Zollinger Ellison syndrome symptoms causes and treatment

Zollinger-Ellison Syndrome (ZES) is a rare disorder that affects the digestive system and causes excessive acid production in the stomach. This leads to severe health problems like ulcers and chronic pain. Although this syndrome is not common, understanding its symptoms, causes, and available treatments can help many individuals manage it effectively. In this article by Daly Medical, we will discuss the main causes of Zollinger-Ellison Syndrome, the symptoms that may appear in patients, and the various medical and surgical treatments available. Learn everything you need to know about this condition and how to manage it to improve your quality of life.

What is Zollinger-Ellison Syndrome (ZES)?

Zollinger-Ellison Syndrome (ZES) is a rare condition that causes severe digestive ulcers and chronic diarrhea, resulting from the presence of gastrin-secreting tumors (gastrinomas) in the pancreas or duodenum (the upper part of the small intestine). These tumors release excessive amounts of the hormone gastrin, which stimulates the stomach to produce large amounts of acid. This excess acid leads to ulcers, acid reflux, and other digestive problems. Approximately 60% of gastrinomas are malignant, and the condition is sometimes referred to as "pancreatic ulcer tumor syndrome."

Can Zollinger-Ellison Syndrome be cured completely?

Yes, if the syndrome is diagnosed early and the tumors are successfully treated, either surgically or with chemotherapy, the symptoms may disappear completely or improve significantly. However, if the tumors are inoperable or the condition has progressed significantly, symptoms may persist for long periods.

Can Zollinger-Ellison Syndrome be prevented?

It is not possible to fully prevent Zollinger-Ellison Syndrome, particularly when caused by gastrinomas. However, early detection of tumors and timely treatment can help minimize serious complications.

What is the role of nutrition in treating Zollinger-Ellison Syndrome?

Nutrition plays an important role in managing the symptoms. It is crucial to avoid foods that stimulate acid production in the stomach, such as spicy foods, acidic foods, and caffeine. Eating smaller, more frequent meals instead of large meals can help reduce pressure on the stomach and improve digestion.

Can exercise be done with Zollinger-Ellison Syndrome?

Yes, moderate exercise can be done if symptoms are under control. However, activities that increase pressure on the stomach, such as heavy weightlifting, should be avoided. It is always recommended to consult a doctor before starting any exercise program.

Does Zollinger-Ellison Syndrome affect daily life?

Yes, if left untreated, it can significantly affect daily life, particularly due to symptoms such as chronic stomach pain, severe heartburn, and persistent diarrhea. These symptoms can interfere with work or social activities.

Is there a life-threatening risk if Zollinger-Ellison Syndrome is left untreated?

Yes, if left untreated, Zollinger-Ellison Syndrome can lead to serious complications such as severe bleeding in the stomach or intestines. In advanced cases, the risk of stomach cancer increases, especially if the tumors are malignant.

Who is at risk for Zollinger-Ellison Syndrome?

Anyone can develop Zollinger-Ellison Syndrome, but individuals with Multiple Endocrine Neoplasia Type 1 (MEN1) are more likely to develop the condition. Men between the ages of 30 and 50 are at higher risk.

How common is Zollinger-Ellison Syndrome?

Zollinger-Ellison Syndrome is very rare, with approximately 0.5 to 3 cases per million people diagnosed annually.

Causes of Zollinger-Ellison Syndrome (ZES)

Gastrinomas:
- Gastrinomas are rare tumors that originate from the cells that secrete the hormone gastrin. This hormone stimulates the stomach to produce gastric acid.
- The tumors may be found in the pancreas or small intestine, and in some cases, they may also appear in the liver or lymph nodes.
Genetic Mutations:
- About 25% of Zollinger-Ellison cases result from the "MEN1" syndrome, a rare inherited condition that causes tumors to form in the endocrine glands.
- MEN1 syndrome increases the likelihood of developing gastrinomas, leading to ZES.
Increased Gastrin Secretion:
- Gastrin is normally secreted by cells in the stomach lining, but in gastrinomas, excessive amounts are produced, leading to stomach irritation and ulcer formation.
Benign or Malignant Tumors:
- Gastrinomas may be benign or malignant. Malignant tumors may spread to other parts of the body.

