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Gastrinoma

Disease Details

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Description: A gastrinoma is a rare tumor that typically originates in the pancreas or duodenum and secretes excessive amounts of gastrin, leading to increased stomach acid production and recurrent peptic ulcers.
Type: Gastrinoma is a type of neuroendocrine tumor that typically arises in the pancreas or the duodenum.

The type of genetic transmission associated with some cases of gastrinoma is autosomal dominant. This is particularly true in cases where it is part of Multiple Endocrine Neoplasia type 1 (MEN1) syndrome.
Signs And Symptoms: Gastrinoma in the early stages will have signs and symptoms of indigestion or similar to irritable bowel disease (IBD) such as:

Hypergastrinemia
Refractory or recurrent peptic ulcers involving duodenum
Chronic diarrhea
Generalized cancer symptoms
Abdominal pain
Gastrointestinal bleeding
Obstruction of intestine
Weight loss/poor appetite
Anemia (Due to vitamin B12 malabsorption, and bleeding)
Hematemesis
Gastroesophageal reflux disease
Esophageal complications (Barrett's esophagus, esophagitis, stricture formation)
Vomiting
Steatorrhea
Prognosis: Patients with gastrinomas that are also known to be part of neuroendocrine neoplasms must have to deal with two factors related to this tumor. First, controlling the high amounts by using medications that inhibit gastrin levels. The second part is stabilizing the tumor progression. Gastrinomas have a rate of 60–90% that will become malignant. Patients who do not seek medical treatment such anti-ulcer medication have high rate of recurrence and death secondary to ulcer disease. The prognosis of gastrinoma depends on the level of metastases of the tumor. If patients present with hepatic metastases they might have remaining life span of one year with a five-year survival rate of 20–30%. In patients with localized tumor or localized lymph spread the survival rate of five years is 90%. Lastly, surgical resection of local tumor could lead to complete cure without recurrence in 20–25% of patients.
Onset: Gastrinoma typically presents in adults between the ages of 30 and 50. However, it can occur at any age, including in children.
Prevalence: The prevalence of gastrinoma, a type of neuroendocrine tumor that primarily affects the pancreas and duodenum, is estimated to be around 0.5 to 2 cases per million people annually. This condition is part of a group of disorders called Zollinger-Ellison syndrome and often leads to severe peptic ulcers due to excessive gastric acid secretion. Gastrinomas are relatively rare but can be life-threatening if not properly managed.
Epidemiology: Gastrinoma is the second most common functional pancreatic neuroendocrine tumor (pNET), with a yearly incidence of approximately 0.5 to 21.5 cases per a million of people worldwide. Gastrinomas are located predominantly in the duodenum (70%) and pancreas (25%). Pancreatic gastrinomas are larger than their duodenal counterparts, may occur in any portion of the pancreas, and comprise 25% of these tumors. Gastrinomas are also the most common functional and malignant pancreatic endocrine tumors. They are characterized by gastric hypersecretion that results in peptic ulcers and diarrhea; this condition is known as Zollinger–Ellison syndrome (ZES).
Intractability: Gastrinoma can be intractable in some cases, meaning it is difficult to manage or treat effectively. This is often due to the tumor's potential to secrete excessive amounts of gastrin, leading to severe ulceration, diarrhea, and other complications associated with Zollinger-Ellison syndrome. Surgical removal of the tumor is the preferred treatment; however, if the tumor is metastatic or cannot be fully resected, controlling symptoms and complications may become challenging.
Disease Severity: Gastrinomas are typically considered severe due to their potential to cause Zollinger-Ellison syndrome, which leads to excessive gastric acid production, resulting in peptic ulcers, gastroesophageal reflux disease (GERD), and diarrhea. If malignant, they can metastasize, most commonly to the liver and bones, which can complicate treatment and reduce survival rates. Prompt diagnosis and management are crucial for improving outcomes.
Healthcare Professionals: Disease Ontology ID - DOID:5577
Pathophysiology: Gastrin is secreted by the G cells. G cells are primarily found in the pyloric antrum but can also be found in the duodenum and the pancreas. The primary function of gastrin is to induce the release of hydrochloric acid (HCl) from the parietal cells located in the fundus of the stomach. Parietal cells are responsible for hydrochloric (HCl) secretion along with intrinsic factor that binds to vitamin B12 and helps with its uptake in the terminal ileum. Other functions of gastrin include stimulating the growth of gastric mucosa and gastric motility and promoting gastric emptying. These mechanisms of the gastrointestinal tract (GIT) are up-regulated by the vagus nerve of the parasympathetic nervous system (PNS), which carries out the majority of its functions by the release of neurotransmitter Acetylcholine (Ach), and to a lesser extent gastrin releasing peptide (GRP) protein. On the contrary, the functions of GIT are down-regulated by the activation sympathetic nervous system (SNS), which carries out its functions mostly via neurotransmitter epinephrine.Meal consumption causes distention of the stomach, leading to stimulation of the parasympathetic vagus nerve in the gastric mucosa, which causes the release of GRP protein. In gastrinoma, GRP protein causes larger than normal amounts of gastrin secretion, which leads to hyperplasia of the parietal cells. Hyperplasia of parietal cells causes an abnormal release of HCl into the duodenum, which causes the ulcers of the duodenum. Excessive HCl production also causes hyperperistalsis, a condition marked by excessive rapidity of the passage of food through the stomach and intestine and inhibits the activity of lipase, causing severe fatty diarrhea known as steatorrhea. Evenly the long-standing hyper-secretion of gastrin stimulate proliferation of the enterochromaffin like cells (ECL). These cells are found along the side the gastric lumen of the digestive tract. They play a main role in regulation of gastric secretion and motility when stimulated by nervous system. These cells in return will undergo progressive dysplastic changes starting with hyperplasia to neoplasia throughout the gastrointestinal tract.
Carrier Status: Gastrinoma is not typically associated with a carrier status because it is a type of tumor, not an inherited condition. It arises from the islet cells of the pancreas or the duodenal wall and often leads to Zollinger-Ellison syndrome, characterized by excessive gastric acid production. In some cases, gastrinomas may be associated with multiple endocrine neoplasia type 1 (MEN1), a hereditary condition, but the gastrinoma itself does not have a "carrier status."
Mechanism: Gastrinoma is a type of neuroendocrine tumor that predominantly arises in the pancreas or the duodenum and is characterized by the excessive secretion of gastrin, a hormone that stimulates the production of gastric acid. This leads to Zollinger-Ellison syndrome, characterized by peptic ulcers, gastroesophageal reflux disease (GERD), and chronic diarrhea.

