Gastrin

Tests for the hormone gastrin, which is secreted by G cells of the gastric antrum and the pancreatic islets of Langerhans, are used to investigate pernicious anemia and achlorhydria and to diagnose gastrinoma that is or is not associated Zollinger-Ellison syndrome.

Normal findings

Adult: 0-180 pg/mL or 0-180 ng/L (SI units) ^[1]

Elderly patients have higher gastrin levels. ^[1]

Child: 0-125 pg/mL ^[1]

In patients who have undergone antrectomy with vagotomy, gastrin levels are reduced. In contrast, gastrin levels are increased in Zollinger-Ellison syndrome. Diagnosis of the syndrome is certain when the plasma gastrin level exceeds 1000 pg/mL and 1 of the following criteria is met ^[2] :

• The basal acid output is greater than 15 mEq/h in patients with an intact stomach

• The basal acid output is greater than 5 mEq/h in patients who have undergone gastrectomy

• The patient's hypergastrinemia is associated with a pH of less than 2

Testing is performed using a Tiger-top tube. The sample must immediately be sent to the laboratory and frozen.

Be certain that the patient is taking neither H₂ blockers nor antacids. An overnight fast is necessary prior to blood collection.

Description

Secretion of the hormone gastrin, by G cells of the gastric antrum and the pancreatic islets of Langerhans, is stimulated by alkaline environment, vagal stimulation, and gastric distension, as well as by the presence of alcohol, amino acids, peptides, and calcium in the stomach. Gastrin secretion is inhibited by gastric acid.

The principal forms of gastrin in the stomach, which include big gastrin (G-34), small gastrin (G-17), and mini-gastrin (G-14), circulate in sulfated and nonsulfated forms. ^[3] The diagnosis of Zollinger-Ellison syndrome may require both fasting and post–secretin infusion gastrin levels. ^[2]

The characteristics of Zollinger-Ellison syndrome include severe diarrhea, refractory peptic ulcer disease, and gastric acid hypersecretion related to a neuroendocrine tumor of the pancreas (gastrinoma) or duodenum. Sixty-two percent to 80% of cases are sporadic, while 20-38% of cases are associated with multiple endocrine neoplasia type 1 (MEN1). The diagnosis of Zollinger-Ellison syndrome can be made with certainty when the plasma gastrin level exceeds 1000 pg/mL and 1 of the following criteria exists ^[2] :

• The basal acid output is greater than 15 mEq/h in patients with an intact stomach

• The basal acid output is greater than 5 mEq/h in patients who have undergone gastrectomy

• The patient's hypergastrinemia is associated with a pH of less than 2

Differentiation between the causes of hypergastrinemia can be made with the aid of gastrin provocative tests. These tests—the secretin stimulation test and the calcium infusion study—are especially helpful in patients whose acid secretory studies have yielded indeterminate findings.

Of the 2 tests, the secretin study is the most sensitive and specific for the diagnosis of gastrinoma. If gastrin levels rise 120 pg within 15 minutes of secretin injection, the test has a sensitivity and specificity for Zollinger-Ellison syndrome of greater than 90%. A false-positive secretin test result may occur, however, if the patient has proton pump inhibitor–induced hypochlorhydria or achlorhydria, which means that this agent must be stopped for 1 week prior to testing.

In the calcium infusion study, a calcium infusion of 15 mg Ca/kg in 500 mL normal saline is administered over 4 hours. Prior to infusion, serum is drawn in a fasting state; it is then drawn at 1, 2, 3, and 4 hours afterward. The response is considered normal if little or no increase occurs over the baseline gastrin level. ^[4]

Calcium infusion studies are more cumbersome and less sensitive and specific than secretin tests, and the potential for adverse effects from these studies is higher. Consequently, calcium infusion testing is rarely used, although it can be administered when the presence of Zollinger-Ellison syndrome is strongly suggested by the patient's clinical characteristics but secretin stimulation yields inconclusive results. ^[5]

Indications/Applications

Gastrin testing is employed in the diagnosis of gastrinoma, either with or without Zollinger-Ellison syndrome, and in the investigation of pernicious anemia and achlorhydria.

Considerations

Gastrin levels, which follow a circadian rhythm, are lowest in the early morning and highest during the day. Gastrin stimulation testing using secretin produces either no response or a slight suppression of gastrin, while calcium infusion testing results in either no response or a slight increase in gastrin over baseline.

A consistent relationship between Helicobacter pylori and serum gastrin levels has not been established. ^[3] In response to a meal, G cells of the gastric antrum release gastrin into the circulation. Gastrin release is inhibited by fasting and increased gastric acidity, and is stimulated by a high gastric pH. To determine the capacity of gastric acid secretion, the stimulation of histamine and acid secretion with the gastrin analogue pentagastrin has been put to clinical use in various diagnostic tests. ^[6]