Zollinger-Ellison Syndrome

Overview

Zollinger-Ellison syndrome is characterised by the growth of tumours in the small intestine or pancreas. These tumours, known as gastrinomas, produce excessive hormone gastrin. High levels of gastrin lead the stomach to create excessive acid, resulting in peptic ulcers. Additionally, elevated gastrin levels may cause symptoms such as diarrhoea, abdominal discomfort, and other related issues.

This syndrome is considered rare and can occur at any age, but it is typically diagnosed in individuals between the ages of 20 and 50. The standard treatment involves medications to reduce stomach acid and promote the healing of the ulcers. In some cases, surgery may be necessary to remove the tumours.

What is a Zollinger-Ellison Syndrome?

ZES or Zollinger-Ellison syndrome is an uncommon condition that affects the digestive system. It arises from the presence of gastrinomas, which are tumours that can form in the pancreas or the duodenum, the initial segment of the small intestine. These gastrinomas secrete excessive amounts of the hormone gastrin, stimulating the stomach to produce high levels of gastric acid. This overproduction can lead to the development of ulcers in both the stomach and duodenum.

ZES is sometimes referred to as pancreatic ulcerogenic tumour syndrome due to its association with ulcer formation. The primary treatments involve managing the hypersecretory state through the medical suppression of gastric acid creation along with surgically removing the primary tumour to prevent metastatic complications and malignant transformation. Additionally, medical therapy with the help of proton pump inhibitors helps to significantly reduce the necessity for surgical procedures aimed at reducing acid production.

Types of Zollinger-Ellison Syndrome

Two main variants of the condition are there: sporadic cases and those associated with parathyroid and pituitary tumours, or multiple endocrine neoplasia type 1 (MEN-1).

Zollinger-Ellison Syndrome Symptoms

Zollinger-Ellison syndrome (ZES) can present with a variety of symptoms that differ widely among individuals, as not everyone with the condition experiences noticeable effects from elevated gastrin levels. People with smaller or fewer tumours may produce less gastrin, resulting in lower stomach acid levels, while some may have “silent ulcers” that go unnoticed. In a small percentage of cases, chronic diarrhoea may be the first noticeable symptom.

However, most people with ZES experience classic symptoms similar to peptic ulcer disease, with severity ranging from mild to severe. Indigestion, particularly after eating fatty foods, is common. Patients often experience burning or gnawing stomach pain in the upper abdomen, persistent acid reflux, and heartburn due to acid regurgitation. Absorption of fats may lead to fatty or greasy stools and chronic diarrhoea.

In cases where peptic ulcers or high acid levels lead to complications, additional symptoms may occur. Esophagitis, or inflammation of the oesophagus, often develops due to chronic acid reflux. Gastrointestinal bleeding can occur, leading to blood in the vomit (hematemesis) or stools (melena), which may further cause anaemia from blood loss. Anaemia symptoms include pale skin, fatigue, and weakness. Some people may also experience a loss of appetite, nausea, vomiting, and weight loss, often because of ongoing discomfort and digestive complications.

Zollinger-Ellison Syndrome Causes

The Zollinger-Ellison syndrome’s exact cause remains unclear, but the condition typically develops following a specific sequence of events. It begins with the formation of one or more tumours, called gastrinomas, in the pancreas or the duodenum, the portion of the small intestine connected to the stomach. In some cases, these tumours may also arise in other locations, such as the lymph nodes near the pancreas.

Located behind the stomach, the pancreas plays a crucial role in digestion by producing enzymes and hormones, including insulin, which regulates blood sugar levels. The duodenum is where digestive juices from the liver, pancreas, and gallbladder combine, facilitating the majority of food digestion.

In Zollinger-Ellison syndrome, the tumours produce excessive amounts of the hormone gastrin, leading to the overproduction of stomach acid. This excess acid often results in peptic ulcers and may also cause diarrhoea. Because these tumours are gastrin-secreting, the condition is sometimes referred to as gastrinoma syndrome.

While the tumours associated with ZES are generally slow-growing, they are often malignant. The cancer can spread, most commonly to nearby lymph nodes or the liver.

Zollinger-Ellison Syndrome Diagnosis and Tests

A healthcare professional typically relies on several key components to diagnose conditions related to gastrin levels:

Chromogranin A Testing: Doctors may test the blood for chromogranin A, a protein typically elevated in individuals with gastrinomas (gastrin-secreting tumours).

Blood Tests: Doctors analyse blood samples to determine gastrin levels. Elevated gastrin levels may indicate the presence of tumours in the pancreas or duodenum. However, other factors also influence the blood tests that are required for Zollinger-Ellison syndrome. For instance, gastrin levels can increase if the stomach is not producing acid, if a person has undergone gastric surgery, or if they are taking acid-reducing medications. It is important to fast before this test and possibly discontinue any acid-reducing drugs beforehand, as gastrin levels can fluctuate, leading to retesting in some cases.

Imaging Tests: Doctors utilise various imaging modalities, including CT scans, MRI scans, and Ga-DOTATATE PET-CT scans to visualise potential tumours.

Secretin Stimulation Test: This test involves an initial measurement of gastrin levels, followed by an injection of secretin, a hormone that helps regulate gastric acid. After the injection, doctors recheck gastrin levels. A significant rise in these levels could indicate Zollinger-Ellison syndrome.

Endoscopic Ultrasound: This technique involves using an endoscope equipped with an ultrasound probe, enhancing the ability to detect tumours in the stomach, duodenum, and pancreas. Similar fasting and sedation procedures apply, and tissue samples may be collected if necessary.

Medical History: The healthcare provider will begin by inquiring about the symptoms and reviewing the medical background of the patient to gather relevant information.

Upper Gastrointestinal Endoscopy: Performed under sedation, this procedure involves the insertion of a flexible endoscope through the throat into the stomach and duodenum. This allows the healthcare provider to visually examine the area for ulcers and obtain tissue samples via biopsy. Doctors analyse these samples for gastrin-producing tumours. Additionally, the procedure can help in the evaluation of whether the stomach is producing acid. If acid is present alongside high gastrin levels, a Zollinger-Ellison diagnosis may be confirmed. Fasting after midnight before this test is required for appropriate results.

Treatment Options for Zollinger-Ellison Syndrome

Proton pump inhibitors are a class of medications that effectively manage excess stomach acid and prevent the formation of ulcers. Common examples include esomeprazole, lansoprazole, pantoprazole, dexlansoprazole, rabeprazole, and omeprazole.

In certain situations, surgical intervention may be necessary to remove tumours located in the digestive tract. For more advanced cases, particularly when tumours have metastasised to other areas of the body, the doctor might recommend chemotherapy to target and destroy these cancerous cells.

The surgical method of treating sporadic and MEN-1-associated Zollinger-Ellison syndrome varies on the condition's natural history and the likelihood of achieving a cure. It is recommended to perform a resection in both cases to ensure a negative microscopic margin. Postoperative monitoring includes measuring gastrin levels, with imaging if levels are elevated.

Preventive Measures for Zollinger-Ellison Syndrome

There is no preventive measure to stop Zollinger-Ellison syndrome. Individuals who have a family record of this disease should think about getting genetic counselling. These genetic counsellors evaluate the chance of passing the condition to the future generation and advise accordingly.