The hallmark of VIPoma in terms of symptomatology is the presence of prolonged profuse watery diarrhea, usually more than 3000 ml/day. Such profound water loss results in significant hypokalemia, which can have detrimental effects on the cardiac and skeletal system leading to arrhythmias and diffuse muscle weakness. In addition to watery diarrhea and hypokalemia, nausea and vomiting are frequent symptoms, which lead to achlorhydria. These symptoms comprise the WDHA syndrome that describes patients with VIPomas. WDHA syndrome is also known as pancreatic cholera because profuse water loss mimics the syndrome seen in patients with Vibrio cholera infection. Other symptoms that are reported include flushing (which is one of the main features of carcinoid syndrome), weight loss, lethargy, abdominal pain and bloating [12].

Symptoms that appear in patients can be intermittent, which is one of the reasons why establishing the diagnosis may be difficult, although diarrhea is usually a constant finding in these patients.

• Weight Loss

  Abnormal Weight Loss Abnormal weight loss is unexplained weight loss. Unintentional weight loss is a very non specific symptom but may be indicative of a serious illness or sudden weight loss after grief. [evidence.nhs.uk]

  Weight loss. Diagnosis: VIPomas are usually found incidentally while testing for other conditions, usually during a stool lest for prolonged diarrhea. Abnormal electrolyte levels can indicate cancer, but not necessarily VIPoma. [medigoo.com]

  Clinical features WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria) Weight loss Abdominal pain, nausea, vomiting Achlorhydria → ↓ iron and B12 absorption → anemia Diagnosis ↑ Serum VIP concentration (> 75 pg/mL) Hypokalemia, hypercalcemia, hyperglycemia [amboss.com]

  Symptoms in detail Weight Loss Patients diagnosed with pancreatic cancer may have lost at least 10% of their body weight. This symptom is common where the cancer is located in the head of the pancreas. [raisingawarness.wordpress.com]

  loss.[14851][2109] When a person has a VIPoma and these associated symptoms, it is referred to as VIPoma syndrome, also called WDHA syndrome or Verner-Morrison syndrome.[14851] The majority of people with a VIPoma have VIPoma syndrome.[14852] VIPomas [rarediseases.org]

• Fever

  Diabetes, itching, sickness, changes in bowel movements, fever and shivering. I must stress that if you do show any of these symptoms it doesn’t necessarily mean you have the early signs of cancer. [raisingawarness.wordpress.com]

  She denied abdominal pain, fever/chills, recent travel or antibiotic use. Laboratory studies showed dehydration, metabolic acidosis, hypokalemia, hyperglycemia and hypercalcemia. VIP level was 1317. [journals.lww.com]

  Post-Doctoral Degree 19,897 satisfied customers I am recently having a strange flushing sensation-it goes I am recently having a strange flushing sensation-it goes through my forehead, ears, nose-they are all hot to the touch (hubby verified) but no fever [justanswer.com]

  On presentation she denied any abdominal pain, fever, bleeding per rectum or any recent travel. She had noticed that there had been some weight loss but this could not be quantified. Apart for the antibiotics, she was on no other medications. [jscimedcentral.com]

  The patient reported no abdominal pain, weight loss, fevers, chills, or night sweats and noted no other recent episodes of diarrhea. Her medical history was remarkable for depression, endometriosis, and gastroesophageal reflux disease. [mdmag.com]

• Inflammation

  Treatment consists of medical management of symptoms and complete surgical removal of the tumor Tumor Inflammation when possible. Last updated: Sep 1, 2022 [lecturio.com]

  The NLRP1 gene provides instructions for making a protein that is involved in the immune system, helping to regulate the process of inflammation. [ghr.nlm.nih.gov]

  You may also be sick if the cancer, or the surrounding inflammation, begins to block the duodenum. This prevents digested food from passing through to the small bowel. Bowel changes If you develop jaundice you may also develop steatorrhoea. [raisingawarness.wordpress.com]