Factors Contributing to the Development of ZES:

Genetic Factors:
- Individuals with MEN1 syndrome are at a higher risk of developing ZES, as multiple types of tumors may form in the endocrine glands.
Environmental Factors:
- Although environmental causes are rare, factors like psychological stress or changes in diet may play a role in triggering symptoms.
Age and Gender:
- Zollinger-Ellison Syndrome is typically diagnosed in adults, with men between 30 and 50 years of age being at higher risk. However, women can also be affected.
Family History:
- People with a family history of MEN1 may be more likely to develop Zollinger-Ellison Syndrome.

Symptoms of Zollinger-Ellison Syndrome (ZES)

Stomach Pain and Heartburn:
- A common symptom is burning stomach pain, often occurring in the upper stomach after eating, sometimes accompanied by sour burps or a bitter taste in the mouth.
Gastric and Intestinal Ulcers:
- Gastrinomas cause excessive acid production, leading to erosion of the stomach and intestinal walls, resulting in painful ulcers.
- In some cases, ulcers may also develop in the small intestine, which may be difficult to heal.
Chronic Diarrhea:
- Chronic diarrhea is a hallmark symptom and can lead to malnutrition, as the excess acid interferes with nutrient absorption.
Nausea and Vomiting:
- Some patients experience persistent nausea or frequent vomiting, particularly after meals.
Unexplained Weight Loss:
- Unexplained weight loss can occur due to chronic pain and persistent diarrhea, leading to malnutrition.
Fatigue:
- Due to nutrient deficiencies and weight loss, patients often experience constant fatigue and lack of energy.
Abdominal Swelling or Pain:
- Some patients may have abdominal bloating or pain due to the acid's effect on the stomach and intestines.
Advanced Symptoms:
- In advanced cases or when gastrinomas spread, additional symptoms like persistent abdominal pain or internal bleeding may appear.
Digestive Problems or Loss of Appetite:
- Difficulty digesting food or loss of appetite can result from the effect of ulcers or excess acid.
Elevated Gastrin Levels:
- Blood tests may show an elevated level of gastrin, further complicating digestive issues.

Stages of Zollinger-Ellison Syndrome (ZES)

Early Stage:
- Symptoms may be mild or unclear, with patients experiencing increased acidity or mild stomach pain after eating.
- Mild diarrhea or nausea may occur without a clear cause. Early diagnosis is difficult as it resembles other conditions, like peptic ulcers.
Progressive Stage:
- If left untreated, symptoms worsen, leading to severe ulcers in the stomach and intestines.
- Stomach pain becomes more intense, potentially radiating to other parts of the abdomen or back.
- Chronic diarrhea persists, and weight loss may occur. Vomiting blood or passing blood in stools may occur due to ulcer bleeding.
Severe or Complicated Stage:
- Untreated cases may develop complications like blood clot formation or tissue damage.
- Bowel obstruction or a general decline in health may occur due to continuous pain, diarrhea, and weight loss.
- This stage may also pose a risk for pancreatic cancer and severe anemia due to chronic bleeding.
Chronic Stage:
- Symptoms become persistent and permanent, significantly impacting quality of life.
- Patients may suffer from chronic stomach pain, ongoing diarrhea, and nutrient deficiencies due to malabsorption.
- Prolonged weight loss and fatigue further weaken the patient’s general health.

Types of Zollinger-Ellison Syndrome (ZES)

Sporadic Zollinger-Ellison Syndrome:
- Occurs spontaneously (without a genetic cause) with gastrinomas found in the pancreas or small intestine.
- Tumors are often benign, but in some cases, they may be malignant.
- Gastrinomas lead to excessive gastric acid secretion, causing ulcers in the stomach and intestines, along with symptoms like pain, heartburn, and diarrhea.

Familial Zollinger-Ellison Syndrome (Secondary Zollinger-Ellison Syndrome)

Definition: This occurs when Zollinger-Ellison Syndrome is caused by Multiple Endocrine Neoplasia Type 1 (MEN1), a rare genetic disorder.

MEN1 Syndrome: This syndrome causes tumors to develop in the endocrine glands, such as the pituitary gland, thyroid, and pancreas. Gastrinomas appear as part of a collection of other tumors.

