The role of corticotropin-releasing factor in the investigation of endocrine diseases.

Abstract

Since the discovery and structural elucidation of corticotropin-releasing factor (CRF) synthetic ovine and human CRF have become useful tools for the diagnosis of pituitary and adrenocortical disorders. The stimulation of release of adrenocorticotropic hormone (ACTH) after a dose of 100 micrograms CRF allows differentiation of the various causes of secondary adrenal insufficiency. In patients with specific autoimmune corticotroph disorders or general inflammatory or tumorous destruction of the anterior pituitary there is no rise of ACTH after intravenous administration of CRF. In contrast, patients with secondary adrenal failure due to suprasellar lesions show a rise of ACTH from a low or unmeasurable basal level without an accompanying cortisol response, demonstrating the integrity of the corticotroph and the atrophy of the cRF neuron and the adrenocortical cell. Similar observations are made in patients with secondary adrenal failure resulting from long-term glucocorticoid treatment. This demonstrates that the main reason for adrenal insufficiency after glucocorticoid treatment is the persisting suppression of the activity of CRF neurons. In patients with adrenocortical hyperfunction (Cushing's syndrome) the CRF stimulation test differentiates unequivocally between autonomous adrenal hypercortisolism and ACTH-dependent bilateral adrenal hyperplasia. However, the differential diagnosis between eutopic pituitary (Cushing's disease) and paraneoplastic ACTH secretion (ectopic ACTH syndrome) is difficult. Recent results show that catheterization of the sinus petrous inferior and measurement of ACTH in central and peripheral blood before and after CRF injection allows this differential diagnosis to be made with confidence. The usefulness of measuring CRF plasma levels is not established. The only exception to this is in cases of ectopic CRF syndrome, which is a rare cause of Cushing's syndrome.