Gastrin is a peptide hormone produced primarily by G cells located in the antrum, the lower part of the stomach. It is a major regulator of digestion, instructing the stomach to release hydrochloric acid (gastric acid). Gastrin also promotes the growth and maintenance of the stomach lining and stimulates muscle contractions for motility. Hypergastrinemia is the medical condition characterized by abnormally high levels of gastrin circulating in the bloodstream. This elevation can lead to an imbalance in the digestive system, resulting in excessive acid production, causing significant gastrointestinal distress.
Recognizing the Signs
The symptoms of hypergastrinemia are often related to the overproduction of stomach acid, a condition called hyperchlorhydria, which irritates the digestive tract. Patients frequently report persistent or severe heartburn, a hallmark symptom of gastroesophageal reflux disease (GERD), which can also cause a chronic sore throat or hoarseness. Abdominal pain is a common complaint, often described as a burning or gnawing sensation in the upper abdomen, typically signaling peptic ulcers in the stomach or the first part of the small intestine. In severe cases, such as Zollinger-Ellison Syndrome, patients may experience chronic diarrhea, nausea, vomiting, or unexplained weight loss. The diarrhea is caused by the large volume of acid overwhelming the small intestine’s ability to absorb water and nutrients.
Primary Mechanisms of Elevation
Hypergastrinemia results from two fundamental physiological mechanisms: disruption of the normal acid-feedback loop or autonomous, unregulated production of the hormone. Gastrin secretion is controlled by a negative feedback system. High levels of gastric acid (low pH) inhibit G cells from releasing more gastrin. Conversely, when the stomach environment becomes less acidic (high pH), gastrin release is stimulated to restore acid levels.
Impaired Acid Feedback
The most common cause of hypergastrinemia involves conditions that reduce stomach acid, removing the natural inhibitory signal. Long-term use of Proton Pump Inhibitors (PPIs), medications used to treat acid reflux and ulcers, powerfully suppresses acid secretion. This sustained acid reduction causes G cells to continuously produce gastrin, often leading to moderate elevation. Withdrawal of PPIs usually reverses this type of hypergastrinemia within several days. Another cause is chronic atrophic gastritis, involving the destruction of acid-producing parietal cells. When these cells are destroyed, the stomach cannot produce acid, resulting in a high pH that triggers a significant compensatory release of gastrin. Autoimmune disorders and chronic Helicobacter pylori infection contribute to this gastritis. Impaired gastrin clearance, such as in kidney failure, can also elevate gastrin levels because the hormone is not efficiently removed from circulation.
Autonomous Production
The second mechanism is the uncontrolled release of gastrin, independent of the stomach’s acid level, which results in very high concentrations. The main example is a gastrinoma, a neuroendocrine tumor that secretes massive amounts of the hormone. When this tumor is present, the condition is known as Zollinger-Ellison Syndrome (ZES), characterized by severe acid hypersecretion and aggressive peptic ulcers. Gastrinomas are usually located in the duodenum or pancreas and secrete gastrin continuously, overwhelming regulatory mechanisms. The high gastrin levels in ZES persist even when stomach acid levels are profoundly high, which helps distinguish ZES from other causes.
Identifying the Underlying Condition
Diagnosis begins with a blood test to measure the fasting serum gastrin level, confirming hypergastrinemia. Since PPIs commonly cause elevation, patients are often instructed to temporarily stop taking them before the test for accuracy. A gastrin level significantly above the upper limit of normal, particularly over 1,000 picograms per milliliter, strongly suggests a gastrinoma. To differentiate Zollinger-Ellison Syndrome (ZES) from other causes, doctors perform specialized provocative tests. The Secretin Stimulation Test is the preferred method, measuring the change in gastrin levels after a secretin injection. In patients with gastrinomas, secretin causes a dramatic, paradoxical increase in gastrin levels, while the response is minimal or absent in other forms of hypergastrinemia. Once ZES is suspected, imaging techniques are used to locate the tumor, which can be small and difficult to find. Endoscopic ultrasound combines an endoscope with an ultrasound probe to provide detailed images of the pancreas and duodenum, the most common sites for gastrinomas. Other modalities, such as CT scans, MRI, or somatostatin receptor scintigraphy, are used to visualize the tumor and check for metastasis.
Treatment Approaches
Management of hypergastrinemia focuses on treating the specific underlying cause.
PPI and Infection-Related Causes
For PPI-induced hypergastrinemia, the primary approach is to reduce the dosage or discontinue the medication. If the PPI cannot be stopped, doctors may switch the patient to an alternative acid-suppressing medication, such as an H2 receptor blocker. Gradual tapering of the PPI is often recommended to prevent a rebound increase in acid production. For cases related to H. pylori-induced chronic gastritis, a course of antibiotics is administered to eradicate the bacteria. Successful eradication leads to decreased inflammation and normalization of gastrin levels. Kidney-related hypergastrinemia is managed by optimizing treatment for the underlying renal disease.
Zollinger-Ellison Syndrome (ZES) Treatment
Treatment for ZES involves two goals: controlling excessive acid and managing the tumor. High doses of PPIs are the standard medical therapy to suppress acid secretion and prevent peptic ulcers, with the dosage often being higher than that used for typical GERD. If the gastrinoma is localized and has not spread, surgical removal offers the potential for a cure. For tumors that are unresectable or have metastasized, somatostatin analogs like octreotide may be used to inhibit gastrin release and slow tumor growth.