  […] skin Family history (heredity) A trigger event, such as sunburn, stress or exposure to industrial chemicals Complications People with vitiligo may be at increased risk of: Social or psychological distress Sunburn and skin cancer Eye problems, such as inflammation [mayoclinic.org]

  Infilterated by dense sizable lympoid follicles with germinal centers, calcifications, ischemic infarctions and mixed inflammation. No evidence of atypical mitosis or invasive malignancy could be seen. [cardiothoracicsurgery.biomedcentral.com]

• Surgical Procedure

  The Carcinoid and vipoma share a common symptom, diarrhea, and similar treatment through surgical procedures. [cancerwall.com]

  Excision (Removal) The only treatment that will completely remove a lipoma is a surgical procedure called excision. Procedure. In this procedure, a local anesthetic is typically injected around the tumor to numb the area. [orthoinfo.aaos.org]

  In cases of metastasis (which takes place frequently), a combination of chemotherapy, radiation therapy, and surgical procedures may be used The prognosis of Pancreatic VIPoma depends upon many factors including the stage of the tumor, the age and overall [dovemed.com]

  The surgical procedure in metastatic VIPoma includes an aggressive surgical therapy and is recommended when all disease can be safely removed [Song et al. 2009]. [journals.sagepub.com]

• Ecchymosis

  […] histology prior to complete excision • Symptomatic lipoma • Enlarging soft-tissue mass • Cosmetic considerations • Kenalog steroid injection is an alternative to excision (results in fat atrophy) • Physical exam to detect "recurrence" • Surgical infection • Ecchymosis [accesssurgery.mhmedical.com]

  Possible Risks and Complications Lipoma excision may cause some complications, which include: Surgical infection Cellulitis Fasciitis Ecchymosis Hematoma formation Injury to nearby nerves or blood vessels Permanent deformity (in the case of large lipomas [docdoc.com.sg]

• Dyspnea

  Carcinoid syndrome – characterized by diarrhea, flushing, dyspnea, and wheezing – may occur if a serotonin-producing tumor has metastasized to the liver, bypassing first-pass metabolism. Elevated 5-HIAA in the urine helps to establish the diagnosis. [amboss.com]

  He was managed as a chest infection case then persistence of pain and dyspnea mandated performing the chest X Ray (CXR); it showed an apparent huge mass occupying most of the right hemi-thorax obscuring lung field (Fig. 1). [cardiothoracicsurgery.biomedcentral.com]

• Abnormal Breathing

  Volume Depletion and Dehydration, as well as wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. [lecturio.com]

• Diarrhea

  Fluids are often given through a vein (intravenous fluids) to replace fluids lost in diarrhea. The next goal is to slow the diarrhea. Medicines can help control diarrhea. Discuss the medical options with your PCP (primary care physician). [medigoo.com]

  Serum VIP should be ideally tested during an episode of watery diarrhea. [icliniq.com]

  After 7 months, because NETs were stable on computed-tomography images, sunitinib was discontinued because of vomiting, leading to the recurrence of watery diarrhea. Sunitinib (25 mg/day) was reintroduced, which resolved diarrhea within 2 days. [eje.bioscientifica.com]

  Pharmacological measures include octreotide and lanreotide to stop the diarrhea and inhibit the secretion of VIP. [xpertdox.com]

  Subsequently, the patient did well and had no further diarrhea. A 50-year-old woman presented with a five-month history of fatigue, weakness, and diarrhea. Her electrocardiogram disclosed prominent U waves and ST-segment depression. [nejm.org]

• Abdominal Pain

  Symptoms: Symptoms may include: Abdominal pain and cramping. Diarrhea (watery, and often in large amounts). Flushing or redness of the face. Nausea. Weight loss. [medigoo.com]

  References:[3][4][5][1][6][7] Clinical features Asymptomatic Abdominal pain Carcinoid syndrome Diarrhea and abdominal cramps Cutaneous flushing Possible triggers: alcohol consumption, food intake, stress In severe cases, may be accompanied by tachycardia [amboss.com]

  pain and cramping, severe watery diarrhea, dehydration, flushing of the face, muscle cramps due to low potassium levels (hypokalemia), and weight loss.[14851][2109] When a person has a VIPoma and these associated symptoms, it is referred to as VIPoma [rarediseases.org]

