Plasma substance-P in neuroendocrine tumors and idiopathic flushing: the value of pentagastrin stimulation tests and the effects of somatostatin analog

Abstract

We examined the role of the potent vasoactive kinin substance-P (SP) in flushing derived from various causes. SP was measured in plasma after acetone/ether extraction using an antiserum directed at the carboxy-terminal 5-11 amino acid region of undecapeptide SP. The antiserum had less than 1% cross-reaction with the other neurokinins, neurokinin-A and neuropeptide-K, that derive from the beta-preprotachykinin gene and share carboxy-terminal residues. Basal and pentagastrin-stimulated SP levels were measured in 22 healthy controls, 11 patients with histologically proven carcinoid tumors, 8 patients with tumors other than carcinoid, and 7 patients with idiopathic flushing (IF). Basal SP levels were less than 10 pg/mL in normal subjects. All patients with midgut carcinoid tumors had SP levels greater than 25 pg/mL, as did 7 of 8 patients with noncarcinoid tumors and 5 of 7 patients with IF. Using 50 pg/mL as the cutoff point, the sensitivity was 63% for detection of a tumor, and 100% of nontumor patients were excluded. Pentagastrin administration uniformly induced flushing and caused a rise in SP levels greater than 150 pg/mL in 5 of 10 patients with carcinoid tumors, 3 of 8 with noncarcinoid tumors, and 0 of 7 with IF, i.e. a SP rise of more than 100 pg/mL suggests a tumor. Administration of somatostatin (150 micrograms) 0.5 h before the pentagastrin abolished flushing in all carcinoid patients and reduced SP levels, but not into the normal range. Long term treatment with SMS significantly reduced flushing and lowered SP levels, but did not restore these to normal. We conclude that 90% of patients with carcinoid/noncarcinoid tumor have raised COOH-terminal SP levels. A basal level above 50 pg/mL or a pentagastrin-stimulated rise of more than 100 pg/mL distinguishes carcinoid from IF. The dissociation between SP concentrations and flushing suggests that SP may not be the only kinin involved in the flushing associated with carcinoid tumors.