Adrenal Rest Tumor of the Liver Causing Cushing's Syndrome: Treatment withKetoconazole preceding an Apparent Surgical Cure*

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Abstract
Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg'24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng'ml; serum 17β-estradiol fell likewise from 1096 to 150 pg'ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17α-OH-progesterone levels increased 63' above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.