Effects of exogenous adrenocorticotropic hormone (ACTH) upon pituitary ACTH concentration after prolonged cortisone treatment and stress.

Symptoms and metabolic abnormalities closely resembling those of hypoadrenalism have been reported following cessation of prolonged treatment with adrenal steroids (1-5). Sudden death following surgery has been reported in association with this syndrome and has been ascribed to failure of the hypothalamic-pituitary-adrenal system to respond to stress (6-9). Since prolonged administration of corticosteroids produces adrenal atrophy in both man and laboratory animals (7, 10, 11), this failure has been attributed to adrenal insufficiency. Exogenous corticotropin (ACTH) will repair or maintain normal adrenal weight in the cortisone-treated animal (12). Consequently the addition of ACTH in various dosage schedules has been advocated for the purpose of maintaining or restoring normal adrenal responsiveness to stress (5, 13-16). The efficacy of such combined therapy is not firmly established. In addition to producing adrenal atrophy, chronic treatment with steroids results in decreased pituitary ACTH content (17, 18). The failure of steroid-treated subjects to respond to stress may therefore reflect pituitary ACTH insufficiency rather than, or in addition to, adrenal insufficiency. ACTH administration, on the other hand, has been shown to increase pituitary ACTH content in the intact rat, despite stimulation of secretion of endogenous steroids (18). For this reason ACTH therapy has been studied in the cortisonetreated animal to determine whether such adjunctive therapy is capable of modifying the pituitary ACTH depletion which follows steroid administration, and whether it can enhance the pituitary response to stress.