title: The Zollinger-Ellison syndrome and mismeasurement of gastrin.
abstract: OBJECTIVE
  Zollinger-Ellison syndrome (ZES) is characterized by hypersecretion of gastric acid, severe peptic ulcerations in the upper small intestine, and diarrhea. It is usually diagnosed by measuring increased levels of gastrin in plasma.
  
  
  METHODS
  We examined the accuracy of commercial kits to measure gastrin (7 radioimmunoassays and 5 enzyme-linked immunosorbent assays), using plasma from 40 patients suspected or known to have ZES. Each sample was analyzed using the 12 kits and a reference assay that measures bioactive gastrin in plasma, irrespective of size and amino acid derivatization. Known concentrations of peptides with identical sequences to circulating gastrins were also assessed by all assays. Molecular patterns in plasma from patients with ZES were examined by chromatography and monitored by kits that measure false-low or false-high concentrations of gastrin.
  
  
  RESULTS
  Failure to diagnose gastrinomas has serious consequences. Four kits found false-low concentrations of gastrin in 20% to 80% of the patients. Specificity assessment showed that the antibodies used in these kits bound only gastrin-17. Three kits found false-high concentrations of gastrin, because the reagents had increased reactions to sulfated gastrins or to unspecific factors in plasma. Thus, only 5 of 12 kits tested accurately measure plasma concentrations of gastrin.
  
  
  CONCLUSIONS
  Seven of 12 tested commercial kits inaccurately measure plasma concentrations of gastrin; these assays used antibodies with inappropriate specificity that were insufficiently validated. Misdiagnosis of gastrinoma based on lack of specificity of assays for gastrin results in ineffective or inappropriate therapy for patients with ZES.
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: Marie-Hélène
authors.initials: MH
authors.lastname: Gingras
authors.forename: Linda
authors.initials: L
authors.lastname: Bardram
authors.forename: Linda
authors.initials: L
authors.lastname: Hilsted
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.forename: Pierre
authors.initials: P
authors.lastname: Poitras
mesh_terms: D000328:Adult; D000368:Aged; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005260:Female; D005755:Gastrins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D015203:Reproducibility of Results; D055815:Young Adult; D015043:Zollinger-Ellison Syndrome / Q000097:blood* / Q000175:diagnosis
chemical_list: D005755:Gastrins