Effects of aminoglutethimide upon adrenal function and cortisol metabolism in Cushing's syndrome

Abstract

The effects of aminoglutethimide upon adrenal cortical function have been investigated in 3 patients with Cushing's syndrome. One of them harbored a pulmonary oat cell carcinoma which was secreting an ACTH-like substance. Two other patients had nontumorous adrenal cortical hyperfunction. In the first individual, aminoglutethimide induced temporary inhibition of cortisol secretion. In the second patient, the drug reduced cortisol secretion and urinary 17-OHCS but plasma 17-OHCS did not change. In the third patient, the drug induced a fall in urinary 17-OHCS without change in either cortisol secretion or plasma 17-OHCS. A control subject without Cushing's syndrome, similarly treated, exhibited the same response as the third patient. Transient natruresis occurred in 3 of the 4 subjects studied. In 2 of the 3 individuals with Cushing's syndrome, a transient suppression of aldosterone excretion was observed. The data suggest that aminoglutethimide does not effectively suppress adrenal cortical function of patients with nontumorous adrenal cortical hyperplasia. This is different from its effects in a patient with metastatic adrenal carcinoma, previously reported, in whom prompt and sustained inhibition of cortisol production occurred. The marked fall in urinary 17-OHCS, as compared with less marked changes in cortisol secretion rates noted in patients receiving aminoglutethimide, indicates that this compound has important effects on cortisol metabolism. The nature of this extra-adrenal effect as well as the mechanism by which a different response was elicited in a patient with adrenal cancer and in individuals with nontumorous adrenal cortical hyperfunction remain obscure.