Responsiveness of hypophyseal-adrenocortical axis to repetitive administration of synthetic ovine corticotropin-releasing hormone in patients with isolated adrenocorticotropin deficiency.

The primary lesion site in isolated ACTH deficiency was studied in three patients by examining the responses of immunoreactive ACTH to insulin-induced hypoglycemia, lysine vasopressin, and synthetic ovine corticotropin-releasing hormone (CRH). In all patients, no significant changes in immunoreactive ACTH followed insulin-induced hypoglycemia or lysine vasopressin. Fifty micrograms (greater than or equal to 1 microgram/kg BW) of CRH administered as an iv bolus dose daily for 6 consecutive days elicited no significant increase in plasma immunoreactive ACTH, beta-lipotropin, or cortisol levels in all patients. Eight iv bolus injections of 0.63 microgram/kg BW CRH at 4-h intervals also failed to induce a significant response of immunoreactive ACTH to an iv bolus dose of 1 microgram/kg CRH at 36 h in one patient. In contrast, a single bolus dose of 50 micrograms CRH induced a response of plasma immunoreactive ACTH in a patient with Cushing's disease and a patient with Addison's disease. The present results suggest that the primary lesion of isolated ACTH deficiency is not the hypothalamus, but, rather, is located in pituitary ACTH-secreting cells.