Clinical Information

Gastrin is a peptide hormone produced by mucosal G cells of the gastric antrum. It is synthesized as preprogastrin and then cleaved to progastrin, which undergoes several posttranslational modifications, particularly, sulfation. It 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's 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 non-beta 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.

Basal and secretin-stimulated serum gastrin measurements are the best laboratory tests for gastrinoma.