  Symptoms Diarrhoea Watery stools Abdominal pain Back pain Flushing Sweating Failure to thrive Colonic dilatation Diarrhoea Watery stools Abdominal pain Back pain Flushing Sweating Failure to thrive Colonic dilatation Watery diarrhea Hypokalemia Absence [checkorphan.org]

  A 46 year old women presented with abdominal pain and diarrhea. [ncbi.nlm.nih.gov]

• Nausea

  Nausea. Weight loss. Diagnosis: VIPomas are usually found incidentally while testing for other conditions, usually during a stool lest for prolonged diarrhea. Abnormal electrolyte levels can indicate cancer, but not necessarily VIPoma. [medigoo.com]

  […] include hypokalemia, secretory diarrhea, anorexia (loss of appetite), chronic fatigue, dehydration, diabetes mellitus, erythema, abdominal pain, hepatomegaly (enlargement of liver), generalized muscle weakness, hypercalcemia, muscle cramps, malabsorption, nausea [xpertdox.com]

  Signs and symptoms of VIPoma include chronic watery diarrhea, dehydration, abdominal pain, nausea, flushing or redness in the face, weight loss, and very low levels of potassium in the blood. [drlogy.com]

  Hypokalemia has been reported in most patients with VIPoma and can be accompanied by lethargy, nausea, and muscular discomfort. [endocrinediseases.org]

  Symptoms of VIPoma may include any of the following: Abdominal pain and cramping Diarrhea (watery, and often in large amounts) Dehydration Flushing or redness of the face Muscle cramps due to low blood potassium ( hypokalemia ) Nausea Weight loss The [nlm.nih.gov]

• Vomiting

  After 7 months, because NETs were stable on computed-tomography images, sunitinib was discontinued because of vomiting, leading to the recurrence of watery diarrhea. Sunitinib (25 mg/day) was reintroduced, which resolved diarrhea within 2 days. [eje.bioscientifica.com]

  […] hypokalemia, secretory diarrhea, anorexia (loss of appetite), chronic fatigue, dehydration, diabetes mellitus, erythema, abdominal pain, hepatomegaly (enlargement of liver), generalized muscle weakness, hypercalcemia, muscle cramps, malabsorption, nausea, vomiting [xpertdox.com]

  […] will experience the following symptoms and signs: Nausea Abdominal cramping and pain Facial redness Diarrhea Losing of weight Dehydration Hypokalemia or low potassium level Achlorhydria or low acid stomach Appetite is reduced Lethargy Muscular weakness Vomiting [cancerwall.com]

  Clinical features WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria) Weight loss Abdominal pain, nausea, vomiting Achlorhydria → ↓ iron and B12 absorption → anemia Diagnosis ↑ Serum VIP concentration (> 75 pg/mL) Hypokalemia, hypercalcemia, hyperglycemia [amboss.com]

• Chronic Diarrhea

  […] or chronic diarrhea. [platform.almanhal.com]

  diarrhea is defined as diarrhea lasting for more than four weeks. [journals.lww.com]

  CONCLUSIONS: A high index of suspicion is important when diagnosing chronic diarrhea. Minimally invasive surgery is an option in the surgical treatment of pancreatic VIPoma. [amjcaserep.com]

  • A non-beta islet cell tumor of the pancreas that secretes VIP • VIPomas cause the WDHH syndrome (watery diarrhea, hypokalemia, hypochlorhydria) • Chronic profuse watery diarrhea • Massive fecal loss of potassium • Low serum potassium • Extreme weakness [accesssurgery.mhmedical.com]

  When the tumor is present, it causes an overproduction of VIP in the pancreas, which, in turn, causes a host of gastrointestinal and general symptoms: diarrhea (can become chronic diarrhea) dehydration abdominal pain and cramping hypokalemia (muscle cramps [carygastro.com]

• Hypotension

  Generalized vasodilation with systemic venous and arterial hypotension gave away to vasoconstriction with severe venous and arterial hypertension. [ncbi.nlm.nih.gov]

