Hypergastrinemia is a medical condition characterized by abnormally high levels of the hormone gastrin in the bloodstream. Gastrin is a hormone primarily responsible for stimulating acid secretion in the stomach, which plays a role in digestion. Elevated gastrin can lead to various health issues, impacting the gastrointestinal system and beyond.
The Role of Gastrin
Gastrin is a hormone produced primarily by G cells in the stomach’s antrum, with smaller amounts from the small intestine. Its primary function is to stimulate parietal cells in the stomach to produce hydrochloric acid (gastric acid), which is essential for breaking down food and absorbing nutrients.
Gastrin also promotes the growth of stomach lining cells, a process known as a trophic effect. It works alongside other compounds like histamine and acetylcholine to regulate acid production. It also plays a role in gut motility, influencing the movement of food through the digestive tract.
What Causes High Gastrin Levels?
One cause of high gastrin levels is Zollinger-Ellison Syndrome (ZES), a rare disorder characterized by gastrin-producing tumors called gastrinomas. These tumors, often found in the pancreas or duodenum, secrete excessive gastrin, leading to extremely high levels, sometimes exceeding 1000 pg/mL. In some ZES cases, it is associated with Multiple Endocrine Neoplasia type 1 (MEN1), an inherited genetic disorder.
Another cause is atrophic gastritis, a condition where chronic inflammation or damage to the stomach lining reduces gastric acid output. When stomach acid production is low (achlorhydria or hypochlorhydria), the stomach compensates by increasing gastrin production from G cells. This compensatory mechanism is a feedback loop where low acid signals G cells to release more gastrin to stimulate acid secretion. For example, autoimmune atrophic gastritis involves the immune system attacking parietal cells, leading to decreased acid and subsequent hypergastrinemia.
Long-term use of Proton Pump Inhibitor (PPI) medications, commonly prescribed to reduce stomach acid, can also result in hypergastrinemia. PPIs work by inhibiting the proton pumps responsible for acid secretion, thereby raising the stomach’s pH. This reduced acidity removes the normal negative feedback on gastrin release, causing G cells to produce more gastrin. Gastrin levels often increase 3-4 fold above normal with PPI treatment.
Impaired kidney function, such as in kidney failure, can also lead to increased gastrin levels. The kidneys are involved in clearing gastrin from the body. When kidney function is compromised, gastrin clearance is reduced, leading to its accumulation in the bloodstream.
Finally, G-cell hyperplasia, an overgrowth of gastrin-producing G cells in the stomach, can also cause hypergastrinemia. This condition often occurs as a compensatory response to reduced stomach acid production, such as in atrophic gastritis. The increased number of G cells leads to elevated synthesis and secretion of gastrin, sometimes resulting in very high gastrin levels.
How Hypergastrinemia Affects the Body
Chronically elevated gastrin levels primarily impact gastric acid secretion and cell growth. When hypergastrinemia leads to excessive stomach acid production, common symptoms include heartburn, acid reflux (GERD), abdominal pain, nausea, vomiting, and diarrhea. This excess acid can erode the stomach lining, causing peptic ulcers in the stomach and duodenum, which may manifest as burning discomfort. Weight loss can also occur due to chronic gastrointestinal distress.
In Zollinger-Ellison Syndrome (ZES), severe and recurrent peptic ulcers are characteristic, often appearing in unusual locations. The high acid output in ZES can also lead to severe diarrhea and malabsorption, impacting nutrient uptake.
When hypergastrinemia results from conditions like atrophic gastritis, where acid production is low, nutrient deficiencies can arise. For instance, reduced stomach acid impairs vitamin B12 absorption. Long-term consequences of persistent hypergastrinemia can include a higher risk of persistent ulcers, gastrointestinal bleeding, and perforation. Chronic hypergastrinemia, particularly with atrophic gastritis, is also associated with an increased risk of certain types of stomach cancer, such as gastric carcinoids.
Diagnosis and Treatment Approaches
Diagnosing hypergastrinemia typically begins with blood tests to measure fasting gastrin levels. A normal fasting serum gastrin level is usually between 50-60 pg/mL, with values above 150 pg/mL considered elevated. Levels exceeding 1000 pg/mL are highly suggestive of Zollinger-Ellison Syndrome (ZES), especially when accompanied by high gastric acid secretion.
To differentiate between various causes, particularly ZES from other forms of hypergastrinemia with low acid, a secretin stimulation test may be performed. A significant rise in gastrin levels after secretin injection indicates a gastrinoma. Imaging studies are then used to locate any potential gastrinomas, including:
Endoscopy to visualize ulcers and obtain biopsies.
CT scans, MRI, or somatostatin receptor scintigraphy for tumor localization.
Endoscopic ultrasound (EUS) for finding small tumors, especially in the pancreas and duodenum.
Treatment for hypergastrinemia is primarily focused on addressing the underlying cause. For ZES, surgical removal of gastrinomas is the preferred approach when feasible. If the tumors are widespread or cannot be removed, other treatments like chemotherapy or somatostatin analogs may be considered to control tumor growth.
Medications that reduce stomach acid, such as Proton Pump Inhibitors (PPIs) or H2 blockers, are commonly used to manage symptoms caused by excess acid secretion. High-dose PPIs are often the primary treatment for controlling acid hypersecretion in ZES. For hypergastrinemia caused by long-term PPI use, gradually reducing and discontinuing the medication under medical supervision is often recommended. Regular monitoring of gastrin levels and endoscopic surveillance are important for all patients to track the condition and manage symptoms.