Summary
Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volunteers were included as controls.
Total thyroxine (T4) concentrations were reduced in patients taking enzyme-inducing drugs (carbamazepine and/or phenytoin) compared with both controls and patients taking sodium valproate. Similar differences were shown with each individual drug. All nine patients whose circulating T4 was below the lower limit of the reference range were taking enzyme inducers. Free thyroxine concentrations were also reduced in individuals treated with carbamazepine and phenytoin with five values falling beneath the reference range. Tri-iodothyronine and thyrotropin appeared unaffected by anticonvulsant administration. Thyrotropin releasing hormone stimulation revealed no true hypothyroidism.
The lowering effect of anticonvulsant drugs on circulating total and free T4 was not exhibited by the non-inducing sodium valproate. These data support the influence of enzyme induction as a likely mechanism for reduced thyroxine concentrations in treated epileptic patients.
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References
Anderud S, Myking OL, Strandjord RE (1981) The influence of carbamazepine on thyroid hormones and thyroid binding globulin in hypothyroid patients substituted with thyroxine. Clin Endocrinol 15: 247–252
Aanderud S, Standjord RE (1980) Hypothyroidism induced by antiepileptic therapy. Acta Neurol Scand 61: 330–332
Chin W, Schussler GC (1968) Decreased serum free thyroxine concentration in patients treated with diphenylhydantoin. J Clinl Endocrinol Metab 28: 181–186
Chopra IJ, Solomon DH, Chopra V, Wu SY, Fisher DA, Nakamura Y (1978) Pathways of metabolism of thyroid hormones. Recent Prog Horm Res 34: 521–545
Connacher AA, Borsey DR, Browning MCK, Davidson DLW, Jung RT (1987) The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic. Postgrad Med J 63: 841–845
Connell JMC, Rapeport WG, Gordon S, Brodie MJ (1984) Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine. Eur J Clin Pharmacol 26: 453–456
Haidukewych D, Rodin EA (1987) Chronic anti-epileptic drug therapy: Classification by medication regimen and incidence of decreases in serum thyroxine and free thyroxine index. Ther Drug Monit 9: 392–398
Heyma P, Larkins RG, Perry-Keene D, Peter CT, Ross D, Sloman JG (1977) Thyroid hormone levels and protein binding in patients on long-term diphenylhydrantoin treatment. Clin Endocrinol 6: 369–376
Larsen PR (1982) Thyroid-pituitary interaction. Feedback regulation of thyrotrophin secretion by thyroid hormones. N Engl J Med 306: 23–32
Larsen PR, Atkinson AJ, Wellman HN, Goldsmith RE (1970) The effect of diphenylhydantoin on thyroxine metabolism in man. J Clin Invest 49: 1266–1279
Levy RH, Koch KM (1982) Drug interactions with valproic acid. Drugs 24: 543–556
Liewendahl K, Majuri H, Helenius T (1978) Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs. Clin Endocrinol 8: 185–191
Macphee GJA, Mitchell J, Wiseman L, McLellan AR, Park BK, McInnes GT, Brodie MJ (1988) Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man. Br J Clin Pharmacol 25: 59–66
Mendoza DM, Flock EV, Owen Jr CA, Paris J (1966) Effect of 5,51-diphenylhydantoin on the metabolism of L-thyroxine-131I in the rat. Endocrinology 79: 106–118
Ohnhaus EE, Studer HA (1983) Link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br J Clin Pharmacol 15: 71–76
Oppenheimer JH, Fisher LV, Nelson KM, Jailer JW (1961) Depression of the serum protein-bound iodine level by diphenylhydantoin. J Clin Endocrinol 21: 252–262
Oppenheimer JH, Tavernetti RR (1962) Displacement of thyroxine from human thyroxine-binding globulin by analogues of hydantoin. Steric aspects of the thyroxine-binding site. J Clin Invest 41: 2213–2220
Park BK (1982) Assessment of the drug metabolism capacity of the liver. Br J Clin Pharmacol 14: 631–651
Perucca E, Hedges A, Makki KA, Ruprah M, Wilson JF, Richens A (1984) A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol 18: 401–410
Smith PJ, Surks MI (1984) Multiple effects of 5-51-diphenylhydantoin on the thyroid hormone system. Endocrinol Rev 5: 514–525
Surks MI, Ordene KW, Kumara-Siri MH, Munn DN (1983) Effect of diphenylhydantoin on TSH secretion in man and in the rat. J Clin Endocrinol Metab 56: 940–945
Wolff J, Standaert ME, Rall JE (1961) Thyroxine displacement from serum proteins and depression of serum protein-bound iodine by certain drugs. J Clin Invest 40: 1373–1379
Yeo PPB, Bates D, Howe JG, Ratcliffe WA, Schardt CW, Heath A, Evered DC (1978) Anticonvulsants and thyroid function. Br Med J 1: 1581–1583
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Larkin, J.G., Macphee, G.J.A., Beastall, G.H. et al. Thyroid hormone concentrations in epileptic patients. Eur J Clin Pharmacol 36, 213–216 (1989). https://doi.org/10.1007/BF00558149
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DOI: https://doi.org/10.1007/BF00558149