Plasma pattern of immunoreactive ACTH in normal man and in patients with Nelson's syndrome

A radioimmunoassay for ACTH determinations in human plasma was developed using an N-terminal antiserum. Plasma ACTH levels at 6 a.m. in 39 patients with normal pituitary-adrenal function were below 4 pmol/l in two individuals. The remaining had a mean of 32.7 +/- 4 pmol/l (n = 37). Gel filtration on Sephadex G-50 medium and G-75 revealed that a high molecular weight immunoreactive ACTH was found in plasma from both normal individuals and patients with Nelson's syndrome. The stimulation of ACTH secretion with metyrapone (750 mg perorally) significantly increased the mean plasma levels of 1-39 ACTH after 3 h (from 0.9 to 6.6 pmol/l) in 10 healthy individuals. The level of the high molecular weight form remained constant. In one patient with Nelson's syndrome hydrocortisone iv (100 mg/h for 3 h) suppressed the total ACTH levels from 360 to 83 pmol/l following corticoid withdrawal on the previous evening, but did not affect the high molecular weight form of ACTH. The difference between the amounts of immunoreactive ACTH found in plasma from normal individuals and from patients with Nelson's syndrome was attributed to 1-39 ACTH.