Abstract
Cortisol production and metabolism were compared in 21 patients with convulsive disorders before and during diphenylhydantoin (DPH) therapy up to 24 months. Cortisol secretion rates (CSR) were measured by the ‐urinary isotope‐dilution method, based on the specific activity in urine of the metabolites tetrahydrocortisol and tetrahydrocortisone. Cortisol metabolism was evaluated by the ratio in urine of 6‐hydroxycortisol to 17‐hydroxycorticosteroids (6‐OHF/17‐OHCS). During DPH therapy there was a positive correlation of CSR with the increase in ratio of 6‐OHF/17‐OHCS. A significant mean increase in CSR, of 35 per cent above control, was found when the ratio increased more than 0.14. Since the increase in 6‐OHF/17‐OHCS is probably related to enhancement of hepatic microsomal enzyme activity by DPH, it can be concluded that, in epileptic patients treated with the drug, cortisol production will increase if there is sufficient enzyme stimulation. No deleterious effect has been observed in association with these changes in cortisol production and metabolism.
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