Zollinger–Ellison Syndrome

Overview

Zollinger–Ellison syndrome (ZES) is a rare disorder characterized by the development of one or more tumors called gastrinomas that produce excessive levels of the hormone gastrin. This hormonal overproduction leads to overstimulation of the stomach lining, resulting in increased gastric acid secretion and the formation of severe, recurrent peptic ulcers. The syndrome was first described by doctors Robert Zollinger and Edwin Ellison in 1955. Although it can occur sporadically, it is sometimes associated with a genetic condition called Multiple Endocrine Neoplasia type 1 (MEN1).

Causes

Zollinger–Ellison syndrome is caused by tumors known as gastrinomas, most commonly found in the duodenum or pancreas. These tumors secrete large amounts of gastrin, which in turn stimulates the stomach to produce excessive hydrochloric acid. There are two main contexts in which ZES occurs:

• Sporadic cases: Most cases arise randomly without any known genetic predisposition.

• Inherited cases: About 25% of cases occur in individuals with MEN1, an inherited condition that leads to tumors in multiple endocrine glands.

The gastrinomas may be benign or malignant. In over half of the cases, the tumors are cancerous and can spread to the liver or lymph nodes.

Symptoms

The excessive acid production in ZES leads to a range of gastrointestinal symptoms. Common clinical features include:

• Recurrent or severe peptic ulcers (in the stomach or duodenum)

• Abdominal pain or discomfort

• Gastroesophageal reflux disease (GERD)

• Chronic diarrhea (due to high acid interfering with digestion)

• Weight loss and fatigue

• Nausea or vomiting, especially if ulcers cause obstruction

Ulcers in ZES are often resistant to standard treatment and tend to recur quickly after stopping acid-suppressing medications.

Diagnosis

Diagnosis of Zollinger–Ellison syndrome involves a combination of biochemical tests, imaging, and clinical evaluation. Steps include:

• Fasting serum gastrin levels: Significantly elevated levels suggest ZES, especially if gastric pH is low (high acid).

• Secretin stimulation test: Used to confirm the diagnosis in borderline cases.

• Gastric pH monitoring: To confirm that the stomach is producing excess acid.

• Endoscopy: To visualize ulcers and rule out other causes.

• Imaging studies: CT scan, MRI, or somatostatin receptor scintigraphy (SRS) to localize gastrinomas and detect metastases.

• Genetic testing: Recommended if MEN1 is suspected.

Treatment

The treatment of Zollinger–Ellison syndrome includes medical management of acid hypersecretion and surgical or oncological treatment of the tumors:

• Proton pump inhibitors (PPIs): High-dose medications like omeprazole or pantoprazole are used to reduce stomach acid production effectively.

• Somatostatin analogs: Such as octreotide, may help control gastrin levels in some cases.

• Surgical removal: If the tumor can be localized and safely resected, surgery may provide a cure in non-metastatic cases.

• Chemotherapy or targeted therapy: Used for metastatic or inoperable gastrinomas.

• Management of MEN1: Requires ongoing monitoring and treatment of other endocrine tumors.

Prognosis

The prognosis of Zollinger–Ellison syndrome depends on whether the gastrinoma is benign or malignant and whether it has metastasized. Key points include:

• With effective acid suppression, most patients experience symptom relief and ulcer healing.

• Localized, benign tumors that are completely removed surgically can result in a cure.

• In cases of malignant gastrinoma with metastasis (especially to the liver), long-term survival varies and requires ongoing treatment.

• Patients with MEN1 need lifelong surveillance due to the risk of multiple tumors.

With advances in medical therapy and early diagnosis, many patients with ZES can achieve good symptom control and long-term management of the disease.