1. Overview
Gastrin is a peptide hormone produced by G cells located mainly in the gastric antrum and the duodenum. It plays a central role in gastrointestinal physiology by stimulating gastric acid (hydrochloric acid) secretion, enhancing gastric mucosal growth, and increasing gastric motility.
Gastrin exists in several molecular forms, with G-17 and G-34 being the most prominent circulating forms. After release, gastrin acts on enterochromaffin-like (ECL) cells in the gastric fundus to stimulate histamine secretion, which in turn activates parietal cells to produce gastric acid. Through these mechanisms, gastrin is essential for digestion and the regulation of gastric function.
2. Symptoms
Gastrin itself does not cause symptoms; clinical manifestations arise from conditions associated with abnormal gastrin levels.
Elevated gastrin levels may lead to symptoms of excessive gastric acid secretion, such as epigastric pain, heartburn, recurrent or refractory peptic ulcers, chronic diarrhea, and gastrointestinal bleeding. In severe cases, patients may present with complications such as ulcer perforation or malabsorption.
Low or normal gastrin levels are usually asymptomatic and are interpreted in the context of gastric acid production and mucosal integrity.
3. Causes
Abnormal gastrin levels result from altered regulation of gastric acid secretion or pathological conditions affecting G cells.
Gastrin secretion is stimulated by vagal activation, gastric distension, and the presence of food peptides and amino acids. Gastrin release is inhibited when gastric acidity falls below a pH of 3 through negative feedback mediated by somatostatin. Other inhibitory hormones include secretin, gastric inhibitory peptide (GIP), glucagon, and calcitonin.
Elevated gastrin levels are caused by long-term use of proton pump inhibitors (PPIs) or antacids, Helicobacter pylori infection, chronic atrophic gastritis, pernicious anemia, post-gastrectomy states, and acid-reducing medications. Markedly high gastrin levels are characteristic of Zollinger–Ellison syndrome, caused by gastrin-secreting tumors (gastrinomas) of the pancreas or duodenum.
4. Risk Factors
Risk factors for hypergastrinemia include prolonged acid suppression therapy, chronic gastric inflammation, autoimmune gastric disorders, and neuroendocrine tumors.
Patients with recurrent or refractory peptic ulcer disease, unexplained hyperacidity, chronic diarrhea, or a history of gastrinoma are at increased risk. Individuals with atrophic gastritis or pernicious anemia may also develop elevated gastrin levels due to reduced acid production and loss of negative feedback.
Following gastric surgery, altered anatomy and reduced acid secretion can also predispose to increased gastrin concentrations.
5. Prevention and Clinical Management
Gastrin testing is primarily used for diagnostic evaluation and monitoring rather than prevention. Indications include suspected Zollinger–Ellison syndrome, recurrent or treatment-resistant peptic ulcer disease, unexplained hyperacidity symptoms, evaluation of gastrinoma recurrence, assessment of hypergastrinemia causes, investigation of atrophic gastritis or pernicious anemia, monitoring of long-term PPI therapy, post-gastrectomy assessment, and evaluation of unexplained chronic diarrhea.
For accurate testing, patients should avoid alcohol for at least 24 hours before sample collection and remain fasting, although water is permitted. A thorough review of medications, supplements, and herbal products is essential. H2 receptor antagonists should be stopped at least 72 hours before testing when clinically feasible.
Blood samples are collected in EDTA tubes and transported to the laboratory on ice. Hemolysed samples are unsuitable for analysis. In specific diagnostic protocols, such as suspected Zollinger–Ellison syndrome, a secretin stimulation test may be performed, involving baseline gastrin measurement followed by timed sampling after secretin administration.
Laboratory estimation methods include radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay (CLIA), immunoradiometric assay (IRMA), and electrochemiluminescence immunoassay (ECLIA).
Normal gastrin reference ranges are approximately 0–180 pg/mL in adults and 0–125 pg/mL in children. Markedly elevated levels strongly suggest gastrinoma when correlated with clinical findings.
Clinically, gastrin measurement aids in diagnosing gastrin-secreting tumors, monitoring acid-suppressive therapy, evaluating refractory peptic ulcer disease, and assessing precancerous gastric conditions. Chromogranin A (CgA), a neuroendocrine tumor marker, is often measured alongside gastrin to support diagnosis and monitor tumor burden, although it is less specific.
Overall, gastrin testing provides valuable insight into gastric physiology and pathology when interpreted in conjunction with clinical presentation, gastric acid output, and complementary investigations.
