Concomitant falls of plasma cortisol and ACTH levels in a case of Cushing's disease during treatment with trilostane.
A 72-year-old man with Cushing's disease was treated with trilostane, a competitive inhibitor of adrenal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH). The treatment with trilostane successfully lowered urinary excretion of 17-hydroxycorticosteroids (17-OHCS) and plasma levels of cortisol and elevated the plasma level of dehydroepiandrosterone. Unexpectedly, plasma ACTH fell from 109.7 +/- 45.0 to 42.7 +/- 27.3 pg/ml (P less than 0.01) in parallel with plasma cortisol. The hyperresponsiveness of plasma ACTH observed both in the metyrapone test and the lysine-vasopressin test was also ameliorated by treatment with trilostane. Then low dose of pituitary irradiation with cobalt-60 was added and his urinary excretion of 17-OHCS and plasma levels of cortisol decreased further. After treatment with trilostane was finally stopped, the plasma ACTH increased from 45.9 +/- 21.9 to 69.6 +/- 25.3 pg/ml (P less than 0.05) in parallel with plasma cortisol. Since then he has had no recurrence for 12 months. These observations suggest that trilostane, like other adrenal enzyme-inhibiting drugs, may induce unexpected improvement of the abnormality of the hypothalamic-pituitary axis present in Cushing's disease.
D015065:17-Hydroxycorticosteroids / Q000652:urine; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000368:Aged; D003480:Cushing Syndrome / Q000188:drug therapy*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008236:Lypressin / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology
D015065:17-Hydroxycorticosteroids; D013196:Dihydrotestosterone; D008236:Lypressin; D000324:Adrenocorticotropic Hormone; C009954:trilostane; D006854:Hydrocortisone; D008797:Metyrapone