### Mechanism
1. **Gastrin Overproduction:** Gastrinomas secrete large amounts of gastrin, leading to hypergastrinemia.
2. **Increased Gastric Acid Production:** Elevated gastrin levels stimulate the parietal cells in the stomach to secrete excessive gastric acid.
3. **Mucosal Damage:** High gastric acid levels cause damage to the gastrointestinal mucosa, resulting in peptic ulcers.
4. **Malabsorption:** The excessive acid can also impair the digestion and absorption of nutrients, causing malabsorption and chronic diarrhea.

### Molecular Mechanisms
1. **Genetic Mutations:** Sporadic gastrinomas may arise from mutations in genes such as MEN1. MEN1 mutations are also implicated in multiple endocrine neoplasia type 1 (MEN1) syndrome, where gastrinomas can co-occur with other endocrine tumors.
2. **Signaling Pathways:** Altered signaling pathways involving the MEN1 gene lead to dysregulated cell growth and proliferation in endocrine cells.
3. **Chromosomal Abnormalities:** Abnormalities in chromosomes 11q13, where the MEN1 gene is located, can also be associated with the development of gastrinomas.

Understanding these fundamental mechanisms and molecular pathways is crucial for the diagnosis and treatment of gastrinoma, often involving surgical resection, proton pump inhibitors, and somatostatin analogs for managing symptoms and controlling tumor growth.
Treatment: Surgery is first line treatment in gastrinomas; however it often fails to be curative.
Proton-pump inhibitors such as omeprazole. This group of medications suppress the acid secretion.
H2-receptor antagonist similarly decrease acid secretion.
Octreotide injections directly release somatostatin hormone that inhibits gastrin release.
Chemotherapy.
Compassionate Use Treatment: Gastrinoma, a type of neuroendocrine tumor that primarily affects the pancreas and duodenum, often leads to Zollinger-Ellison syndrome. In terms of compassionate use treatment, off-label or experimental treatments, the following options might be considered:

1. **Proton Pump Inhibitors (PPIs):** Though not experimental, the use of high-dose PPIs like omeprazole or lansoprazole is common to manage gastric acid hypersecretion.

2. **Somatostatin Analogs:** Drugs such as octreotide or lanreotide may be used off-label to control symptoms and potentially inhibit tumor growth.

3. **Targeted Therapies:** Everolimus and sunitinib, primarily approved for other types of neuroendocrine tumors, may be considered for off-label use.

