vasoactive-intestinal-peptide and 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.

Topics: Adenoma, Islet Cell; Animals; Diagnosis, Differential; Humans; Pancreatic Neoplasms; Radioimmunoassay; Syndrome; Vasoactive Intestinal Peptide; Vipoma

A case of malignant pheochromocytoma, with a recurrence 15 years after adrenalectomy and with an associated watery diarrhea, hypokalemia, achlorhydria syndrome, is reported. Histological evaluation of the tumors revealed composite malignant pheochromocytoma-ganglioneuroblastoma (well differentiated type). Vasoactive intestinal polypeptide and catecholamine levels were high both in the plasma and in the tumors. Somatostatin was also rich in the metastatic tumor of the liver, but not in the plasma. Immunohistochemical studies have demonstrated that immunoreactive vasoactive intestinal polypeptide is present in the ganglioneuroblastoma component, and that immunoreactive somatostatin is present in the pheochromocytoma component. Literature on the watery diarrhea, hypokalemia, achlorhydria syndrome associated with pheochromocytoma was reviewed.

Topics: Achlorhydria; Adrenal Gland Neoplasms; Adult; Diarrhea; Ganglioneuroma; Humans; Hypokalemia; Male; Neoplasm Recurrence, Local; Pheochromocytoma; Syndrome; Vasoactive Intestinal Peptide

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Animals; Bicarbonates; Brain; Dehydration; Digestive System; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Nerve Fibers; Neurotransmitter Agents; Pancreas; Pancreatic Neoplasms; Swine; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Adenoma, Islet Cell; Adult; Aged; Diagnosis, Differential; Diarrhea; Female; Gastric Juice; Humans; Hypokalemia; Male; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Diarrhea; Gastrointestinal Hormones; Glucagon; Humans; Intestinal Diseases; Intestinal Neoplasms; Skin; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adolescent; Adult; Aged; Carcinoid Tumor; Child; Dehydration; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Humans; Hyperplasia; Hypokalemia; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Precancerous Conditions; Serotonin; Somatostatin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Cholecystokinin; Dogs; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Pancreatic Diseases; Radioimmunoassay; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Diarrhea; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neurosecretory Systems; Pancreatic Hormones; Paraneoplastic Endocrine Syndromes; Prostaglandins; Serotonin; Syndrome; Vasoactive Intestinal Peptide; Werner Syndrome; Zollinger-Ellison Syndrome

Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP).. A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on. A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.

Topics: Acidosis; Adrenal Gland Neoplasms; Adrenalectomy; Aged; Chromaffin Cells; Diarrhea; Humans; Hypokalemia; Male; Peptides, Cyclic; Peripheral Nervous System Neoplasms; Pheochromocytoma; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin; Syndrome; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Weight Loss

Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion-related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described.. To describe MHSs in patients with sporadic PNETs.. Retrospective, multicenter study.. 4 French referral centers.. Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014.. Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling.. Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs.. Retrospective data collection and heterogeneity of pathologic specimen size and origin.. Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates.. None.

Topics: Adult; Aged; Biomarkers, Tumor; Disease Progression; Female; Gastrins; Glucagon; Hormones; Humans; Insulin; Insulin Secretion; Ki-67 Antigen; Male; Middle Aged; Pancreatic Neoplasms; Retrospective Studies; Syndrome; Vasoactive Intestinal Peptide

We report a case of VIPoma in a 72-year-old female patient who presented with excessive diarrhea, severe hypokalemia, and acidemia. She had been referred to our hospital three times because of severe diarrhea. No primary tumor site was found by conventional techniques, including contrast-enhanced CT and MRI, angiography, endoscopy, and positron emission tomography (PET), but a tumor was subsequently found in the head of the pancreas by octreotide scanning. Her diarrhea diminished dramatically after octreotide treatment, while her diarrhea has ceased without the therapy of octreotide at the first admission in the course of 2 years of her disease. Immunohistochemial analysis of the excised tumor tissue revealed the expression of both vasoactive intestinal peptide (VIP) and VIP and pituitary adenylate cyclase-activating peptide 1 (VPAC1) receptors. This is the first case report of a VIPoma that immunostains for VIP and VPAC1 receptors and indicates that abundant VIP produced by VIPoma might inhibit its growth and reduce VIP secretion via the VPAC1 receptor in vivo.

