Tests of Pituitary-Adrenal Suppressibility in the Diagnosis of Cushing's Syndrome*

Past attempts to test suppressibility of pituitary-adrenal function by the use of exogenous corticoids have yielded inconsistent findings in patients with Cushing's syndrome. The present study indicates that, with proper selection of suppressive agent and adjustment of dosage, valuable diagnostic information can be obtained from such tests. Δ1-9α-Fluorocortisol (ΔFF) and its 16α:-methylated analog (dexamethasone) were employed as suppressive agents. At dosage levels of 0.5 mg. every six hours for 8 doses these agents induced almost complete suppression of 17-hydroxycorticoid excretion in all 54 endocrinologically normal subjects tested. In contrast, all 35 of the patients with true Cushing's syndrome who were studied maintained relatively high urinary 17-hydroxycorticoid levels during such treatment. At these low dosages, therefore, the suppressive agents were useful in separating patients with Cushing's syndrome from those with normal adrenal function. Administration of ΔFF or dexamethasone in larger dosages of 2.0 mg. every six hours for 8 doses was used to separate patients with ACTH-dependent hyperadrenocorticism from those with autonomously functioning adrenal tissue. In response to large doses of suppressive agents, all patients with bilateral adrenocortical hypersecretion exhibited a definite decrease in 17-hydroxycorticoid excretion, whereas patients with adrenocortical tumors did not. The results support the view that the primary disorder in Cushing's syndrome with bilateral adrenocortical hypersecretion involves alteration of pituitary function in such a way that ACTH secretion is not suppressed by normal levels of cortisol.