Somatostatinomas 

  • Author: Eric J Hanly, MD; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 11, 2010
 

Background

In 1977, Larsson et al[1] and Ganda et al[2] independently reported the first 2 cases of somatostatinoma. Ganda and colleagues' case was that of a 46-year-old woman with an 8-year history of diabetes mellitus. During a cholecystectomy for cholelithiasis, a pancreatic mass was visualized. She was initially thought to have a nonfunctional islet cell tumor. Histologically, however, the tumor cells resembled D cells, and they contained large quantities of somatostatin. Complete resection of the tumor resulted in euglycemia for the patient.

A full description of somatostatinoma syndrome followed in 1979 when Krejs and colleagues described the morphologic and biochemical properties of a tumor of the ampulla of Vater in a 52-year-old man with distinct clinical symptoms and excessive somatostatin levels.[3] Somatostatinomas are associated with excessive production of somatostatin by tumor cells of D-cell origin, and they are frequently associated with a classic clinical pentad of diabetes mellitus, cholelithiasis, weight loss, steatorrhea and diarrhea, and hypochlorhydria and achlorhydria.

Somatostatinomas are the most rare of the commonly accepted functional APUD (amine precursor uptake and decarboxylation) cell neuroendocrine tumors of the gastrointestinal tract, and they are found with almost equal frequency in the pancreas and duodenum.[4, 5, 6]

In an unusual case reported by Colovic et al, a 57-year-old woman was found to have 2 synchronous nonfunctioning somatostatinomas: one solid duodenal lesion and one cystic lesion in the pancreatic head.[7] The patient had no secondary lesions in the liver or in the removed lymph nodes. Both tumors were successfully resected with a pylorus-preserving Whipple procedure, and the patient remained well and symptom free 18 months postoperatively.[7]

Somatostatinomas very rarely arise in other locations (eg, lungs, liver, kidneys). Larger tumors are usually found in the pancreas (5 cm vs 2.5 cm in the duodenum), although malignancy is of equal incidence for primary tumors of the pancreas and duodenum (65%). Metastases are present in most patients at the time of clinical presentation.[4, 5, 6] Pancreatic and duodenal somatostatinomas can sometimes be distinguished by their clinical presentations.

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Pathophysiology

Somatostatin is a cyclic peptide present in both 14-amino acid and 28-amino acid forms. It acts in both an endocrine and a paracrine manner to inhibit secretion of many hormones, including insulin, glucagon, growth hormone, gastrin, cholecystokinin (CCK), secretin, and vasoactive intestinal peptide (VIP). This inhibitory action is thought to be responsible for the clinical manifestations that mark the disease. The generalized inhibition of gastrointestinal hormones results in restriction of gallbladder contractility, pancreatic exocrine function, and intestinal secretion and motility.

Somatostatin's reduction of insulin secretion results in diminished glucose use and hepatic glucose overproduction. Thus, the associated inhibitory syndrome leads to development of diabetes mellitus in 95% of patients. The clinical severity of diabetes can range from mild glucose intolerance to frank ketoacidosis. Cholelithiasis and biliary tract disease occur in 25-68% of patients with somatostatinoma; the conditions are secondary to suppression of CCK, inhibition of biliary motility, and altered fat metabolism. Diarrhea and steatorrhea are common symptoms of pancreatic somatostatin tumors and contribute to weight loss. In most patients, hypochlorhydria or achlorhydria occurs because of inhibited gastric acid secretion.

Somatostatinomas often simultaneously produce other hormone products, including insulin, gastrin, VIP, glucagon, corticotropin (previously adrenocorticotropic hormone [ACTH]), calcitonin, pancreatic polypeptide, and others. If these products are secreted into the bloodstream in significant quantities, they affect clinical presentation and diagnosis.

Duodenal somatostatinomas may be associated with neurofibromatosis, which is an autosomal dominant disorder characterized by abnormalities of growth and differentiation of the nervous system. Features of neurofibromatosis include multiple café-au-lait spots, neurofibromas, and congenital abnormalities (eg, abnormal bone and joint formation, mental retardation). Malignant tumors such as pheochromocytoma, Wilms tumor, and sarcoma may also occur in association with this syndrome.

