Long‐Term Treatment of Children with Epilepsy with Valproate or Carbamazepine May Cause Subclinical Hypothyroidism

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Abstract
Summary: Purpose: The aim of the study was to evaluate serum thyroid hormone balance in children receiving long‐term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB). Methods: We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine‐binding globulin (TBG), and thyroid‐stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12–161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control‐group mean + 2 SD (4.37 mIU/L in our study) and 12 mIU/L. Results: In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ‐ and VPA‐treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal‐range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA‐treated children, accounting for 26% of patients with subclinical hypothyroidism. Conclusions: Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.