VIPoma Syndrome Research Articles

A Rare Cause of Refractory Chronic Diarrhea and Cachexia: A Case Report

VIPoma is an unusual neuroendocrine neoplasm that autonomously secretes VIP. It is associated with secretory diarrhea and electrolyte disturbances. Herein we report a case of a male patient, who was hospitalized in the Department of Endocrinology in Hedi Chaker Hospital, Sfax, Tunisia. He presented VIPoma syndrome, with hepatic metastases at diagnosis. He had a history of chronic, watery diarrhea. He was dehydrated with many electrolytic disorders as hypokalemia, hyponatremia and metabolic acidosis. Abdominal CT scan showed a heterogeneous mass in the pancreatic head with multiple hepatic lesions. A high VIP hormone level was found. Histological study of a liver biopsy revealed hepatic metastases of neuroendocrine carcinoma. The patient received analogues of somatostatin and systemic chemotherapy, with a transient symptomatic relief. Sadly the patient was lost to follow-up.

1337 Persistent Diarrhea in a Patient With a Pancreatic Tail Mass: VIPoma Diagnosed With Endoscopic Ultrasound-Guided Fine-Needle Biopsy

INTRODUCTION: Vasoactive intestinal peptide-secreting tumors (VIPoma) are extremely rare with a worldwide incidence of 1 in 10 million per year. Approximately 56-80% of VIPomas metastasize before a diagnosis can be established. We present a case of a VIPoma localized to the pancreatic tail diagnosed with endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) and treated successfully with octreotide and surgery. CASE DESCRIPTION/METHODS: A 64-year-old male presented with a 10-month history of gradually worsening diarrhea, muscle cramps, and a 30-lbs weight loss. He was tachycardic but hemodynamically stable. His abdomen was mildly distended and tympanic, but the remainder of his exam was unremarkable. Sodium was 125 mmol/L (ref: 135-146 mmol/L), potassium 1.6 mmol/L (ref: 3.5-5.1 mmol/L), bicarbonate 16 mmol/L (ref: 22-32 mmol/L), and chloride 87 mmol/L (ref: 98-107 mmol/L). Computed tomography showed a 4 cm lobulated, heterogeneously enhancing mass abutting the antero-inferior pancreatic tail with calcifications and pancreatic duct measuring 4.5 mm. Patient subsequently underwent EUS-FNB of the mass (Figure 1) with a 25-gauge fork-tip biopsy needle (Medtronic, Minneapolis, MN). Cytology revealed plasmacytoid cells with pleomorphic nuclei, abundant cytoplasm, and frequent naked nuclei indicative of neuroendocrine tumor (NET), grade II (Figure 2). Two consecutive vasoactive intestinal peptide (VIP) levels of 1170 pg/ml and 600 pg/ml (ref <75 pg/ml) along with an octreotide scintigraphy scan showing the presence of a radiotracer avid pancreatic tail mass, confirmed the diagnosis of VIPoma (Figure 3). Patient was started on octreotide and underwent laparoscopic distal pancreatectomy and splenectomy with resolution of symptoms. DISCUSSION: Pancreatic NETs are very rare and constitute only 1-2% of all pancreatic solid-mass tumors. VIPoma is one such NET and is intrapancreatic in 95% of cases. Approximately 56-80% of patients present with metastatic disease before a diagnosis is made. Also known as pancreatic cholera, VIPoma syndrome is characterized by a low osmotic gap secretory diarrhea, hypokalemia, hypochlorhydria, and acidosis. Infections, being more common, can delay diagnosis and treatment. Diagnosis is made by EUS-FNB and octreotide scan, as seen in our case. Treatment includes complete resection in rare cases where metastasis has not occurred. In patients presenting with secretory diarrhea and metabolic derangements in the setting of a pancreatic mass, EUS-FNB can be utilized to diagnose and stage the tumor.

Management of the hormonal syndrome of neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis. Five somatostatin receptors (SSTR1-SSTR5) have been cloned and characterized. Somatostatin analogues include octreotide and lanreotide are effective medical tools in the treatment and present selectivity for SSTR2 and SSTR5. During treatment is seen disapperance of flushing, normalization of bowel movements and reduction of serotonin and 5-hydroxyindole acetic acid (5-HIAA) secretion. Telotristat represents a novel approach by specifically inhibiting serotonin synthesis and as such, is a promising potential new treatment for patients with carcinoid syndrome. To pancreatic functionig neuroendocrine tumors belongs insulinoma, gastrinoma, glucagonoma and VIP-oma. Medical management in patients with insulinoma include diazoxide which suppresses insulin release. Also mTOR inhibitors may inhibit insulin secretion. Treatment of gastrinoma include both proton pump inhibitors (PPIs) and histamine H2 – receptor antagonists. In patients with glucagonomas hyperglycaemia can be controlled using insulin and oral blood glucose lowering drugs. In malignant glucagonomas smatostatin analogues are effective in controlling necrolytic migratory erythemia. Severe cases of the VIP-oma syndrome require supplementation of fluid losses. Octreotide reduce tumoral VIP secretion and control secretory diarrhoea.

