Abstract
1. Plasma and urine steroid and plasma ACTH levels were measured for 2 weeks in eight subjects (six female, two male) with Cushing's disease with each given 200 mg ketoconazole orally four times daily. 2. Treatment was associated with major falls in excretion of free cortisol and the cortisol metabolites tetrahydrocortisol, 5 alpha-tetrahydrocortisol and tetrahydrocortisone. 3. Plasma cortisol and ACTH levels did not change significantly. 4. Excretion of the androgen metabolites, androsterone, 11 beta-hydroxyandrosterone and aetiocholanolone was also reduced but there was no significant fall in plasma testosterone. Plasma levels of progesterone, 17 alpha-hydroxyprogesterone and 11 beta-deoxycortisol and excretion of pregnanediol, pregnanetriol and tetrahydrodeoxycortisol rose with treatment. 5. Analysis of steroid precursor/product ratios indicated that ketoconazole significantly inhibited 11 beta-hydroxylase and 17,20-lyase but not 17 alpha-hydroxylase in these patients with Cushing's disease.
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