A POSSIBLE EXPLANATION FOR CUSHING'S SYNDROME ASSOCIATED WITH ADRENAL HYPERPLASIA*

Abstract

The postulate that Cushings syndrome associated with bilatera adrenal hyperplasia results from an increased secretion of adrenocorticotropin (ACTH) satisfactory explains many aspects of the disorder. However, the absence of a measurable increase in blood concentration of ACTH in such patients has led some investigators to assume that abnormal ACTH secretion does not account for the disorder. In the present investigation, constant intravenous infusions of small amounts of ACTH (1.5-5.0 I.U. per day) were given for four-day periods to 7 normal young men at a rate calibrated so that they should not result in a measurable elevation of the blood ACTH level. In 4 of the 7 subjects, a fairly constant elevation of the plasma level of 17-hydro-xycorticosteroids (17-OH-CS) developed during the four-day infusions. In 5 of the 7 subjects the response of the plasma 17-OH-CS level to maximal stimulation with ACTH, when tested two hours after ending the constant infusion, was increased above the control response. A relatively constant elevation of plasma 17-OH-CS concentration, with loss of the normal diurnal variation and increased responsiveness to ACTH, also characterized the plasma 17-OH-CS pattern in patients with Cushing''s syndrome and adrenal hyperplasia. Thus, in view of the limits of sensitivity of present methods for the detection of ACTH in the blood, the absence of a measurable elevation of blood ACTH concentration is not a valid objection to the hypothesis that a constant secretion of ACTH is the basis for Cushing''s syndrome associated with adrenal hyperplasia.