Clinical manifestations and diagnosis of Zollinger-Ellison syndrome (gastrinoma)

INTRODUCTION

In 1955, Zollinger and Ellison described a syndrome characterized by ulceration of the upper jejunum, hypersecretion of gastric acid, and non-beta islet cell tumors of the pancreas [1]. Unlike typical peptic ulcer disease, this syndrome was often progressive, persistent, and frequently life-threatening. Since then, gastrin has been identified as the humoral agent responsible for the syndrome. With current assays for serum gastrin, increasing numbers of patients are being diagnosed with the Zollinger-Ellison syndrome. Furthermore, the diagnosis is often established before development of the complications of peptic ulcer disease or spread of a malignant gastrinoma, and therapy that alters the course of the disease is almost always possible [2].

The clinical manifestations and diagnosis of the Zollinger-Ellison syndrome will be reviewed here. The approach to therapy of this disorder is discussed separately. (See "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)".)

EPIDEMIOLOGY

The epidemiology of the Zollinger-Ellison syndrome is incompletely understood. It was initially estimated that the incidence in the United States ranged from 0.1 to 1 percent of patients with peptic ulcer disease [3]. However, this may be an underestimation because patients with undiagnosed Zollinger-Ellison syndrome often have symptoms similar to those caused by typical peptic ulcer disease related to H. pylori infection or nonsteroidal antiinflammatory drugs. These symptoms may be controlled by standard doses of an antisecretory drug, and the patients may not be tested for hypergastrinemia [4].

Most patients are diagnosed between the ages of 20 and 50, but patients as young as 7 and as old as 90 have been identified. The male to female ratio ranges between 1.5:1 to 2:1 [4]. Gastrinomas can be either sporadic or associated with multiple endocrine neoplasia type 1. (See "Clinical manifestations and diagnosis of multiple endocrine neoplasia type 1".) Approximately 80 percent of patients have the sporadic form [5], although somatic (acquired) mutations in the MEN1 gene are observed commonly in sporadic gastrinomas (table 1) [6].

PATHOLOGY

Gastrinomas are derived from multipotential stem cells of endodermal origin. Known as enteroendocrine cells, they arise mainly in the pancreas as well as the small intestine. They have a particular affinity for chromium and silver salts, which are useful markers for the histopathologist [7].