Multiple effects of 5,5′-diphenylhydantoin on the thyroid hormone system

The INFLUENCE of 5,5′-diphenylhydantoin (DPH) on the thyroid hormone system continues to intrigue clinicians and endocrine scientists more than two decades after Oppenheimer et al. (1) reported that the serum protein-bound iodine (PBI) concentration was decreased in patients treated with the drug. Early investigations indicated that DPH interacted with T₄ at binding sites on serum thyroxine-binding globulin (TBG) in a competitive and reversible fashion (2, 3) and this interaction was initially considered to be responsible for the depression of serum PBI in DPH-treated patients (1). However, refinements in measurements of serum free-T₄ concentration resulted in the demonstration that serum free-T₄ concentration was actually decreased in DPH-treated patients (4), not unchanged as anticipated if the drug had a primary effect on T₄-binding by TBG (5). Further investigations indicated that DPH treatment resulted in an increase in the fractional rate of T₄ metabolism in association with decreased serum T₄ and free-T₄ (6).