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

Disclosures

Clin Endocrinol. 2014;80(5):685-690. 

In This Article

Abstract and Introduction

Abstract

Objective The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease.

Design Prospective observational study in a single institutional study.

Patients and Measurements One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin A were also measured.

Results One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin A; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up.

Conclusions Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications.

Introduction

Autoimmune thyroid disease (AITD) is encountered in 10–15% of the general population and is often associated with various other autoimmune diseases, such as autoimmune gastritis (AG).[1] In patients with AITD, the prevalence of antiparietal cell antibodies (APCA) has been reported to range from 12–40%,[1,2] as opposed to 2·5–9% in the general population.[1,3] The target of APCA is the H+/K+ ATP-ase of parietal cell, leading to damage of the oxyntic glands[1,4] of the gastric corpus, thus resulting in hypochlorhydria, hypergastrinaemia and hyperplasia of enterochromaffin-like (ECL-cells).[5,6] This latter phenomenon is due to the expression of the cholecystokinin-B/gastrin receptor by the ECL cells, which upon stimulation by the excessive circulating gastrin promotes ECL-cell hyperplasia.[7] Besides gastrin, Helicobacter pylori (HP) infection has also been suggested to induce ECL-cell growth probably secondary to accompanying gastric mucosal inflammation.[7,8]

Enterochromaffin-like cell hyperplasia constitutes the substrate for the development of gastric neuroendocrine neoplasms type 1 (GNEN1), which represents the most common (65–75%) type of GNENs.[9,10] These tumours can be multiple, and although exert an indolent course, a subset, up to 5%, may develop lymph node and/or hepatic metastases.[9,10] In the context of these tumours, ECL-cell hyperplasia along with dysplastic lesions is frequently observed in the surrounding gastric mucosa. This is of potential clinical significance as a recent study showed that GNEN1 is the commonest gastroenteropancreatic neuroendocrine tumour (GEP-NET).[11]

The best means to detect AG, ECL-cell hyperplasia and GNEN1 remain upper gastrointestinal tract endoscopy (UGE, gastroscopy) with biopsy of all the identified lesions and surrounding mucosa.[7] Endoscopic ultrasound may prove useful in cases of GNEN1 to determine the depth of invasion through the various layers of the gastric wall and identify regional lymph node involvement.[7]

It is well known that AITD is relatively commonly associated with AG, but as there are no data regarding the prevalence of ECL-cell hyperplasia and GNEN1 in patients with AITD, we aimed to prospectively investigate these associations in a cohort of patients with known AITD, but newly diagnosed with AG.

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