Overview

Zollinger-Ellison syndrome (ZES) is a rare but serious digestive disorder caused by the development of gastrin-secreting tumors called gastrinomas. These tumors typically form in the pancreas or the duodenum—the first part of the small intestine. The excessive gastrin released by these tumors triggers the stomach to produce too much acid, leading to a range of gastrointestinal symptoms and complications.

This overproduction of stomach acid can result in frequent, severe peptic ulcers, chronic diarrhea, and gastroesophageal reflux disease (GERD). ZES affects approximately 1 to 3 people per million each year. Although rare, it is important to diagnose and manage the condition early, especially since over 50% of gastrinomas can be cancerous.

Common Symptoms

People with ZES often experience symptoms caused by high levels of gastric acid. These symptoms may mimic or overlap with other common gastrointestinal disorders. Common symptoms include:

  • Persistent or recurrent abdominal pain

  • Severe or recurring peptic ulcers

  • Chronic diarrhea

  • Bloating and excessive gas

  • Heartburn or acid reflux

  • Nausea and vomiting

  • Loss of appetite and unintended weight loss

  • Fatigue or general weakness

In more advanced or untreated cases, additional symptoms may emerge:

  • Black, tarry stools (indicating bleeding)

  • Vomiting blood or coffee-ground-like material

  • Muscle cramps or weakness (due to electrolyte imbalances)

  • Difficulty swallowing

  • Sharp, sudden abdominal pain (may signal perforation)

Causes

Zollinger-Ellison syndrome is caused by the formation of tumors known as gastrinomas, which produce excessive amounts of the hormone gastrin. Under normal conditions, gastrin is released in response to food intake, helping regulate stomach acid levels. However, in ZES, this process becomes uncontrolled.

While the exact cause of gastrinoma formation is unknown, around 20-25% of ZES cases are linked to an inherited genetic condition called multiple endocrine neoplasia type 1 (MEN1). This syndrome increases the likelihood of tumors developing in hormone-producing glands, including the pancreas and parathyroid glands.

Risk Factors

Although ZES is a rare condition, certain risk factors may increase a person's chances of developing the syndrome:

  • Age between 20 and 50 years

  • Male sex assigned at birth (ZES is slightly more common in males)

  • Family history of MEN1 or other endocrine tumors

  • Personal history of peptic ulcer disease that is resistant to standard treatment

Diagnostic Process

Diagnosing Zollinger-Ellison syndrome can be challenging due to symptom overlap with more common digestive conditions like GERD or peptic ulcers. A comprehensive diagnostic workup is required, including the following steps:

1. Medical history and physical examination: Your provider will assess your symptoms, medical history, and family background to determine if ZES is a possibility.

2. Gastrin level test: A fasting blood test is used to measure gastrin levels. Elevated levels may suggest ZES. Sometimes a secretin stimulation test is done to confirm the diagnosis, as secretin normally suppresses gastrin but causes a paradoxical rise in people with ZES.

3. Stomach pH test: This test checks if the stomach’s acidity is abnormally high (low pH), further supporting a ZES diagnosis.

4. Imaging tests to locate tumors:

  • Endoscopic ultrasound

  • CT scan or MRI

  • Somatostatin receptor scintigraphy (OctreoScan)

  • PET scan with gallium-68 DOTATATE

  • ERCP (Endoscopic retrograde cholangiopancreatography)

These tests help identify the location and spread of gastrinomas, which is crucial for planning treatment.

Treatment Options

Though there is no definitive cure for Zollinger-Ellison syndrome, the condition can be effectively managed through a combination of medication and surgical interventions, depending on the severity.

1. Proton Pump Inhibitors (PPIs): PPIs are the mainstay treatment for controlling acid overproduction. High-dose PPIs such as:

  • Pantoprazole (Protonix)

  • Omeprazole (Prilosec)

  • Esomeprazole (Nexium)

These help reduce symptoms, promote ulcer healing, and protect the stomach lining. Long-term use is often required.

2. H2-receptor antagonists: These medications, like ranitidine and cimetidine, are less potent than PPIs but may be used in mild cases or as adjunct therapy.

3. Somatostatin analogs: Drugs like octreotide may help reduce gastrin secretion in certain patients, particularly if tumors are inoperable.

4. Surgery: Surgical removal of gastrinomas may be considered, especially if tumors are localized and not associated with MEN1. Surgery is more complex if tumors are multiple or have metastasized.

5. Chemotherapy and targeted therapies: For metastatic or malignant gastrinomas, chemotherapy or targeted therapies (such as sunitinib or everolimus) may be recommended.

6. Liver-directed treatments: If tumors have spread to the liver, procedures like hepatic artery embolization or radiofrequency ablation may help reduce tumor burden.

Living With ZES

Living with Zollinger-Ellison syndrome involves ongoing medical management and routine monitoring. Patients are typically advised to:

  • Adhere to prescribed medications strictly

  • Maintain a GERD-friendly diet (low in acid, fat, caffeine, and spicy foods)

  • Avoid NSAIDs and smoking

  • Manage stress to prevent symptom flare-ups

Regular follow-up with a gastroenterologist and endocrinologist is essential. Blood tests, endoscopies, and imaging scans are typically performed at intervals to monitor tumor growth and acid levels.

Prevention

Unfortunately, there is currently no known way to prevent Zollinger-Ellison syndrome, particularly in sporadic cases. However, individuals with MEN1 or a family history of endocrine tumors should undergo routine screening to detect early signs of gastrinomas.

For diagnosed patients, adhering to treatment plans and monitoring symptoms closely can reduce the risk of severe complications.

Possible Complications

If left untreated or poorly managed, ZES can lead to significant health issues, including:

  • Chronic and severe peptic ulcers

  • Gastrointestinal bleeding

  • Perforation of the stomach or intestines

  • Strictures or obstruction of the digestive tract

  • Malabsorption and nutrient deficiencies

  • Increased risk of gastric cancer

  • Metastasis of gastrinomas to the liver or lymph nodes

Prompt diagnosis and treatment help mitigate these risks.

Related Conditions

Zollinger-Ellison syndrome is closely linked to several gastrointestinal and endocrine conditions, such as:

  • Peptic Ulcer Disease: Nearly all people with ZES experience recurring ulcers.

  • GERD: Due to high acid levels, reflux is a common complaint.

  • Multiple Endocrine Neoplasia Type 1 (MEN1): A genetic syndrome that increases the likelihood of developing ZES.

  • Pancreatic neuroendocrine tumors (pNETs): Gastrinomas are a type of pNET.

Final Thoughts

Zollinger-Ellison syndrome is a complex and rare condition that demands attention and ongoing care. While the disease itself is not preventable, early diagnosis and a tailored treatment approach can significantly improve long-term outcomes. For many, a combination of medication, lifestyle changes, and regular medical monitoring is enough to manage symptoms and live a full, active life.

If you experience persistent digestive issues that don’t respond to standard treatments, consult your healthcare provider to rule out rare conditions like ZES. Awareness, timely diagnosis, and proactive care make all the difference.