Sunitinib achieved fast and sustained control of VIPoma symptoms

VIPomas are rare-functioning neuroendocrine tumors (NETs). Overproduction of vasointestinal peptide (VIP) leads to the Verner-Morrison syndrome, whose management is challenging when refractory to somatostatin analogs. Two patients with progressive metastatic pancreatic NETs and refractory VIPoma symptoms were treated with sunitinib. This led to fast and sustained total relief of VIPoma symptoms, enabling earlier discharge from hospital and improvement in their quality of life. In both cases, sunitinib discontinuation led to the quick recurrence of watery diarrhea, which resolved within a few days after reintroducing sunitinib. The anti-secretory effect of sunitinib on VIPoma syndrome was probably not related to any anti-tumor effect. These observations agree with the rare reported cases of anti-secretory effects with targeted therapies. The sunitinib-driven inhibition of multiple-tyrosine kinase receptors might act on secretory pathways and describe sunitinib's ability to improve VIPoma symptoms. Sunitinib could be a therapeutic option to control refractory VIPoma symptoms in patients with NETs.

Significant Symptom Relief with Hepatic Artery Embolization in a VIPoma with Liver Metastases

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) cause VIPoma syndrome, which is characterized by watery diarrhea, hypokalemia, and achlorhydria. The treatment options for metastatic VIPomas include somatostatin analogs, cytoreductive surgery, and chemotherapy. We report the case of a 54-year-old male who presented with a peripancreatic mass with multiple hepatic metastases on computed tomography. After resection, the peripancreatic mass was demonstrated pathologically to be a neuroendocrine tumor. Although the patient received systemic chemotherapy and somatostatin analogs for the hepatic metastatic masses, the tumor increased in size. The patient then experienced severe diarrhea, despite treatment with the somatostatin analogs. Elevated serum VIP levels (3,260 pg/mL) and typical symptoms confirmed the diagnosis of VIPoma. We performed hepatic artery embolization (HAE) to reduce the tumor volume and control his symptoms, which led to a very rapid symptomatic response. The patient has remained symptom-free for 18 months with repeated HAE. (Korean J Med 2014;87:363-368)

Lung Adenocarcinoma Presenting with WDHA Syndrome and Marie-Bamberger Syndrome: A Case Report

Watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome), also known as Vermer-Morrison syndrome or vipoma syndrome, was first reported by Verner and Morrison in 1958. It is characterized by watery diarrhea, hypokalemia and achlorhydria (or metabolic acidosis), most commonly associated with pancreatic islet cell tumors in adults.

The Place of Somatostatin Analogs in the Diagnosis and Treatment of the Neuoroendocrine Glands Tumors

Somatostatin (SS) was originally discovered as a hypothalamic neurohormone which inhibits growth hormone secretion. The synthesis of the first two metabolically stabilized and more potent SS analogs, octreotide and lanreotide leads to the establishment of applications for them and to introduction into routine therapies. The effectiveness of octreotide or lanreotide in controlling symptoms and GH/IGF-I hypersecretion in acromegalic patients, both preoperatively and postoperatively is well proven. Similarly, these drugs are also very effective in the treatment of TSH-secreting adenomas. The introduction of these drugs into therapy of the functional neuroendocrine tumors of the gastrointestinal tract was a crucial step in the treatment. Octreotide and lanreotide are the drugs of choice in the treatment of patients with: VIPoma, glucagonoma and carcinoid syndrome. Somatostatin receptor scintigraphy with OctreoScan has been recommended as the best imaging technique in these tumors in the localization and staging procedure. SS analogs, coupled to radioisotope or cytotoxic drugs, create another class of SS molecules, very promising in the therapy of the endocrine glands tumors and in other tumors. Another class of SS analogs comprises hybrid molecules, which are chimera of sst2 agonist and D2 agonist, possessing more potent activity than these agonists, applied together.

Diagnosis and treatment of VIPoma in a female patient

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. Abdominal computed tomography (CT) revealed a 4x6 cm mass in the body of the pancreas. Laboratory analysis showed elevated levels of both vasoactive intestinal polypeptide (VIP; 153 pmol/l) and pancreatic polypeptide (161 pmol/l). In view of the patient's age, physical condition, and tumour size, surgical resection was not performed. The patient was treated with a long-acting octreotide, after which her symptoms diminished. After 24 months of follow-up, the patient remained in good physical condition without any further serious gastrointestinal symptoms. The VIPoma syndrome is caused by a neuroendocrine tumour, usually located in the pancreas, which secretes VIP, causing severe diarrhoea, dehydration and hypokalaemia. Treatment options include resection of the tumour, chemotherapy or the reduction of symptoms with somatostatin analogues. We provide an overview of the incidence, pathophysiology, diagnosis, treatment strategies, and prognosis of this rare syndrome.

