Zollinger-Ellison Syndrome: Symptoms, Causes, Treatment & Diagnosis

ZES is classified into two main types: sporadic and hereditary.

• Sporadic ZES: This type of ZES occurs randomly in individuals without any family history of the condition. It accounts for about 75-80% of all cases of ZES.
• Hereditary ZES: This type of ZES is rare and runs in families. It is caused by an inherited genetic mutation that affects the function of cells in the pancreas that produce gastrin. This type of ZES is associated with multiple endocrine neoplasia type 1 (MEN1), characterized by the development of tumours in various endocrine glands.
• In some cases, the cause of ZES is unknown. These cases are referred to as idiopathic ZES.

Note that regardless of the type of ZES, the excessive production of gastrin caused by the tumours leads to the development of peptic ulcers and other gastrointestinal complications

The symptoms of Zollinger Ellison Syndrome can vary from person to person and depend on the severity of the condition. Some of the common symptoms Zollinger Ellison Syndrome include:

• Abdominal pain
• Diarrhoea
• Nausea
• Vomiting
• Gastrointestinal bleeding
• Loss of appetite
• Weight loss
• Heartburn
• Acid reflux
• Peptic ulcers
• Fatigue

These symptoms Zollinger Ellison Syndrome can occur intermittently and can be mistaken for other medical conditions such as acid reflux, irritable bowel syndrome, or inflammatory bowel disease. One should seek medical attention if these symptoms persist or worsen.

ZES is primarily caused by the growth of gastrinomas, usually benign, non-cancerous tumours that develop in the pancreas. However, in rare cases, these tumours can become malignant and spread to other body parts. Pancreatic gastrinoma can also develop in other body parts that produce gastrin, such as the small intestine, stomach, or lymph nodes.

The excessive gastrin production caused by these tumours is responsible for developing peptic ulcers and other gastrointestinal complications. Gastrin is a hormone that stimulates the release of acid in the stomach. In normal circumstances, the release of gastrin is regulated by negative feedback, which means that gastrin production decreases as the level of acid in the stomach increases. However, in people with ZES, the constant release of gastrin due to the presence of gastrinomas leads to an overproduction of stomach acid. This excess acid can erode the lining of the stomach and cause the formation of peptic ulcers.

In some cases, the cause of ZES is unknown. However, research suggests that genetic mutations may play a crucial role in the spreading the condition. In particular, mutations in a gene called MEN1 have been associated with the development of ZES. MEN1 is a tumour suppressor gene that helps prevent the growth of tumours in the pancreas and other organs. When this gene is mutated, it can lead to the development of pancreatic gastrinoma and other types of tumours.

Some of the risk factors for ZES include:

• Zollinger-Ellison Syndrome (ZES) is a rare condition caused by the formation of tumours that produce excessive amounts of gastrin, a hormone that stimulates acid production in the stomach. While the exact cause of ZES is unknown, certain factors can raise a person's risk of developing the condition.
• One of the common risk factors for ZES is having a family history of the condition or multiple endocrine neoplasia type 1 (MEN1), a genetic disorder that can cause tumours in various endocrine glands, including the pancreas. Individuals with a family history of these conditions should know the increased risk and discuss appropriate screening with their healthcare provider.
• Age is also a factor, as ZES is more common in people between 30 and 60. Additionally, men are slightly more likely to develop ZES than women.
• Other medical conditions can also increase the risk of developing ZES. For example, people with hyperparathyroidism, where the parathyroid gland produces too much parathyroid hormone, have an increased risk of developing ZES. Chronic atrophic gastritis, a condition where the stomach lining becomes thin and inflamed, can also increase the risk of ZES.
• Long-term use of certain medications, such as proton pump inhibitors (PPIs) and H2 blockers, commonly used to treat acid reflux and ulcers, may also increase the risk of developing ZES.
• Smoking and alcohol consumption have also been linked to an increased risk of ZES. Therefore, individuals who smoke or consume alcohol heavily should consider reducing or eliminating their use of these substances to reduce their risk of developing ZES.

These preventative measures can be taken to reduce the risk of developing this condition.

One of the key ways to prevent ZES is to identify and address the underlying medical conditions or risk factors that can contribute to the development of this syndrome. For example, people with a family history of ZES or multiple endocrine neoplasia type 1 (MEN1) may need genetic testing to identify potential risk factors. Then, if specified, appropriate surveillance and management strategies can be implemented to minimize the risk of developing ZES.

Another important preventative measure is to avoid the long-term use of certain medications, such as proton pump inhibitors (PPIs) and H2 blockers. While these medications are commonly used to treat acid reflux and ulcers, they have been linked to an increased risk of developing ZES. Therefore, taking these medications as prescribed and discussing any concerns with your healthcare provider is essential.

Lifestyle changes can also help to reduce the risk of developing ZES. For instance, quitting smoking can significantly lower the risk of developing this condition, as studies have shown that smokers have a higher risk of developing ZES than non-smokers. Similarly, limiting alcohol consumption can also help to lower the risk of ZES.

Maintaining a healthy diet and weight is also crucial for preventing ZES. For example, a diet high in fruits, vegetables, minerals, and whole grains can help reduce the risk of developing gastrointestinal issues that can lead to ZES. Additionally, regular exercise can help to maintain a healthy weight and reduce the risk of developing obesity-related conditions that can contribute to the development of ZES.

Regular check-ups with a healthcare provider can also help to prevent ZES. If you have any symptoms Zollinger Ellison Syndrome or risk factors for ZES, discussing them with your healthcare provider is essential. They can help identify potential issues and provide appropriate management or prevention guidance.