Topics: Achlorhydria; Aged; Diarrhea; Female; Gene Expression; Humans; Hypokalemia; Immunohistochemistry; Indium Radioisotopes; Isotope Labeling; Magnetic Resonance Imaging; Octreotide; Pancreatic Neoplasms; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; Syndrome; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

Mild hypokalemia is common and encountered in a multitude of diseases, but severe hypokalemia leading to rhabdomyolysis is relatively rare. The watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP)-producing tumors, is an extremely rare cause of hypokalemic rhabdomyolysis and the literature is limited to one case report. We report a second case of an adult who presented with rhabdomyolysis due to severe hypokalemia. Further evaluation revealed that he had a VIP-producing pancreatic neuroendocrine tumor (NET), which was the cause of his hypokalemic rhabdomyolysis. Although rare in occurrence, a high index of suspicion is of paramount importance for establishing the correct diagnosis and treatment.

Topics: Achlorhydria; Adult; Diarrhea; Humans; Hypokalemia; Male; Pancreatic Neoplasms; Rhabdomyolysis; Syndrome; Vasoactive Intestinal Peptide; Vipoma

Topics: Adult; Female; Heart Atria; Heart Neoplasms; Humans; Migraine with Aura; Myxoma; Syndrome; Vasoactive Intestinal Peptide

A 47-year-old woman with neurofibromatosis type 1 suffered from general muscle weakness and watery diarrhea. Laboratory findings showed elevated muscular enzymes, severe hypokalemia and excessive production of catecholamines and vasoactive intestinal polypeptide (VIP). A computed tomography scan showed a 10 cm left adrenal mass, in which [(131)I]-metaiodobenzylguanidine scintigraphy showed high uptake. After she underwent surgical removal of the tumor, all the symptoms and signs subsided. A histological study revealed that the mass consisted of pheochromocytoma and ganglioneuroma, respectively producing catecholamines and VIP. In immunohistochemical staining of neurofibromin, pheochromocytoma and ganglion cells showed positive staining, whereas the staining was negative for nerve bundles and Schwann cells. We concluded that the patient had hypokalemic rhabdomyolysis due to watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome, which was induced by a VIP-producing composite pheochromocytoma. Composite pheochromocytoma is a neuroendocrine tumor that is composed of pheochromocytoma and ganglioneuroma, both derived from the neural crest. Deficiency of neurofibromin in Schwann cells might have played an important role in the development and the growth of the composite pheochromocytoma in this patient.

Topics: 3-Iodobenzylguanidine; Achlorhydria; Adrenal Gland Neoplasms; Diarrhea; Female; Humans; Hypokalemia; Middle Aged; Neurofibromatosis 1; Pheochromocytoma; Radionuclide Imaging; Radiopharmaceuticals; Rhabdomyolysis; Syndrome; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide

To explore the nature of pathology of sluggishness of lung-defensive qi and to offer objective experimental indexes for weifen syndrome (defensive phase syndrome).. According to the completely random design, the plasma levels of vasoactive intestinal peptide (VIP) and thromboxane B2 (TX2) of 19 patients with weifen syndrome and 13 patients with qifen syndrome (qi phase syndrome) were detected by radioimmunoassay. The plasma levels of VIP and TX2 at different stages of weifen syndrome and qifen syndrome were observed.. The plasma levels of VIP in weifen syndrome and in the late stage of weifen syndrome increased greatly at different stages as compared to qifen syndrome and the blank group (P < 0.01), while the plasma level of TX2 of weifen syndrome was higher only at the late stage than the blank group and qifen syndrome (P < 0.01). As for the levels of VIP and TX2 in weifen syndrome with different internal organs infected, there was no significant difference (P > 0.05).. VIP may be an index reflecting the pathology of weifen syndrome, and it is one of the material foundations of sluggishness of lung-defensive qi, but it has nothing to do with the infected internal organs. The level of TX2 increases only after the fever of patients with weifen syndrome subsided, so it can not be the basis for diagnosis of the early stage of weifen syndrome. It doesn't increase in qifen syndrome either, the mechanism remains to be further studied.

Topics: Female; Humans; Lung Diseases; Male; Radioimmunoassay; Syndrome; Thromboxane B2; Vasoactive Intestinal Peptide

Microwave radiation from mobile phones enhanced skin wheal responses induced by house dust mite and Japanese cedar pollen while it had no effect on wheal responses induced by histamine in patients with atopic eczema/dermatitis syndrome (AEDS). Microwave radiation also increased plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP) in patients with AEDS. These results indicate that microwave radiation from mobile phones may enhance allergen-induced wheal responses in association with the release of SP and VIP. This finding may be useful in elucidating the pathophysiology and treatment of AEDS.

