Repetitive and continuous administration of human corticotropin releasing factor to human subjects

ACTH secretion was studied in response to repetitive and continuous administration of human corticotropin releasing factor (CRF) in 14 healthy volunteers and 2 patients with secondary adrenal insufficiency. ACTH increases during repetitive CRF administration were within the same range in normal subjects independent of the intervals (60-180 min) between the CRF pulses (100 micrograms iv). When CRF was infused continuously (100 micrograms/h for 3 h) after an initial CRF bolus injection (100 micrograms iv), ACTH and cortisol remained elevated during the infusion at a nearly constant level (ACTH: 60 +/- 5 pg/ml; cortisol: 21.2 +/- 1 micrograms/dl; means +/- SE). A second CRF bolus injection at the end of the infusion did not lead to a significant further increase of ACTH and cortisol levels. This shows that there is no desensitisation or depletion of a ready releasable pool, as it is observed with other pituitary hormones after releasing hormone stimulation. Pulsatile administration of CRF in 2 patients with secondary adrenal insufficiency due to previous cortisol or glucocorticoid excess, respectively, revealed a blunted response to the first pulse which became normal after the following pulses. The latter could not be sustained until the next morning without CRF given overnight. These findings point to a hypothalamic defect being the cause of hypocortisolism after long-term cortisol suppression.