vasoactive-intestinal-peptide and Diarrhea

Vasoactive intestinal peptide-secreting tumors (VIPomas) are a group of rare neuroendocrine tumors, which cause a typical syndrome of watery diarrhea. Most of these tumors are found in the pancreas and are usually detected at a later stage. Although curative resection is not possible in most of these tumors, both symptom and tumor control can be achieved by a multidimensional approach, to enable a long survival of most patients. There are no clear-cut guidelines for the management of VIPomas because of the rarity of this neoplasm and lack of prospective data. In this review, we discuss the available evidence on the clinical features and management of these rare tumors.

Topics: Diarrhea; Humans; Magnetic Resonance Imaging; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Survival Analysis; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

According to the World Health Organization, there are approximately 2 billion annual cases of diarrhea worldwide. Diarrhea is the leading cause of death in children younger than 5 years and kills 1.5 million children each year. It is especially prevalent in the developing world, where mortality is related to dehydration, electrolyte disturbance, and the resultant acidosis, and in 2001, it accounted for 1.78 million deaths (3.7% of total deaths) in low- and middle-income countries. However, diarrhea is also a common problem in the developed world, with 211 million to 375 million episodes of infectious diarrheal illnesses in the United States annually, resulting in 73 million physician consultations, 1.8 million hospitalizations, and 3100 deaths. Furthermore, 4% to 5% of the Western population suffers from chronic diarrhea. Given the high prevalence of diarrhea, research has been directed at learning more about the cellular mechanisms underlying diarrheal illnesses in order to develop new medications directed at novel cellular targets. These cellular mechanisms and targets are discussed in this article.

Topics: Anti-Infective Agents; Antidiarrheals; Bismuth; Calcium Channel Blockers; Calmodulin; Chloride Channels; Cholestyramine Resin; Diarrhea; Fluid Therapy; Humans; Narcotics; Neprilysin; Receptors, sigma; Serotonin Antagonists; Somatostatin; Substance P; Vasoactive Intestinal Peptide

VIPomas are rare pancreatic endocrine tumors associated with a well-defined clinical syndrome characterized by watery diarrhea, hypokalemia, and metabolic acidosis. The objective of this study was to review a single institution's experience with VIPomas, as well as to review the English literature. A retrospective review of the Johns Hopkins pancreatic database revealed four cases of VIPoma, with three patients being male. All patients presented with watery diarrhea, hypokalemia, hypercalcemia, and acidosis. All patients had no family history of multiple endocrine neoplasia. Computed tomography revealed the primary pancreatic tumor in all patients, with three tumors located in the tail of the pancreas. One tumor involved the entire pancreas. Computed tomography and/or octreotide radionuclide scans identified hepatic metastasis in three patients. Mean serum vasoactive intestinal polypeptide levels were 683 pg/ml (range 293 to 1,500 pg/ml). All patients underwent resection of the pancreatic primary tumor. Two patients also had simultaneous liver resections. All patients had evidence of malignancy as defined by the presence of metastatic lymph nodes and/or hepatic metastases. Two patients had complete resolution of symptoms after surgical resection. One patient required radioablation of liver metastases and adjuvant octreotide therapy for control of symptoms. One patient died of progressive metastatic disease 96 months after surgery, whereas the other three remain alive. Extended, meaningful survival can be achieved for VIPoma patients, combining an aggressive surgical approach with additional strategies for treatment of unresected disease.

Topics: Algorithms; Diagnosis, Differential; Diarrhea; Humans; Liver Neoplasms; Pancreatectomy; Pancreatic Neoplasms; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review.

