Corticotropin releasing factor (CRF): diagnostic implications

Abstract

Nine normal volunteers received an intravenous bolus injection of 50, 100, and 200 micrograms ovine Corticotropin releasing factor. There was no dose response relationship between the injected oCRF dosage and stimulated ACTH, beta-endorphin, and cortisol secretion. When human synthetic CRF was injected (50 and 100 micrograms i.v.) no significant difference compared to the oCRF induced ACTH stimulation was observed. In contrast to the lacking relationship between the CRF dosage and the biological response there was a clearcut dose response relationship between the amount of oCRF injected and the CRF immunoreactivity measured 15 minutes after injection with a specific oCRF radioimmunoassay. No serious side effects were observed when the 100 micrograms CRF dosage was used as standard dose in the CRF test in patients with diseases of the hypothalamo-pituitary-adrenal axis. In patients with Cushing's syndrome the CRF test is helpful for the differential diagnosis (ACTH dependent Cushing's disease, autonomous cortisol secretion due to an adrenal adenoma or carcinoma, ectopic ACTH syndrome). In addition the CRF test is of prognostic value after surgical or neurosurgical therapy of Cushing's syndrome. Furthermore secondary adrenal failure after operative therapy can be documented by the CRF test. In patients on corticoid therapy the degree of suppression of CRF induced ACTH secretion correlated to the dosage and the duration of corticoid therapy. The main suppressive effect of corticoids on the hypothalamo-pituitary-adrenal axis seems to take place at the pituitary level. In patients with secondary adrenal failure the analysis of ACTH secretion after CRF administration allows the differential diagnosis between hypothalamic and pituitary ACTH hyposecretion. In conclusion the administration of oCRF has been shown to be a well tolerated and useful tool in the differential diagnosis of the causes of hyper- and hypofunction of the hypothalamo-pituitary-adrenal axis. Though there was only 10% cross reactivity with synthetic human CRF, CRF immunoreactivity could be detected in 53 out of 55 pregnant females. The results of measuring endogenous CRF levels in patients with diseases of the hypothalamo-pituitary-adrenal axis are preliminary but endogenous CRF levels measured by the heterologous oCRF radioimmunoassay, correlated well to the clinical situation and the ACTH-levels. These results have to be verified with a homologous hCRF radioimmunoassay.