title: Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in type 1 diabetes.
abstract: OBJECTIVE
  Parietal cell antibodies (PCAs) are found in 20% of type 1 diabetic patients, denoting autoimmune gastritis and pernicious anemia, which may predispose to enterochromaffin-like (ECL) cell hyper/dysplasia and gastric carcinoid tumors. We evaluated whether chromogranin A (CgA), 5-hydroxyindole acetic acid (5-HIAA), and neuron-specific enolase (NSE) contribute to screening for ECL cell hyper/dysplasia.
  
  
  METHODS
  Sera from 93 type 1 diabetic patients (53 men and 40 women, 31 PCA(+) and 62 PCA(-), aged 45 +/- 13 years) were analyzed for PCAs by indirect immunofluorescence and for CgA, NSE, and gastrin by radioimmunoassay. Urinary 5-HIAA was tested by high-performance liquid chromatography. Corpus atrophy and ECL cell proliferation were assessed in gastric biopsies.
  
  
  RESULTS
  PCA(+) patients had higher gastrin (P < 0.0001) and CgA levels (P = 0.003) and were more prone to autoimmune gastritis (odds ratio [OR] 17, P < 0.0001) and ECL cell hyper/dysplasia (OR = 23, P = 0.005) than PCA(-) subjects. ECL cell hyper/dysplasia was present in seven PCA(+) patients who showed higher CgA levels (P < 0.0001) than subjects without ECL cell hyper/dysplasia, but NSE and 5-HIAA levels were similar. CgA levels correlated with gastrinemia (r = 0.50, P < 0.0001), PCA titer (r = 0.42, P = 0.001), and 5-HIAA levels (r = 0.38, P = 0.012). Logistic regression identified the CgA level (beta = 0.01, P = 0.027) as an independent risk factor for ECL cell hyper/dysplasia when PCA, CgA, 5-HIAA, NSE, gastrin, sex, and age were tested. Multivariate linear regression demonstrated that CgA level was determined by ECL cell density (r = 0.59, P < 0.0001) and gastrin level (r = 0.67, P = 0.02). One PCA(+) patient with elevated gastrin, CgA, and 5-HIAA levels had a gastric carcinoid tumor.
  
  
  CONCLUSIONS
  PCA(+) patients, particularly those with high gastrin and CgA levels, risk developing ECL cell hyper/dysplasia. The determination of CgA, but not NSE and 5-HIAA, may complement histology in evaluating ECL cell mass.
authors.affiliation: Department of Endocrinology-Diabetology, Faculty of Medicine, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium. christophe.deblock@ua.ac.be
authors.forename: Christophe E M
authors.initials: CE
authors.lastname: De Block
authors.forename: Gert
authors.initials: G
authors.lastname: Colpin
authors.forename: Kristof
authors.initials: K
authors.lastname: Thielemans
authors.forename: Willy
authors.initials: W
authors.lastname: Coopmans
authors.forename: Johannes J P M
authors.initials: JJ
authors.lastname: Bogers
authors.forename: Paul A
authors.initials: PA
authors.lastname: Pelckmans
authors.forename: Eric A E
authors.initials: EA
authors.lastname: Van Marck
authors.forename: Viviane
authors.initials: V
authors.lastname: Van Hoof
authors.forename: Manou
authors.initials: M
authors.lastname: Martin
authors.forename: Ivo H
authors.initials: IH
authors.lastname: De Leeuw
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Luc F
authors.initials: LF
authors.lastname: Van Gaal
mesh_terms: D001323:Autoantibodies / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology / Q000473:pathology; D004759:Enterochromaffin Cells / Q000473:pathology / Q000502:physiology*; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000453:epidemiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood*; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood*; D010751:Phosphopyruvate Hydratase / Q000097:blood
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D006897:Hydroxyindoleacetic Acid; D010751:Phosphopyruvate Hydratase