Corticotropin releasing factor (CRF)-stimulation test in normal controls and patients with disturbances of the hypothalamo-pituitary-adrenal axis

Abstract

Intravenous application of 100 micrograms synthetic ovine corticotropin releasing factor (CRF) led to stimulation of ACTH-secretion in nine normal controls, with a maximum 30 min after CRF. Cortisol, corticosterone, cortisone and 11-deoxycortisol increased with a maximum at 60 min after CRF, whereas no rise was seen in aldosterone, 11-deoxycorticosterone, 17-alpha-hydroxyprogesterone, progesterone, DHEA-S and testosterone. The specificity of CRF-stimulation was also shown by unchanged TSH, LH, FSH, hGH, prolactin and thyroid hormone levels, als well as unchanged insulin and gastrin levels. No serious side-effects were observed during the test period and afterwards. CRF-tests were performed in ten patients with disturbances of the hypothalamo pituitary adrenal axis (HPAA). Preliminary findings show hyperresponsiveness of ACTH in all situations of ACTH-hypersecretion (two patients with Cushing's disease, one patient with Nelson's syndrome, and one with Addison's disease). In contrast, one patient with successful microadenomectomy showed no response of ACTH to CRF, whereas in another patient with a macroadenoma ACTH and cortisol-levels still increased postoperatively. Divergent patterns in ACTH-responsiveness to CRF were seen in four patients with secondary adrenal insufficiency, allowing the localization of the defect. These data point to the possible importance of the "CRF-test" as a differential diagnostic tool and prognostic factor in diseases of the HPAA.