THYROID-FUNCTION WITH ANTIEPILEPTIC DRUGS

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT. The effects of VPA on serum thyroid hormone and TSH levels may be mediated by effects on TSH secretion and on the protein binding of thyroid hormones.