Topics: Achlorhydria; Adrenal Gland Neoplasms; Adrenalectomy; Catecholamines; Diarrhea; Female; Humans; Hypokalemia; Incidental Findings; Middle Aged; Pheochromocytoma; Tomography, X-Ray Computed; Treatment Outcome; Vasoactive Intestinal Peptide; Vipoma

Topics: Achlorhydria; Diarrhea; Humans; Hypokalemia; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Somatostatin is a peptide synthesized in many tissues that can act as a neurotransmitter, a systemic hormone, or a local hormone, and inhibits the secretion of hormones or other cell products. A long-acting synthetic analogue of somatostatin (SMS 201-995) has been developed which when administered subcutaneously has a biologic half-life of 90 to 120 minutes and can be administered 2 or 3 times per day. SMS 201-995 can lower plasma concentrations of growth hormone and somatomedin-C in patients with pituitary acromegaly, but no controlled trials to assess symptomatic response or change in tumor size have been done. In patients with pituitary thyrotropin-producing pituitary tumors, SMS 201-995 has been remarkably effective in producing biochemical and clinical responses and is the drug of first choice in this syndrome when tumor resection is not possible. In patients with the carcinoid syndrome, SMS 201-995 effectively reduces diarrhea, is the best available drug for treatment of carcinoid flush (effective in approximately 90% of cases), and is useful in treating carcinoid crisis. Eighty-five percent of patients with pancreatic islet cell tumors that produce vasoactive intestinal peptide will respond to SMS 201-995 with a reduction in diarrhea that often has been resistant to all other therapy. SMS 201-995 may also be useful in treating the symptoms in some patients with glucagonomas, growth hormone releasing hormone-producing tumors and insulinomas. Whether SMS 201-995 has a significant effect on gut neuroendocrine tumor growth remains uncertain. Certain nonmalignant diseases of the gut respond to somatostatin, including secretory diarrhea and fistulas of unknown cause. In general, SMS 201-995 has proved safe with few significant side effects, but whether the long-term use of the drug will result in an iatrogenic form of the somatostatinoma syndrome is uncertain.

Topics: Acromegaly; Adenoma, Islet Cell; Diarrhea; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Growth Hormone; Humans; Intestinal Fistula; Malignant Carcinoid Syndrome; Octreotide; Pancreatic Neoplasms; Pancreatitis; Pituitary Neoplasms; Thyrotropin; Vasoactive Intestinal Peptide

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

The etiological factors involved in diarrhea are multiple. Also the mechanisms and mediators involved are multiple: intracellular mediators (Ca, cAMP, cGMP, calmodulin, phospholipids), extracellular mediators (hormones, neurotransmitters, prostaglandins, enterotoxins...), intramural blood flow and oxygen, intestinal motility (local- and peristaltic motility). Till now, antidiarrheals are not so versatile that they provide a solution to all types of diarrhea. The mechanisms of action of fluid replacement therapy, loperamide, alpha 2 agonist and some nonsteroidal anti-inflammatory substances are reviewed.

Topics: Acetylcholine; Animals; Antidiarrheals; Bacterial Toxins; Biological Transport; Calcium; Catecholamines; Chlorides; Cyclic AMP; Cyclic GMP; Diarrhea; Fluid Therapy; Glucagon; Histamine; Intestinal Absorption; Intestinal Mucosa; Intestinal Secretions; Intestines; Lipid Metabolism; Loperamide; Regional Blood Flow; Serotonin; Sodium; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Water-Electrolyte Balance

Topics: Cyclic AMP; Cyclic GMP; Diarrhea; Humans; Intestinal Absorption; Intestinal Secretions; Prostaglandins; Vasoactive Intestinal Peptide

The intestinal epithelial cell, or enterocyte, performs a dual function: absorption and secretion. Absorption takes place in the villi and secretion in the crypts (and perhaps also in the villi). Both functions are controlled by complex extra- and intracellular systems. The extracellular system is mediated by neuromediators released in the subcellular space. Some mediators, like the vasoactive intestinal peptide (VIP) or the prostaglandins, stimulate secretion while others, like enkephalins, stimulate absorption. All these mediators act on intracellular metabolic processes by activating "second messengers" (e.g. amp or intracellular calcium) which in turn regulate the enterocyte transport system. Diarrheogenic processes are frequently due to disturbances in enterocyte control with abnormal stimulation of the secretory processes. Some pancreatic cancers and sympathicoblastomas release VIP into the blood stream in sufficient amounts to stimulate cAMP production by the enterocytes and, consequently, secretion. The cholera toxin and the E-coli thermolabile toxin can also induce stimulation of intracellular cAMP production. Conversely, the most promising antidiarrhoeal drugs are antisecretory agents, like opiates, which stimulate the enterocyte absorption processes.

