OCTREOTIDE-ASSOCIATED BILIARY-TRACT DYSFUNCTION AND GALLSTONE FORMATION - PATHOPHYSIOLOGY AND MANAGEMENT

Octreotide exerts a wide range of biological actions, many of which ha ve important clinical applications, notably in treatment of acromegaly , gastroenteropancreatic endocrine tumors, and secretory diarrhea, In most patients, octreotide is well tolerated, Side effects are primaril y gastrointestinal and are usually transient, Short term (less than or equal to 1 month) octreotide therapy appears to pose minimal risk of gallstone formation, but the risk may increase with longer treatment p eriods. Chronic octreotide administration may increase the incidence o f small, cholesterol gallstones that are typically asymptomatic.The me chanism of octreotide-associated gallstone formation is not delineated but may involve inhibition of gallbladder emptying, hepatic bile secr etion, and sphincter of Oddi motility, as well as modification of bile composition, Gallbladder stasis may sequentially lead to increased bi le concentration, precipitation of cholesterol and calcium salts, rete ntion of biliary precipitates, and maturation of gallstones. Octreotid e-associated gallstones are usually asymptomatic and do not require su rgical or medical therapy. Some physicians advocate periodic gallbladd er ultrasound evaluations, but, in most cases, the results would not i nfluence management of asymptomatic patients, Symptomatic gallstones m ay require surgery or nonsurgical treatments after an appropriate work -up, Gallstone prevention strategies (e.g., bile acid or nonsteroidal anti-inflammatory drug therapy) during long term octreotide therapy ar e under investigation. Currently, clinicians may want to consider noni nvasive strategies to reduce gallstone incidence, such as timing octre otide injections in relation to meals or periodic cessation of octreot ide treatment, Octreotide is a valuable therapeutic option in managing a variety of hypersecretory states associated with high morbidity and mortality (e.g,, acromegaly, carcinoid syndrome, and VIP-secreting tu mors), so the benefits of long term octreotide therapy (such as increa sed quality of life) outweigh the risk of asymptomatic gallstone forma tion in many patients.