Topics: Adult; Allergens; Cell Phone; Dermatitis, Atopic; Female; Humans; Male; Microwaves; Middle Aged; Skin Tests; Substance P; Syndrome; Vasoactive Intestinal Peptide

A patient with neurofibromatosis type 1 and watery diarrhoea syndrome due to a VIP-producing adrenal phaeochromocytoma (Case Report). J Intern Med 1999; 246: 231-234. A 43-year-old patient with neurofibromatosis type 1 suffered from watery diarrhoea syndrome induced by excessive production of vasoactive intestinal polypeptide (VIP) in an adrenal phaeochromocytoma. This case report emphasizes that patients with neurofibromatosis are prone to develop more than one disease induced by tumours originating from the neural crest. Since excessive VIP production in a phaeochromocytoma may mask the symptoms of catecholamine overproduction, and in view of the therapeutic consequences, neurofibromatosis patients with hyperVIP-aemia must be checked for the presence of a phaeochromocytoma.

Topics: Adrenal Gland Neoplasms; Adult; Diarrhea; Female; Humans; Neurofibromatosis 1; Pheochromocytoma; Syndrome; Vasoactive Intestinal Peptide

Authors report a case of Verner-Morrison syndrome which occurred in a 75-year-old man. The syndrome was caused by a pancreas VIP-oma with the histological structure of adenocarcinoma. Treatment with somatostatin analogous (octreotid) was effective, but the outcome was lethal due to subsequent pulmonary embolism.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Fatal Outcome; Humans; Male; Octreotide; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide; Vipoma

A typical case of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is reported. The patient, an infant girl, was fed only by total intravenous nutrition and is now 3 years old. The distribution of several gut peptides was examined in the resected small intestine using an immunohistochemical method. Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM)-containing nerve fibers were decreased; however, substance P- and leucine enkephalin (Leu-ENK)-containing fibers were increased. The imbalance between several kinds of gut peptides might be one the causes of aperistalsis in MMIHS. This is the first report about the gut peptides of MMIHS.

Topics: Autonomic Nervous System; Colon; Colonic Pseudo-Obstruction; Cystitis; Female; Follow-Up Studies; Humans; Hypertrophy; Infant, Newborn; Intestinal Pseudo-Obstruction; Intestine, Small; Peristalsis; Syndrome; Vasoactive Intestinal Peptide

After closed cranial trauma with paralysis of the facial nerve, a patient had a fracture into the petrosus apex with a bony bridge over the nerve, and a subdural haematoma, which were dealt with during an operation for nerve decompression. Examination of the patient 2.5 years later revealed the presence of the crocodile tears syndrome, mucus secretion and the salivary atropine paradox, i.e. severe hyperaemia of the paretic half of the face during intense salivation in response to atropine. Other patients who suffered similar trauma but had no operation demonstrated the same syndrome. The crocodile tears syndrome is considered to be a result of an ephaptic union of the central portion of the damaged lesser superficial petrosal nerve (SPN) with the peripheral portion of the greater SPN. The salivary atropine paradox is then due to the loss of the peripheral portion of the former nerve combined with denervation of the salivary parotid gland. Facial hyperaemia during intense salivation after atropine administration is explained as a result of the intensified release of vasoactive intestinal polypeptide from the gland, stimulated by atropine, into the blood circulation.

Topics: Adult; Atropine; Facial Nerve Injuries; Glossopharyngeal Nerve Injuries; Humans; Lacrimal Apparatus; Parasympathetic Nervous System; Parotid Gland; Salivation; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Adenoma, Islet Cell; Diarrhea; Female; Hormones, Ectopic; Humans; Hypokalemia; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

The watery diarrhea-hypokalemia-achlorhydria syndrome associated with ectopic secretion of vasoactive intestinal peptide has only been conclusively documented with tumors originating in the pancreas or sympathetic chain. We report here the case of a 50-yr-old woman who developed this syndrome 3 wk after an apparently effective course of radiotherapy for an obstructing, mixed-cell carcinoma of the esophagus. High concentrations of vasoactive intestinal peptide were found in plasma (100-200 pmol/L; normal less than 20 pmol/L) and in the metastatic skin nodules (750 pmol/g) that later developed and that contained one of the two cell types from the original tumor. Stool volumes reached a plateau of 15-20 L/day, and potassium requirements were greater than 1000 mmol/day. Symptoms failed to respond to any of the regimens previously described as effective in this syndrome. After 14 wk of massive fecal fluid and electrolyte losses, symptoms resolved dramatically with the first dose of 5-fluorouracil. Plasma vasoactive intestinal peptide concentration returned to normal, where it remained despite subsequent evidence of renewed tumor spread. This case illustrates the unpredictability of the response of this syndrome to medical treatment, and suggests that vasoactive intestinal peptide secretion may occur in a wider range of tumors than has so far been described.