Topics: Animals; Calcium; Cyclic AMP; Cyclic GMP; Diarrhea; Enkephalins; Epithelial Cells; Epithelium; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Neurotransmitter Agents; Peptides; Somatostatin; Vasoactive Intestinal Peptide

The salvage of unabsorbed nutrients, salt and water in the colon requires the integration of functions of bacterial digestion and epithelial transport with motor activity. However, the motor and transport functions of the colon are poorly understood owing to the inaccessibility of that organ. This paper discusses some of the ways in which motor activity may influence colonic absorption and vice versa, using examples taken from studies carried out in the small intestine. In particular, the effect of factors such as convection, transit time, reflex secretion and blood flow are discussed.

Topics: Animals; Bile Acids and Salts; Colon; Diarrhea; Dogs; Ferrets; Gastrointestinal Motility; Humans; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Rabbits; Regional Blood Flow; Time Factors; Vasoactive Intestinal Peptide

Topics: Adrenal Cortex Hormones; Adult; Cell Membrane Permeability; Child; Colitis, Ulcerative; Crohn Disease; Diarrhea; Diet; Energy Intake; Gastrointestinal Motility; Humans; Intestinal Absorption; Intestinal Mucosa; Prostaglandins; Sulfasalazine; Vasoactive Intestinal Peptide; Water-Electrolyte Imbalance; Zinc

Information concerning GEP hormones has progressively advanced since the initial discovery of a GEP hormone, secretin, in 1902. Studies in this area flourished with the advent of radioimmunoassay, and have provided an understanding of the secretion, regulation, metabolic actions, and role in certain diseases of major GEP hormones. Measurement of GEP hormones has achieved importance in clinical medicine and allowed understanding of the pathophysiology of several clinical disorders. The decade to come should witness additional advances in this rapidly expanding field.

Topics: Chemical Phenomena; Chemistry; Cholecystokinin; Diabetes Mellitus; Diarrhea; Endocrine System Diseases; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypoglycemia; Motilin; Neoplasms; Neurotensin; Pancreatic Polypeptide; Peptic Ulcer; Secretin; Skin Diseases; Somatostatin; Substance P; 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: alpha 1-Antitrypsin; Bacterial Toxins; Cholestyramine Resin; Colonic Diseases; Deoxycholic Acid; Diarrhea; Humans; Immunoglobulin G; Iodine Radioisotopes; Malabsorption Syndromes; Prostaglandins; Protein-Losing Enteropathies; Serum Albumin; Vasoactive Intestinal Peptide; Water-Electrolyte Imbalance

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

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

Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood.. We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS.. Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined.. Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group.. Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.

Topics: Adult; Analysis of Variance; Case-Control Studies; Catheterization; Cholecystokinin; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Dietary Fats; Female; Humans; Male; Middle Aged; Motilin; Neuropeptide Y; Pain Threshold; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Pressure; Statistics, Nonparametric; Stomach; Vasoactive Intestinal Peptide