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Epidemiology

Frequency

United States

Somatostatinomas occur with an annual incidence of 1 case per 40 million population. Somatostatinomas occur sporadically in 93% of cases, and 7% of cases are seen in conjunction with multiple endocrine neoplasia type 1 (MEN 1) syndrome. MEN 1 involves parathyroid, pancreatic, and pituitary neoplasms. Neurofibromatosis and pheochromocytoma are associated with the duodenal form of somatostatinoma.

Mortality/Morbidity

Postoperative 5-year survival rates of patients with metastatic somatostatinoma is 30-60%, but patients without metastases have a 5-year survival rate approaching 100%. Tanaka and associates reviewed 32 cases of duodenal somatostatinomas and found that primary tumors of patients with metastases were significantly larger (>2 cm) than tumors of patients without metastases.[8] Extremely elevated somatostatin levels that persist suggest large malignant tumors with metastases. Some of the clinical symptoms of unresectable metastatic somatostatinoma can be controlled medically.

Race

No racial predilection has been identified.

Sex

Both males and females are equally affected.

Age

Most patients are in their fourth, fifth, or sixth decade of life.

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Contributor Information and Disclosures
Author

Eric J Hanly, MD  Resident, Department of Surgery, The Johns Hopkins University School of Medicine; Fellow, Department of Surgery, The Johns Hopkins University School of Medicine

Eric J Hanly, MD is a member of the following medical societies: American Medical Association, Association of Military Surgeons of the US, MedChi, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Michael Cooperman, MD  Clinical Associate Professor of Endocrinology, Temple University; Chair, Department of Internal Medicine, Division of Endocrinology, Jeanes Hospital

Michael Cooperman, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, and Endocrine Society

Disclosure: Nothing to disclose.

Michael R Marohn, DO  Associate Professor, Department of Surgery and Surgical Sciences, John Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Leon W Kundrotas, MD, Col, USAF, MC  Chief, Medical Staff 48th Medical Group, Malcolm Grow Medical Center; Assistant Professor, Department of Medicine, USAF Hospital

Leon W Kundrotas, MD, Col, USAF, MC is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Charles J Yeo, MD  Samuel D Gross Professor and Chair of Surgery at Jefferson Medical College of Thomas Jefferson University and at Thomas Jefferson University Hospital

Charles J Yeo, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Endocrine Surgeons, American College of Surgeons, American Gastroenterological Association, American Hepato-Pancreato-Biliary Association, American Surgical Association, Association for Academic Surgery, Johns Hopkins Medical and Surgical Association, Pancreas Club, Phi Beta Kappa, Sigma Xi, Society for Surgery of the Alimentary Tract, and Society of University Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Mounzer Al Al Samman, MD  Department of Internal Medicine, Division of Gastroenterology, Assistant Professor, Texas Tech University School of Medicine

Mounzer Al Al Samman, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Noel Williams, MD  Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

  1. Larsson LI, Hirsch MA, Holst JJ, et al. Pancreatic somatostatinoma. Clinical features and physiological implications. Lancet. Mar 26 1977;1(8013):666-8. [Medline].

  2. Ganda OP, Weir GC, Soeldner JS. "Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas. N Engl J Med. Apr 28 1977;296(17):963-7. [Medline].

  3. Krejs GJ, Orci L, Conlon JM, et al. Somatostatinoma syndrome. Biochemical, morphologic and clinical features. N Engl J Med. Aug 9 1979;301(6):285-92. [Medline].

  4. Boden G, Shimoyama R. Somatostatinoma. In: Cohen S, Soloway RD, eds. Hormone-Producing Tumors of the Gastrointestinal Tract. New York, NY: Churchill Livingstone; 1985:85.

  5. Norton JA, Levin B, Jensen RT. Cancer of the endocrine system. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 4th ed. Philadelphia, Pa: Lippincott-Raven; 1993:1333-435.

  6. Yeo CJ. Neoplasms of the endocrine pancreas. In: Greenfield LJ, Mulholland MW, Oldham KT, eds. Surgery: Scientific Principles and Practice. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:899-913.

