Use of ketoconazole in the treatment of Cushing's syndrome.
The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period. Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another. The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.
D015065:17-Hydroxycorticosteroids / Q000652:urine; D015068:17-Ketosteroids / Q000652:urine; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007654:Ketoconazole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D015065:17-Hydroxycorticosteroids; D015068:17-Ketosteroids; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007654:Ketoconazole; D006854:Hydrocortisone