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  • Author: Praveen K Roy, MD, AGAF; Chief Editor: Julian Katz, MD  more...
Updated: Jun 29, 2015


Somatostatinomas are rare neuroendocrine tumors that arise from the pancreas or the gastrointestinal tract and are characterized by excessive secretion of somatostatin hormone by tumor cells of D-cell origin. They are frequently associated with a classic clinical pentad of diabetes mellitus, cholelithiasis, weight loss, steatorrhea and diarrhea, and hypochlorhydria and achlorhydria.[1, 2, 3, 4, 5, 6]

In 1977, Larsson et al[7] and Ganda et al[8] independently reported the first 2 cases of somatostatinoma. 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.[9]

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.[10] 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.[10]

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.[3, 4, 5] Pancreatic and duodenal somatostatinomas can sometimes be distinguished by their clinical presentations.



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 the 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 the 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.

A case of somatostatinoma of the duodenal papilla (minor ampulla) in a patient with neurofibromatosis 1 has been reported.[11] The lesion was removed via uncomplicated open local excision.




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.

Race-, sex-, and age-related demographics

No racial predilection has been identified, and males and females are equally affected.

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



Prognosis primarily depends on the presence or absence of metastatic disease at the time of presentation and initial treatment. Most somatostatinomas (84%) are metastatic at the time of presentation, but a number of 5-year survivors following combination surgery and chemotherapy have been reported among patients with metastatic disease. If treated with appropriate resection, virtually all patients with nonmetastatic somatostatinoma enjoy a cure.


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.[12] 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.

Contributor Information and Disclosures

Praveen K Roy, MD, AGAF Chief of Gastroenterology, Presbyterian Hospital; Medical Director of Endoscopy, Presbyterian Medical Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute

Praveen K Roy, MD, AGAF is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.


Rajan Kanth, MD Hospitalist, Ministry Saint Joseph’s Hospital

Rajan Kanth, MD is a member of the following medical societies: American College of Physicians, Society of Hospital Medicine, Nepal Medical Association

Disclosure: Nothing to disclose.

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

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, Physicians for Social Responsibility

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Mounzer Al Samman, MD Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, 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.

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.

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

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Michael G House, MD Fellow, Department of Oncology, Johns Hopkins University

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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

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

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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.

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.

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