Topics: Achlorhydria; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromatography, High Pressure Liquid; Diarrhea; Esophageal Neoplasms; Female; Fluorouracil; Humans; Hypokalemia; Middle Aged; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Diarrhea; Humans; Hypokalemia; Male; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Aged; Diabetes Mellitus, Type 1; Humans; Hypokalemia; Liver Neoplasms; Male; Pancreatic Neoplasms; Streptozocin; Syndrome; Vasoactive Intestinal Peptide; Vipoma

This report presents an adrenal ganglioneuroblastoma containing several kinds of neuronal peptides. The tumour was found in the autopsy case of a 3-year-old girl with clinical manifestation of intractable diarrhea, hypokalemia, achlorhydria, and with elevated levels of plasma vasoactive intestinal peptide (VIP). Immunoperoxidase staining showed many immunoreactive VIP- containing cells, some somatostatin-and substance P-containing cells on the tumour sections. Ultrastructurally, the tumour cells contained numerous secretory granules that could be divided mainly two types; one is a small cored vesicle (50-150 nm in diameter) and the other large electron dense secretory granule (200-500 nm in diameter). It was suggested that the cells in ganglioneuroblastoma derived from neural crest are closely related to the cells that could differentiate into gut-hormone-producing cells.

Topics: Adrenal Gland Neoplasms; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Histocytochemistry; Humans; Immunoenzyme Techniques; Microscopy, Electron; Peptides; Syndrome; Vasoactive Intestinal Peptide; Vipoma

Topics: Achlorhydria; Adenoma, Islet Cell; Diarrhea; Female; Gastrointestinal Hormones; Humans; Hypokalemia; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

An 8-mo-old male child presented with generalized flushing and apnea which followed irritation of a 1.5 x 0.5 cm cutaneous mastocytoma on the left upper arm. Peripheral venous blood samples were drawn before and after manipulation of the tumor, immediately after excision, and again 30 days later. The plasma vasoactive intestinal polypeptide level before excision was high (345 pg/ml) and was accompanied by low acid secretion (15.4 mEq/L) and hypergastrinemia (209 pg/ml), all of which returned to normal after excision of the tumor (50 pg/ml, 35.7 mEq/L, and 131 pg/ml, respectively). Serum histamine levels were undetectable. Histology of the tumor showed only mast cells and no enterochromaffin tissue. The immunoreactive vasoactive intestinal polypeptide content of the tumor was 28 ng/g wet wt and the extracted vasoactive intestinal polypeptide was immunologically indistinguishable from natural porcine vasoactive intestinal polypeptide. The child has remained asymptomatic postoperatively. We conclude that the symptoms associated with this mastocytoma may have been produced by oversecretion of vasoactive intestinal polypeptide and not histamine.

Topics: Apnea; Gastrointestinal Hormones; Histamine Release; Humans; Hyperemia; Infant; Male; Mast-Cell Sarcoma; Skin Neoplasms; Syndrome; Vasoactive Intestinal Peptide

A 23-month-old girl with intractable diarrhea that had persisted for the past 6 months showed typical evidence of water-diarrhea-hypokalemia-achlorhydria (WDHA) syndrome. Serum vasoactive intestinal peptide (VIP)-like immunoactivity was very high, and urine homovanillic acid and noradrenaline were also abnormally increased. A calcified tumor in the right paravertebral region was noted radiologically. Soon after resection of the tumor, the diarrhea dramatically improved. A ganglioneuroblastoma was histologically confirmed. Serum VIP decreased to normal level at 1 h after the removal of the tumor. VIP activity in the tumor was extraordinarily high, and the cells were stained by the indirect immunofluorescence technique with anti-VIP serum. This is to report the rapid turnover of serum level of VIP after resection of ganglioneuroblastoma with WDHA syndrome in a child.

Topics: Achlorhydria; Child; Child, Preschool; Diarrhea, Infantile; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Hypokalemia; Infant; Male; Retroperitoneal Neoplasms; Syndrome; Time Factors; Vasoactive Intestinal Peptide

Some physiological digestive processes thought to be under the control of VIP-ergic neurones are presented. The etiological role of the Vasoactive Intestinal Polypeptide in the Verner Morrison syndrome is discussed.

Topics: Adenoma, Islet Cell; Colon; Dilatation, Pathologic; Gastrointestinal Hormones; Humans; Intestinal Mucosa; Intestine, Small; Pancreatic Juice; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide; Vasodilation

Topics: Adenoma, Islet Cell; Angiography; Diagnosis, Differential; Diarrhea; Female; Gastrointestinal Hormones; Humans; Middle Aged; Pancreatic Neoplasms; Syndrome; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Water-Electrolyte Imbalance

An APUD adenoma of the right adrenal was discovered in an adult after angiography and compted tomography The tumor had provoked a WDHH syndrome. Selective venous sampling before operation demostrated the presence in the tumor of hormonal secretions (VIP and catecholamines). The patient recovered after excision of the tumor, which contained large quantities of intracellular somatostatin and VIP.