Previous studies showed increased plasma motilin and substance P concentrations and accelerated motor function in the small bowel and colon in patients with carcinoid diarrhea. Octreotide is beneficial in patients with carcinoid syndrome. Our hypothesis was that octreotide inhibits accelerated motility and gut neuropeptides in carcinoid syndrome.. In 12 patients with metastatic carcinoid syndrome, we investigated the effect of octreotide 50 microg s.c. t.i.d (n = 6) or placebo (n = 6) on postprandial symptoms, GI transit, colonic motility, and circulating levels of selected circulating peptides and amines.. Octreotide reduced postprandial flushing (p = 0.03) but not pain. Octreotide significantly retarded overall colonic transit and proximal colonic emptying (p < 0.05); it tended to prolong small bowel transit time (p = 0.13) and to reduce postprandial colonic tone (p = 0.08) compared with placebo. Octreotide also reduced circulating levels of peptide YY, neurotensin, vasoactive intestinal polypeptide, and substance P but had no effect on plasma motilin, neuropeptide Y, calcitonin gene-related peptide, or histamine after meal ingestion.. Octreotide ameliorates gut motor dysfunctions that characterize carcinoid diarrhea; the potential role of specific antagonism of serotonin, substance P, and vasoactive intestinal polypeptide alone or in combination with agents that inhibit their release in carcinoid diarrhea deserves further study.

Topics: Aged; Antineoplastic Agents, Hormonal; Calcitonin Gene-Related Peptide; Colon; Colonic Diseases; Diarrhea; Digestion; Double-Blind Method; Female; Flushing; Gastrointestinal Agents; Gastrointestinal Motility; Gastrointestinal Transit; Histamine; Humans; Intestine, Small; Male; Malignant Carcinoid Syndrome; Middle Aged; Motilin; Neuropeptide Y; Neuropeptides; Neurotensin; Octreotide; Peptide YY; Placebos; Serotonin Antagonists; Substance P; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide-secreting tumors (VIPomas) are extremely rare functional pancreatic neuroendocrine neoplasms (p-NENs) characterized by watery diarrhea, hypokalemia, and achlorhydria. Here, we report the case of a 51-year-old female patient with VIPoma that recurred after a long-term disease-free interval. This patient had been asymptomatic for approximately 15 years after the initial curative surgery for pancreatic VIPoma, with no metastasis. The patient underwent a second curative surgery for the locally recurrent VIPoma. Whole-exome sequencing of the resected tumor revealed a somatic mutation in MEN1, which is reportedly responsible not only for multiple endocrine neoplasia type 1 (MEN1) syndrome but also sporadic p-NENs. Symptoms were controlled with lanreotide before and after surgery. The patient is alive with no relapse following 14 months after surgery. This case demonstrates the importance of long-term observation of patients with VIPoma.

Topics: Diarrhea; Female; Humans; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Traumatic brain injury (TBI) is the main cause of death and can lead to a variety of physiological complications, including gastrointestinal dysfunction. The present study aimed to confirm the miR-19a-mediated suppression of diarrhea after TBI through the regulation of VIP expression.. A rat model of TBI induced by controlled cortical injury was used to observe gastrointestinal morphology by opening the abdomen after TBI. After 72 h of injury, the fecal water content of the rats was measured. The end ileal segments were removed, and HE staining was used to observe the histopathological changes in the intestine. The levels of serum miR-19a and VIP mRNA were detected by qRT-PCR. ELISA was performed to detect VIP levels in serum. Immunohistochemistry was used to detect the level of VIP in ileal tissues, and immunofluorescence was used to detect c-kit expression in ileal tissue. CCK-8 assay was used to detect the cell viability of interstitial cells of Cajal (ICCs), and TUNEL assay was used to detect apoptosis of ICCs.. miR-19a and VIP were highly expressed in the serum of TBI rats, and the knockdown of miR-19a alleviated TBI-induced diarrhea. In addition, the overexpression of miR-19a or VIP inhibited the proliferation of ICCs, promoted apoptosis, and suppressed intracellular Ca. Knockdown of miR-19a inhibits activation of the VIP-NO-cGMP-PKG pathway through suppression of VIP expression, which in turn inhibits diarrhea after TBI.