  VIPoma Description, Causes and Risk Factors: An endocrine tumor, usually originating in the pancreas, which produces a vasoactive intestinal polypeptide, believed to cause profound cardiovascular and electrolyte changes with vasodilatory hypotension, [medigoo.com]

  VI·Po·ma (vi-pō'mă), An endocrine tumor, usually originating in the pancreas, which produces a vasoactive intestinal polypeptide believed to cause profound cardiovascular and electrolyte changes with vasodilatory hypotension, watery diarrhea, hypokalemia [medical-dictionary.thefreedictionary.com]

  Generalized vasodilation with systemic venous and arterial hypotension gave way to vasoconstriction with severe venous and arterial hypertension. [jamanetwork.com]

• Hypertension

  Multi-visceral resection of pancreatic VIPoma in a patient with sinistral portal hypertension. [wjso.biomedcentral.com]

  Generalized vasodilation with systemic venous and arterial hypotension gave away to vasoconstriction with severe venous and arterial hypertension. [ncbi.nlm.nih.gov]

  Generalized vasodilation with systemic venous and arterial hypotension gave way to vasoconstriction with severe venous and arterial hypertension. [jamanetwork.com]

  Case report: A 55 year old Hispanic female with past medical history significant for hepatitis C and hypertension presented with a one-year history of large volume watery diarrhea. [journals.lww.com]

• Heart Failure

  These changes might explain the unexpected and sometimes fatal heart failure that has complicated the removal of these tumors from some patients. [ncbi.nlm.nih.gov]

  These changes might explain the unexpected and sometimes fatal heart failure that has complicated the removal of these tumors from some patients (Arch Intern Med 139:467-471, 1979) Full Text [jamanetwork.com]

  […] disease Tricuspid insufficiency and/or pulmonary stenosis Symptoms of right-sided heart failure Possible pellagra (niacin deficiency) Presents as a triad of dermatitis, diarrhea, and dementia. [amboss.com]

  The left side of the heart is usually not affected because the lungs can break down serotonin. Right sided heart failure symptoms include swelling (edema) in the extremities and enlargement of the heart. [ronnyallan.com]

• Flushing

  In a patient presenting with secretory diarrhea, episodic flushing, wheezing, and cardiac valvular abnormalities, consider a carcinoid tumor! [amboss.com]

  Flushing or redness of the face. Nausea. Weight loss. Diagnosis: VIPomas are usually found incidentally while testing for other conditions, usually during a stool lest for prolonged diarrhea. [medigoo.com]

  […] inhibits the absorption) of sodium, chloride, potassium and water within the small intestine.[14851] Excessive secretion can increase bowel motility and lead to signs and symptoms such as abdominal pain and cramping, severe watery diarrhea, dehydration, flushing [rarediseases.org]

  Symptoms Diarrhoea Watery stools Abdominal pain Back pain Flushing Sweating Failure to thrive Colonic dilatation Diarrhoea Watery stools Abdominal pain Back pain Flushing Sweating Failure to thrive Colonic dilatation Watery diarrhea Hypokalemia Absence [checkorphan.org]

  Differential diagnoses for flushing? The facial flushing associated with NETs should be distinguished from other causes of flushes. [ronnyallan.com]

• Muscle Weakness

  Abstract We report a case of VIPoma in an 83-year-old female patient, who presented with frequent and excessive diarrhoea, muscle weakness, and severe hypokalaemia. [ncbi.nlm.nih.gov]

  Signs and symptoms : Main signs and symptoms include hypokalemia, secretory diarrhea, anorexia (loss of appetite), chronic fatigue, dehydration, diabetes mellitus, erythema, abdominal pain, hepatomegaly (enlargement of liver), generalized muscle weakness [xpertdox.com]

  A 76-year-old male, with a background of type 2 diabetes, presented to hospital with a 3-day history of confusion, muscle weakness, lethargy and profuse diarrhoea. [library.sath.nhs.uk]

