Frågedatum: 1994-06-07
RELIS database 1994; id.nr. 10101, DRUGLINE
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Are there any reports of Valproic acid-induced hypothyreosis?/nThe question concerns a woman born i



Fråga: Are there any reports of Valproic acid-induced hypothyreosis?

The question concerns a woman born in 1949 who had surgery for meningeoma in November 1992. After the operation the patient has had causal attacks with secondary generalisation. She has tried carbamazepine, phenytoin and phenobarbital with unsatisfactory effects. She has now been treated with valproic acid since May 1993 at a dosage of 300 mg three times daily and a plasma level of 620 umol/L. Before beginning the valproic acid treatment the patient already had a slight elevation of her thyrotropin (TSH) levels. The level of TSH has increased further and is now 9.7 (ref 0.4-4.0 mU/L). Her thyroxine and triiodothyronine levels are normal. Does valproic acid affect the levels of thyrotropin?

Sammanfattning: It is possible that valproic acid may contribute to an increased level of thyrotropin (TSH) by inhibiting the release of somatostatin, which inhibits TSH secretion.

Svar: A question concerning thyroid hormone levels and antiepileptics has been dealt with earlier at the Drug Research & Information Centre (1). Thyroxine concentrations are reduced in patients taking enzyme-inducing drugs (carbamazepine and/or phenytoin compared with controls or patients taking sodium valproate) (2). Triiodothyronine is unaffected by administration anticonvulsant drugs (2). Thyrotropin (TSH) levels are unaffected by carbamazepine and phenytoin (2,3). Valproic acid does not affect (2) or increase (3) thyrotropin (TSH) levels. In (3) the TSH levels were 2.9 +/- 1.8 or 2.5 +/- 1.0 mU/L in patients treated with valproic acid or carbamazepine and valproic acid in comparison with control subjects (1.7 +/- 0.8 mU/L). The authors suggest that the increased basal level of thyrotropin could be due to the GABA-ergic properties of valproic acid inhibiting somatostatin´s inhibitory effect on TSH secretion. 1 Drugline nr 05076 (year 1986) 2 Larkin JG, Macphee GJA, Beastall GH, Brodie MJ: Thyroid hormone concentrations in epileptic patients. Eur J Clin Pharmacol 1989; 36: 213-216 3 Isojärvi JIT, Pakarinen AJ, Myllylä VV: Thyroid function with antiepileptic drugs. Epilepsia 1992; 33: 142-148 (enclosed)

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