Topics: Achlorhydria; Adrenal Gland Neoplasms; Angiography; Apudoma; Catecholamines; Diarrhea; Gastrointestinal Hormones; Hypokalemia; Somatostatin; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Administration, Oral; Diarrhea; Female; Humans; Hypokalemia; Lithium; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Topics: Acidosis; Adenoma, Islet Cell; Diarrhea; Female; Gastrointestinal Hormones; Humans; Hypokalemia; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Aged; Diarrhea; Female; Humans; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Three patients with the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome were studied. All had watery diarrhea, hypokalemia and hypercalcemia. Plasma vasoactive intestinal polypeptide (VIP) levels determined by radioimmunoassay were markedly elevated in these patients, indicating that they had VIP-producing tumors. Plasma VIP levels determined serially after the operation indicate that its determination is useful in estimating the effect of a treatment. As for multiple endocrine neoplasia type 1 (MEN1), two out of the three cases belonged to this category. Patient 1 had a brother with insulinoma, and in case 2, even though there was no family history, the autopsy revealed not only multiple tumors of the pancreas but also pituitary adenomas, chief cell hyperplasia of the parathyroid glands, thyroid adenomas and adrenocortical adenomas. VIP and other hormones in the tumors as well as in the plasma were examined extensively in these cases. In case 1, VIP, gastrin and calcitonin were produced in the tumor and only plasma VIP levels were elevated. In case 2, with multiple tumors, tumor 1 produced VIP, glucagon pancreatic polypeptide, gastrin and calcitonin, and tumor 2, VIP, pancreatic polypeptide, gastrin and beta-melanocyte stimulating hormone. In this case, plasma VIP, pancreatic polypeptide and glucagon levels were elevated. In case 3, VIP and calcitonin were produced in the tumor, and plasma VIP and calcitonin levels were elevated. These results indicate that (1) VIP is a good tumor marker for the WDHA syndrome due to VIP-producing tumors; (2) patients with the WDHA syndrome are sometimes associated with MEN1; and (3) VIP-producing tumors are multiple hormone-producing tumors, and VIP predominantly elevated in the plasma results in the WDHA syndrome, although other hormones such as pancreatic polypeptide, glucagon and calcitonin are sometimes found to be elevated in plasma without contributing to the clinical features.

Topics: Achlorhydria; Adult; Calcitonin; Diarrhea; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypokalemia; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Parathyroid Hormone; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Cholecystokinin; Diarrhea; Endocrine System Diseases; Humans; Hypokalemia; Malignant Carcinoid Syndrome; Neoplasms; Pancreatic Diseases; Paraganglioma; Paraneoplastic Endocrine Syndromes; Peptides; Prostaglandins E; Somatostatin; Syndrome; Thyroid Neoplasms; Vasoactive Intestinal Peptide

The authors present a brief report on a familial case of Wermer's syndrome, and review the principal characteristics of this "multiple endocrine neoplasm" which usually affects the parathyroids, pancreas, and anterior pituitary.

Topics: Adult; Female; Gastrins; Glucagon; Humans; Insulin; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Two gastrointestinal peptides, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide, suspected of being associated with symptoms of WDHA syndrome (pancreatic cholera) were tested on the rat small and large intestine for their effects on water and electrolyte transport. Intravenous infusion of VIP (14.3 microgram/kg/hr) inhibited net absorption of water and electrolytes in the ileum and reversed net absorption to net secretion in the colon. In contrast, bovine pancreatic polypeptide (52 microgram/kg/hr) did not inhibit absorption or stimulate secretion. These data indicate VIP causes colonic secretion in vivo, an effect previously shown only in vitro, and that bovine pancreatic polypeptide (at this dose) is not a secretagogue in the small or large intestine of the rat. Thus, while consistent with VIP being a contributory agent to the secretion of pancreatic cholera, the data do not support the notion that pancreatic polypeptide might be a causative agent in this syndrome.

Topics: Adenoma, Islet Cell; Animals; Biological Transport; Colon; Diarrhea; Gastrointestinal Hormones; Ileum; Intestinal Absorption; Male; Pancreatic Polypeptide; Rats; Syndrome; Vasoactive Intestinal Peptide; Water-Electrolyte Balance

An early diagnosis of the Verner-Morrison syndrome will greatly enhance the chances of curative resection. There is a striking need for a simple diagnostic test. A number of suggestions have been made for the presumed hormone mediator of this syndrome. Numerous reports have led to a wide acceptance that vasoactive intestinal peptide (VIP) is the responsible mediator for the pharmacologic actions of this peptide are similar to the physiological characteristics noted in the watery diarrhea syndrome. A raised plasma VIP concentration, on the other hand, would suggest the presence of a tumour. These observations argue for the radioimmunoassay measurement of plasma VIP in a patient with the watery diarrhea syndrome.