  7. Colovic RB, Matic SV, Micev MT, et al. Two synchronous somatostatinomas of the duodenum and pancreatic head in one patient. World J Gastroenterol. Dec 14 2009;15(46):5859-63. [Medline]. [Full Text].

  8. Tanaka S, Yamasaki S, Matsushita H, et al. Duodenal somatostatinoma: a case report and review of 31 cases with special reference to the relationship between tumor size and metastasis. Pathol Int. Feb 2000;50(2):146-52. [Medline].

  9. Anene C, Thompson JS, Saigh J, et al. Somatostatinoma: atypical presentation of a rare pancreatic tumor. Am J Gastroenterol. May 1995;90(5):819-21. [Medline].

  10. Angeletti S, Corleto VD, Schillaci O, et al. Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours. Gut. Jun 1998;42(6):792-4. [Medline].

  11. Berger JF, Laissy JP, Limot O, et al. Differentiation between multiple liver hemangiomas and liver metastases of gastrinomas: value of enhanced MRI. J Comput Assist Tomogr. May-Jun 1996;20(3):349-55. [Medline].

  12. Bieligk S, Jaffe BM. Islet cell tumors of the pancreas. Surg Clin North Am. Oct 1995;75(5):1025-40. [Medline].

  13. Caiazzo R, Mariette C, Piessen G, et al. [Type I neurofibromatosis, pheochromocytoma and somatostatinoma of the ampulla. Literature review] [French]. Ann Chir. Jul-Aug 2006;131(6-7):393-7. [Medline].

  14. Chetty R, Vajpeyi R. Vasculopathic changes, a somatostatin-producing neuroendocrine carcinoma and a jejunal gastrointestinal stromal tumor in a patient with type 1 neurofibromatosis. Endocr Pathol. Fall 2009;20(3):177-81. [Medline].

  15. Dayal Y, Tallberg KA, Nunnemacher G, et al. Duodenal carcinoids in patients with and without neurofibromatosis. A comparative study. Am J Surg Pathol. May 1986;10(5):348-57. [Medline].

  16. Debas HT, Mulvihill SJ. Neuroendocrine gut neoplasms. Important lessons from uncommon tumors. Arch Surg. Sep 1994;129(9):965-71; discussion 971-2. [Medline].

  17. Fendrich V, Ramaswamy A, Slater EP, Bartsch DK. Duodenal somatostatinoma associated with Von Recklinghausen's disease. J Hepatobiliary Pancreat Surg. 2004;11(6):417-21. [Medline].

  18. Fraker DL, Alexander HR. The surgical approach to endocrine tumors of the pancreas. Semin Gastrointest Dis. Apr 1995;6(2):102-13. [Medline].

  19. Friesen SR. Update on the diagnosis and treatment of rare neuroendocrine tumors. Surg Clin North Am. Apr 1987;67(2):379-93. [Medline].

  20. Frilling A, Malago M, Martin H, Broelsch CE. Use of somatostatin receptor scintigraphy to image extrahepatic metastases of neuroendocrine tumors. Surgery. Dec 1998;124(6):1000-4. [Medline].

  21. Gibril F, Doppman JL, Jensen RT. Recent advances in the treatment of metastatic pancreatic endocrine tumors. Semin Gastrointest Dis. Apr 1995;6(2):114-21. [Medline].

  22. Gibril F, Reynolds JC, Doppman JL, et al. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study. Ann Intern Med. Jul 1 1996;125(1):26-34. [Medline].

  23. Glover JR, Shorvon PJ, Lees WR. Endoscopic ultrasound for localisation of islet cell tumours. Gut. Jan 1992;33(1):108-10. [Medline].

  24. Goudet P, Murat A, Binquet C, et al. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d'Etude des Tumeurs Endocrines) cohort study among 758 patients. World J Surg. Dec 1 2009;epub ahead of print. [Medline].

  25. Grant CS, van Heerden J, Charboneau JW, et al. Insulinoma. The value of intraoperative ultrasonography. Arch Surg. Jul 1988;123(7):843-8. [Medline].

