Decreased Serum Free Thyroxine Concentration in Patients Treated with Diphenylhydantoin1

Abstract

When diphenylhydantoin is added to serum in vitro the free thyroxine fraction increases. The apparent magnitude of this effect is diminished by diluting serum prior to analysis. In contrast to the in vitro effect of diphenylhydantoin, there was no significant difference in the free thyroxine fraction of undiluted serum obtained from diphenylhydantoin treated and control patients. Administration of diphenylhydantoin to normal subjects also failed to increase the free thyroxine fraction. Because of a decrease in total hormonal iodine concentration in the serum, the free thyroxine concentration in diphenylhydantoin treated patients and experimental subjects was lower than in their respective controls. Electrophoretic analysis of serum from diphenylhydantoin treated patients showed that a decreased fraction of total serum thyroxine was bound to thyroxine binding globulin. Since free thyroxine concentration was depressed despite the competitive effects of diphenylhydantoin, it appears that the maintenance of a constant free thyroxine concentration is not the controlling factor in determining the extent to which diphenylhydantoin lowers serum thyroxine.