Apparent Increase in Type I 5’-Deiodinase Activity Induced by Antiepileptic Medication in Mentally Retarded Subjects

Abstract

Background/Objectives: Thyroid function measurements in 3 mentally retarded patients treated with antiepileptic drugs (phenytoin or carbamazepine) showed normal thyroid-stimulating hormone (TSH) responses in spite of markedly low levels of total thyroxine (T₄), triiodothyronine (T₃), and free thyroxine (FT₄) concentrations; free triiodothyronine (FT₃), as well as mean thyroxine-binding globulin (TBG) concentrations were normal. The objective of the present investigations was to determine if antiepileptic medication in these patients contributed to the disparate TSH and thyroid hormone (TH) levels. Methods: Thyroid tests and other laboratory parameters were measured by conventional techniques. Results: Circulating TH changes noted in retarded patients were similar to those observed in control subjects receiving carbamazepine alone. Reverse T₃ (rT₃) levels in all patients were either undetectable or below the normal range. Conclusions: As type I 5′-deiodinase has a higher affinity for rT₃ than T₄, an increased activity of this enzyme would enhance rT₃ deiodination and reduce serum rT₃ concentration whereas enhanced T₄ deiodination would aid in normalizing intracellular FT₃ concentration. The finding of normal serum FT₃ concentration was consistent with normal TSH response and clinical euthyroidism in both retarded and control subjects. While phenytoin-induced increase in type I 5′-deiodinase has been previously noted, the present studies demonstrate a similar effect of carbamazepine on 5′-deiodinase.