Effects of carbamazepine on the hypothalamic-pituitary-thyroid axis

To evaluate the effects of treatment with carbamazepine on the hypothalamic-pituitary-thyroid axis and thyroid hormone concentrations in patients with epilepsy.

We undertook a prospective study in seven subjects in whom the diagnosis of epilepsy had been established and a regimen of carbamazepine (200 mg three times a day) was initiated. All participants underwent 24-hour 123 I thyroid uptake studies, as well as assessment of the basal thyrotropin concentration and the thyrotropin response to intravenous administration of thyrotropin-releasing hormone. In addition, thyroxine (T(4)), free T(4) index, triiodothyronine (T(3)), free T(3) index, reverse T(3), and T(3) resin uptake were determined before initiation of carbamazepine treatment and again after 3 to 4 months of carbamazepine therapy.

Serum T(4), T(3), and free T(4) index decreased significantly (P<0.05) after therapy with carbamazepine, whereas no significant alterations were noted in T(3) resin uptake, free T(3) index, and reverse T(3) concentrations. A significant increase occurred in basal serum thyrotropin level (P<0.05). Moreover, the peak thyrotropin concentration, the absolute change from the basal thyrotropin level, and an integrated thyrotropin response expressed as cumulative response to thyrotropin-releasing hormone stimulation were all significantly increased after carbamazepine therapy in comparison with values documented before initiation of therapy (P<0.05 for all comparisons). Finally, 24-hour 123 I uptake by the thyroid gland increased slightly after carbamazepine therapy, but the change was not statistically significant. All values determined both before and after carbamazepine therapy remained within normal ranges.

Carbamazepine therapy induces significant alterations in serum thyroid hormone concentrations as well as in the hypothalamic-pituitary-thyroid axis. Nevertheless, patients receiving carbamazepine treatment continue to remain euthyroid despite these significant changes.