Gastrinomas: These tumors are multiple and scattered across the pancreas and small intestine.

Impact: The tumors lead to increased acid secretion, which results in symptoms such as ulcers in the stomach and intestines, heartburn, and diarrhea.

Pancreatic Cancer-Associated Zollinger-Ellison Syndrome

Definition: In some rare cases, Zollinger-Ellison Syndrome is part of pancreatic cancer.

Malignant Gastrinomas: The malignant tumors grow rapidly and can spread to other parts of the body.

Impact: The malignant tumor increases the risk of serious complications such as bleeding or intestinal obstruction. Treatment involves addressing both the cancer and Zollinger-Ellison Syndrome.

Damages Caused by Zollinger-Ellison Syndrome (ZES)

Stomach and Intestinal Ulcers:
- Cause: Excessive stomach acid production due to elevated gastrin levels leads to the erosion of the stomach and intestinal walls.
- Damages:
  - Chronic ulcers that may be resistant to treatment.
  - Internal bleeding that may result in anemia or become life-threatening.
  - Deterioration of tissue health due to continuous inflammation and ulcers.
Chronic Diarrhea:
- Cause: Excess stomach acid disrupts the digestion process in the small intestine.
- Damages:
  - Malabsorption of essential nutrients.
  - Fluid and electrolyte loss, which may lead to dehydration and general health deterioration.
Unexplained Weight Loss:
- Cause: Chronic diarrhea and loss of appetite due to pain and ulcers.
- Damages:
  - Malnutrition and deficiency in essential nutrients.
  - Fatigue and body weakness.
Severe Stomach and Abdominal Pain:
- Cause: Irritation of the stomach and intestinal walls due to excess acid.
- Damages:
  - Persistent stomach or abdominal pain, which can be burning and distressing.
  - Increased pain during eating or drinking.
Gastrointestinal Infections:
- Cause: Increased stomach acid causes damage to the stomach and intestinal walls, making them more prone to infections.
- Damages:
  - Gastritis and enteritis, which worsen pain and affect digestion.
Blood Clot Formation (Especially in Venous Cases):
- Cause: In some venous cases, excessive gastrin secretion may lead to the formation of blood clots.
- Damages:
  - Swelling in the arms or hands due to vascular obstruction.
  - Pulmonary embolism if a clot travels to the lungs, posing a life-threatening risk.
Infection Due to Weakened Immune System:
- Cause: Malnutrition due to malabsorption and ulcers weakens the immune system.
- Damages:
  - Increased susceptibility to frequent infections.
Psychological Stress and Mental Changes:
- Cause: Chronic pain and persistent diarrhea can affect daily quality of life.
- Damages:
  - Depression and anxiety due to ongoing pain.
  - Social isolation due to distressing symptoms.
Long-Term Complications (If Left Untreated):
- Cause: If left untreated, symptoms worsen and cause severe health problems.
- Damages:
  - Further deterioration of the stomach and intestines due to constant acid pressure.
  - Gastrinomas may develop into cancer, complicating treatment.

