Carbamazepine and risk of hypothyroidism: a prospective study

OBJECTIVES - While carbamazepine (CBZ) decreases thyroid hormone concentrations it rarely causes hypothyroidism. We assessed prospectively the early effect of CBZ on thyroid status in thyroxine-supplemented hypothyroid patients, when compared with patients without a thyroid disorder. METHODS - In 29 patients, thyrotropin (TSH), total thyroxine (TT4) and free thyroxine (FT4) serum levels were assayed before starting CBZ, and then weekly for 7 weeks. Nineteen patients with no thyroid disorder (group A) were compared with 10 thyroxine-supplemented hypothyroid patients, stable before CBZ treatment (group B). RESULTS - In group A, TT4 decreased significantly by ca. 15-25%, starting from the first week (Friedman, P < 0.001). FT4 decline was smaller (ca. 10-15%) and delayed till the second week. FT4/TT4 ratio increased significantly (P < 0.001), while TSH only slightly (P = 0.073), never exceeding normal range. In group B, similar TT4 and FT4 decline was followed by significantly increasing TSH (P = 0.011), while the FT4/TT4 ratio was not significantly changed. In 3 of 10 patients TSH rose over 5 mIU/l, necessitating treatment adjustment. CONCLUSIONS - In patients with no thyroid disorder, CBZ causes hormonal changes of no clinical relevance, due to adaptive response. In T4-supplemented hypothyroid patients this adaptation is lacking, CBZ may precipitate subclinical or overt hypothyroidism, and early thyroid function monitoring seems advisable.