A 15 years old girl with diabetes mellitus and grand mal epilepsy is being treated with valproic ac

Fråga: A 15 years old girl with diabetes mellitus and grand mal epilepsy is being treated with valproic acid and carbamazepine. The actual data of T3, T4 and TSH are in the low range of normal values. Can the treatment with valproic acid and/or carbamazepine influence the thyroid tests?

Sammanfattning: Carbamazepine and/or valproate therapy can decrease thyroid hormone levels although the development of clinical hypothyroidism is rare.

Svar: Several studies have investigated the action of anticonvulsant drugs on the thyroid function. Treatment with carbamazepine has been reported to alter thyroid hormone levels in adults as well as in epileptic children, being found in most of them a decrease in T3 and T4 without a concomitant increase in TSH (1,2,3,4,5). Despite of that, patients are in a euthyroid state and clinical hypothyroidism is quite rare, only two cases of clinical hypothyroidism caused by treatment with phenytoin and/or carbamazepine have been reported (6).

Hegedus et al (4) found an increase in thyroid size in 28 epileptic patients treated with carbamazepine compared to control subjects, but this was not accompanied by clinical manifestations of hypothyroidism.

The thyroid function of 50 affectively ill patients treated with carbamazepine (600-1600 mg/day) has also been investigated (7). One month treatment caused a 30 per cent decrease of T3, T4, free T4 and a slight increase in TSH.

Concerning the effect of valproic acid on thyroid hormone levels, less number of patients treated with this drug have been studied and although in most of the studies the thyroid hormone levels are decreased (8,2), also contradictory results are found (1,5). One case of hypothyroidism after valproate therapy has been reported (9).

The mechanism of the effect of these drugs on the thyroid hormone levels is not clear.

It has been speculated that carbamazepine could decrease these levels due to the property this drug has on inducing hepatic microsomal enzymes, but this cannot explain the decreased levels found during treatment with valproic acid, as this drug is not an enzyme inducer. 1 Liewendahl K, Majuri H, Helenius T: Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs. Clin Endocrinol 1978; 8: 185-191 2 Bentsen KD, Gram L, Veje A: Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate. Acta Neurol Scand 1983; 67: 235-241 3 Conran MJC, Kearney PJ, Callaghan MN, Murphy D, Goggin T: Hypothalamic pituitary function testing on children receiving carbamazepine or sodium valproate. Epilepsia 1985; 26: 585-588 4 Hegedus L, Hansen JM, Luhdorf K, Perrild H, Feldt-Rasmussen U, Kampmann JP: Increased frequency of goitre in epileptic patients on long-term phenytoin or carbamazepine treatment. Clin Endocrinol 1985; 23: 423-429 5 Ericsson UB, Bjerre I, Forsgren M, Ivarsson SA: Thyroglobulin and thyroid hormones in patients on long-term treatment with phenytoin, carbamazepine, and valproic acid. Epilepsia 1985; 26: 594-596 6 Aanderud S, Strandjord RE: Hypothyroidism induced by anti-epileptic therapy. Acta Neurol Scand 1980; 61: 330-332 7 Roy-Byrne PP, Joffe RT, Uhde TW, Post RM: Carbamazepine and thyroid function in affectively ill patients. Clinical and theoretical implications. Arch Gen Psychiatry 1984; 41: 1150-1153 8 Luhdorf K: Endocrine function and antiepileptic treatment. Acta Neurol Scand 1983; suppl 94: 15-19 9 Salvatoni A, Martini C, Cammareri V: Hypothyroidism and sodium valproate. J Pediatr 1983; 103: 1005-1006