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. 1995 Jan;36(1):126–132. doi: 10.1136/gut.36.1.126

Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.

S H Hussaini 1, S P Pereira 1, G M Murphy 1, C Kennedy 1, J A Wass 1, G M Besser 1, R H Dowling 1
PMCID: PMC1382366  PMID: 7890216

Abstract

Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.

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Selected References

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  1. Admirand W. H., Small D. M. The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest. 1968 May;47(5):1043–1052. doi: 10.1172/JCI105794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbara L., Sama C., Morselli Labate A. M., Taroni F., Rusticali A. G., Festi D., Sapio C., Roda E., Banterle C., Puci A. A population study on the prevalence of gallstone disease: the Sirmione Study. Hepatology. 1987 Sep-Oct;7(5):913–917. doi: 10.1002/hep.1840070520. [DOI] [PubMed] [Google Scholar]
  3. Brakel K., Laméris J. S., Nijs H. G., Terpstra O. T., Steen G., Blijenberg B. C. Predicting gallstone composition with CT: in vivo and in vitro analysis. Radiology. 1990 Feb;174(2):337–341. doi: 10.1148/radiology.174.2.2296642. [DOI] [PubMed] [Google Scholar]
  4. Buscail L. E., Puel-Bousquet C., Harris A. G., Tauber J. P., Escourrou J. R., Delvaux M. M., Vaysse N. M., Bayard F., Ribet A. Effets sur la lithogenèse biliaire du traitement au long cours par octréotide (SMS 201-995) chez des patients acromégales. Gastroenterol Clin Biol. 1991;15(11):800–804. [PubMed] [Google Scholar]
  5. Carey M. C., Small D. M. The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. J Clin Invest. 1978 Apr;61(4):998–1026. doi: 10.1172/JCI109025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caroli A., Del Favero G., Di Mario F., Spigariol F., Scalon P., Meggiato T., Zambelli C., Naccarato R. Computed tomography in predicting gall stone solubility: a prospective trial. Gut. 1992 May;33(5):698–700. doi: 10.1136/gut.33.5.698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Catnach S. M., Anderson J. V., Fairclough P. D., Trembath R. C., Wilson P. A., Parker E., Besser G. M., Wass J. A. Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly. Gut. 1993 Feb;34(2):270–273. doi: 10.1136/gut.34.2.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dowling R. H., Hussaini S. H., Murphy G. M., Besser G. M., Wass J. A. Gallstones during octreotide therapy. Metabolism. 1992 Sep;41(9 Suppl 2):22–33. doi: 10.1016/0026-0495(92)90027-8. [DOI] [PubMed] [Google Scholar]
  9. Gleeson D., Ruppin D. C., Saunders A., Murphy G. M., Dowling R. H. Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones. Q J Med. 1990 Jul;76(279):711–729. [PubMed] [Google Scholar]
  10. Gollish S. H., Burnstein M. J., Ilson R. G., Petrunka C. N., Strasberg S. M. Nucleation of cholesterol monohydrate crystals from hepatic and gall-bladder bile of patients with cholesterol gall stones. Gut. 1983 Sep;24(9):836–844. doi: 10.1136/gut.24.9.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hickman M. S., Schwesinger W. H., Bova J. D., Kurtin W. E. Computed tomographic analysis of gallstones. An in vitro study. Arch Surg. 1986 Mar;121(3):289–291. doi: 10.1001/archsurg.1986.01400030043007. [DOI] [PubMed] [Google Scholar]
  12. Ho K. Y., Weissberger A. J., Marbach P., Lazarus L. Therapeutic efficacy of the somatostatin analog SMS 201-995 (octreotide) in acromegaly. Effects of dose and frequency and long-term safety. Ann Intern Med. 1990 Feb 1;112(3):173–181. doi: 10.7326/0003-4819-112-3-173. [DOI] [PubMed] [Google Scholar]
  13. Holan K. R., Holzbach R. T., Hermann R. E., Cooperman A. M., Claffey W. J. Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology. 1979 Oct;77(4 Pt 1):611–617. [PubMed] [Google Scholar]