Topics: Animals; Brain Injuries, Traumatic; Diarrhea; MicroRNAs; Rats; Vasoactive Intestinal Peptide

VIPomas are generally rare functioning pancreatic neuroendocrine tumors (PanNETs) that cause watery diarrhea, hypokalemia, and achlorhydria. Due to their extreme rarity, the clinicopathological features and outcomes of VIPomas have not been well reported. This study aimed to determine the diagnostic and therapeutic characteristics and prognosis of VIPomas and to compare them with other PanNETs at a Japanese reference hospital. Medical records of 293 patients with PanNETs were collected. Patient and tumor characteristics and outcomes were retrospectively reviewed. This cohort had only 1.4% (four patients) of patients with VIPomas, and three of these patients changed from non-functioning (NF-) PanNETs during their disease course. Recurrences of hormonal symptoms were observed in all patients despite the initial controls, and all of them died from their disease, more specifically mainly from hormonal symptoms. Compared to the other PanNETs, VIPomas were all located at the pancreatic tail, were larger, and had a higher Ki-67 index and more metastasis. The median survival time was significantly shorter for patients with VIPoma than for those with NF-PanNET (5.9 vs. 26.7 years, p < 0.0001), insulinoma (21.8 years, p < 0.0001), and gastrinoma (12.3 years, p = 0.0325). This study presents the possibility of shifting from non-symptomatic to symptomatic VIPomas as they grow or of transforming from NF-PanNETs to VIPomas. VIPomas should be considered in patients with relatively large NF-PanNETs, especially those located in the pancreatic tail, when diarrhea is continuously observed. As hormonal symptoms are an important cause of death in VIPomas, long-term symptomatic control, which is relatively difficult, is of great significance.

Topics: Diarrhea; Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Retrospective Studies; Vasoactive Intestinal Peptide; Vipoma

Neuroendocrine tumors are rare, heterogeneous neoplasms that produce a wide variety of clinical symptoms. Diarrhea in neuroendocrine tumors is incredibly common and is usually benign in nature. We report two extreme cases of diarrhea in metastatic neuroendocrine tumors that threatened fatality and provide evidence for steroids as a novel agent in the management of vasoactive intestinal peptide tumors.. A 63-year-old Caucasian male with a grade 2 (Ki-67 17%) metastatic small bowel neuroendocrine tumor, and a 43-year-old female with a grade 2 (Ki-67 5%) metastatic pancreatic vasoactive intestinal peptide tumor. Both patients suffered life-threatening diarrhea despite extensive treatment modalities, including new systemic agents. This case explains how a lack of compliance and patient under-reporting of symptoms contributed to their challenging clinical course. Only steroids had a significant sustained effect on the diarrhea of the patient with vasoactive intestinal peptide tumor.. This report discusses two rare cases of life-threatening diarrhea in neuroendocrine tumors and stresses the importance of accurate clinical history taking, patient education, and compliance for symptom control. The report suggests steroids as a potential novel pharmaceutical option in the management of vasoactive intestinal peptide tumors; this is of great significance as it may provide a new approach to their management and potentially act as a life-saving agent in other oncology patients.

Topics: Adult; Diarrhea; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Topics: Cholangiopancreatography, Magnetic Resonance; Diarrhea; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Liver Neoplasms; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

Atractylodes lancea (Thunb.) DC. is a widely used traditional herb that is well known for treating spleen deficiency and diarrhea. According to traditional Chinese medicine (TCM) theory, diarrhea-predominant irritable bowel syndrome (IBS-D) is caused by cold and dampness, resulting in diarrhea and abdominal pain. Nevertheless, the effect and mechanism of Atractylodes on IBS-D are still unclear.. This study was designed to confirm the therapeutic effect of Atractylodes lanceolata oil (AO) in a rat model of IBS-D, and to determine the mechanisms by which AO protects against the disease.. The chemical components in AO were determined using gas chromatography-mass spectrometry (GC-MS). The expression levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and surfactant protein (SP) in serum and colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR), western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) were used to elucidate the mechanism of action of AO toward inflammation and the intestinal barrier in a rat model of IBS-D.. The 15 chemical substances of the highest concentration in AO were identified using GC-MS. AO was effective against IBS-D in the rat model, in terms of increased body weight, diarrhea grade score, levels of interleukin-10 (IL-10), aquaporin 3 (AQP3), and aquaporin 8 (AQP8), and reduced fecal moisture content, levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 5-HT, VIP, and SP, while also reducing intestinal injury, as observed using hematoxylin-eosin (HE) staining. In addition, the results indicated that AO increased the mRNA and protein expression levels of stem cell factor (SCF) and c-kit and enhanced the levels of zonula occludens-1 (ZO-1) and occludin, as well as decreased the levels of myosin light chain kinase (MLCK) and inhibited the phosphorylation of myosin light chain 2 (p-MLC2).. AO was found to be efficacious in the rat model of IBS-D. AO inhibited the SCF/c-kit pathway, thereby reducing inflammation and protecting against intestinal barrier damage via the MLCK/MLC2 pathway.

