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Test Code GAST Gastrin, Serum

Reporting Name

Gastrin, S

Useful For

Investigation of patients with achlorhydria or pernicious anemia

 

Investigation of patients suspected of having Zollinger-Ellison syndrome

 

Diagnosis of gastrinoma; basal and secretin-stimulated serum gastrin measurements are the best laboratory tests for gastrinoma

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Serum


Specimen Required


Collection Container/Tube: 

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: 

1. Fasting (8 hours).

2. If multiple specimens are drawn, submit each vial under a separate order.

3. Label specimens with corresponding draw time.

Forms: If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

Oncology Test Request Form (T729) (http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)

Benign Hematology Test Request Form (T755) (http://www.mayomedicallaboratories.com/it-mmfiles/benign-hematology-test-request-form.pdf)


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Frozen (preferred) 30 days
  Refrigerated  24 hours

Reference Values

<100 pg/mL

There is no evidence that fasting serum gastrin levels differ between adults and children. Although 8-hour fasts are difficult or impossible to enforce in small children, serum gastrin levels after shorter fasting periods (3-8 hours) may be 50% to 60% higher than the 8-hour fasting value.

Day(s) and Time(s) Performed

Monday through Friday; 5 a.m.-12 a.m.

Saturday; 6 a.m.-6 p.m.

Test Classification

This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

82941

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GAST Gastrin, S 2333-3

 

Result ID Test Result Name Result LOINC Value
GAST Gastrin, S 2333-3

Clinical Information

Gastrin is a peptide hormone produced by mucosal G cells of the gastric antrum. It is synthesized as preprogastrin, cleaved to progastrin, which undergoes several posttranslational modifications, in particular sulfation, and is finally processed into the mature 34-amino acid, gastrin-34. Gastrin-34 may be cleaved further into the shorter 17-amino acid, gastrin-17. Either may be secreted as a c-terminal amidated or unamidated isoform. A number of additional, smaller gastrin fragments, as well as gastrin molecules with atypical posttranslational modifications (eg, absent sulfation), may also be secreted in small quantities. Gastrin half-life is short, 5 minutes for amidated gastrin-17, and 20 to 25 minutes for amidated gastrin-34. Elimination occurs through peptidase cleavage and renal excretion.

 

Gastrin-17 I (nonsulfated form) and gastrin-17 II (sulfated) appear equipotent. Their biological effects are chiefly associated with the amidated isoforms and consist of promotion of gastric epithelial cell proliferation and differentiation to acid-secreting cells, direct promotion of acid secretion, and indirect stimulation of acid production through histamine release. In addition, gastrin stimulates gastric motility and release of pepsin and intrinsic factor. Most gastrin isoforms with atypical posttranslational modifications and most small gastrin fragments display reduced or absent bioactivity. This assay measures predominately gastrin-17. Larger precursors and smaller fragments have little or no cross-reactivity in the assay.

 

Intraluminal stomach pH is the main factor regulating gastrin production and secretion. Rising gastric pH levels result in increasing serum gastrin levels, while falling pH levels are associated with mounting somatostatin production in gastric D cells. Somatostatin, in turn, downregulates gastrin synthesis and release. Other, weaker factors that stimulate gastrin secretion are gastric distention, protein-rich foods, and elevated secretin or serum calcium levels.

 

Serum gastrin levels may also be elevated in gastric distention due to gastric outlet obstruction, and in a variety of conditions that lead to real or functional gastric hypo- or achlorhydria (gastrin is secreted in an attempted compensatory response to achlorhydria). These include atrophic gastritis with or without pernicious anemia; a disorder characterized by destruction of acid-secreting (parietal) cells of the stomach, gastric dumping syndrome, and surgically excluded gastric antrum. In atrophic gastritis, the chronic cell-proliferative stimulus of the secondary hypergastrinemia may contribute to the increased gastric cancer risk observed in this condition.

 

Gastrin levels are pathologically increased in gastrinoma, a type of neuroendocrine tumor that can occur in the pancreas (20%-40%) or in the duodenum (50%-70%). The triad of nonbeta islet cell tumor of the pancreas (gastrinoma), hypergastrinemia, and severe ulcer disease is referred to as the Zollinger-Ellison syndrome. Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and the liver. About 25% of gastrinomas occur as part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome and are associated with hyperparathyroidism and pituitary adenomas. These MEN 1-associated tumors have been observed to occur at an earlier age than sporadic tumors and often follow a more benign course.

