VIPoma - Symptoms, Causes, and Treatment

What Is a VIPoma?

A VIPoma, otherwise called a VIPoma, is a tumor made up of non-beta islet cells of the pancreas that secretes vasoactive intestinal peptide (VIP). It is a rare neuroendocrine tumor and affects around 1 in 10,000,000 individuals every year. Around 90 % of all VIPomas originate from the non-β pancreatic islet cells, and in some cases, they are associated with multiple endocrine neoplasia type 1 (MEN1). MEN1 is a hereditary condition that results in endocrine tumors.

In 1958, Verner and Morrison initially described the symptoms of VIPoma as WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome. In 1970, Said and Nutt found the hormone responsible for these symptoms. In 1973, Bloom linked WDHA syndrome to this hormone. In 1975, Swift et al. reported a pediatric patient who exhibited watery diarrhea and had ganglioneuroma (a rare benign tumor) that secreted VIP.

Around 50 to 75 percent of all VIPomas are malignant or cancerous. Around 5 percent of VIPomas are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome, and approximately 17 percent of MEN1 patients develop VIPomas. Even a benign (noncancerous) VIPoma is a problem, as the excess secretion of VIP results in a specific syndrome called Verner-Morrison syndrome (VMS). This syndrome can result in prolonged watery diarrhea, which can result in dehydration, low levels of potassium, and other complications in the long run.

In 90 percent of cases, it arises from the pancreas, but sometimes, VIPoma can be seen, especially in children, in the colon, adrenal glands, liver, etc. They are generally bigger than 3 cm in diameter. VIPoma is diagnosed based on the levels of VIP (vasoactive intestinal peptide) in the blood. The tumor is then visualized with the help of a CT (computerized tomography) scan or ultrasound and then removed surgically.

What Are the Signs of VIPoma?

As the tumor secretes excessive VIP, a neurotransmitter, it affects multiple organs in the body. It primarily affects the gastrointestinal (GI) system. VIP stimulates intestinal cyclic adenosine monophosphate (cAMP) production and inhibits the secretion of gastric acids. This results in vasodilation (widening of blood vessels), bone resorption, glycogenolysis (the breakdown of glycogen), and lipolysis (the breakdown of fats). These effects cause the secretion of excess water and electrolytes from the gastrointestinal epithelial cells and result in the following signs:

1. Hypokalemia (low potassium levels).

2. Facial flushing.

3. Reduced gastric acid secretion (achlorhydria).

4. Hyperglycemia (elevated blood glucose levels).

5. Hypercalcemia (elevated calcium levels).

6. Chronic watery diarrhea.

7. Dehydration.

8. Acidosis (too much acid in body fluids).

9. Hypotension (low blood pressure) due to vasodilation.

10. Tiredness.

11. Muscular weakness.

12. Abdominal cramps.

13. Weight loss.

14. Nausea.

What Are the Symptoms of VIPoma?

A VIPoma is a neoplasm that is considered to be molto raro and this neoplasm arises from the endocrine cells in the pancreas. These tumors produce unduly large quantities of peptide hormone VIP, resulting in Verner-Morrison syndrome or pancreatic cholera. There are various symptoms of overproduction of VIP, and most of the symptoms are the result of the VIP action on the gastrointestinal tract.

VIPomas have only one obvious symptom, which is chronic diarrhea, although the diarrhea may be watery. This can be severe sometimes and may present as dehydration and electrolyte disturbances. Such patients may shed up to 3 to 20 liters of diarrhea daily. Other related symptoms include:

• Mild abdominal pain or discomfort; no specific sign or symptom points to this disease.

• Rushing, flushing, also known as erythroplasia– a sudden skin redness.

• In many cases, patients may have muscle weakness, which can be associated with disturbances in electrolyte balance.

• Stomach discomfort and vomiting because of acute dehydration.

• Obesity reduction, which may result from chronic diarrhea and fat maldigestion.

What Is Pancreatitis Hypokalemia?

VIPomas are capable of causing several life-threatening complications, such as pancreatitis and hypokalemia.

• Pancreatitis: Pancreatitis may also result from the effect of VIPoma on pancreatic function or from causes such as dehydration and hypercalcemia. Dietary alterations due to VIP-induced diarrhea can cause massive losses of fluids and predispose the patient to acute pancreatitis. Patients with pancreatitis may feel pains in their abdomen, have a high temperature, feel sick, and have wretched indigestion.

