Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones

• Published in: Gut 1999-05, Vol.44 (5), p.675-681
• Main Authors: Veysey, M J, Thomas, L A, Mallet, A I, Jenkins, P J, Besser, G M, Wass, J A H, Murphy, G M, Dowling, R H
• Format: Article
• Language: English
• Subjects: Acids; acromegaly; Acromegaly - blood; Acromegaly - drug therapy; Acromegaly - physiopathology; Adult; Age; Aged; Bile; Bile Acids and Salts - blood; Biological and medical sciences; Bladder; Cholelithiasis - chemically induced; Cholesterol; Colorectal cancer; Constipation; deoxycholic acid; Deoxycholic Acid - blood; Drug Administration Schedule; Enzymes; Fasting; Fasting - physiology; Female; gallstones; Gastroenterology; Gastrointestinal Agents - pharmacology; Gastrointestinal Agents - therapeutic use; Gastrointestinal Motility; Gastrointestinal Transit - drug effects; Growth hormones; Hormones. Endocrine system; Humans; Insulin-like growth factors; Intestine, Large - physiopathology; large bowel transit time; Male; Medical sciences; Middle Aged; mouth to caecum transit time; octreotide; Octreotide - pharmacology; Octreotide - therapeutic use; Pathogenesis; Pharmacology. Drug treatments; Risk Factors; Studies
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.44.5.675

BACKGROUND Treatment of acromegaly with octreotide increases the proportion of deoxycholic acid in, and the cholesterol saturation of, bile and induces the formation of gallstones. Prolongation of intestinal transit has been proposed as the mechanism for the increase in the proportion of deoxycholic acid in bile. AIMS To study the effects of octreotide on intestinal transit in acromegalic patients during octreotide treatment, and to examine the relation between intestinal transit and bile acid composition in fasting serum. METHODS Mouth to caecum and large bowel transit times, and the proportion of deoxycholic acid in fasting serum were measured in non-acromegalic controls, acromegalic patients untreated with octreotide, acromegalics on long term octreotide, and patients with simple constipation. Intestinal transit and the proportion of deoxycholic acid were compared in acromegalic patients before and during octreotide. RESULTS Acromegalics untreated with octreotide had longer mouth to caecum and large bowel transit times than controls. Intestinal transit was further prolonged by chronic octreotide treatment. There were significant linear relations between large bowel transit time and the proportion of deoxycholic acid in the total, conjugated, and unconjugated fractions of fasting serum. CONCLUSIONS These data support the hypothesis that, by prolonging large bowel transit, octreotide increases the proportion of deoxycholic acid in fasting serum (and, by implication, in bile) and thereby the risk of gallstone formation.