eMedicine Specialties > Gastroenterology > Stomach

Gastrinoma

Author: Jennifer Lynn Bonheur, MD, Attending Physician, Division of Gastroenterology, Lenox Hill Hospital
Coauthor(s): Senthil Nachimuthu, MD, FACP, Fellow in Cardiology, Heart and Vascular Institute, Tulane University School of Medicine
Contributor Information and Disclosures

Updated: Aug 29, 2009

Introduction

Background

A gastrinoma is a gastrin-secreting tumor that can occur in the pancreas, although it is most commonly found in the duodenum. Duodenal wall gastrinomas have been identified in 40-50% of patients. These duodenal wall tumors are frequently small and multiple. Sporadic tumors occurring in the pancreas tend to be solitary and have greater malignant potential as compared to duodenal gastrinomas.1

More than 80% of gastrinomas arise within the triangle defined as the confluence of the cystic and common bile duct superiorly, the second and third portions of the duodenum inferiorly, and the neck and body of the pancreas medially.

Rarely, primary tumors also occur in a variety of ectopic sites, including the body of the stomach, jejunum, peripancreatic lymph nodes, splenic hilum, omentum, liver, gallbladder, common bile duct, and the ovary.

Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and the liver. One fourth of gastrinomas are related to multiple endocrine neoplasia (MEN) type I and are associated with hyperparathyroidism and pituitary adenomas. These MEN I associated tumors have been observed to occur at an earlier age than sporadic tumors and often follow a more benign course.

The triad of nonbeta islet cell tumors of the pancreas (gastrinomas), hypergastrinemia, and severe ulcer disease was described by Zollinger and Ellison in 1955, hence the eponym Zollinger-Ellison syndrome (ZES).

Pathophysiology

Enormous secretion of gastrin from the tumor cells leads to hyperplasia of fundic parietal cells and increased basal acid secretion. This results in severe ulcer disease. Ulceration might even extend into the small intestine. The acidic content of the small intestine causes the release of secretin, which is responsible for the diarrhea, in part, caused by the outpouring of water and bicarbonate from the pancreas and small intestine.

A recent small study by Kohan et al describes duodenal bulb mucosa with hypertrophic heterotopia in patients with ZES.2 The investigators evaluated the incidence of duodenal gastric oxyntic hypertrophic heterotopia in 7 patients with ZES over an average period of 5 years. The patients underwent endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa every 3-6 months.

Of the 7 patients with ZES and an intact stomach and duodenum, 2 had no evidence of duodenal mucosal hypertrophic heterotopia, but 5 did, in whom bowel mucosa biopsies revealed patchy replacement of surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria.2 In addition, the patients with gastric oxyntic hypertrophic heterotopia had higher levels of average serum gastrin and basal acid output levels than those without gastric oxyntic hypertrophic heterotopia, a finding that Kohan et al suggest not only could hypertrophic and heterotopic gastric mucosa result from increased gastrin levels but that an increased incidence of postbulbar ulcers may result in affected patients.2

Frequency

International

The true incidence of ZES is not known. ZES constitutes 0.1% or more of cases of peptic ulcer disease. Although rare, gastrinomas are the most common pancreatic islet cell tumors.

Mortality/Morbidity

With the advent of antiulcer medications, the number of deaths secondary to ulcer complications decreased significantly. The primary determinants of survival for patients with gastrinomas are the size of the primary tumor and the occurrence of tumor metastasis.

  • Patients with hepatic metastases may have a remaining life span of less than 1 year.
  • In patients with liver metastasis, the 5-year survival rate is 20-30%.
  • In patients with localized disease or metastasis to local lymph nodes without liver metastasis, the 5-year survival rate is 90%.

Sex

Gastrinomas are more common in males than in females, with ratios from 1.5:1 to 2:1.

Age

Although gastrinomas can occur at any age, the initial clinical manifestation usually appears in people aged 30-50 years.

Clinical

History

  • The symptoms in 90-95% of patients with gastrinomas are similar to the symptoms of common peptic ulcer disease. Usually, persistent abdominal pain exists that is less responsive to medical treatment.
  • Sometimes, symptoms may relate to a complication of peptic ulcer disease, such as bleeding (eg, melena, hematemesis), gastric outlet obstruction (eg, vomiting), and perforation (eg, peritoneal irritation).
  • Other symptoms include gastroesophageal reflux, diarrhea, steatorrhea, and weight loss, all of which are secondary to acid hypersecretion. Vitamin B-12 malabsorption, which is not correctable by oral intrinsic factor, may also be observed.
  • Chronic acid reflux may lead to esophageal complications (eg, esophagitis, stricture formation, Barrett esophagus) in up to two thirds of patients with Zollinger-Ellison syndrome.

Physical

  • Epigastric tenderness is the most frequent abnormal physical finding. Depending on the possible ulcer complications, signs may vary.
  • Nearly 75% of ulcers in patients with gastrinomas are present in the first portion of the duodenum. These ulcers usually are single or multiple and are indistinguishable from peptic ulcer disease.
  • Nearly 10% of patients with ZES have no demonstrable ulcer. Ulcers located in the second, third, or fourth portion of the duodenum or jejunum should increase the possibility of gastrinoma.
  • The other factors that alert one to the presence of underlying gastrinomas are the following:
    • Ulcers that are refractory to standard therapy
    • Multiple ulcers
    • Giant ulcers, larger than 2 cm
    • Recurrent ulcers
    • Ulcers with unexplained diarrhea
    • Strong family history of ulcers
    • Hypercalcemia
    • Duodenal ulcer that is not related to Helicobacter pylori infection or nonsteroidal anti-inflammatory drug use

More on Gastrinoma

Overview: Gastrinoma
Differential Diagnoses & Workup: Gastrinoma
Treatment & Medication: Gastrinoma
Follow-up: Gastrinoma
References
Further Reading
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References

  1. Ruiz-Tovar J, Priego P, Martinez-Molina E, et al. Pancreatic neuroendocrine tumours. Clin Transl Oncol. Aug 2008;10(8):493-7. [Medline].