Topics: Adenoma, Islet Cell; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Pancreatic Neoplasms; Radioimmunoassay; Syndrome; Vasoactive Intestinal Peptide

The clinical features of the Verner-Morrison syndrome are surveyed. This rare clinical entity still needs to be more clearly defined. Especially in relation to the role of VIP and the clinical value of VIP measurements. A case with a good correlation between the activity of the disease and circulating VIP is presented.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrointestinal Hormones; Humans; Pancreatic Neoplasms; Radioimmunoassay; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Syndrome; Ultrasonics; Vasoactive Intestinal Peptide

A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Evidence that VIP is the principal humoral mediator of the watery diarrhea syndrome includes: (a) actions of VIP in experimental anaimals parallel the clinical manifestations of the syndrome; (b) infusions of VIP induce watery diarrhea in intestinal loops of dogs and a picture resembling the clinical syndrome in pigs, at circulating levels of the peptide similar to those observed in human disease; (c) most patients with the watery diarrhea syndrome and underlying tumors have elevated plasma levels of VIP; (d) in those patients in whom pre- and postoperative measurements were made, plasma VIP levels fell to the normal range with removal of the tumor and relief of the diarrhea; and (e) extracts of such tumors are rich in VIP-immunoreactivity and VIP-like biologic activity. A few patients with the syndrome have been reported to have normal plasma VIP levels, and it is possible that other humoral agents (such as pancreatic polypeptide, prostaglandins) may contribute to the production of the diarrhea.

Topics: Adenocarcinoma; Adenoma; Adenoma, Islet Cell; Animals; Diarrhea; Dogs; Gastrointestinal Hormones; Humans; Neoplasms; Pancreatic Neoplasms; Swine; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adrenal Medulla; Aged; Diarrhea; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

A patient with a vipoma of the pancreas and persistently elevated blood levels of vasoactive intestinal polypeptide (VIP) had watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). In the untreated state, the diarrhea was never profuse. Fecal volumes ranged from 0.16 to 1.24 L/day. Attempts to correct the dehydration by fluid and electrolyte loading resulted in a massive increase in fecal water and electrolyte loss. Prednisone cured the diarrhea and was associated with a decrease in plasma VIP levels. The patient had a marked circulatory disturbance with systemic arterial hypotension and cutaneous vasodilation that caused a subnormal body temperature. Removal of the tumor led to a dramatic change in the patient's circulation. Generalized vasodilation with systemic venous and arterial hypotension gave away to vasoconstriction with severe venous and arterial hypertension. Central venous pressure rose from -4.4 to +4.0 cm H2O and arterial pressure rose from 80/55 to 195/110 mm Hg. These changes might explain the unexpected and sometimes fatal heart failure that has complicated the removal of these tumors from some patients.

Topics: Achlorhydria; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Hypotension; Male; Middle Aged; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Topics: Animals; Diarrhea; Gastrointestinal Hormones; Humans; Neoplasms; Swine; Syndrome; Vasoactive Intestinal Peptide

A sensitive and specific radioimmunoassay for the detection of vasoactive intestinal peptide has been used to study patients with the watery diarrhea syndrome. In eleven patients the syndrome was associated with tumors, and plasma levels of vasoactive intestinal peptide were elevated. VIP levels returned towards normal in five treated patients coincident with amelioration of symptoms. Normal values were obtained in patinets with chronic pancreatitis, sprue, medullary carcinoma, Zollinger-Ellison Syndrome and laxative abuse. In six other patients with indistinguishable syndrome and no findings of tumor at laparotomy and autopsy, vasoactive intestinal peptide levels were normal. The results suggest that VIP may be the causative agent in patients with the watery diarrhea syndrome and tumors, but that an indistinguishable syndrome exists for which VIP is not the cause.

Topics: Diarrhea; Female; Gastrointestinal Hormones; Humans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Streptozocin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

A case with the clinical appearance of WDHA syndrome is described in which serum concentrations of the newly recognized hormonal principle pancreatic polypeptide (PP) were highly elevated, while plasma levels of vasoactive intestinal peptide were within the normal range. The symptoms of the patient seem to be derived from the high levels of circulating PP, as illustrated by an improvement after resection of liver metastases accompanied by a marked decrease of serum PP concentration. Streptozotocin treatment was without effect upon the watery diarrhoea, and PP levels also remained unchanged during medical treatment. The appearance of a PP-secreting tumour leading to a clinical WDHA syndrome widens the spectrum of hormone assays that have to be performed in these patients.