  14. Holzbach R. T., Marsh M., Olszewski M., Holan K. Cholesterol solubility in bile. Evidence that supersaturated bile is frequent in healthy man. J Clin Invest. 1973 Jun;52(6):1467–1479. doi: 10.1172/JCI107321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Janowitz P., Swobodnik W., Wechsler J. G., Zöller A., Kuhn K., Ditschuneit H. Comparison of gall bladder bile and endoscopically obtained duodenal bile. Gut. 1990 Dec;31(12):1407–1410. doi: 10.1136/gut.31.12.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maton P. N., Murphy G. M., Dowling R. H. Ursodeoxycholic acid treatment of gallstones. Dose-response study and possible mechanism of action. Lancet. 1977 Dec 24;2(8052-8053):1297–1301. doi: 10.1016/s0140-6736(77)90358-0. [DOI] [PubMed] [Google Scholar]
  17. Qureshi M. Y., Murphy G. M., Dowling R. H. The enzymatic determination of total phospholipids in bile and bile-rich duodenal aspirates. Clin Chim Acta. 1980 Aug 19;105(3):407–410. doi: 10.1016/0009-8981(80)90123-0. [DOI] [PubMed] [Google Scholar]
  18. Ransohoff D. F., Gracie W. A., Wolfenson L. B., Neuhauser D. Prophylactic cholecystectomy or expectant management for silent gallstones. A decision analysis to assess survival. Ann Intern Med. 1983 Aug;99(2):199–204. doi: 10.7326/0003-4819-99-2-199. [DOI] [PubMed] [Google Scholar]
  19. Reuben A., Maton P. N., Murphy G. M., Dowling R. H. Bile lipid secretion in obese and non-obese individuals with and without gallstones. Clin Sci (Lond) 1985 Jul;69(1):71–79. doi: 10.1042/cs0690071. [DOI] [PubMed] [Google Scholar]
  20. Ros E., Navarro S., Fernández I., Reixach M., Ribó J. M., Rodés J. Utility of biliary microscopy for the prediction of the chemical composition of gallstones and the outcome of dissolution therapy with ursodeoxycholic acid. Gastroenterology. 1986 Sep;91(3):703–712. doi: 10.1016/0016-5085(86)90642-6. [DOI] [PubMed] [Google Scholar]
  21. Röschlau P., Bernt E., Gruber W. Enzymatische Bestimmung des Gesamt-Cholesterins im Serum. Z Klin Chem Klin Biochem. 1974 Sep;12(9):403–407. [PubMed] [Google Scholar]
  22. Sassolas G., Harris A. G., James-Deidier A. Long term effect of incremental doses of the somatostatin analog SMS 201-995 in 58 acromegalic patients. French SMS 201-995 approximately equal to Acromegaly Study Group. J Clin Endocrinol Metab. 1990 Aug;71(2):391–397. doi: 10.1210/jcem-71-2-391. [DOI] [PubMed] [Google Scholar]
  23. Sedaghat A., Grundy S. M. Cholesterol crystals and the formation of cholesterol gallstones. N Engl J Med. 1980 Jun 5;302(23):1274–1277. doi: 10.1056/NEJM198006053022302. [DOI] [PubMed] [Google Scholar]
  24. Stolk M. F., van Erpecum K. J., Koppeschaar H. P., de Bruin W. I., Jansen J. B., Lamers C. B., van Berge Henegouwen G. P. Postprandial gall bladder motility and hormone release during intermittent and continuous subcutaneous octreotide treatment in acromegaly. Gut. 1993 Jun;34(6):808–813. doi: 10.1136/gut.34.6.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sutor D. J., Wooley S. E. A statistical survey of the composition of gallstones in eight countries. Gut. 1971 Jan;12(1):55–64. doi: 10.1136/gut.12.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Swobodnik W., Hagert N., Janowitz P., Wenk H. Diagnostic fine-needle puncture of the gallbladder with US guidance. Radiology. 1991 Mar;178(3):755–758. doi: 10.1148/radiology.178.3.1994414. [DOI] [PubMed] [Google Scholar]
  27. TALALAY P. Enzymic analysis of steroid hormones. Methods Biochem Anal. 1960;8:119–143. doi: 10.1002/9780470110249.ch3. [DOI] [PubMed] [Google Scholar]
  28. Thomas P. J., Hofmann A. F. Letter: A simple calculation of the lithogenic index of bile: expressing biliary lipid composition on rectangular coordinates. Gastroenterology. 1973 Oct;65(4):698–700. [PubMed] [Google Scholar]
  29. Walters J. R., Hood K. A., Gleeson D., Ellul J. P., Keightley A., Murphy G. M., Dowling R. H. Combination therapy with oral ursodeoxycholic and chenodeoxycholic acids: pretreatment computed tomography of the gall bladder improves gall stone dissolution efficacy. Gut. 1992 Mar;33(3):375–380. doi: 10.1136/gut.33.3.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. van der Linden W., Nakayama F. Occurrence of cholesterol crystals in human bile. Gut. 1974 Aug;15(8):630–635. doi: 10.1136/gut.15.8.630. [DOI] [PMC free article] [PubMed] [Google Scholar]

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