Interpretation

Achlorhydria is the most common cause of elevated serum gastrin levels. The most common cause for achlorhydria is treatment of gastroduodenal ulcers, nonulcer dyspepsia, or gastroesophageal reflux with proton pump inhibitors (substituted benzimidazoles, eg, omeprazole). Other causes of hypo- and achlorhydria include chronic atrophic gastritis with or without pernicious anemia, gastric ulcer, gastric carcinoma, and previous surgical or traumatic vagotomy.

 

If serum B12 levels are significantly low (<150 ng/L), even if the intrinsic factor blocking antibody tests are negative, a serum gastrin level above the reference range makes it likely the patient is nonetheless suffering from pernicious anemia.

 

Hypergastrinemia with normal or increased gastric acid secretion is suspicious of a gastrinoma (Zollinger-Ellison syndrome). Gastrin levels <100 pg/mL are observed so uncommonly in untreated gastrinoma patients with intact upper gastrointestinal anatomy as to virtually exclude the diagnosis. The majority (>60%) of patients with gastrinoma have very significantly elevated serum gastrin levels (>400 pg/mL). Levels of >1,000 pg/mL in a gastric- or duodenal-ulcer patient without previous gastric surgery, on no drugs, who has a basal gastric acid output of >15 mmol/hour (>5 mmol/hour in patients with prior acid-reducing surgery) are considered diagnostic of gastrinoma. If there are any doubts about gastric acid output, an infusion of 0.1 N HCl into the stomach reduces the serum gastrin in patients with achlorhydria, but not in those with gastrinoma.

 

Other conditions that may be associated with hypergastrinemia in the face of normal or increased gastric acid secretion include gastric and, rarely, duodenal ulcers, gastric outlet obstruction, bypassed gastric antrum, and gastric dumping. Occasionally, diabetes mellitus, autonomic neuropathy with gastroparesis, pheochromocytoma, rheumatoid arthritis, thyrotoxicosis, and paraneoplastic syndromes can also result in hypergastrinemia with normal acid secretion. None of these conditions tends to be associated with fasting serum gastrin levels >400 pg/mL, and levels >1,000 pg/mL are virtually never observed.

 

Several provocative tests can be used to distinguish these patients from individuals with gastrinomas. Patients with gastrinoma, who have normal or only mildly to modestly increased fasting serum gastrin levels, respond with exaggerated serum gastrin increases to intravenous infusions of secretin or calcium. Because of its greater safety, secretin infusion is preferred. The best validated protocol calls for a baseline fasting gastrin measurement, followed by an injection of 2 clinical units of secretin per kg body weight (0.4 microgram/kg) over 1 minute and further serum gastrin specimens at 5-, 10-, 15-, 20-, and 30-minutes postinjection. A peak-gastrin increase of >200 pg/mL above the baseline value has >85% sensitivity and near 100% specificity for gastrinoma. Secretin or calcium infusion tests are not carried out in the clinical laboratory, but are usually performed at gastroenterology or endocrine testing units under the supervision of a physician. They are progressively being replaced (or supplemented) by imaging procedures, particularly duodenal and pancreatic endoscopic ultrasound.

 

All patients with confirmed gastrinoma should be evaluated for possible multiple endocrine neoplasia type 1 (MEN 1), which is the underlying cause in approximately 25% of cases. If clinical, biochemical, or genetic testing confirms MEN 1, other family members need to be screened.

Clinical Reference

1. Ellison EC, Johnson JA: The Zollinger-Ellison syndrome: a comprehensive review of historical, scientific, and clinical considerations. Curr Probl Surg. 2009;46:13-106

2. McColl KE, Gillen D, El-Omar E: The role of gastrin in ulcer pathogenesis. Ballieres Best Pract Res Clin Gastroenterol 2000;14:13-26

3. Dockray GJ, Varro A, Dimaline R, Wang T: The gastrins: their production and biological activities. Ann Rev Phys 2001;63:119-139

4. Brandi ML, Gagel R, Angeli A, et al: Consensus: guidelines for the diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86:5658-5671

5. Ward PC: Modern approaches to the investigation of vitamin B12 deficiency. Clin Lab Med 2002;22:435-445

Analytic Time

Same day/1 day

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross OK

Icterus

NA

Other

Nonfasting specimens

 

Method Name

Automated Chemiluminescent Immunometric Assay