  2. Kohan E, Oh D, Wang H, et al. Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients with Zollinger Ellison syndrome. Diagn Ther Endosc. 2009;2009:298381. [Medline]. [Full Text].

  3. Granberg D, Jacobsson H, Oberg K, Gustavsson J, Lehtihet M. Regression of a large malignant gastrinoma on treatment with Sandostatin LAR: a case report. Digestion. 2008;77(2):92-5. [Medline].

  4. Campana D, Piscitelli L, Mazzotta E. Zollinger-Ellison syndrome. Diagnosis and therapy. Minerva Med. Jun 2005;96(3):187-206. [Medline].

  5. Del Valle J, Scheiman J. Zollinger-Ellison Syndrome. Textbook of Gastroenterology, 4th Edition. 2003;1377-1388.

  6. Delvalle J, Yamada T. Zollinger-Ellison Syndrome. Textbook of Gastroenterology. 1995;1430.

  7. Feldman M, Sleisenger MW, McGuigan JE. Zollinger-Ellison syndrome and other hypersecretory states. In: Feldman M, Scharschmidt BF, Sleisenger M, Zorab R, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 6th ed. Philadelphia, Pa: WB Saunders; 1998:. 679-90.

  8. Hirschowitz BI. Zollinger-Ellison syndrome: pathogenesis, diagnosis, and management. Am J Gastroenterol. Apr 1997;92(4 Suppl):44S-48S; discussion 49S-50S. [Medline].

  9. Jensen RT, Gibril F. Somatostatin receptor scintigraphy in gastrinomas. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S179-85. [Medline].

  10. Mignon M, Cadiot G. Natural history of gastrinoma: lessons from the past. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S98-103. [Medline].

  11. Nobels FR, Kwekkeboom DJ, Coopmans W. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab. Aug 1997;82(8):2622-8. [Medline].

  12. Norton JA. Gastrinoma: advances in localization and treatment. Surg Oncol Clin N Am. Oct 1998;7(4):845-61. [Medline].

  13. Norton JA. Surgical treatment and prognosis of gastrinoma. Best Pract Res Clin Gastroenterol. Oct 2005;19(5):799-805. [Medline].

  14. Norton JA, Fang TD, Jensen RT. Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. J Natl Compr Canc Netw. Feb 2006;4(2):148-53.

  15. Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. Oct 2005;19(5):753-81.

  16. Passaro E, Howard TJ, Sawicki MP. The origin of sporadic gastrinomas within the gastrinoma triangle: a theory. Arch Surg. Jan 1998;133(1):13-6; discussion 17. [Medline].

  17. Pellicano R, De Angelis C, Resegotti A. Zollinger-Ellison syndrome in 2006: concepts from a clinical point of view. Panminerva Med. Mar 2006;48(1):33-40.

  18. Price TN, Thompson GB, Lewis JT, Lloyd RV, Young WF. Zollinger-Ellison syndrome due to primary gastrinoma of the extrahepatic biliary tree: three case reports and review of the literature. Endocr Pract. Jun 2 2009;1-38. [Medline].

  19. Sugg SL, Norton JA, Fraker DL. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann Surg. Aug 1993;218(2):138-44. [Medline].

  20. Wong H, Yau T, Chan P, et al. PPI-delayed diagnosis of gastrinoma: oncologic victim of pharmacologic success. Pathol Oncol Res. Aug 20 2009;[Medline].

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Further Reading

Related eMedicine Topics

Clinical Trials

National Guideline Clearinghouse

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Keywords

gastrinoma, Zollinger-Ellison syndrome, ZES, ZE syndrome, pancreatic tumor, pancreas tumor, duodenal tumor, duodenal wall tumor, lymph node tumor, gastrin-secreting tumor, tumor, pancreatic islet cell tumors, malignancy, malignant tumor, basal acid output, BAO, ulcer, severe ulcer disease, multiple endocrine neoplasia type I, MEN type I, ulcerogenic islet cell tumor

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Contributor Information and Disclosures

Author

Jennifer Lynn Bonheur, MD, Attending Physician, Division of Gastroenterology, Lenox Hill Hospital
Jennifer Lynn Bonheur, MD is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, New York Academy of Sciences, New York Society for Gastrointestinal Endoscopy, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Senthil Nachimuthu, MD, FACP, Fellow in Cardiology, Heart and Vascular Institute, Tulane University School of Medicine
Senthil Nachimuthu, MD, FACP is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

Manoop S Bhutani, MD, FACG, FACP, Professor, Department of Medicine, Division of Gastroenterology, Director, Center for Endoscopic Ultrasound, Co-Director, Center for Endoscopic Research, Training and Innovation, University of Texas Medical Branch at Galveston
Manoop S Bhutani, MD, FACG, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Institute of Ultrasound in Medicine, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
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 and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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