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      Carbamazepine, Oxcarbazepine, and Valproate Reduce Serum Thyroid Hormone Concentrations in Female Adolescents

      A DGReview of :"Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication"
      Epilepsia

      03/23/2004
      By Emma Hitt, PhD


      Carbamazepine (CBZ) and oxcarbazepine (OXC) reduce serum thyroid hormone concentrations in female adolescents with epilepsy, while valproate (VPA) is associated with normal serum thyroid hormone and increased thyrotropin levels, according to a new study.

      The effects of the anti-epileptic drugs CBZ, OXC, and VPA on thyroid hormone levels are not fully established. CBZ and OXC are known to induce cytochrome p450 enzymes, whereas the effect of valproate on thyroid hormone function is more controversial.

      Leena K. Vainionpaa, MD, with the University of Oulu, Finland, and colleagues studied 78 females, aged 8 to 18 years old, with epilepsy; 41 were taking VPA, 19 taking CBZ, and 18 taking OXC. Fifty-four healthy age-matched controls also participated.

      Participants were examined clinically, and their pubertal stage was assessed. Thyroid function was assessed at baseline and after a mean follow up of 5.8 years; 64 patients and 42 controls participated in the follow up.

      In the first evaluation, the mean serum thyroxine (T4) and free T4 hormone concentrations were lower in the girls taking CBZ or OXC compared to in the control group (P < .001, all comparisons), but thyrotropin (TSH) concentrations were normal. Approximately two-thirds of the participants taking CBZ or OXC had serum T4 and/or free T4 levels below the lower limit of the reference range.

      The VPA-treated participants with epilepsy had normal serum T4 and free T4 concentrations, but slightly increased TSH levels (P < .01) compared with the controls. Normal serum hormone concentrations were restored in the patients who discontinued the medication.

      "These results further support the view that hepatic P450 enzyme induction is not the main or the only reason for decreased thyroid hormone concentrations during CBZ or OXC treatments," Dr. Vainionpaa and colleagues conclude.

      They note that all antiepileptic drugs studied had an effect on thyroid function, but the hormonal changes had no effect on growth or development.

      "It appears that measurement of serum TSH concentration is the most reliable means to evaluate the true thyroidal state of patients taking CBZ, OXC, or VPA for epilepsy," they suggest.


      Epilepsia 2004;45:197-203. "Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication"

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