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

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 μg/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.