Adrenocortical Cancer: Steroid Biosynthesis and Metabolism Evaluated by Urinary Metabolites

Abstract

In order to survey characteristic metabolic abnormalities in adrenal cancer, we have measured important urinary metabolites of intermediates and end-products of steroid biosynthesis. The adrenal cancer in 9 of 10 cases could not efficiently 11β- hydroxylate Substance S, as shown by the elevated excretion of tetrahydro Substance S both absolute and relative to cortisol metabolites. In 2 patients, the tumor seemed to have a complete block of Ilβ-hydroxylation of Substance S. Hydroxylation of 17α-hydroxyprogesterone was relatively inefficient in 6 of 10 cases, as judged by the excretion of pregnanetriol relative to corticoid excretion. Pregnanediol excretion was high in the 4 subjects studied. The neoplasm of one patient was probably lacking in the 3β-hydroxysteroid dehydrogenase. The ll-oxy-17-ketosteroids were excreted in amounts greater than could be predicted from the excretion of cortisol metabolites. The most quantitatively important in this group was 11β-hydroxyandrosterone. Urinary dehydroepiandrosterone was increased in each patient, as was the excretion of etiocholanolone and androsterone. Analysis of these findings suggests that the urinary metabolites in patients with adrenal cancer reflect overproduction of pregnenolone, inefficient utilization of intermediates at several stages of steroid synthesis, and abnormal metabolism of the steroids either within the tumor tissue or peripherally.