Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine

Summary The effect of short-term hepatic enzyme induction with carbamazepine (CBZ) on circulating thyroid hormone concentrations was studied in 10 healthy male subjects. CBZ 400 mg per day was given for 21 days in 6 subjects and for 14 days in a further 4. In the former group the effect of therapy on the pituitary/thyroid axis was also assessed by measuring thyroid stimulating hormone (TSH) response to thyrotrophin-releasing hormone. CBZ therapy resulted in induction of hepatic monooxygenase activity, evidenced by a fall in antipyrine half-life (11.1±0.7 to 7.6±0.7 h; p<0.001), and a rise in antipyrine clearance (0.72±0.06 to 0.98±0.1 ml min^–1 kg^–1; p<0.001). A significant fall in total serum thyroxine (T4) (81.9±2.9 to 75.1±2.9 nmol l^–1), and triiodothyronine (T3); (1.59±0.07 to 1.37±0.05 nmol l^–1) and free T4 (16.03±0.82 to 14.2±0.8 pmol l^–1) was seen after CBZ therapy. (all p<0.05). No significant change in reverse T3 or thyroid binding globulin occurred. In the 6 subjects studied for 21 days, maximal changes were found following 14 days' treatment. Basal and stimulated TSH remained unaltered. These effects on circulating thyroid hormone concentrations are likely to be secondary to hepatic enzyme induction leading to accelerated nondeiodinative hepatic hormone disposal. The reason for the failure of pituitary TSH secretion to rise in response to the fall in circulating T4 and T3 is unclear but may have implications for chronic treatment with CBZ in epileptic patients.