CLINICAL APPLICATION OF A NEW TEST OF PITUITARY RESERVE*

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Abstract
SU-4885, [2-methyl-1,2-bis(3-pyridyl)-1-propanone] inhibits 11[beta]-hydroxylation of steroids by the human adrenal cortex and leads to a decrease in cortisol secretion, a "compensatory" rise in ACTH secretion, and the secretion of large quantities of 11-desoxycorticosteroids such as compound S [11-desoxycortisol]. Compound S and its metabolites are readily measurable in biologic fluids as 17-hydroxycorticoids. In normal subjects, therefore, SU-4885 induces a rise in total blood and urinary 17-hydroxycorticoids. Since this response to SU-4885 is dependent upon a rise in ACTH secretion it affords, in patients who do not have frank adrenal insufficiency, a sensitive means of testing the reserve capacity of the pituitary gland to secrete ACTH. Of 9 patients with chromophobe adenomas tested in this manner, 6 were found to have "limited pituitary reserve." This was true also of 2 out of 5 patients with acromegaly, 3 out of 6 patients with cachexia, and 1 patient with post-traumatic diabetes insipidus. Of 7 patients with active Cushing''s disease due to adrenal hyperplasia, all exhibited responses which were greater than the average response of normal subjects. Of 4 patients who had been successfully treated for Cushing''s disease by pituitary irradiation, all exhibited subnormal responses to SU-4885. Of 3 patients with Cushing''s syndrome secondary to adrenal tumor, none exhibited increases in 17-hydroxycorticoid excretion in response to SU-4885. Of 6 patients with myxedema due to primary hypothyroidism all responded normally. It is concluded that SU-4885 affords a sensitive means of testing the responsiveness of the ACTH-secreting mechanism in various clinical situations.