Somatostatinoma: Clinical manifestations, diagnosis, and management
- Emily Bergsland, MD
Emily Bergsland, MD
- Professor of Medicine
- University of California San Francisco
- Section Editors
- David M Nathan, MD
David M Nathan, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Diabetes Mellitus
- Professor of Medicine
- Harvard Medical School
- David C Whitcomb, MD, PhD
David C Whitcomb, MD, PhD
- Section Editor — Pancreatic Diseases
- Professor of Medicine
- University of Pittsburgh School of Medicine
Somatostatinomas are rare neuroendocrine tumors of D-cell origin that contain and sometimes secrete excessive amounts of somatostatin (figure 1) . This topic will review the clinical manifestations, diagnosis, and management of somatostatinomas. An overview of the clinical manifestations, diagnosis, and management of pancreatic neuroendocrine tumors is discussed in detail separately. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine tumors (islet-cell tumors)" and "Surgical resection of sporadic pancreatic neuroendocrine tumors" and "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion" and "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion" and "Insulinoma" and "Glucagonoma and the glucagonoma syndrome" and "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis" and "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)" and "VIPoma: Clinical manifestations, diagnosis, and management".)
Somatostatinomas are rare neuroendocrine tumors with an annual incidence of 1 in 40 million . The mean age at diagnosis of somatostatinomas is 50 to 55 years (range 26 to 84), with a roughly equal gender distribution . Approximately 55 percent of somatostatinomas are in the pancreas, and, of these, two-thirds arise within the head of the pancreas. The remainder arises in the ampulla and periampullary region of the duodenum or rarely in the jejunum . Other rare primary sites include the liver, colon, and rectum [3,5]. Approximately 75 percent of somatostatinomas are malignant, and 70 to 92 percent present with metastatic disease .
Although 45 percent of somatostatinomas occur in association with multiple endocrine neoplasia (MEN)-1 syndrome, somatostatinomas are among the least common functioning pancreatic neuroendocrine tumors in patients with MEN-1 syndrome, occurring in less than 1 percent of patients . Up to 10 percent of patients with neurofibromatosis I (NF-1; von Recklinghausen disease) develop somatostatinomas. NF-1-associated somatostatinomas are characteristically duodenal, are rarely associated with somatostatinoma syndrome, and are less likely to metastasize as compared with sporadic somatostatinomas [4,8].
Somatostatin is a tetradecapeptide that normally acts in a paracrine manner to inhibit secretion of many hormones, including insulin, glucagon, gastrin, and growth hormone. It also has direct effects on a number of gastrointestinal functions . In patients with somatostatinomas, cholelithiasis may result from inhibition of cholecystokinin release, which reduces gallbladder contractility . Diarrhea and steatorrhea result from inhibition of pancreatic enzyme and bicarbonate secretion and intestinal absorption of lipids. Many patients with somatostatinomas also have gastric hypochlorhydria due to decreased gastrin secretion. (See 'Clinical manifestations' below and "Physiology of somatostatin and its analogues".)
Some somatostatinomas, particularly those arising in the ampullary and periampullary area, contain immunoreactive granules but are not associated with any functional syndrome [8,11]. In contrast, those arising in the pancreas may secrete large amounts of somatostatin, resulting in a constellation of symptoms of somatostatinoma syndrome. (See 'Clinical manifestations' below.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Friesen SR. Update on the diagnosis and treatment of rare neuroendocrine tumors. Surg Clin North Am 1987; 67:379.
- Jensen RT, Norton JA. Endocrine tumors of the pancreas. In: Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management, 7th ed, Feldman M, Scharschmidt BF, Sleisenger MH (Eds), WB Saunders, Philadelphia 2002. p.988.
- Harris GJ, Tio F, Cruz AB Jr. Somatostatinoma: a case report and review of the literature. J Surg Oncol 1987; 36:8.
- Soga J, Yakuwa Y. Somatostatinoma/inhibitory syndrome: a statistical evaluation of 173 reported cases as compared to other pancreatic endocrinomas. J Exp Clin Cancer Res 1999; 18:13.
- Ohwada S, Joshita T, Ishihara T, et al. Primary liver somatostatinoma. J Gastroenterol Hepatol 2003; 18:1218.
- Doherty GM. Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol 2005; 19:807.
- Garbrecht N, Anlauf M, Schmitt A, et al. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer 2008; 15:229.
- Mao C, Shah A, Hanson DJ, Howard JM. Von Recklinghausen's disease associated with duodenal somatostatinoma: contrast of duodenal versus pancreatic somatostatinomas. J Surg Oncol 1995; 59:67.
- Jensen RT, Norton JA. Endocrine neoplasms of the pancreas. In: Textbook of Gastroenterology, Yamada T (Ed), JB Lippincott Co, Philadelphia 1995. p.2131.
- Snow ND, Liddle RA. Neuroendocrine Tumors. In: Gastrointestinal Cancers: Biology, Diagnosis and Therapy, Rustgi AK (Ed), Lippincott-Raven, Philadelphia 1995. p.585.
- Angeletti S, Corleto VD, Schillaci O, et al. Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours. Gut 1998; 42:792.
- O'Brien TD, Chejfec G, Prinz RA. Clinical features of duodenal somatostatinomas. Surgery 1993; 114:1144.
- Deppen SA, Liu E, Blume JD, et al. Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of Neuroendocrine Tumors. J Nucl Med 2016; 57:708.
