Effects of Mitotane Treatment on Human Steroid Metabolism: Implications for Patient Management

The study investigated the effects of mitotane on steroid metabolism in patients with adrenocortical carcinoma (ACC) who were treated with hydrocortisone alone or with mitotane and hydrocortisone. The study included 20 patients (9 males and 11 females) and found that mitotane treatment led to increased excretion of polar unconjugated steroids, particularly 6β-hydroxycortisol and 6β-hydroxy-20-dihydrocortisols. The study observed a significant decrease in the ratios of 5α-/5β- and 20β-/20α-metabolites of administered cortisol, indicating specific inhibition of 5α-reductase 2. These changes in cortisol catabolism did not interfere with the early detection of ACC recurrence. The induction of 6β-hydroxylation by mitotane explained the reported decrease in cortisol bioavailability and suggested its potential as a unique steroid metabolic probe for 20β-reduction.