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)