Metastatic jejunal VIPoma: beneficial effect of combination therapy with interferon-α and 5-fluorouracil

The VIPoma syndrome is rare. It is usually caused by a neuroendocrine tumor located in the pancreas. Somatostatin analogs and interferon-α can be helpful in the symptomatic control of the disease, but the efficacy of chemotherapy in metastatic disease is limited. We report the case of a 32-yr-old patient who had a primary intestinal VIPoma with peritoneal carcinomatosis and hepatic metastases. Somatostatin analogs and conventional chemotherapy regimens were not effective on VIPoma syndrome and tumor progression. The combination of 5- fluorouracil and interferon-α was associated with a major clinical improvement and tumor regression. Further investigations should evaluate the place of such a combination as a first line treatment for patients with metastatic neuroendocrine tumors.

Calcitonin, as SMS 201–995, ameliorates the VIPoma syndrome

A 72-year-old woman was referred to our hospital for diarrhea, abdominal and back pain, weight loss, low serum potassium level. Pathological findings and high circulating Vasoactive Intestinal Peptide (VIP) levels allowed us to diagnose "VIPoma syndrome". The patient underwent a treatment with SMS 201-995 with improvement of symptomatology and reduction of circulating VIP levels. After a wash-out period the patient was treated with salmon calcitonin with a net improvement of diarrhea, normalization of potassium serum level and reduction of VIP level. The symptomatology recurred after calcitonin withdrawal. These data confirm the effectiveness of SMS 201-995 in the VIPoma syndrome and suggest that calcitonin may ameliorate symptomatology and reduce circulating VIP level in patients with VIPoma tumor.

Vipoma Syndrome Simultaneously Occurring With Small-Cell Carcinoma of the Lung

To the Editor .—The watery diarrhea syndrome, best called vipoma syndrome, as it is mediated by a raised plasma vasoactive intestinal polypeptide (VIP) concentration, is known to be associated with pancreatic and neural crest, but not lung, tumors. 1 We describe a patient who presented with metastatic small-cell carcinoma of the lung (SCCL) and vipoma syndrome. Report of a Case .—A 62-year-old woman was admitted for diarrhea, loss of weight, and back pain for several weeks. She had been a heavy smoker and drinker for many years. At the time of admission, she took no medication. Physical examination disclosed signs of dehydration and major liver enlargement. She had a watery diarrhea, exceeding 1.5 L daily. Results of laboratory tests showed the following results: urea nitrogen, 17.3 mmol/L; creatinine, 62 μmol/L; potassium, 2.5 mmol/L; arterial pH, 7.29; bicarbonate, 17 mmol/L; chloride, 112 mmol/L; calcium, 3.19 mmol/L;

Vipoma syndrome simultaneously occurring with small-cell carcinoma of the lung

Vipoma syndrome simultaneously occurring with small-cell carcinoma of the lung

Vipoma syndrome

Since the description of the watery diarrhea syndrome by Verner and Morrison 29 years ago, clinical and experimental observations have elucidated the pathophysiology of this disease. Vasoactive intestinal polypeptide (VIP) is produced and released by a tumor of the pancreatic islets or by a tumor of neural crest origin such as a ganglioneuroma. Under normal conditions, current evidence suggests that VIP is a neurotransmitter in the central and peripheral nervous systems and particularly in the peptidergic nervous system. The low VIP plasma concentration observed in healthy subjects is viewed as a neuronal overflow since it has been impossible to ascertain any endocrine role for circulating VIP. Markedly elevated VIP plasma levels in the VIPoma syndrome lead to intestinal secretion with severe secretory diarrhea, resulting in hypovolemia, hypokalemia, and acidosis. These symptoms subside after successful tumor removal. Approximately 50 percent of patients have metastatic spread at the time of diagnosis. For these patients, a new and promising therapeutic modality is available in the form of a subcutaneously administered somatostatin analogue that relieves symptoms through potent inhibition of VIP release from tumor tissue.

Vipoma syndrome: Effect of a somatostatin analogue on intestinal water and ion transport

Vipoma syndrome: Effect of a somatostatin analogue on intestinal water and ion transport

Case of the fall season

Since the description of the watery diarrhea syndrome by Verner and Morrison 29 years ago, clinical and experimental observations have elucidated the pathophysiology of this disease. Vasoactive intestinal polypeptide (VIP) is produced and released by a tumor of the pancreatic islets or by a tumor of neural crest origin such as a ganglioneuroma. Under normal conditions, current evidence suggests that VIP is a neurotransmitter in the central and peripheral nervous systems and particularly in the peptidergic nervous system. The low VIP plasma concentration observed in healthy subjects is viewed as a neuronal overflow since it has been impossible to ascertain any endocrine role for circulating VIP. Markedly elevated VIP plasma levels in the VIPoma syndrome lead to intestinal secretion with severe secretory diarrhea, resulting in hypovolemia, hypokalemia, and acidosis. These symptoms subside after successful tumor removal. Approximately 50 percent of patients have metastatic spread at the time of diagnosis. For these patients, a new and promising therapeutic modality is available in the form of a subcutaneously administered somatostatin analogue that relieves symptoms through potent inhibition of VIP release from tumor tissue.