Topics: Adult; Body Water; Diarrhea; Female; Gastrins; Humans; Pancreatic Neoplasms; Pancreatic Polypeptide; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Adult; Animals; Child; Diarrhea; Dogs; Gastrointestinal Hormones; Humans; Intestine, Small; Pancreatic Neoplasms; Streptozocin; Swine; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Animals; Diarrhea; Gastrointestinal Hormones; Humans; Neoplasm Metastasis; Pancreatic Neoplasms; Pancreatic Polypeptide; Swine; Syndrome; Vasoactive Intestinal Peptide

A patient is described who presented with the classical symptomatology and profound electrolyte disturbance of the Verner-Morrison syndrome due to a pancreatic apudoma secreting vasoactive intestinal polypeptide (VIP). Diagnosis was confirmed by plasma VIP as measured by a radio-immunoassay technique now available. It is suggested that the cyclical nature of the symptoms in this case was due to cyclical release of VIP from the tumour in response to an unknown stimulus. Perfusion studies confirmed the excess secretory state of water, sodium and chloride in the small intestine. Symptoms were completely abolished by surgery and the progress is being monitored by means of serial plasma VIP estimations to detect any early recurrence of metastatic disease.

Topics: Adenoma, Islet Cell; Aged; Apudoma; Female; Gastrointestinal Hormones; Humans; Pancreatic Neoplasms; Syndrome; Time Factors; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Adrenal Gland Neoplasms; Adult; Angiography; Diarrhea; Female; Gastrointestinal Hormones; Humans; Hypokalemia; Pheochromocytoma; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Adult; Diarrhea; Female; Gastrointestinal Hormones; Humans; Hypokalemia; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Topics: Adenoma; Adrenal Cortex Hormones; Carcinoma, Bronchogenic; Diarrhea; Gastrointestinal Hormones; Humans; Lung Neoplasms; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Vaso-active intestinal polypeptide (VIP) is a recently discovered polypeptide widely distributed throughout the gastro-intestinal tract and nervous system. Elevated plasma VIP levels are found in gut and neural endocrine tumours producing the watery diarrhoea syndrome. Fifty per cent of these tumours are intrinsically malignant and the mortality rate may be as high as 30% even from the bening growths owing to the serious metabolic sequelae of the syndrome. The plasma VIP level is not elevated in any other non-tumourous diarrhoeal condition. The biological action of VIP closely resembles the clinical features of the Verner-Morrison syndrome and experimental evidence strongly suggests that VIP is the causal agent. The measurement of plasma VIP is of exceptional diagnostic value, since detection of elevated levels enables early removal of the tumour and may be life-saving.

Topics: Adrenal Gland Neoplasms; Diagnosis, Differential; Diarrhea; Ganglioneuroma; Gastrointestinal Hormones; Humans; Hypokalemia; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

We have infused pure porcine vasoactive intestinal peptide (VIP) into 8 healthy ambulant unsedated pigs. At plasma VIP levels closely comparable to those found in the human Verner-Morrison syndrome, gross watery diarrhea and hypokalemia were produced. When the VIP infusion was discontinued the water diarrhea ceased abruptly. This study therefore provides some evidence to implicate VIP as a possible causal agent in the pathogenesis of the human watery diarrhea syndrome.

Topics: Animals; Blood Glucose; Calcium; Diarrhea; Gastrointestinal Hormones; Potassium; Sodium; Swine; Syndrome; Vasoactive Intestinal Peptide

A 32-year old patient presented with recurrent pancreatitis, severe watery diarrhea and elevated serum levels of vasoactive intestinal polypeptide. His diarrhea appeared to respond to intramuscular propantheline. Initially he improved but had another attack of pancreatitis while hospitalized. Evaluation by ultrasound revealed the presence of a pseudocyst and endoscopic retrograde pancreatography demonstrated complete occlusion of the main pancreatic duct. Exploratory laparotomy was performed with drainage of a pseudocyst. Analysis of the pseudocyst fluid revealed an elevated amylase, lipase and vasoactive intestinal polypeptide level. It is believed that this patient's severe diarrhea was related to his pancreatitis and pancreatic pseudocyst with elevated levels of vasoactive intestinal polypeptide.

Topics: Adult; Diarrhea; Gastrointestinal Hormones; Humans; Male; Pancreatic Cyst; Pancreatitis; Propantheline; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Adult; Diarrhea; Female; Gastrointestinal Hormones; Humans; Hypokalemia; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

A patient with the Watery-Diarrhoea syndrome and episodic hypercalcaemia is reported. Plasma levels of vasoactive intestinal peptide (VIP) were elevated, and an islet cell adenoma of the pancreas was removed following which VIP levels decreased and diarrhoea ceased. During a hypercalcaemic episode, serum parathyroid hormone (PTh) levels were suppressed indicating the hypercalcaemia was independent of PTh and probably due to a direct action of VIP on calcium turnover.