4. **Peptide Receptor Radionuclide Therapy (PRRT):** An emerging treatment involving radiolabeled somatostatin analogs like ^177Lu-DOTATATE, which targets somatostatin receptors on tumor cells to deliver targeted radiation.

5. **Chemotherapy:** Agents like streptozotocin combined with doxorubicin or 5-fluorouracil might be used in certain cases, though this is more experimental for gastrinomas.

6. **Immunotherapy:** Although not standard for gastrinoma, experimental approaches involving immune checkpoint inhibitors are being investigated.

These treatments are typically considered when conventional therapies are ineffective or inappropriate. It's essential for patients to discuss risks, benefits, and eligibility with their healthcare provider.
Lifestyle Recommendations: For gastrinoma, lifestyle recommendations include:

1. **Dietary Adjustments:**
- Avoid foods and beverages that can stimulate gastric acid production such as caffeine, alcohol, spicy foods, and fatty foods.
- Eat smaller, more frequent meals to avoid overproduction of stomach acid.

2. **Stress Management:**
- Practice stress-reducing techniques like meditation, yoga, or deep-breathing exercises, as stress can worsen symptoms.

3. **Medication Adherence:**
- Follow your healthcare provider's medication plan precisely, which may include proton pump inhibitors or H2-receptor antagonists to reduce acid production.

4. **Avoid Smoking:**
- If you smoke, seek help to quit, as smoking can increase stomach acid.

5. **Regular Monitoring:**
- Keep up with regular medical check-ups to monitor the progression of the disease and the effectiveness of treatments.

6. **Hydration:**
- Maintain adequate hydration, though avoid drinks that can irritate the stomach lining.

7. **Elevate the Head While Sleeping:**
- Sleeping with the head elevated can help prevent acid reflux symptoms.

Your healthcare provider can offer personalized advice based on your specific condition and overall health.
Medication: Gastrinoma is often treated with proton pump inhibitors (PPIs) such as omeprazole or lansoprazole to reduce stomach acid production. Octreotide, a somatostatin analog, may also be used to control symptoms by inhibiting hormone release.
Repurposable Drugs: Potential repurposable drugs for gastrinoma include:

1. Proton pump inhibitors (PPIs) like omeprazole or lansoprazole, which reduce gastric acid secretion.
2. Somatostatin analogs like octreotide, which inhibit the release of various hormones.
3. H2 receptor antagonists such as ranitidine, which also decrease acid production.
4. Chemotherapeutic agents like streptozocin, often combined with other drugs such as doxorubicin.

The role of newer targeted therapies and immune checkpoint inhibitors in the context of hormonal tumor control and gastrointestinal cancers might also be considered under clinical guidance.
Metabolites: Gastrinoma is a type of neuroendocrine tumor that primarily secretes gastrin, a hormone that stimulates gastric acid production. Elevated levels of gastrin and gastric acid can lead to peptic ulcers and gastroesophageal reflux disease (GERD). Gastrin is the primary metabolite monitored to diagnose and manage gastrinoma.
Nutraceuticals: Nutraceuticals are food-derived products with potential health benefits, including the prevention and treatment of diseases. In the context of gastrinoma, which is a type of neuroendocrine tumor that secretes excessive gastrin leading to peptic ulcers and gastric hypersecretion, there is no direct evidence to suggest that nutraceuticals can treat the tumor itself. However, some nutraceutical approaches might help alleviate symptoms or support overall health.

For symptom management and support in gastrinoma patients, the following nutraceuticals may be considered:

1. **Probiotics**: May support gut health and help manage gastrointestinal symptoms.
2. **Omega-3 Fatty Acids**: Possess anti-inflammatory properties that could help reduce gastrointestinal inflammation.
3. **Curcumin**: An extract from turmeric with anti-inflammatory and antioxidant properties; it might help manage inflammation.
4. **Vitamin D**: Supports immune function, and deficiencies have been linked to various gastrointestinal diseases.
5. **Ginger**: Known for its anti-inflammatory and anti-nausea properties.

It's important to note that while these nutraceuticals can support overall health and manage symptoms, they are not a substitute for conventional treatments like surgical resection, proton pump inhibitors, or somatostatin analogs, which are crucial for managing gastrinoma. Always consult with a healthcare provider before starting any new supplement regimen.
Peptides: Gastrinomas are tumors that secrete excessive amounts of the peptide hormone gastrin. This hormone stimulates the stomach to produce too much acid, leading to peptic ulcers and other gastrointestinal issues. Gastrinomas are often associated with a condition called Zollinger-Ellison syndrome. They can occur sporadically or as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome.