Abstract

PurposeSomatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA).Methods91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness.Results61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present.ConclusionBiliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.

Highlights

  • Somatostatin receptor ligands (SRL) are the first-line medical treatment in acromegaly disease because of their action in inhibiting pituitary growth hormone (GH) secretion

  • The aim of this study was to analyse the incidence of biliary adverse events (BAE) and the predictive factors for the BSD onset in a large population of acromegaly patients treated with long acting release (LAR) SRL

  • Fifty-nine patients (65%) were treated with octreotide LAR and 32 (35%) with lanreotide autogel; 5 patients were subsequently shifted to pasireotide LAR because they revealed treatment resistant

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Summary

Introduction

Somatostatin receptor ligands (SRL) are the first-line medical treatment in acromegaly disease because of their action in inhibiting pituitary growth hormone (GH) secretion. SRL represent long-term treatment, sometimes even lifelong. SRL treatment is well tolerated and Cholesterol gallstones form when the cholesterol concentration in bile exceeds the ability of bile to hold it in solution, so that crystals form and grow as stones. Gallbladder sludge, thickened gallbladder mucoprotein with tiny entrapped cholesterol crystals, is thought to be the usual precursor of gallstones. Sludge can sometimes cause biliary pain, cholecystitis, or acute pancreatitis, but sludge may resolve without treatment [2]. Somatostatin inhibits the secretion of bile salts, promotes sodium and water absorption by the gallbladder (increasing bile concentration) and causes a reduction in the post-prandial release of cholecystokinin (CCK) [3].

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