Topics: Adenoma, Islet Cell; Diarrhea; Female; Humans; Hypercalcemia; Middle Aged; Pancreatic Neoplasms; Parathyroid Hormone; Syndrome; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

Small-intestinal perfusion studies with a triple-lumen tube were performed in the jejunum and ileum of 11 patients with a presumptive diagnosis of pancreatic cholera syndrome (PCS). Ultimately PCS was proven to be present in only 3 patients, whereas 6 were discovered to be taking either laxatives or diuretics surreptitiously. In 2 of the 11 patients the cause of the diarrhea could not be determined. In PCS the major abnormality which we observed was that the jejunal mucosa secreted rather than absorbed when perfused with a plasma-like solution. By contrast, the ileum of the PCS patients absorbed a plasma-like solution in a normal fashion; however, one patient failed to absorb sodium and chloride when a solution with low (50 mM) sodium chloride concentration was perfused in the ileum. The volume of endogenous fluid was high in both the jejunum and ileum, presumably because of proximal small-intestinal secretion. Glucose stimulated sodium movement in an absorptive direction in each patient. Studies were repeated in one PCS patient after tumor removal, and his intestinal absorption of water and electrolytes was normal. Patients with diarrhea due to surreptitious ingestion of laxatives and diuretics showed normal absorption in the jejunum and ileum. This study shows that proximal small-bowel secretion was the major cause for diarrhea in our 3 patients with PCS. This cannot be a consequence of diarrhea per se since it was not found in patients with long-standing diarrhea due to surrepitious drug ingestion. Small-intestinal perfusion studies may be helpful in the diagnosis and management of selected cases of severe chronic diarrhea. On the other hand, measurement of plasma VIP concentration, especially by methods currently used in the United States, is of little use and may be misleading.

Topics: Adult; Aged; Cathartics; Diarrhea; Diuretics; Female; Gastrointestinal Hormones; Glucose; Humans; Intestinal Absorption; Intestinal Mucosa; Jejunum; Male; Middle Aged; Pancreatic Diseases; Perfusion; Self Medication; Sodium; Substance-Related Disorders; Syndrome; Vasoactive Intestinal Peptide

A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

Topics: Acidosis; Adenylyl Cyclases; Adipose Tissue; Adult; Calcitonin; Catecholamines; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Hypokalemia; In Vitro Techniques; Pheochromocytoma; Retroperitoneal Neoplasms; Syndrome; Vasoactive Intestinal Peptide

A patient with watery diarrhea, hypokalemia, hypochlorhydria, and a non-beta islet cell carcinoma of the pancreas (Verner-Morrison syndrome) was found to have an elevated vasoactive intestinal peptide (VIP) concentration in the plasma as well as in the tumor. Treatment with streptozocin resulted in a dramatic subjective and objective tumor response in this patient. Plasma VIP concentration fell into the normal range after four courses of treatment, diarrhea ceased after the third course of therapy, and measurable tumor mass markedly decreased during that same period of time. The patient remains in clinical remission with no evidence of tumor regrowth 18 months after the beginning of treatment. In this patient, plasma VIP measurements were an excellent marker of tumor activity and correlated well with objective disease measurements and clinical response.

Topics: Adenoma, Islet Cell; Diarrhea; Female; Humans; Hypokalemia; Middle Aged; Pancreatic Neoplasms; Stomach Diseases; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

1. Plasma VIP immunoreactivity is always diagnostically raised in patients with pancreatic tumour causing the Verner-Morrison syndrome. 2. Human tumour VIP is physico-chemically similar to porcine VIP. 3. The only other situation in which plasma VIP is very elevated is in patients with ganglioneuroblastomas associated with diarrhoea. 4. VIP is not elevated in patients with diarrhoea associated with pancreatic islet hyperplasia, designated the pseudo Verner-Morrison syndrome.

Topics: Adenoma, Islet Cell; Diagnosis, Differential; Diarrhea; Gastrointestinal Hormones; Humans; Ileum; Pancreatic Neoplasms; Radioimmunoassay; Syndrome; Tissue Extracts; Vasoactive Intestinal Peptide

Topics: Diarrhea; Gastrointestinal Hormones; Humans; Syndrome; Vasoactive Intestinal Peptide

Topics: Diarrhea; Gastrointestinal Hormones; Humans; Syndrome; Vasoactive Intestinal Peptide