CLINICAL APPLICATION OF A NEW TEST OF PITUITARY RESERVE*

TLDR

SU‑4885 blocks adrenal 11β‑hydroxylation, lowering cortisol and raising ACTH, which in turn produces measurable 17‑hydroxycorticoids that can be used to assess pituitary function. The study seeks to determine whether SU‑4885‑induced ACTH release can sensitively evaluate pituitary reserve in patients without adrenal insufficiency. By administering SU‑4885 and quantifying the resulting 17‑hydroxycorticoid excretion, the authors assess the ACTH‑secreting capacity of the pituitary. SU‑4885 revealed limited pituitary reserve in most chromophobe adenoma, acromegaly, cachexia, and diabetes insipidus patients, exaggerated responses in adrenal‑hyperplasia Cushing’s disease, subnormal responses after pituitary irradiation, no response in adrenal‑tumor Cushing’s, and normal responses in myxedema, confirming its sensitivity for ACTH‑secretion testing.

Abstract

SU-4885 inhibits 11β-hydroxylation of steroids by the human adrenal cortexand 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. 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-traumaticdiabetes 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.