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Multiple Effects of 5,5'-Diphenylhydantoin on the Thyroid Hormone System^*

PAMELA J. SMITH and MARTIN I. SURKS

Division of Endocrinology and Metabolism, Department of Medicine, Montefiore Medical Center and the Albert Einstein College of Medicine Bronx, New York 10467

Correspondence: Address requests for reprints to: Martin Surks M.D., Montefiore Medical Center, 111 East 210th St., Bronx, NY 10467.

Abstract

Introduction: 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).

Footnotes

^* This work was supported by Grants CA16463-10 and CA24604-05 from the United States Public Health Service.

Supported by a Training Grant in Investigative Endocrinology (AM 07004).

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