- Clinical science
A gastrinoma (Zollinger-Ellison syndrome) is a gastrin-secreting neuroendocrine tumor that is most often localized to the duodenum and pancreas. Most gastrinomas occur sporadically, but some are associated with other endocrine neoplasias (e.g., pituitary adenomas, parathyroid adenomas, insulinomas). Although some gastrinomas are benign, more than half of all gastrinomas are malignant. Gastrinomas release high levels of gastrin, which then increases the production of gastric acid. Patients typically present with recurrent, therapy-resistant peptic ulcer disease and diarrhea. Patients with gastrinomas have low gastric pH and elevated serum gastrin. Furthermore, serum gastrin levels increase with the administration of secretin (positive secretin stimulation test). Surgical resection of the tumor is indicated in patients with localized disease. Proton pump inhibitors (PPIs) and octreotide may be used to control acid secretion.
- Sex: ♂ > ♀ (2:1)
- Age of onset: 30–50 years
Epidemiological data refers to the US, unless otherwise specified.
- Gastrinomas are neuroendocrine tumors of the GI tract that secrete gastrin.
- Hypergastrinemia → stimulation of parietal cells → gastric acid hypersecretion, which leads to:
- Tumor location
- ∼ 60% of gastrinomas are malignant (but slow-growing)
Best initial test: esophagogastroduodenoscopy
- Important to rule out H. pylori infection and malignant ulcers
- Typically reveals multiple ulcers and thick gastric folds
- ↓ Gastric pH and ↑ basal acid output (> 10 mEq/h)
↑ Serum gastrin (in a fasting serum sample)
- A gastrin level > 1000 pg/mL (or 10-fold increase in gastrin levels) is conclusive evidence of a gastrinoma. A gastrin level > 1000 pg/mL is conclusive evidence of a gastrinoma; however, in most patients with gastrinomas (∼ 66%), fasting levels of gastrin will lie between 100 and 1000 pg/mL.
- If serum gastrin levels increase (> 100 pg/mL) but are not more than 1000 pg/mL, a secretin stimulation test should be performed.
Secretin stimulation test (if fasting serum gastrin test is inconclusive)
- A two-fold increase in gastrin above the basal level is indicative of a gastrinoma.
- No increase or only a very slight increase is observed in cases of secondary hypergastrinemia.
- ↑ Serum gastrin (in a fasting serum sample)
- Imaging: only after diagnosis is confirmed to localize the tumor
The presence of multiple, large (> 2 cm) ulcers in atypical locations (e.g., the jejunum) should raise suspicion of gastrinoma!
- Reduce acid production
- Nonmetastatic disease: surgical resection of the gastrinoma
- Metastatic disease: chemotherapy
In approximately 50% of cases, the tumor has already metastasized at the time of diagnosis!