Effect of Diphenylhydantoin on Pituitary-Adrenal Interrelations

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Abstract
This report describes the effect of short-term administration of therapeutic amounts of diphenylhydantoin (Dilantin) on the adrenal cortical function in 8 normal adults. The integrity of the pituitary-adrenal axis was evaluated by measuring alterations in the urinary excretion of 17-hydroxycorticosteroids after oral administration of SU-4885 (Metopirone). Adrenal cortical responsiveness was assessed by determining the increase in plasma 17-hydroxycorticosteroid levels following intramuscular ACTH gel. These studies were performed before and during diphenylhydantoin administration. Before receiving diphenylhydantoin, all 8 subjects had a normal plasma 17-hydroxycorticosteroid response to intramuscular ACTH, and an increased urinary excretion of 17-hydroxycorticosteroids following the administration of SU-4885. While receiving diphenylhydantoin, the effect of ACTH was unaltered in all 8 subjects, whereas 7 subjects now manifested an abnormal response to SU-4885. In 3, this was characterized by a lack of change in urinary 17-hydroxycorticosteroid levels following SU-4885 administration. In the remaining 4, the magnitude of this change was depressed when compared with their prediphenylhydantoin studies. These results suggest that short-term administration of diphenylhydantoin affects the pituitary-adrenal function by blocking the pituitary release of adrenocorticotropic hormone.