title: Pitfalls in diagnostic gastrin measurements.
abstract: BACKGROUND
  Gastrin measurements are performed primarily for the diagnosis of gastrin-producing tumors, gastrinomas, which cause the Zollinger-Ellison syndrome (ZES). Gastrin circulates as several bioactive peptides, however, and the peptide pattern in gastrinoma patients often deviates from normal. Therefore, it is necessary to measure all forms of gastrin.
  
  
  BACKGROUND
  Only immunoassays are useful for measurement of gastrin in plasma. The original assays were RIAs developed in research laboratories that used antibodies directed against the C terminus of gastrin peptides. Because the C-terminal tetrapeptide amide sequence constitutes the active site of gastrin peptides, these assays were well suited for gastrinoma diagnosis. More recently, however, most clinical chemistry laboratories have switched to commercial kits. Because of recent cases of kit-measured normogastrinemia in patients with ZES symptoms, the diagnostic sensitivity and analytical specificity of the available kits have been examined. The results show that gastrin kits frequently measure falsely low concentrations because they measure only a single gastrin form. Falsely high concentrations were also encountered, owing to overreactivity with O-sulfated gastrins or plasma proteins. Thus, more than half of the gastrin kits on the market are unsuited for diagnostics.
  
  
  CONCLUSIONS
  Gastrinomas are neuroendocrine tumors, some of which become malignant. A delay in diagnosis leads to fulminant ZES, with major, even lethal, complications. Consequently, it is necessary that the diagnostic sensitivity of gastrin kits be adequate. This diagnostic sensitivity requires antibodies that bind the C-terminal epitope of bioactive gastrins without the influence of O-sulfation.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. jens.f.rehfeld@rh.regionh.dk
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Linda
authors.initials: L
authors.lastname: Bardram
authors.forename: Linda
authors.initials: L
authors.lastname: Hilsted
authors.forename: Pierre
authors.initials: P
authors.lastname: Poitras
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000097:blood*; D015408:Gastrinoma / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D005755:Gastrins / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008969:Molecular Sequence Data; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D015043:Zollinger-Ellison Syndrome / Q000175:diagnosis / Q000209:etiology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D005755:Gastrins; D011933:Reagent Kits, Diagnostic; C013550:gastrin 17