Different therapeutic efficacy of ketoconazole in patients with Cushing's syndrome.
The property of ketoconazole to inhibit adrenal biosynthesis of cortisol was used in a clinical study of 14 patients with Cushing's syndrome (pituitary-dependent Cushing's disease, n = 10; adrenocortical adenoma, n = 2; adrenocortical carcinoma, n = 1; ectopic ACTH syndrome, n = 1). Five patients were treated in a short-term manner (1000 mg over 24 h) and nine patients for a longer period (600 mg/die from 1 week up to 12 months). After short-term administration of ketoconazole, serum cortisol levels fell distinctly only in the patient with adrenocortical adenoma, but not at all or only slightly in the other patients, whereas serum levels of progesterone and 11-deoxy-compounds increased markedly in all patients, with the exception of the patient with adrenocortical carcinoma. Plasma ACTH levels increased in the patients with Cushing's disease but not in the patients with tumor. After long-term treatment of three patients with Cushing's disease over 3, 10, and 12 months, the clinical signs of hypercortisolism persisted or were only slightly ameliorated. In these three patients as well as in three other patients with Cushing's disease treated for a shorter period of 1 to 4 weeks, serum and urinary cortisol levels decreased, but were not normalized, whereas plasma ACTH levels increased variably. Only in one patient with Cushing's disease, in the second patient with adrenocortical adenoma, and in the patient with ectopic ACTH syndrome, serum and urinary cortisol levels returned to normal. We conclude from our data, that the antimycotic drug inhibits biosynthesis of cortisol by blocking adrenal 11 beta- and 17 alpha-hydroxylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Engelhardt
D
D
Medizinische Klinik II, Universität, München.
Jacob
K
K
Doerr
H G
HG
D000182:ACTH Syndrome, Ectopic / Q000188:drug therapy; D000236:Adenoma / Q000188:drug therapy; D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy*; D003907:Dexamethasone; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007654:Ketoconazole / Q000008:administration & dosage*; D008297:Male
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D007654:Ketoconazole; D006854:Hydrocortisone