- Sadowski SM, Neychev V, Millo C, et al. Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites. J Clin Oncol 2016; 34:588.
- Reidy-Lagunes DL, Gollub MJ, Saltz LB. Addition of octreotide functional imaging to cross-sectional computed tomography or magnetic resonance imaging for the detection of neuroendocrine tumors: added value or an anachronism? J Clin Oncol 2011; 29:e74.
- Nikou GC, Toubanakis C, Nikolaou P, et al. VIPomas: an update in diagnosis and management in a series of 11 patients. Hepatogastroenterology 2005; 52:1259.
- Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology 2012; 95:120.
- Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012; 61:6.
- Öberg K, Knigge U, Kwekkeboom D, et al. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 Suppl 7:vii124.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm504524 (Accessed on June 08, 2016).
- Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006; 449:395.
- Strosberg JR, Cheema A, Weber JM, et al. Relapse-free survival in patients with nonmetastatic, surgically resected pancreatic neuroendocrine tumors: an analysis of the AJCC and ENETS staging classifications. Ann Surg 2012; 256:321.
- Strosberg JR, Cheema A, Weber J, et al. Prognostic validity of a novel American Joint Committee on Cancer Staging Classification for pancreatic neuroendocrine tumors. J Clin Oncol 2011; 29:3044.
- Cho JH, Ryu JK, Song SY, et al. Prognostic Validity of the American Joint Committee on Cancer and the European Neuroendocrine Tumors Staging Classifications for Pancreatic Neuroendocrine Tumors: A Retrospective Nationwide Multicenter Study in South Korea. Pancreas 2016; 45:941.
- Bergsland EK, Woltering EA, Rindo G. Neuroendocrine tumors of the pancreas. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.407.
- House MG, Yeo CJ, Schulick RD. Periampullary pancreatic somatostatinoma. Ann Surg Oncol 2002; 9:869.
- Caplin ME, Pavel M, Ćwikła JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371:224.
- Rinke A, Wittenberg M, Schade-Brittinger C, et al. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival. Neuroendocrinology 2017; 104:26.
- Anene C, Thompson JS, Saigh J, et al. Somatostatinoma: atypical presentation of a rare pancreatic tumor. Am J Gastroenterol 1995; 90:819.
- Eriksson B, Oberg K. An update of the medical treatment of malignant endocrine pancreatic tumors. Acta Oncol 1993; 32:203.
- O'Dorisio TM, Mekhjian HS, Gaginella TS. Medical therapy of VIPomas. Endocrinol Metab Clin North Am 1989; 18:545.
- Swärd C, Johanson V, Nieveen van Dijkum E, et al. Prolonged survival after hepatic artery embolization in patients with midgut carcinoid syndrome. Br J Surg 2009; 96:517.
- Ruszniewski P, Rougier P, Roche A, et al. Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients. Cancer 1993; 71:2624.
- Eriksson BK, Larsson EG, Skogseid BM, et al. Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 1998; 83:2293.
- Christante D, Pommier S, Givi B, Pommier R. Hepatic artery chemoinfusion with chemoembolization for neuroendocrine cancer with progressive hepatic metastases despite octreotide therapy. Surgery 2008; 144:885.
- Drougas JG, Anthony LB, Blair TK, et al. Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors. Am J Surg 1998; 175:408.
- Loewe C, Schindl M, Cejna M, et al. Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. AJR Am J Roentgenol 2003; 180:1379.
- de Baere T, Deschamps F, Teriitheau C, et al. Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol 2008; 19:855.
- Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 2008; 31:271.
- Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg 2008; 247:1029.
- King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer 2008; 113:921.
- Gaur SK, Friese JL, Sadow CA, et al. Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine tumor metastatic to the liver. Cardiovasc Intervent Radiol 2011; 34:566.
- Arrese D, McNally ME, Chokshi R, et al. Extrahepatic disease should not preclude transarterial chemoembolization for metastatic neuroendocrine carcinoma. Ann Surg Oncol 2013; 20:1114.
- Gupta S, Johnson MM, Murthy R, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 2005; 104:1590.
- Cao CQ, Yan TD, Bester L, et al. Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg 2010; 97:537.
- Memon K, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys 2012; 83:887.
- Gupta S, Yao JC, Ahrar K, et al. Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience. Cancer J 2003; 9:261.
- Moug SJ, Leen E, Horgan PG, Imrie CW. Radiofrequency ablation has a valuable therapeutic role in metastatic VIPoma. Pancreatology 2006; 6:155.
- Hamy A, Heymann MF, Bodic J, et al. [Duodenal somatostatinoma. Anatomic/clinical study of 12 operated cases]. Ann Chir 2001; 126:221.
- Kulke MH, Anthony LB, Bushnell DL, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010; 39:735.
- Bilimoria KY, Bentrem DJ, Merkow RP, et al. Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors. J Am Coll Surg 2007; 205:558.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- CLINICAL MANIFESTATIONS
- TUMOR LOCALIZATION
- Approach to imaging
- DIFFERENTIAL DIAGNOSIS
- Pancreatic resection
- Treatment of advanced/metastatic disease
- - Somatostatin analogue
- - Liver-directed therapy for metastatic disease
- - Molecularly targeted therapy
- - Cytotoxic chemotherapy
- POST-TREATMENT SURVEILLANCE