Are Patients With Autoimmune Thyroid Disease and Autoimmune Gastritis at Risk of Gastric Neuroendocrine Neoplasms Type 1?

Krystallenia I. Alexandraki; Argiro Nikolaou; Dimitrios Thomas; Vassiliki Syriou; Penelope Korkolopoulou; Stavros Sougioultzis; Gregory Kaltsas


Clin Endocrinol. 2014;80(5):685-690. 

In This Article

Materials and Methods


Between January 2006 and June 2007, a total of 120 euthyroid patients with AITD were prospectively studied. All the patients with AITD recruited in this study had positive thyroid antibodies, either thyroid peroxidase (anti-TPO) or thyroglobulin (anti-Tg) autoantibody or both.

All participants underwent a detailed physical examination [such as age and gender registration, body mass index (BMI, kg/m2) calculation] and a complete medical (including symptoms as dyspepsia) and family history. All patients were off antibiotics, and dyspeptic patients were off proton pump inhibitors (PPIs) for at least 30 days. On the day of the study, fasting blood samples were collected from all patients between 08:00 and 10:00 h. Samples were centrifuged immediately, and serum was stored at −80 °C until assayed for gastrin, chromogranin A (CgA), APCA, ferrum, ferritin, folic acid, vitamin B12, free thyroxine, thyroid-stimulating hormone (TSH), anti-TPO and anti-Tg levels. TSH receptor antibody measurements, thyroid ultrasonography and scintigraphy were performed when clinically indicated. The clinical, epidemiological and laboratory parameters of the 120 patients are shown in Table 1 and Table 2 . An UGE followed blood sample collection. The protocol was approved by the local bioethical committee of the University of Athens, and informed consent was obtained from all patients.

Study Protocol

Anti-Tg, anti-TPO and APCA levels, and gastrin and CgA levels were measured using commercial kits.

Upper Gastrointestinal Tract Endoscopy

Upper gastrointestinal tract endoscopy was performed in all the patients recruited fasting by the same operator (SS). The general appearance of gastric mucosa was characterized, and all visible nodular lesions were removed. In addition, multiple biopsies were taken from apparently normal mucosa of the antrum, corpus and fundus to assess the topography of gastritis. In particular, the gastritis was categorized, as antrum predominant (AP), corpus predominant (CP) and AG.[12] An assessment of gastric acid production was not performed by means of pH-metry because oxyntic mucosal atrophy was histologically proved and our aim was to simplify the screening procedure.


Gastric mucosa tissue biopsies were fixed in 10% buffered neutral formalin for 18–20 h at room temperature, followed by routine processing in paraffin wax. Approximately 4-μm-thick sections were cut and routinely stained with haematoxylin–eosin. Gastritis parameters (chronic inflammation, activity, atrophy, intestinal metaplasia and HP infection) were graded according to the updated Sydney classification.[12] Autoimmune gastritis was defined as atrophy of the gastric corpus and/or fundus with replacement of oxyntic glands by metaplastic pseudopyloric and/or intestinal epithelium in the context or hypergastrinaemia and APCA positivity.[13,14] Immunostaining for CgA, synaptophysin and Ki-67 labelling index (LI) was applied in all ECL-cell lesions. Foci of endocrine cell hyperplasia were microscopically defined as diffuse, linear or nodular as previously defined.[13,14]


Patients with AITD and ECL-cell hyperplasia underwent UGE annually (range: 9–14 months) thereafter. Each visit also included clinical assessment, biochemical evaluation and when indicated imaging studies.[10] If HP infection was diagnosed at initial endoscopy, patients were appropriately treated till HP eradication and then regularly assessed.

Statistical Analysis

Statistical significance was accepted at a P-value<0·05. Values are presented as mean values ± standard deviation (±SD). The normal distribution of continuous variables was assessed by applying the nonparametric Kolmogorov–Smirnov test. Quantitative data were compared using independent samples t-test or Mann–Whitney U-test for normally or non-normally distributed variables, respectively. Correlations between categorical variables were estimated by the chi-square test or by Fisher's exact test, as appropriate. Mean values of clinical and biochemical parameters among patients with specific phenotypes of gastritis were compared using analysis of variance (ANOVA). Post hoc comparisons were made using Scheffe's test. If Levene's test for homogeneity of variances had statistically significant P- value (for example gastrin and CgA levels), non-parametric analysis of variance (Kruskal-Wallis one way ANOVA) was applied. In such cases, post hoc comparisons were made using Mann-Whitney U-test with a downward adjustment of α level to compensate for multiple comparisons. Univariate and multiple logistic analyses were calculated to evaluate the factors that affect ECL-cell hyperplasia. Analysis was performed using SPSS (Statistical Package for the Social Sciences, version 20; SPSS, Chicago, IL, USA) for Windows XP (Microsoft).