  Symptoms associated with dehydration and hypokalemia include lethargy, nausea, vomiting, muscle weakness, and muscle cramps. Abdominal pain is mild or absent. [neurologyadvisor.com]

• Lethargy

  Hypokalemia has been reported in most patients with VIPoma and can be accompanied by lethargy, nausea, and muscular discomfort. [endocrinediseases.org]

  Symptoms Persons with vipoma will experience the following symptoms and signs: Nausea Abdominal cramping and pain Facial redness Diarrhea Losing of weight Dehydration Hypokalemia or low potassium level Achlorhydria or low acid stomach Appetite is reduced Lethargy [cancerwall.com]

  A 76-year-old male, with a background of type 2 diabetes, presented to hospital with a 3-day history of confusion, muscle weakness, lethargy and profuse diarrhoea. [library.sath.nhs.uk]

  Other symptoms that are reported include flushing (which is one of the main features of carcinoid syndrome), weight loss, lethargy, abdominal pain and bloating. [symptoma.com]

  Symptoms associated with dehydration and hypokalemia include lethargy, nausea, vomiting, muscle weakness, and muscle cramps. Abdominal pain is mild or absent. [neurologyadvisor.com]

In order to establish the diagnosis of VIPoma, key steps include detailed patient history, obtaining levels of serum electrolytes and VIP and various imaging techniques to identify the location the tumor.

Patient history may be the key for suspecting VIPoma as a possible etiology for the symptoms. Supporting facts include prolonged diarrhea without an established cause, accompanied by other symptoms that are typical for this tumor. In all patients who suffer from dehydration and severe diarrhea, assessment of serum electrolytes is vital in preventing complications that may be quite severe. Severe dehydration may lead to hypotension, cardiogenic shock and even cardiac arrest, which is why serum potassium, sodium, chloride, bicarbonate and calcium levels should be obtained promptly. Significant hypokalemia and hypochlorhydria may be observed, while hypercalcemia is also a common finding, which presents a significant risk for the cardiac muscle. Additional tests can include evaluation of gastric pH (which will show alkalosis, due to inhibition of gastric acid secretion), while hyperglycemia and anion-gap metabolic acidosis may be reported as well.

Serum VIP levels can confirm the diagnosis of VIPoma. VIP has a very short half-life in the circulation (< 1 min), and its serum levels are usually below 200 pg/ml. Elevated VIP levels together with imaging studies should confirm the diagnosis.

CT and MRI are primary studies of choice for finding the exact location of this tumor, as tumors are up to several centimeters in diameter in a majority of the cases. However, PET scan may be used in patients in whom prior imaging studies have not identified the location of the tumor, while endoscopic ultrasound and scintigraphy using octreotide as contrast have been recommended as well [13]. Imaging studies should also investigate possible metastatic disease, which includes a full body workup with either CT or MRI, with the most common sites being the liver, lungs, lymph nodes proximal to the primary site and kidneys.

• Hypochlorhydria

  VIPoma an endocrine tumor, usually a type of islet cell tumor, that produces excessive amounts of vasoactive intestinal polypeptide, producing severe diarrhea, hypokalemia, and hypochlorhydria, leading to renal failure that can be fatal. [medical-dictionary.thefreedictionary.com]

  Vipoma: A tumor that secretes VASOACTIVE INTESTINAL PEPTIDE, a neuropeptide that causes VASODILATION; relaxation of smooth muscles; watery DIARRHEA; HYPOKALEMIA; and HYPOCHLORHYDRIA. [kmle.com]

  Salivary Glands, Sensorineural Hearing Loss, and Enamel Hypoplasia somatostatinoma vipoma + A tumor that secretes VASOACTIVE INTESTINAL PEPTIDE, a neuropeptide that causes VASODILATION; relaxation of smooth muscles; watery DIARRHEA; HYPOKALEMIA; and HYPOCHLORHYDRIA [rgd.mcw.edu]

  […] search=v vipoma An endocrine tumour, usually arising in the pancreas, that produces vasoactive intestinal polypeptide, which is the mediator of a syndrome of watery diarrhoea, hypokalaemia, and hypochlorhydria, leading to renal failure and death. ... [encyclo.co.uk]