  26. Gunther RW, Klose KJ, Ruckert K, et al. Localization of small islet-cell tumors. Preoperative and intraoperative ultrasound, computed tomography, arteriography, digital subtraction angiography, and pancreatic venous sampling. Gastrointest Radiol. 1985;10(2):145-52. [Medline].

  27. Hammond PJ, Jackson JA, Bloom SR. Localization of pancreatic endocrine tumours. Clin Endocrinol (Oxf). Jan 1994;40(1):3-14. [Medline].

  28. He X, Wang J, Wu X, Kang L, Lan P. Pancreatic somatostatinoma manifested as severe hypoglycemia. J Gastrointestin Liver Dis. Jun 2009;18(2):221-4. [Medline].

  29. Heitz PU, Kasper M, Polak JM, Kloppel G. Pancreatic endocrine tumors. Hum Pathol. Mar 1982;13(3):263-71. [Medline].

  30. Hendi JM, Horton KM, Fishman EK. Somatostatinoma of the ampulla and appendical carcinoid in a patient with von Recklinghausen disease. J Comput Assist Tomogr. May-Jun 2005;29(3):418-9.

  31. House MG, Yeo CJ, Schulick RD. Periampullary pancreatic somatostatinoma. Ann Surg Oncol. Nov 2002;9(9):869-74. [Medline].

  32. Kimura R, Hayashi Y, Takeuchi T. Large duodenal somatostatinoma in the third portion associated with severe glucose intolerance. Intern Med. Aug 2004;43(8):704-7. [Medline].

  33. Kirkwood KS, Debas HT. Neuroendocrine tumors: common presentations of uncommon diseases. Compr Ther. Dec 1995;21(12):719-25. [Medline].

  34. Kloppel G, Anlauf M. Epidemiology, tumour biology and histopathological classification of neuroendocrine tumours of the gastrointestinal tract. Best Pract Res Clin Gastroenterol. Aug 2005;19(4):507-17.

  35. Konomi K, Chijiiwa K, Katsuta T, Yamaguchi K. Pancreatic somatostatinoma: a case report and review of the literature. J Surg Oncol. Apr 1990;43(4):259-65. [Medline].

  36. Krausz Y, Bar-Ziv J, de Jong RB, et al. Somatostatin-receptor scintigraphy in the management of gastroenteropancreatic tumors. Am J Gastroenterol. Jan 1998;93(1):66-70. [Medline].

  37. Lamberts SW, Bakker WH, Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med. Nov 1 1990;323(18):1246-9. [Medline].

  38. Levy-Bohbot N, Merle C, Goudet P. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol. Nov 2004;28(11):1075-81. [Medline].

  39. Lillemoe KD, Kaushal S, Cameron JL, et al. Distal pancreatectomy: indications and outcomes in 235 patients. Ann Surg. May 1999;229(5):693-8; discussion 698-700. [Medline].

  40. Madeira I, Terris B, Voss M, et al. Prognostic factors in patients with endocrine tumours of the duodenopancreatic area. Gut. Sep 1998;43(3):422-7. [Medline].

  41. Mansour JC, Chen H. Pancreatic endocrine tumors. J Surg Res. Jul 2004;120(1):139-61. [Medline].

  42. Marcial MA, Pinkus GS, Skarin A, et al. Ampullary somatostatinoma: psammomatous variant of gastrointestinal carcinoid tumor--an immunohistochemical and ultrastructural study. Report of a case and review of the literature. Am J Clin Pathol. Nov 1983;80(5):755-61. [Medline].

  43. Maton PN. The use of the long-acting somatostatin analogue, octreotide acetate, in patients with islet cell tumors. Gastroenterol Clin North Am. Dec 1989;18(4):897-922. [Medline].

  44. Menegaux F, Schmitt G, Mercadier M, Chigot JP. Pancreatic insulinomas. Am J Surg. Feb 1993;165(2):243-8. [Medline].

  45. Metz DC. Diagnosis and treatment of pancreatic neuroendocrine tumors. Semin Gastrointest Dis. Apr 1995;6(2):67-78. [Medline].

