Last updated: July 20, 2023

Summarytoggle arrow icon

A gastrinoma (i.e., Zollinger-Ellison syndrome) is a gastrin-secreting neuroendocrine tumor and is most often located in the duodenum and pancreas. Most gastrinomas occur sporadically, but some are associated with other endocrine neoplasias (e.g., pituitary adenomas, parathyroid adenomas, insulinomas). More than half of all gastrinomas are malignant. Gastrinomas release high levels of gastrin, which stimulates the production of gastric acid. Patients typically present with recurrent, therapy-resistant peptic ulcer disease and diarrhea. Diagnosis is confirmed by findings of a fasting gastric pH ≤ 2 and fasting serum gastrin (FSG) > 1000 pg/mL. In case of diagnostic uncertainty after initial testing, a secretin stimulation test is obtained. The primary objectives of management are controlling acid hypersecretion and managing the malignant tumor. Proton pump inhibitors (PPIs) are the preferred therapy to control acid secretion. Surgical tumor resection is indicated in patients with localized disease. Chemotherapy and radiation may be considered in advanced disease.

Epidemiologytoggle arrow icon

  • Sex: > (2:1)
  • Age of onset: 30–50 years


Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon


Pathophysiologytoggle arrow icon

Other causes of hypergastrinemia include PPI use, H. pylori infection, atrophic gastritis, chronic renal failure, vagotomy, gastric outlet obstruction, retained antrum syndrome, and extensive small bowel resection. [7]


Clinical featurestoggle arrow icon

Most patients manifest with recurrent, therapy-resistant peptic ulcer disease.


Diagnosticstoggle arrow icon

Approach [9][10][11]

  • Consider gastrinoma in patients with recurrent, therapy-resistant PUD, GERD, abdominal pain, and/or diarrhea.
  • Obtain FSG and gastric pH levels in all patients.
  • If initial studies are inconclusive, order a secretin stimulation test or measure basal gastric acid output.
  • After diagnostic confirmation:
    • Assess for underlying MEN 1 syndrome and other related conditions.
    • Obtain EGD and abdominal imaging to localize the gastrinoma and assess for metastases.

To reduce the risk of severe complications of acid hypersecretion and peptic ulcer disease, avoid abruptly stopping PPIs when adequate coverage with H2RAs and/or antacids is unavailable. [12]

Laboratory studies [7][10]

Confirmatory studies

Consider stopping acid suppression medications prior to testing, if safe to do so. [11]

  • Fasting serum gastrin (FSG) and gastric pH (initial studies) ; [12]
    • FSG > 1000 pg/mL and gastric pH < 2: gastrinoma is confirmed. [10]
    • FSG 101–1000 pg/mL and gastric pH < 2; : inconclusive result; perform a secretin stimulation test [10]
    • Gastric pH ≥ 2: gastrinoma is unlikely [7]
  • Secretin stimulation test
    • Indication: inconclusive results of initial studies
    • Mechanism [12]
      • In healthy individuals, an infusion of secretin inhibits gastrin secretion.
      • In individuals with gastrinoma, secretin infusion causes a dramatic increase in gastrin secretion.
    • Findings
  • Basal acid output [9]
    • Indication: secretin stimulation test is unavailable or unreliable (e.g., due to PPI use)
    • Findings: Basal acid output > 15 mEq/h suggests gastrinoma [9]

When it is safe to do so, stop acid suppression medications prior to performing confirmatory studies (PPIs: ≥ 1 week before; H2 receptor blockers (H2RAs): ≥ 24 hours before). [11]

Follow-up studies

If gastrinoma is confirmed, consider the following studies in consultation with a specialist (e.g., gastroenterology, endocrinology).

Up to 50% of all patients with gastrinoma have concomitant H. pylori infection; H. pylori infection can also cause a false positive on secretin stimulation test. [9][12]

Tumor localization [9]

Esophagogastroduodenoscopy (EGD) [12]

The presence of multiple ulcers in atypical locations (e.g., the jejunum) should raise suspicion of gastrinoma. [15]

Imaging [9]

Obtain cross sectional imaging and either PET/CT or scintigraphy in all patients with confirmed gastrinoma.