  • A non-beta islet cell tumor of the pancreas that secretes VIP • VIPomas cause the WDHH syndrome (watery diarrhea, hypokalemia, hypochlorhydria) • Chronic profuse watery diarrhea • Massive fecal loss of potassium • Low serum potassium • Extreme weakness [accesssurgery.mhmedical.com]

• Hyponatremia

  Patient’s laboratory workup was significant for electrolyte disturbances including hypokalemia, hyponatremia (K 2.6, Na 127) and Vasoactive Intestinal Peptide (VIP) of 1930 (normal 0-60). [radiopaedia.org]

  They reported the case of a 56-year-old male who died from complications of refractory diarrhea, hypokalemia, and hyponatremia in association with a pancreatic neuroendocrine tumor that had recurred after resection. [oncohemakey.com]

  Initial blood investigations on admission demonstrated severe hypokalaemia - 1.73mmol/L (3.5-5.1mmol/L), hyponatremia – 124mmol/L (135-145mmol/L) and hyperchloremia - 123mmol/L (98-106mmol/L). [jscimedcentral.com]

  Laboratory tests were performed, finding moderate hypokalemia (2.74 mEq/L), moderate hyponatremia (126 mEq/L), no hyperlactatemia (0.81 mmol/L), metabolic acidosis (pH: 7.19, HCO3: 6 mmol/L), normokalemia (10.1 mg/dL), normoglycemia (98.5 mg/dL), and [revistas.unal.edu.co]

Once VIPoma is confirmed and staging completed, initial therapy can be started. This includes management of severe water loss and dehydration. Intravenous administration of fluids supplemented with potassium and bicarbonate is pivotal, thereby preventing further deterioration and potential development of acidosis. Additional therapy includes administration of octreotide, which is an analog of somatostatin. Octreotide exerts its effects by reducing the rate of intestinal motility without further reducing gastric acid secretion. It is usually given intramuscularly as one dose of 20-30 mg per month, while 100–300 μg/day is the standard dosing regimen [14], and shows good results in terms of reducing the burden of diarrhea in patients. Additional drugs that have shown benefit in certain studies include prednisone, loperamide, metoclopramide, and interferon.

Once the fluid loss and electrolyte levels have been stabilized, definite treatment measures may be started. Surgical excision is the only form of treatment that may be curable for the patient and is performed even if metastatic disease is noted. Surgery includes removal of all metastases in addition to the primary tumor. Surgical excision provides significant benefit over chemotherapy, which may be useful only as adjuvant therapy. Streptozocin together with doxorubicin is mentioned as the most favorable combination of chemotherapy. Chemoembolization and embolization of metastatic disease leads to significant improvement in survival rates. [15]. As a last resort, liver transplantation has been also been used in the treatment of liver metastases [16].

This tumor is slow growing in nature and between 50-75% of diagnosed tumors are malignant [10]. This tumor has a very good prognosis if diagnosed in its early stages, with 5-year survival rates exceeding 90% when complete surgical excision is achieved [11]. Unfortunately, only a minority of patients are diagnosed in early stages and between 60-80% of patients have evidence of metastatic disease at the time of diagnosis. As it is a slow growing tumor, even patients with metastasis survive long but the treatment in these patients can present significant challenges.

VIPoma is a tumor that develops in non-β pancreatic islet cells and it was initially described during the 1950s [4], when its connection to refractory diarrhea and hypokalemia was established. However, the exact cause of this tumor remains unknown.

According to reported prevalence rates VIPomas occur in approximately 1 in 10,000,000 individuals every year, suggesting that this neuroendocrine tumor is extremely rare [5]. The vast majority of VIPomas arise in the pancreas, with about 80% occurring in the body and tail, while about 20% originate in the head of the pancreas [6]. Other primary sites that have been reported include the lungs, colon, liver, adrenal glands, and ganglia of the sympathetic system [7], while its association with MEN 1 syndrome has also been reported in rare cases.

