Cause of Cushing's Syndrome in Patients with Tumors Arising from “Nonendocrine” Tissue

Abstract

Five patients with “nonendocrine” tumors, bilateral adrenal hyperplasia, hypercorticism and hypokalemia have been studied in an effort to understand the relationship between the tumors and the metabolic disturbance. An ACTH-like material was found in the primary tumor, in metastatic tumors and in the plasma of each patient. The pituitary ACTH content, on the other hand, was subnormal. Urinary corticosteroids, though qualitatively normal, were increased to levels greater than those commonly encountered in ordinary Cushing's disease. Attempts to suppress corticosteroid output with large doses of dexamethasone were ineffectual. All signs of hypercorticism, including the hypokalemia, were corrected following adrenalectomy in 2 cases. It is concluded that certain tumors autonomously elaborate an ACTH-like substance that stimulates the adrenal glands to secrete large quantities of corticosteroids; the corticosteroids, in turn, suppress the normal ACTH-secreting mechanism and, in addition, induce major metabolic aberrations, particularly hypokalemia.