Most gastrinomas are found in an area called the gastrinoma triangle. The superior vertex of the gastrinoma triangle is formed by the junction of the bile and cystic ducts, the medial vertex by the neck of the pancreas, and the inferior vertex by the third portion of the duodenum. [9]

Treatmenttoggle arrow icon

Gastrinomas are primarily managed by specialists (e.g., gastroenterology, oncology, surgery).

Pharmacological therapy [10]

PPIs are preferred because of their long half-life. H2RAs should not be used for initial therapy because of very high and frequent dosing requirements (i.e., every 4–6 hours). [9]

Surgery [10]

  • Exploration laparotomy: all patients with sporadic gastrinomas to identify tumors not seen on imaging
  • Resection considered for:
    • Localized, sporadic gastrinomas
    • Gastrinoma with MEN 1 if tumor size is > 2 cm
  • Liver transplant: considered for patients with metastases confined to the liver [7]

Anticancer therapy [9][10]

Consider the following therapies in patients with advanced or refractory disease.

Monitoring [9]

Consider the following for patients with active nonmetastatic disease.

Referencestoggle arrow icon

  1. Li ML, Norton JA. Gastrinoma. Curr Treat Options Oncol. 2001; 2 (4): p.337-346.doi: 10.1007/s11864-001-0027-3 . | Open in Read by QxMD
  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier Saunders ; 2014
  4. Bergsland E. Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: July 14, 2016. Accessed: February 11, 2017.
  5. Norton JA, Foster DS, Ito T, Jensen RT. Gastrinomas. Endocrinol Metab Clin North Am. 2018; 47 (3): p.577-601.doi: 10.1016/j.ecl.2018.04.009 . | Open in Read by QxMD
  6. Rossi RE, Elvevi A, Citterio D, et al. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J Gastroenterol. 2021; 27 (35): p.5890-5907.doi: 10.3748/wjg.v27.i35.5890 . | Open in Read by QxMD
  7. Walker BR, Colledge NR, Raston SR, Penman ID. Davidson's Principles and Practice of Medicine. Elsevier ; 2013
  8. Williams NS, Bulstrode C, O'Connell PR. Bailey & Love's Short Practice of Surgery. CRC Press ; 2013
  9. Jensen RT, Cadiot G, Brandi ML, et al. ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Functional Pancreatic Endocrine Tumor Syndromes. Neuroendocrinology. 2012; 95 (2): p.98-119.doi: 10.1159/000335591 . | Open in Read by QxMD
  10. Falconi M, Eriksson B, Kaltsas G, et al. ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. Neuroendocrinology. 2016; 103 (2): p.153-171.doi: 10.1159/000443171 . | Open in Read by QxMD
  11. Metz DC, Cadiot G, Poitras P, Ito T, Jensen RT. Diagnosis of Zollinger–Ellison syndrome in the era of PPIs, faulty gastrin assays, sensitive imaging and limited access to acid secretory testing. Int J Endocr Oncol. 2017; 4 (4): p.167-185.doi: 10.2217/ije-2017-0018 . | Open in Read by QxMD
  12. Metz DC. Diagnosis of the Zollinger–Ellison Syndrome. Clin Gastroenterol Hepatol. 2012; 10 (2): p.126-130.doi: 10.1016/j.cgh.2011.07.012 . | Open in Read by QxMD
  13. Shah P, Singh MH, Yang YX, Metz DC. Hypochlorhydria and Achlorhydria Are Associated With False-Positive Secretin Stimulation Testing for Zollinger-Ellison Syndrome. Pancreas. 2013; 42 (6): p.932-936.doi: 10.1097/mpa.0b013e3182847b2e . | Open in Read by QxMD
  14. Thakker RV, Newey PJ, Walls GV, et al. Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1). J Clin Endocrinol Metab. 2012; 97 (9): p.2990-3011.doi: 10.1210/jc.2012-1230 . | Open in Read by QxMD
  15. Epelboym I, Mazeh H. Zollinger-Ellison Syndrome: Classical Considerations and Current Controversies. Oncologist. 2013; 19 (1): p.44-50.doi: 10.1634/theoncologist.2013-0369 . | Open in Read by QxMD

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