This neuroendocrine tumor is seen in both adults and children Extrapancreatic location of the tumor is commonly observed in children, with the adrenal glands and sympathetic ganglia being reported as most frequent sites [8]. Gender predilection has not been established.

Vasoactive intestinal polypeptide (VIP) contains 28 amino acids and is structurally similar to secretin and glucagon. VIP exerts its functions as a neurotransmitter in various parts of the nervous system, including the CNS and nerves of the respiratory, urogenital and enteric systems. Stimulation of enteric smooth muscles, inhibition of gastric acid secretion, regulation of immune system activation, stimulation of exocrine pancreas and modulation of gastrointestinal blood flow are all recognized functions of VIP. Other functions in which VIP may play a role include maintenance of neuronal integrity, glycogen metabolism, prolactin secretion and regulation of catecholamine release [9].

VIP exerts its effect in the intestinal system through stimulation of cyclic adenosine monophosphate (cAMP), and overstimulation of receptors leads to profuse electrolyte and water secretion into the intestinal lumen, ultimately resulting in severe diarrhea and hypokalemia. Inhibition of gastric acid secretion leads to either hypo or achlorhydria, which can have significant effects on bicarbonate concentrations in the circulation, in addition to bicarbonate loss through diarrhea. These factors are combined to form the typical presentation of Watery Diarrhea, Hypokalemia, and Achlorhydria - WDHA syndrome.

Prevention of VIPomas is currently not possible, as the cause of this tumor remains unknown. However, an early diagnosis may be life-saving for many patients, which is why a detailed diagnostic workup should include VIPoma as a possible cause of diarrhea and achlorhydria when all other conditions have been excluded. Regular patient check-ups can reduce the burden of many diseases that are diagnosed in late stages, VIPoma being one of them.

VIPoma is a rare neuroendocrine neoplasia that secretes excessive amounts of vasoactive intestinal polypeptide (VIP) [1]. This hormone acts as a neurotransmitter both in the central and peripheral nervous systems and performs significant functions in the enteric nerves. VIP is classified into a group of hormones and neuropeptides that share similar structures together with secretin, glucagon, growth hormone releasing factor and several others [2]. Its functions in the gastrointestinal tract include smooth muscle stimulation, gastric acid inhibition, and stimulation of exocrine pancreatic secretion. The majority of VIPomas originate as solitary lesions in the pancreas, most commonly in the head and body, but in rare cases, the adrenal glands, liver, colon, and lungs have been reported as its primary site of occurrence. These tumors may be benign, but the majority of tumors are malignant and a significant number of patients have metastatic disease at the time of their diagnosis. Metastases may be identified often in the liver but can also be found in the proximal lymph nodes, kidneys or lungs, as well other organs [3]. The characteristic syndrome of frequent and profuse watery diarrhea, hypokalemia and achlorhydria (known as WDHA syndrome or pancreatic cholera) can be observed in virtually all patients and manifests as severe dehydration, weakness, and lethargy. Flushing may be present as well. The diagnosis may not be established easily, as symptoms tend to be intermittent. VIPoma can be diagnosed through various imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), because tumors are usually several centimeters in size, while positron emission tomography (PET scan) may be necessary to establish smaller tumors. Serum electrolytes, as well as high levels of VIP in the blood, can confirm that the tumor described through imaging studies is VIPoma. In rare cases, VIPoma can be associated with multiple endocrine neoplasia (MEN) type 1 syndrome, in which hyperparathyroidism and presence of pituitary tumors, most commonly prolactinomas, are present. Initial therapy includes adequate rehydration and correction of serum electrolytes, while a surgical excision is the recommended treatment strategy. Administration of octreotide, a somatostatin analog, chemotherapy and additional drugs including corticosteroids and antimotility agents are part of the adjunctive therapy.

