The Corticotropin-Releasing Factor Stimulation Test: An Aid in the Evaluation of Patients with Cushing's Syndrome

We investigated the effect of exogenous corticotropin-releasing factor on plasma levels of ACTH and Cortisol in 13 patients with ACTH-secreting pituitary adenomas (Cushing's disease) and in 9 patients with other forms of Cushing's syndrome. In all patients with Cushing's disease, ovine corticotropin-releasing factor, given intravenously as a bolus injection (1 μg per kilogram of body weight), caused a further increase in the already elevated levels of ACTH and cortisol. Successful transsphenoidal adenomectomy was followed as early as one week after surgery by normalization or near-normalization of the ACTH and cortisol responses to corticotropin-releasing factor. On the other hand, patients with the ectopic ACTH syndrome, who also had high basal plasma concentrations of ACTH and cortisol, had no ACTH or cortisol responses to corticotropin-releasing factor. This difference in responsiveness between these two patient groups cannot be explained on the basis of different metabolic clearance rates of exogenous corticotropin-releasing factor, as shown by similar disappearance curves of immunoreactive corticotropin-releasing factor from plasma. Patients with Cushing's syndrome of adrenal origin who were hypercortisolemic during testing had undetectable plasma levels of ACTH and no ACTH or cortisol responses to corticotropin-releasing factor. We conclude that stimulation of the pituitary-adrenal axis with corticotropin-releasing factor may be useful in differentiating pituitary from ectopic causes of Cushing's syndrome. (N Engl J Med 1984; 310:622–6.) CORTICOTROPIN-releasing factor, a 41-amino acid peptide first isolated from ovine hypothalami, 1 stimulates pituitary adrenocorticotropic hormone (ACTH) and β-endorphin secretion when given to rodents, 2 subhuman primates, 3 and human beings. 4 5 6 Because of its selective stimulation of the corticotrope cells of the pituitary gland and its relative safety, 7 corticotropin-releasing factor offers a possible means for studying conditions of aberrant ACTH secretion. In a previous study, corticotropin-releasing factor given to two patients with Cushing's disease caused variable elevations in plasma ACTH in both. 8 The purpose of our study was to characterize the hormonal responses to this factor in a series of patients with Cushing's . . .