THE PLASMA 17-HYDROXYCORTICOSTEROID RESPONSE TO CORTICOTROPIN, SU-4885 AND LIPOPOLYSACCHARIDE PYROGEN*†

Abstract

Two different mechanisms of pituitary activation were evaluated in 34 normal subjects, 5 patients with anterior pituitary insufficiency, 3 with adrenocortical insufficiency, 2 with Cushing''s syndrome, and 3 with acromegaly, by studying serial changes in plasma 17-hydroxycorticosteroid levels in response to intravenously administered purified lipopolysaccharide pyrogen (Lipexal) and a propanone compound, SU-4885. These responses were compared to those observed following the intramuscular administration of 80 units of corticotropin gel. Similar studies were performed on 15 subjects maintained with corticotropin or corticosteroid therapy. The plasma 17-hydroxycorticosteroid responses to these tests provide a means for distinguishing between normal subjects and patients with pan-hypopituitarism. Addison''s disease or Cushing''s syndrome. Four hours after the fourth injection of corticotropin gel (administered intramuscularly in doses of 80 units every eight hours) there is complete separation between the ranges of response in these various groups of subjects. Since the responses to SU-4885 and to Lipexal differentiate normal subjects from patients with panhypopituitarism, they mar be useful in investigating pituitary adrenal inhibition. Using these technic, pituitary-adrenal responsiveness following cortiosteroid therapy was occasionally found to be suppressed, whereas following corticotropin therapy no suppression could be demonstrated. Evidence is presented which supports the concepts that 1) the site of suppression by corticosteroid therapy may be at the adrenocortical as well as at the pituitary level, and 2) there may be two mechanisms for activation of pituitary corticotropin[long dash]one through negative feed-back stimuli (SU-4885), and one through stressful stimuli (Lipexal).