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Cortisol production in epileptic patients treated with diphenylhydantoin
Author(s) -
Werk Emile E.,
Thrasher Katherine,
Sholiton Leon J.,
Olinger Charles,
Choi Young
Publication year - 1971
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1971124698
Subject(s) - endocrinology , medicine , urine , urinary system , metabolism , chemistry , stimulation , isotope dilution , glucocorticoid , hydrocortisone , enzyme assay , enzyme , biochemistry , chromatography , mass spectrometry
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.