ADRENAL REST TUMOR OF THE LIVER CAUSING CUSHINGS-SYNDROME - TREATMENT WITH KETOCONAZOLE PRECEDING AN APPARENT SURGICAL CURE
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Date
1985
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Abstract
Ketoconazole, an imidazole derivative which inhibits 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 wk 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 1st 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 1 wk of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17.beta.-estradiol fell likewise from 1096 to 156 pg/ml. Cortisol levels in serum and urine increased in the first 2 wk of the trial and subsequently fell to values below the basal levels. Serum 17.alpha.-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. At 9 mo. after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. Ketoconazole was evidently effective in blocking tumoral steroidogenesis, which resulted in clinical benefit.