - 33.68% of boys, 27.59% of girls - the most frequent thyroid anomaly observed. In the ADVIA Centaur subgroup, free-T3 z-scores were higher than the pediatric norms across all age groups, with the largest deviation in boys aged 11-14 years. Among 57 patients with repeat testing (median interval 2.57 years), instability was marked: 53.57% of those initially showing 2IfT3 normalized, while 50% of those initially normal developed 2IfT3.

Isolated increased free-T3 is frequent in medication-naïve pediatric ADHD and most pronounced in boys aged 11-14 years, but its marked temporal instability precludes its use as a stable biomarker. In the absence of a concurrent non-ADHD comparison group, these findings describe the frequency of this biochemical profile within an ADHD cohort rather than establishing an association with ADHD itself. The 2IfT3 profile may reflect a developmentally and state-dependent neuroendocrine pattern, and warrants prospective study incorporating direct pubertal staging, standardized assay methodology, and appropriate controls.