Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy.

To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy. Serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex- and age-matched healthy children. Mean valproic acid treatment duration was 2.80±1.96 years. The valproic acid group had higher serum thyroid-stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid-stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid-stimulating hormone levels. One third of children with normal range serum valproic acid levels may have elevated serum thyroid-stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.