Octreotide inhibition of flushing and colonic motor dysfunction in carcinoid syndrome.
OBJECTIVE
Previous studies showed increased plasma motilin and substance P concentrations and accelerated motor function in the small bowel and colon in patients with carcinoid diarrhea. Octreotide is beneficial in patients with carcinoid syndrome. Our hypothesis was that octreotide inhibits accelerated motility and gut neuropeptides in carcinoid syndrome.


METHODS
In 12 patients with metastatic carcinoid syndrome, we investigated the effect of octreotide 50 microg s.c. t.i.d (n = 6) or placebo (n = 6) on postprandial symptoms, GI transit, colonic motility, and circulating levels of selected circulating peptides and amines.


RESULTS
Octreotide reduced postprandial flushing (p = 0.03) but not pain. Octreotide significantly retarded overall colonic transit and proximal colonic emptying (p < 0.05); it tended to prolong small bowel transit time (p = 0.13) and to reduce postprandial colonic tone (p = 0.08) compared with placebo. Octreotide also reduced circulating levels of peptide YY, neurotensin, vasoactive intestinal polypeptide, and substance P but had no effect on plasma motilin, neuropeptide Y, calcitonin gene-related peptide, or histamine after meal ingestion.


CONCLUSIONS
Octreotide ameliorates gut motor dysfunctions that characterize carcinoid diarrhea; the potential role of specific antagonism of serotonin, substance P, and vasoactive intestinal polypeptide alone or in combination with agents that inhibit their release in carcinoid diarrhea deserves further study.
Saslow
S B
SB
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
O'Brien
M D
MD
Camilleri
M
M
von der Ohe
M
M
Homburger
H A
HA
Klee
G G
GG
Pitot
H C
HC
Rubin
J
J
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D003106:Colon / Q000187:drug effects; D003108:Colonic Diseases / Q000188:drug therapy*; D003967:Diarrhea / Q000188:drug therapy; D004063:Digestion / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005483:Flushing / Q000188:drug therapy*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006632:Histamine / Q000097:blood; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D008303:Malignant Carcinoid Syndrome / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D009037:Motilin / Q000097:blood; D009478:Neuropeptide Y / Q000097:blood; D009479:Neuropeptides / Q000037:antagonists & inhibitors; D009496:Neurotensin / Q000037:antagonists & inhibitors / Q000097:blood; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D019894:Peptide YY / Q000037:antagonists & inhibitors / Q000097:blood; D010919:Placebos; D012702:Serotonin Antagonists / Q000097:blood; D013373:Substance P / Q000037:antagonists & inhibitors / Q000097:blood; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000097:blood
D018931:Antineoplastic Agents, Hormonal; D005765:Gastrointestinal Agents; D009478:Neuropeptide Y; D009479:Neuropeptides; D010919:Placebos; D012702:Serotonin Antagonists; D019894:Peptide YY; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D009037:Motilin; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D015282:Octreotide