The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones

Gastroenterology. 1994 Nov;107(5):1503-13. doi: 10.1016/0016-5085(94)90556-8.

Abstract

Background/aims: Treatment of acromegaly with octreotide inhibits cholecystokinin release and gallbladder contraction and induces gallbladder stones. However, little is known about the effects of octreotide on bile composition.

Methods: Fresh gallbladder bile was obtained from three groups: (1) 11 nonacromegalic patients with cholesterol gallstones, (2) 6 acromegalic patients with octreotide-associated stones (treatment, 300-600 micrograms/day for 3-66 months), and (3) 8 acromogalic patients with no stones before octreotide treatment, 5 of whom were reexamined after 3-24 months of therapy.

Results: Compared with stone-free acromegalic patients untreated with octreotide, bile from patients with cholesterol stones and from acromegalic patients with octreotide-associated stones had greater saturation indices (mean +/- SEM) (1.52 +/- 0.17 and 1.32 +/- 0.14 vs. 0.90 +/- 0.05, respectively; P < 0.01); more cholesterol in vesicles (61.2% +/- 4.5% and 67.7% +/- 7.2% vs. 37.7% +/- 3.5%; P < 0.009); more unstable vesicles (cholesterol/phospholipid ratios, 0.97 +/- 0.12 and 0.81 +/- 0.16 vs. 0.52 +/- 0.05; P < 0.02); more rapid nucleation (< 5 and < 5 days vs. > 18 days; P < 0.003); and more deoxycholic acid (22.8% +/- 2.4% and 23.6% +/- 4.8% vs. 13.9% +/- 1.4%; P < 0.05). In the paired studies, the saturation indices increased from 0.89 +/- 0.07 before octreotide treatment to 1.12 +/- 0.03 during octreotide treatment (P < 0.02), as did the percentage of deoxycholic acid from 13.3% +/- 2.1% to 24.9% +/- 2.7% (P < 0.03).

Conclusions: Acromegalic patients with octreotide-associated gallstones and stone-free acromegalic patients treated with octreotide have similar changes in bile composition to those in patients with "conventional" cholesterol gallstone disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / drug therapy
  • Adult
  • Aged
  • Bile / chemistry*
  • Bile / drug effects
  • Chemical Phenomena
  • Chemistry, Physical
  • Cholelithiasis / chemically induced*
  • Cholelithiasis / chemistry
  • Cholelithiasis / metabolism
  • Cholesterol / analysis
  • Crystallization
  • Deoxycholic Acid / analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Octreotide / adverse effects*
  • Phospholipids / metabolism

Substances

  • Phospholipids
  • Deoxycholic Acid
  • Cholesterol
  • Octreotide