Impact of Antiseizure Medication on Thyroid Function in Children With Epilepsy: A Case-Control Study

Background Epilepsy, chronic monotherapy of antiseizure medications (ASMs), as well as the secondary disturbance of the thyroid axis, which includes both subclinical and clinical hypo- and hyperthyroidism, are crucial endocrine challenges during children's development. In this study, the levels of thyroid hormones in children with epilepsy who underwent chronic monotherapy were compared with those of healthy children with no history of seizures and no experience with anticonvulsants. Moreover, in this study, the goal was to identify the actual rates, dynamics, and dose-dependence of thyroid dysfunction in the aforementioned study population. Methodology A prospective, observational, case-control study was conducted involving 150 patients with epilepsy on ASM treatment (cases) and 150 healthy control subjects who were matched for age and sex from a pediatric outpatient/inpatient department. The history, classification of seizures, and ASMs were documented. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were measured using the electro-chemiluminescent immunoassay test. Statistical analysis was performed using SPSS version 28 through one-way analysis of variance and paired Student's t-test. Results Patients exhibited a significantly higher mean TSH level (3.82 ± 2.21 vs. 2.89 ± 1.12 mIU/L; p < 0.001) and a significantly lower mean fT4 level (1.28 ± 0.29 vs. 1.35 ± 0.31 ng/dL; p = 0.012), while fT3 characteristics did not change (p = 0.45). Analyses of subgroups revealed that atypical febrile seizures (4.56 ± 2.67 mIU/L) and generalized tonic-clonic seizures (4.12 ± 2.45 mIU/L) exhibited the most significant predisposition to extreme elevations in TSH levels (p = 0.004). Regarding treatment options, patients undergoing sodium valproate monotherapy presented the highest mean TSH levels (4.02 ± 2.11 mIU/L; p = 0.001), but levetiracetam appeared to be an effective thyroid-preserving choice and provided a more favorable fT4 profile (1.35 ± 0.33 ng/dL; p = 0.020). Regarding timing, the TSH peak occurred significantly between six and nine months of the drug administration period (4.35 ± 2.41 mIU/L; p = 0.024). In addition, a clear dose-dependent pattern was detected, with mean TSH levels rising progressively to a maximum of 5.20 ± 3.12 mIU/L within the highest 25-30 mg/kg dosing range (p = 0.008), representing a notable 31% endocrine elevation. Conclusions Children with epilepsy receiving maintenance therapies with sodium valproate or phenytoin have a considerable chance of suffering from subclinical hypothyroidism, which increases sharply between six and nine months of treatment at high doses. Thyroid function monitoring is strongly advised within the first year of treatment, along with dose adjustment and evaluation of thyroid-sparing drugs, such as levetiracetam.