Zollinger-Ellison Syndrome is a rare disorder characterised by gastrin-secreting gastrinomas causing severe peptic ulcer disease, with typical imaging findings of hypervascular pancreatic masses and elevated serum gastrin levels.
Description
Zollinger-Ellison Syndrome (ZES) is a clinical disorder characterised by the development of a gastrin-secreting tumour called a gastrinoma, leading to severe peptic ulcer disease, gastroesophageal reflux disease, and chronic diarrhoea. The majority of these gastrinomas are located in the duodenum or the pancreas.
Pathogenesis
Gastrinomas secrete excessive quantities of the hormone gastrin, leading to hypergastrinemia. Gastrin stimulates gastric parietal cells to secrete hydrochloric acid, which results in gastric acid hypersecretion. Over time, excessive acid production causes damage to the gastric and duodenal mucosa, leading to the formation of peptic ulcers.
Epidemiology, Risk Factors & Associations
ZES is a rare disorder, affecting approximately 1 in every 1 million individuals each year. The condition can occur at any age, but most commonly presents in the fourth to sixth decades of life. Males are slightly more affected than females.
Approximately 25% to 30% of ZES cases are associated with Multiple Endocrine Neoplasia type 1 (MEN1), a genetic disorder that affects the endocrine glands.
Clinical Features
The most common clinical features of ZES include abdominal pain, diarrhoea, and symptoms of gastroesophageal reflux disease, such as heartburn and regurgitation. Patients may also experience nausea, vomiting, weight loss, and bleeding from the gastrointestinal tract.
Complications
Complications of ZES predominantly arise due to peptic ulcer disease and include bleeding, perforation, and gastric outlet obstruction. Additionally, untreated ZES can lead to severe diarrhoea and malnutrition.
Pathological Features
Histopathology
Gastrinomas appear as small, well-circumscribed, and often solitary nodules with a solid, trabecular, or glandular architecture. The cells are usually round or polygonal, with eosinophilic cytoplasm and round to oval nuclei.
Serology and Biochemistry
In ZES, there is elevated serum gastrin levels, usually more than 10 times the upper limit of normal.
Genetics
ZES is often sporadic, but in 20-30% of cases, it can be associated with MEN1, an autosomal dominant disorder.
Radiological Features
General Features
- Gastrinomas typically appear as a hypervascular pancreatic mass combined with multiple peptic ulcers and thickened gastric folds
- Can be located anywhere within the gastrinoma triangle, which is defined by the confluence of the:
- Gastrinomas are most common in the pancreas (75% of cases), duodenum (15%), and in the liver and ovaries (10%).
- Ulcers commonly occur in the stomach and duodenal bulb (75% of cases) and less frequently in the post-bulbar region and jejunum (25% of cases)
US
- Endoscopic ultrasonography (EUS): Can detect small gastrinomas better than CT or MR. Gastrinomas usually appear as homogeneously hypoechoic masses
- Intraoperative ultrasonography: Can detect very small tumours, with a sensitivity of 75-100%
FL
- May show the presence of gastric, duodenal, and proximal jejunal ulcers.
- Markedly thickened gastric folds
- Peptic ulcers may be evident as round or ovoid barium collections surrounded by thin or thick radiolucent rim due to edematous mucosa and radiating folds
CT
- May present as small or large lesions with heterogeneous density, potentially with cystic and necrotic areas, and possibly calcification.
- Liver metastases are common.
- Hypervascular primary and secondary lesions may be seen on arterial phase, potentially with local or vascular invasion.
- May also show inflammatory changes in the stomach, duodenum, and proximal small bowel, and signs of ulcer penetration and perforation
- Thickened and hyperenhancing gastric folds
MRI
- T1: Gastrinomas may appear hypointense on fat-saturated sequences
- T2: Gastrinomas may appear hyperintense on spin-echo sequences
- Gd+: Gastrinomas may appear hypervascular on the arterial phase
PET
- Gastrinomas can show increased uptake of Ga-68 DOTATATE, a somatostatin analogue.
Grading and Staging
Grading and staging of gastrinomas follow the ENETS/WHO criteria for neuroendocrine tumours.
Differential Diagnosis
- Other causes of peptic ulcer disease (e.g., Helicobacter pylori infection, NSAID use)
- Gastroenteritis
- Other types of pancreatic or duodenal neoplasms.
Management
- The management of ZES typically involves a multidisciplinary approach.
- PPIs are the mainstay for controlling gastric acid hypersecretion.
- Surgical resection of the gastrinoma is the only curative approach, but it’s not always feasible due to the presence of metastases or multiple tumours.
- Surveillance and management for patients with ZES associated with MEN1 is critical, given the risk of other endocrine tumours.