Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in type 1 diabetes.
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.
De Block
Christophe E M
CE
Department of Endocrinology-Diabetology, Faculty of Medicine, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium. christophe.deblock@ua.ac.be
Colpin
Gert
G
Thielemans
Kristof
K
Coopmans
Willy
W
Bogers
Johannes J P M
JJ
Pelckmans
Paul A
PA
Van Marck
Eric A E
EA
Van Hoof
Viviane
V
Martin
Manou
M
De Leeuw
Ivo H
IH
Bouillon
Roger
R
Van Gaal
Luc F
LF
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
D001323:Autoantibodies; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D006897:Hydroxyindoleacetic Acid; D010751:Phosphopyruvate Hydratase