Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine
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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.
Key wordscarbamazepine thyroid hormones antipyrine enzyme induction
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- Aanderud S, Myking OL, Strandjord RE (1981) The influence of carbamazepine on thyroid hormones and thyroxine binding globulin in hypothyroid patients substituted with thyroxine. Clin Endocrinol 15: 247–252Google Scholar
- Aanderud S, Strandjord RE (1980) Hypothyroidism induced by antiepileptic therapy. Acta Neurol Scand 61: 330–332Google Scholar
- Dana-Hieri J, Oxley J, Richens A (1984) Pituitary responsiveness to genadatrophin releasing and thyrotrophin releasing hormones in epileptic patient receiving carbamazepine or phenytoin. Clin Endocrinol (in press)Google Scholar
- Liewendahl K, Majuri H, Helenius T (1978) Thyroid function tests in patients on long term treatment with various anticonvulsant drugs. Clin Endocrinol 8: 185–191Google Scholar
- Ohnhaus EE, Studer H (1983) A link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br J Clin Pharmacol 15: 71–76Google Scholar
- Oppenheimer JH, Bernstein G, Surks M (1968) Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbitol. J Clin Invest 47: 1399–1406Google Scholar
- Rapeport WG, McInnes GT, Thompson GG, Forrest G, Park BK, Brodie MJ (1983) Hepatic enzyme induction and leucocyte delta-aminolaevulinic acid synthase activity: studies with carbamazepine. Br J Pharmacol 16: 133–137Google Scholar
- Shargel L, Cheung W, Yu ABC (1979) High pressure liquid chromatographic analysis of antipyrine in small plasma samples. J Pharm Sci, 68: 1052–1053Google Scholar
- Yeo PPB, Bates D, Howe JG, Ratcliffe WG, Schardt CW, Heath A, Evered D (1978) Anticonvulsants and thyroid function. Br Med J 1: 1581–1583Google Scholar