Vasoactive intestinal polypeptide enhances ACTH levels in some patients with adrenocorticotropin - secreting pituitary adenomas

Vasoactive intestinal polypeptide (VIP) was administered (75 μg iv over 12 min) to 14 patients with Cushing's disease, 1 patient with Nelson's syndrome, and 8 normal subjects. VIP induced a significant rise of plasma ACTH levels in 6 patients with Cushing's disease, from a baseline of 13.2 pmol/l (9.9-18.5 pmol/l) to a peak of 24.5 pmol/l (7.7-18.9 pmol/l), median and range (P <0.05), and in the patient with Nelson's syndrome, from a bseline of 260.9 to 461.3 pmol/l. A significant elevation of cortisol levels was also observed, from a baseline of 567 nmol/l (185-842 nmol/l) to a peak of 727 nmol/l (364-1029 nmol/l); P <0.05. No modifications in plasma ACTH and cortisol levels were noticed in the other 8 patients with Cushing's disease, or in the normal subjects. In the responsive patients, the median plasma ACTH level reached after VIP was found to be less than that induced by CRH administration. In 2 of the responsive patients, VIP was injected again after successful microadenomectomy and did not then cause changes in ACTH and cortisol concentration. These data demonstrate that VIP specifically stimulates ACTH release in some patients with corticotropinomas but not in normal subjects; the disappearance of such abnormal ACTH responses after successful adenomectomy suggests the presence of specific VIP receptors only on the adenomatous corticotropes.