Thyroid function tests were studied in patients undergoing long-term treatment with various anticonvulsant drugs. Previous reports that diphenylhydantoin induces a decrease in the serum concentrations of total and free thyroxine (T4) and triiodothyronine (T3) without a change in the TSH concentration were confirmed. Diphenylhydantoin had no effect on reverse T3. Carbamazepine was also found to decrease serum T4, the free T4 index and T3 but, with the exception of T3, the decrease was smaller than that induced by diphenylhydantoin. Dipropylacetic acid did not influence the serum thyroid hormone concentrations, and neither did primidone. This demonstrates that the interaction between anticonvulsant drugs of different chemical structure and thyroid hormone metabolism is diverse. None of the drugs tested altered serum TSH or the T3 uptake test for the estimation of unsaturated thyroid hormone binding-capacity in serum. These two tests are considered diagnostically more dependable than the measurement of thyroid hormones in serum when diphenylhydantoin and carbamazepine are administered.

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Serum iodothyronine concentrations were measured in patients on long-term therapy with one or two anticonvulsant drugs. Diphenylhydantoin (DPH) and carbamazepine (CBZ) reduced the serum levels of thyroxine (T4) free T4 index, reverse triiodothyronine (rT3) and 3,3'-diiodothyronine (3,3'-T2), whereas the depressant effect on the serum levels of triiodothyronine (T3) and free T3 index was small but statistically significant. In patients administered DPH and phenobarbital (PB) or CBZ and primidone (PD) the serum iodothyronine levels were also depressed, except for normal T3 and free T3 index. Patients receiving only PB or PD had normal serum levels of total and free thyroid hormones, but decreased concentrations of rT3 and 3,3'-T2. Only supratherapeutic concentrations of DPH and CBZ added in vitro to control sera significantly reduced the number of T4 and T3-binding sites, as reflected in increased T4 and T3 uptake test results. This indicates that the DPH and CBZ-induced decrease in thyroid hormone concentrations in vivo is not due to a displacement of thyroid hormones from their binding sites on serum proteins. The antidepressant drugs amitriptyline and mianserin had no effect on the thyroid hormone levels in serum.