VIPoma is a tumor that predominantly originates in the pancreas and is malignant in most cases. This tumor is very rare and is reported to occur in approximately 1 in 10 million individuals. Although it is often diagnosed when metastases have developed, as it is slow growing, patients continue to live relatively long. It can develop both in adults and in children and the cause remains unknown. The name stems from the fact that cells that undergo malignant transformation secrete vasoactive intestinal polypeptide (VIP), which exerts numerous functions in the body. VIP acts as a neurotransmitter in the nervous system of various organs, including the gastrointestinal system, where most of the symptoms occur. VIP stimulates contraction of smooth muscles in the gut and stimulates the movement of fluids and electrolytes into the intestinal lumen, thus leading to often profuse diarrhea and severe dehydration. A specific term is used for the constellation of symptoms that occur in this condition: the WDHA syndrome (Watery Diarrhea, Hypokalemia, and Achlorhydria). Diarrhea is the main symptom in patients with VIPomas and is usually profuse and causes significant fluid and potassium loss. VIP also inhibits production of gastric acid, which results in reduced acidity of the stomach, thus impairing its normal function. Additional symptoms include nausea, vomiting, abdominal pain, bloating, weakness, and lethargy. Symptoms may be intermittent, which provides a significant challenge in establishing the diagnosis. VIPoma can be diagnosed by obtaining serum levels of VIP, while its location may be identified using various imaging procedures, such as computed tomography (CT scan) and magnetic resonance imaging (MRI) because tumors are usually up to several centimeters in length. Smaller tumors can be identified using positron emission tomography (PET scan). Correction of dehydration and improving levels of potassium and chloride through intravenous fluid administration is very important in managing patients once the diagnosis is made, while administration of various drugs have shown some efficacy in reducing the burden of diarrhea. In most cases, octreotide is the drug of choice, while corticosteroids may provide additional benefit. Definite treatment measures depend on the staging of the tumor, but surgical removal is recommended in all patients, even in those with metastases because it is the only therapeutic strategy that has shown curative effects. Chemotherapy has inferior results compared to surgery and can be used as adjuvant therapy. This tumor can present significant challenges in diagnosis and therapy, but early identification is the key to preventing complications and prolonging the life of the patient.

1. Batcher E, Madaj P, Gianoukakis AG. Pancreatic neuroendocrine tumors. Endocr Res. 2011;36(1):35-43.
2. Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino acids. 2013;45(1):10.1007/s00726-011-1184-1188.
3. Ayub A, Zafar M, Abdulkareem A, et al. Primary hepatic vipoma. Am J Gastroenterol. 1993;88(6):958-961.
4. Verner JV, Morrison AB. Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med. 1958;25:374–380.
5. Friesen SR. Update on the diagnosis and treatment of rare neuroendocrine tumors. Surg Clin North Am 1987;67:379.
6. Perry RR, Vinik AI. Clinical review 72: diagnosis and management of functioning islet cell tumors. J Clin Endocrinol Metab 1995;80:2273.
7. Ectors N. Pancreatic endocrine tumors: diagnostic pitfalls. Hepatogastroenterology 1999;46:679.
8. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill;2012.
9. Harmar AJ, Fahrenkrug J, Gozes I, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR Review 1. Br J Pharmacol. 2012;166(1):4-17.
10. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J. 2011;
11. Oberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumors. Ann Oncol. 2001;12(2):S111-S114.
12. Peng SY, Li JT, Liu YB, Fang HQ, Wu YL, Peng CH, et al. Diagnosis and treatment of VIPoma in China: (case report and 31 cases review) diagnosis and treatment of VIPoma. Pancreas. 2004;28(1):93-97.
13. Ghaferi AA, Chojnacki KA, Long WD, et al. Pancreatic VIPomas: subject review and one institutional experience. J Gastointest Surg. 2008;12:382-393. .
14. Nguyen HN, Backes B, Lammert F, et al. Long-term survival after diagnosis of hepatic metastatic VIPoma: report of two cases with disparate courses and review of therapeutic options. Dig Dis Sci. 1999;44:1148-1155.
15. Ho AS, Picus J, Darcy MD, et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol. 2007;188:1201-1207.
16. Johnston PC, Ardill JE, Johnston BT, et al. Vasoactive intestinal polypeptide secreting pancreatic tumour with hepatic metastases: long term survival after orthotopic liver transplantation. Ir J Med Sci. 2010;179:439-441.