DEPRESSION OF THE SERUM PROTEIN-BOUND IODINE LEVEL BY DIPHENYLHYDANTOIN*

Abstract

The mean serum protein-bound iodine (PBI) level in 36 cases of cerebral disease with seizures treated by administration of diphenylhydantoin was 3.81 [plus or minus] 0.14 (S. E.) ug- per 100 ml. This was significantly lower than the corresponding mean PBI level in 12 cases of cerebral seizure not so treated, viz., 5.39 [plus or minus] 0.16 /[mu]g. per 100 ml. Despite the occurrence of PBI levels as low as 2.4 [mu]g. per 100 ml. in the diphenylhydantoin group, there was no clinical evidence of hypothy-roidism in any of the patients and there were no significant alterations in the other parameters of thyroid function. In 7 of 8 euthyroid subjects, diphenylhydantoin also depressed the serum PBI concentration. The mechanism of action of diphenylhydantoin is apparently extrathyroidal, since this drug depressed the PBI level in hypothyroid patients maintained with a constant dosage of desiccated thyroid. Diphenylhydantoin added in vitro consistently increased the uptake of Il31-labeled 3,5,3[image]-triiodothyronine by red blood cells incubated with plasma. This effect was progressively diminished by the addition of increasing quantities of stable L-thyroxine to the incubating mixture. These data are compatible with the thesis that diphenylhydantoin depresses the level of serum PBI by interfering with the binding of thyroxine by plasma proteins.