Effect of Diphenylhydantoin on the Metabolism of Dexamethasone

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Abstract
Patients on chronic diphenylhydantoin therapy have abnormal plasma corticosteroid and urinary 17-hydroxycorticosteroid responses to low doses of dexamethasone (0.5 mg every six hours for eight doses). Responses to higher doses (2.0 mg every six hours for eight doses) are normal. Even though this pattern resembles Cushing's syndrome associated with adrenal hyperplasia, the history, physical examination and other laboratory findings are not consistent with such a diagnosis. Gastrointestinal absorption of dexamethasone was not impaired in rats treated chronically with diphenylhydantoin, but the biliary excretion and hepatic conjugation of dexamethasone or its metabolites were found to be enhanced. The resulting lower levels of active dexamethasone reaching the pituitary gland would account for the failure of ACTH suppression. Dexamethasone suppression tests should be interpreted cautiously in patients on chronic diphenylhydantoin therapy.