• Hypokalemia: Hypokalemia, the low amount of potassium in the bloodstream, is one of the most common complications of VIPoma. Diarrhea produced by the tumor means great amounts of potassium and other essential electrolytes are flushed out of the body. Some of the clinical manifestations of hypokalemia include muscle twitching, muscle weakness, fatigue, and potentially life-threatening arrhythmias. Hydration and management of potassium levels are critical in patients with VIPoma because of the potentially lethal consequences that may occur.

What Are the Causes of VIPoma?

Scientists and doctors do not know what causes these tumors to develop. They are often diagnosed in adults around 50 or young children. Women are more commonly affected than men.

What Are the VIP Peptide Benefits?

VIP peptide, however, is known to cause disease when produced at high levels; vasoactive intestinal peptide (VIP) has several functions in the body in normal circumstances. It is a neuropeptide that plays a role as the modulator of multiple physiological functions. Some of its key benefits include:

• Regulation of Smooth Muscle Activity: VIP plays an important role in the simultaneous relaxation of the smooth muscles of the intestine, which is involved in the movement of chyme and prevents spasms.

• Stimulation of Water and Electrolyte Secretion: This action helps maintain the intestines' overall water content, enhancing digestion and absorption.

• Immune modulation: VIP has immunosuppressive effects that could prevent over-activation of inflammatory response responses to pathogens.

• Neuroprotective Effects: Studies have indicated that VIP may shield nerve cells from harm and may work in treating specific medical disorders, including neurodegenerative diseases.

• Bronchodilation: VIP has a bronchial muscle-relaxing effect, which is useful in treating asthma and other respiratory disorders.

In VIPoma, this peptide is secreted excessively, thus causing an imbalance in the body and resulting in this tumor.

How Is VIPoma Diagnosed?

The doctor will diagnose a VIPoma based on secretory diarrhea and elevated serum vasoactive intestinal peptide (VIP) levels and confirm the location of the tumor using endoscopic ultrasonography, CT scan, positron emission tomography (PET), or scintigraphy of the abdomen.

Secretory diarrhea occurs when electrolytes are secreted into the intestine, resulting in water build-up. The osmolality of the stool is the same as that of the plasma, and sodium and potassium concentrations are twice as normal. Other causes of secretory diarrhea, such as indiscriminate use of laxatives, bacterial or viral infections, genetic disorders, and inflammatory processes, must be ruled out.

Serum VIP should be ideally tested during an episode of watery diarrhea. Considerably elevated VIP levels are enough to diagnose VIPoma, but mild elevation might be due to short bowel syndrome (SSS—a malabsorption disorder) and inflammatory bowel disease (including ulcerative colitis and Crohn’s disease). The doctor will also conduct blood and metabolic panel tests to check glucose, calcium, and potassium levels. Almost 50 % of patients with VIPoma show elevated glucose and calcium levels.

How Is VIPoma Treated?

1) Medication: Treatment begins by correcting the body's electrolyte levels. The drug Octreotide acetate helps control diarrhea in most VIPoma patients. Somatostatin reduces vasoactive intestinal polypeptide (VIP) levels and controls diarrhea. Prolonged treatment with Octreotide can result in resistance, and in such cases, Interferon alfa may be added.

Steroids (Glucocorticoids) help reduce symptoms in half of the patients. A combination of Streptozocin, Fluorouracil, and Doxorubicin has shown some positive effects. Systemic chemotherapy may be needed in cases of inoperable tumors or progressive disease.

In the United States, agents like Sunitinib and Everolimus are used in advanced, well-differentiated tumors.

2) Surgery: VIPomas are surgically resected when there are no signs of metastasis. If that is not possible in advanced cases, the size of the tumor is reduced surgically (tumor debulking) to relieve symptoms, but it is not always successful.

3) Transarterial Chemoembolization (TACE): A chemotherapeutic agent is administered locally to treat VIPoma patients with extensive liver disease. Depending on the symptoms and tumor growth, this is repeated many times.

4) Radiofrequency Ablation and Cryoablation: These treatment options are used in cases of small metastases (less than 3 cm). Radiofrequency waves damage the cells in the tumor.

5) Radiation Therapy: If the tumor is unresectable, external radiation therapy may be used.

If the tumor has metastasized, it cannot be removed completely, and only symptoms may be managed to prolong survival, as these tumors are slow-growing in nature.

What Is the Prognosis of VIPoma?

VIPomas can be cured with surgery, but in less than half of the patients, by the time of diagnosis, the tumor spreads and cannot be removed surgically.

Conclusion:

VIPoma is a tumor characterized by increased levels of vasoactive intestinal peptides. Several treatment options are available for the treatment of this tumor. Reach out to a healthcare provider, and do not self-medicate when you experience symptoms like watery diarrhea for long periods. Getting diagnosed at an early stage can provide the best prognosis.