• The Zollinger Ellison Syndrome diagnosis (ZES) begins with a comprehensive evaluation of a patient's medical history and symptoms. A healthcare provider may ask about symptoms such as abdominal pain, diarrhoea, vomiting, weight loss, and gastrointestinal bleeding. They may also inquire about a family history of ZES or other related conditions.
• To confirm a diagnosis of ZES, a healthcare provider may order several tests, including blood tests, imaging studies, and endoscopic examinations.
• Blood tests are used to measure the levels of gastrin in the blood. Elevated levels of gastrin may indicate ZES, although other conditions, such as chronic atrophic gastritis or a gastric outlet obstruction, may also cause high gastrin levels.
• Imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans may be used to identify tumours in the pancreas or other areas of the body.
• Endoscopic examinations such as an upper gastrointestinal (GI) endoscopy or a biopsy may also be used to detect tumours or ulcers in the GI tract. During an upper GI endoscopy, a tiny, flexible tube with a high quality camera at the end is inserted through the mouth and into the esophagus, stomach, and small intestine. A biopsy may be taken for further analysis if any suspicious areas are identified.
• Sometimes, a secretin stimulation test may be used to diagnose Zollinger Ellison Syndrome. During this test, a secretin hormone is administered to stimulate gastrin release. Blood samples are then taken to measure the gastrin levels in the blood. In people with ZES, gastrin levels will continue to rise after administering secretin.

ZES is classified into three stages based on the severity of the condition:

• Stage 1: The gastrinomas are confined to the pancreas and are less than 2 cm in size.
• Stage 2: The gastrinomas have spread to nearby lymph nodes but have not reached other organs.
• Stage 3: The gastrinomas have spread to organs such as the liver, lungs, or bones.

The treatment and Zollinger Ellison Syndrome management depends on the stage of the condition and the severity of the symptoms. The primary aim of treatment of Zollinger Ellison Syndrome is to curb the production of stomach acid and control the symptoms of ZES. Some of the treatment options for ZES include:

Medications: Proton pump inhibitors (PPIs) are commonly prescribed to reduce the production of stomach acid. Other drugs, such as H2 blockers and antacids, may also be used to control the symptoms of ZES.

Surgery: Surgery may be recommended to remove the tumours if they are causing significant symptoms Zollinger Ellison Syndrome or have the potential to become cancerous. Surgery may be impossible if the tumours have spread to other organs in some cases.

Chemotherapy: Chemotherapy may be used to shrink tumours and slow down their growth. This treatment is usually reserved for advanced cases of ZES where surgery is not an option.

Radiation therapy: Radiation therapy may kill cancer cells and shrink tumours. This treatment is usually reserved for cases where surgery and chemotherapy are ineffective.

Endoscopic procedures: Endoscopic procedures such as endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) may be used to diagnose and treat ZES. These procedures involve inserting a thin tube with a camera and tools into the digestive tract to examine the pancreas and other organs.

The road to recovery after treatment for ZES can vary based on the condition and the type of treatment received. After treatment, following up with your healthcare provider regularly is essential to monitor the state and ensure that it does not return.

In addition, it is vital to make lifestyle changes to manage the symptoms of ZES. Some of the lifestyle changes that may help include:

• Eating small, frequent meals
• Avoiding spicy, acidic, or fatty foods
• Quitting smoking
• Limiting alcohol intake
• Reducing stress

1. Is Zollinger-Ellison Syndrome hereditary?
   There is no evidence to suggest that Zollinger-Ellison Syndrome is hereditary. However, some cases have been reported in families with a history of multiple endocrine neoplasia type 1 (MEN1), a genetic disorder.
2. Can Zollinger-Ellison Syndrome cause complications?
   Yes, Zollinger-Ellison Syndrome can lead to complications such as bleeding ulcers, perforation of the stomach or intestines, and malabsorption of nutrients.
3. Can Zollinger-Ellison Syndrome increase the risk of stomach cancer?
   Individuals with Zollinger-Ellison Syndrome have an increased risk of developing stomach cancer due to excess gastrin secretion and chronic hyperacidity and inflammation caused by excess gastrin secretion.
4. Can Zollinger-Ellison Syndrome affect children?
   Yes, Zollinger-Ellison Syndrome can affect children, but it is rare. Symptoms may be similar to those in adults and can lead to growth and developmental problems if left untreated.
5. Can lifestyle changes help manage Zollinger-Ellison Syndrome?
   Lifestyle changes such as avoiding trigger foods, eating smaller meals more frequently, and managing stress can help manage symptoms of Zollinger-Ellison Syndrome in addition to medical treatment.
6. Can Zollinger-Ellison Syndrome cause symptoms outside the digestive system?
   Zollinger-Ellison Syndrome can cause symptoms outside the digestive system, such as muscle weakness, joint pain, and skin rash due to the high gastrin levels in the bloodstream.
7. How often should individuals with Zollinger-Ellison Syndrome be monitored?
   Individuals with Zollinger-Ellison Syndrome should be monitored regularly through imaging and blood tests to monitor tumour growth and ensure proper treatment.
8. Can Zollinger-Ellison Syndrome be misdiagnosed?
   Zollinger-Ellison Syndrome can be misdiagnosed as other digestive disorders, such as acid reflux or peptic ulcer disease, which can delay proper treatment and lead to complications.
9. What is the treatment for Zollinger-Ellison Syndrome?
   The primary treatment for Zollinger-Ellison Syndrome is medication to reduce stomach acid production such as proton pump inhibitors (PPIs) and H2 blockers. Surgery may be necessary to remove the tumour causing the excessive gastrin secretion.