  46. Moore NR, Rogers CE, Britton BJ. Magnetic resonance imaging of endocrine tumours of the pancreas. Br J Radiol. Apr 1995;68(808):341-7. [Medline].

  47. Mozell E, Stenzel P, Woltering EA, et al. Functional endocrine tumors of the pancreas: clinical presentation, diagnosis, and treatment. Curr Probl Surg. Jun 1990;27(6):301-86. [Medline].

  48. Norton JA, Sigel B, Baker AR, et al. Localization of an occult insulinoma by intraoperative ultrasonography. Surgery. Mar 1985;97(3):381-4. [Medline].

  49. Pelley RJ, Bukowski RM. Recent advances in diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract. Curr Opin Oncol. Jan 1997;9(1):68-74. [Medline].

  50. Phan GQ, Yeo CJ, Cameron JL, et al. Pancreaticoduodenectomy for selected periampullary neuroendocrine tumors: fifty patients. Surgery. Dec 1997;122(6):989-96; discussion, 996-7. [Medline].

  51. Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. Jun 25 1992;326(26):1721-6. [Medline].

  52. Saifuddin T, Linder C, Banerjee B. Duodenal somatostatinoma presenting as upper gastrointestinal bleeding. Am J Gastroenterol. May 1999;94(5):1405-8. [Medline].

  53. Sawady J, Katzin WE, Mendelsohn G, Aron DC. Somatostatin-producing neuroendocrine tumor of the ampulla (ampullary somatostatinoma). Evidence of prosomatostatin production. Am J Clin Pathol. Mar 1992;97(3):411-5. [Medline].

  54. Schillaci O, Annibale B, Scopinaro F, et al. Somatostatin receptor scintigraphy of malignant somatostatinoma with indium-111-pentetreotide. J Nucl Med. Jun 1997;38(6):886-7. [Medline].

  55. Stelow EB, Woon C, Pambuccian SE, et al. Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms. Diagn Cytopathol. Aug 2005;33(2):100-5. [Medline].

  56. Suzuki H, Kuwano H, Masuda N, et al. Diagnostic usefulness of FDG-PET for malignant somatostatinoma of the pancreas. Hepatogastroenterology. Jul-Aug 2008;55(85):1242-5. [Medline].

  57. Swinburn BA, Yeong ML, Lane MR, et al. Neurofibromatosis associated with somatostatinoma: a report of two patients. Clin Endocrinol (Oxf). Apr 1988;28(4):353-9. [Medline].

  58. Takizawa H, Kaneko H, Koike M, et al. Small duodenal somatostatinoma with high plasma somatostatin level. Am J Gastroenterol. Jun 1997;92(6):1063-4. [Medline].

  59. Tjon A Tham RT, Jansen JB, Falke TH, Lamers CB. Imaging features of somatostatinoma: MR, CT, US, and angiography. J Comput Assist Tomogr. May-Jun 1994;18(3):427-31. [Medline].

  60. Townsend CM Jr, Thompson JC. The clinical use of gastrointestinal hormones for alimentary tract disease. Adv Surg. 1996;29:79-92. [Medline].

  61. Udelsman R, Yeo CJ, Hruban RH, et al. Pancreaticoduodenectomy for selected pancreatic endocrine tumors. Surg Gynecol Obstet. Sep 1993;177(3):269-78. [Medline].

  62. Vinik AI, Delbridge L, Moattari R, et al. Transhepatic portal vein catheterization for localization of insulinomas: a ten-year experience. Surgery. Jan 1991;109(1):1-11; discussion 111. [Medline].

  63. Vinik AI, Strodel WE, Eckhauser FE, et al. Somatostatinomas, PPomas, neurotensinomas. Semin Oncol. Sep 1987;14(3):263-81. [Medline].

  64. Zhang B, Xie QP, Gao SL, Fu YB, Wu YL. Pancreatic somatostatinoma with obscure inhibitory syndrome and mixed pathological pattern. J Zhejiang Univ Sci B. Jan 2010;11(1):22-6. [Medline]. [Full Text].

 
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