Medications for Treating Zollinger-Ellison Syndrome

Proton Pump Inhibitors (PPIs):
- Description: These medications are primarily used to reduce stomach acid production. They decrease the amount of acid produced in the stomach, thus protecting tissues from ulceration caused by excess acid.
- Examples:
  - Omeprazole: Reduces stomach acid secretion.
  - Esomeprazole: Effectively reduces acid production.
  - Lansoprazole: Also used to reduce acid secretion.
- Purpose: Prevent the formation of stomach and intestinal ulcers and reduce symptoms such as heartburn and acid-induced pain.
H2 Receptor Blockers:
- Description: These medications help reduce stomach acid by blocking the effects of histamine, a chemical that stimulates acid secretion.
- Examples:
  - Ranitidine: Reduces stomach acid secretion.
  - Famotidine: Helps reduce acid production.
- Purpose: These medications are used less frequently than PPIs but can be effective for mild cases of Zollinger-Ellison Syndrome.
Gastrin Inhibitors:
- Description: These drugs reduce the secretion of gastrin, the hormone responsible for stimulating acid production in the stomach.
- Examples:
  - Clonidine: May help lower gastrin levels in the blood.
- Purpose: Reduce elevated gastrin levels, which helps control symptoms and prevent ulcers.
Chemotherapy:
- Description: For malignant gastrinomas (such as those caused by tumors in the pancreas or small intestine), chemotherapy may be needed to control and shrink the tumors.
- Examples:
  - Eloxatin (Oxaliplatin): Used to treat cancer associated with pancreatic tumors.
- Purpose: Reduce the size of malignant gastrinomas and stop their growth.
Vasodilators:
- Description: In some cases, pressure on blood vessels due to gastrinomas may affect blood flow to the stomach and intestines. Vasodilators help improve blood circulation.
- Examples:
  - Nitroglycerin: May help dilate blood vessels and improve blood flow.
- Purpose: Improve circulation in the tissues around the stomach.
Antibiotics:
- Description: If infections are caused by ulcers or inflammation in the intestines due to excessive acid secretion, antibiotics may be prescribed.
- Examples:
  - Amoxicillin: For bacterial infections.
- Purpose: Treat any infections resulting from ulcers or damage caused by excess stomach acid.
Tumor Inhibitors:
- Description: In cases where gastrinomas are cancerous, tumor inhibitors may be used to slow the growth of the tumors, including immune therapies.
- Examples:
  - Sunitinib: Used for cancerous tumors.
- Purpose: Shrink tumors and prevent cancer progression.
Injection Therapies:
- Description: Local injections may be used to treat ulcers or other effects of Zollinger-Ellison Syndrome.
- Examples:
  - Insulin injections: If Zollinger-Ellison Syndrome is related to diabetes.
- Purpose: Address symptoms such as chronic ulcers or severe pain.

Surgical and Laser Treatment for Zollinger-Ellison Syndrome

Surgery for Zollinger-Ellison Syndrome:
- Gastrinoma Removal:
  - Description: If Zollinger-Ellison Syndrome is caused by gastrinomas in the pancreas or small intestine, surgical removal of the tumor is a primary treatment option.
  - Goal: Remove the gastrinoma that is producing excessive gastrin, leading to increased stomach acid production.
  - Benefits: Removal of the tumor may eliminate symptoms such as severe ulcers and diarrhea, possibly curing the condition.
  - Drawbacks: Surgery can be complex, especially if the tumors are in difficult-to-reach areas. The recovery period can be long, and risks such as infection or bleeding may occur.
- Partial Pancreas Removal:
  - Description: In cases of large gastrinomas affecting the pancreas, partial removal of the pancreas may be necessary.
  - Goal: Reduce gastrin secretion by removing the affected portion of the pancreas.
  - Benefits: Helps decrease acid secretion, improving symptoms.
  - Drawbacks: Risks include infection or bleeding and potential impacts on pancreatic function.
- Repair of Damaged Blood Vessels:
  - Description: If gastrinomas affect blood vessels in the stomach or intestines, surgery may be needed to repair or replace the damaged vessels.
  - Goal: Restore normal blood flow to the stomach and intestines.
  - Benefits: Improves circulation and relieves symptoms such as gastrointestinal bleeding.
  - Drawbacks: As with any surgery, there are risks like infection or bleeding.
Laser Treatment for Zollinger-Ellison Syndrome:
- Laser Treatment for Ulcers:
  - Description: In some cases, lasers can be used to treat ulcers caused by excessive acid secretion. The laser is directed to stimulate healing and reduce swelling in the stomach lining.
  - Goal: Shrink or remove ulcers and promote healing.
  - Benefits: Non-surgical treatment that can be effective for severe ulcers, providing rapid symptom relief.
  - Drawbacks: May not be effective for advanced cases, especially large tumors or deep tissue involvement.
- Laser for Gastrinoma Removal:
  - Description: In rare cases, laser surgery can be used to shrink or remove gastrinomas.
  - Goal: Reduce the size of gastrinomas or eliminate them to reduce excessive gastrin production.
  - Benefits: Less invasive compared to traditional surgery, with a shorter recovery time.
  - Drawbacks: May not be effective for advanced stages or malignant tumors, and multiple sessions may be required