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 that was 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 % of all VIPomas are malignant or cancerous. Around 5 % of VIPomas are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome, and approximately 17 % 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 in the long run, can result in dehydration, low levels of potassium, and other complications.

In 90 % 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 and Symptoms of VIPoma?

As the tumor secretes excessive VIP, which is 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 and symptoms:

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.

These symptoms are part of the syndrome called Verner-Morrison syndrome (VMS), pancreatic cholera syndrome (PCS), or WDHA syndrome.

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 years of age or young children. Women are more commonly affected than men.

How Is VIPoma Diagnosed?

The doctor will diagnose a VIPoma based on secretory diarrhea, 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 is when electrolytes are secreted into the intestine, which results 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. It is important to rule out other causes of secretory diarrhea, such as indiscriminate use of laxatives, bacterial or viral infections, genetic disorders, and inflammatory processes.

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 (includes ulcerative colitis and Crohn’s disease). The doctor will also conduct blood tests and metabolic panel tests to check the levels of glucose, calcium, and potassium. Almost 50 % of patients with VIPoma show elevated glucose and calcium levels.

How Is VIPoma Treated?

1) Medication:

Initially, treatment is done by correcting the electrolyte levels in the body. The drug Octreotide acetate helps control diarrhea in most VIPoma patients. It is Somatostatin that reduces the levels of 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. And 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:

In cases of small metastases (less than 3 cm), these treatment options are used. Here, radiofrequency waves are used to damage the cells in the tumor.

5) Radiation Therapy:

If the tumor is unresectable, external radiation therapy may be used.

In case the tumor has metastasized, the tumor 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. A number of 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 of time. Getting diagnosed at an early stage can provide the best prognosis.