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.
- Gastrinomas are neuroendocrine tumors of the GI tract that secrete gastrin.
- Hypergastrinemia → stimulation of parietal cells → gastric acid hypersecretion, which leads to:
- ∼ 60% of gastrinomas are malignant (but slow-growing) 
Other causes of PPI use, H. pylori infection, atrophic gastritis, chronic renal failure, vagotomy, gastric outlet obstruction, retained antrum syndrome, and extensive small bowel resection.  include
- 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 gastric acid output. or measure basal
- After diagnostic confirmation:
Laboratory studies 
Consider stoppingprior to testing, if safe to do so. 
- Fasting serum gastrin (FSG) and gastric pH (initial studies) ; 
Secretin stimulation test
- Indication: inconclusive results of initial studies
- Mechanism 
- Basal acid output 
If gastrinoma is confirmed, consider the following studies in consultation with a specialist (e.g., gastroenterology, endocrinology).
- Assessment for MEN 1, e.g.: 
- Assessment for other hormonal syndromes (e.g., ) 
Tumor localization 
Esophagogastroduodenoscopy (EGD) 
- Indication: all patients with confirmed gastrinoma
- Findings 
Obtainand either PET/CT or in all patients with confirmed gastrinoma.
- Findings 
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. 
Gastrinomas are primarily managed by specialists (e.g., gastroenterology, oncology, surgery).
Pharmacological therapy 
- Acid suppression medications: indicated for all patients with gastrinoma
- Somatostatin analog: (e.g., octreotide): consider in advanced disease 
- Exploration laparotomy: all patients with sporadic gastrinomas to identify tumors not seen on imaging
- Resection considered for:
- Liver transplant: considered for patients with metastases confined to the liver 
Anticancer therapy 
Consider the following therapies in patients with advanced or refractory disease.
- Chemotherapy (e.g., streptozocin, 5-fluorouracil, doxorubicin)
- Radiation (e.g., peptide receptor-targeted radiotherapy)
- Liver-directed therapy (e.g., chemoembolization) in patients with metastases primarily in the liver
Consider the following for patients with active nonmetastatic disease.