Topics: Animals; Aquaporins; Atractylodes; Colitis; Cytokines; Diarrhea; Intestinal Mucosa; Irritable Bowel Syndrome; Myosin Light Chains; Myosin-Light-Chain Kinase; Plant Oils; Proto-Oncogene Proteins c-kit; Rats, Sprague-Dawley; Serotonin; Signal Transduction; Stem Cell Factor; Tight Junction Proteins; Vasoactive Intestinal Peptide

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

Very rarely, vasoactive intestinal peptide-related diarrhea (VIP-D) is observed in patients with high-risk neuroblastoma (HR-NB) where the associated fluid and electrolyte abnormalities can pose a major clinical challenge for administering the required aggressive multimodality treatment. Two patients with HR-NB developed VIP-D during induction and were found to have a somatic BRAF V600E mutation. Serum VIP levels and diarrhea promptly resolved in both patients after initiating treatment with BRAF and MEK inhibitors. This illustrates an association of VIP-D with BRAF V600E mutations and demonstrates a therapeutic strategy in the specific context of VIP-D and BRAF V600E mutations in HR-NB patients. The addition of BRAF and MEK inhibitors allows continued conventional tumor-directed treatment by decreasing the severity of symptoms caused by this life-threatening complication.

Topics: Diarrhea; Humans; Mitogen-Activated Protein Kinase Kinases; Mutation; N-Myc Proto-Oncogene Protein; Neuroblastoma; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Vasoactive Intestinal Peptide

A female patient aged 77 years had refractory watery diarrhea caused by a vasoactive intestinal peptide production tumor. She had impaired consciousness. After presenting to our hospital, we administered opium tincture, after which the diarrhea ceased. Intravenous feeding was able to be stopped along with the potassium load and the infusion of octreotide, and loperamide. The antidiarrheal effects continued after opium tincture was stopped, and the patient was discharged home. These results reveal that opium tincture can be efficacious in treating end-stage refractory diarrhea.

Topics: Aged; Diarrhea; Female; Humans; Neoplasms; Octreotide; Opium; Vasoactive Intestinal Peptide

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P<0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P<0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

Topics: Amylases; Animals; Colon; Defecation; Diarrhea; Disease Models, Animal; Female; Gastrins; Gastrointestinal Agents; Intestine, Small; Male; Mice; Rheum; Vasoactive Intestinal Peptide; Wolfiporia; Xylose

VIPoma or Verner Morrison syndrome is a very rare disease with an incidence rate of 1 case per 10 000 000 person-years. It is a neuroendocrine tumor issue from β-pancreatic islets leading to profuse diarrhea, hypokalemia and gastric achlorydria due to secretion of vasoactive intestinal polypeptide (VIP) hormone. Diagnosis is based on histology of tumor and the dosage of VIP in a blood sample. Somatostatin analog is a simple and efficient treatment for diarrhea. Curative treatment with surgery could be proposed for a localized disease. For disseminated disease, there are different treatments and a multimodal assessment that should be discussed in a multidisciplinary team might be curative.. Le VIPome ou syndrome de Verner Morrison est une maladie très rare, avec une incidence annuelle estimée à 1/10 000 000 habitants. Il s’agit d’une tumeur neuroendocrine issue des îlots β pancréatiques qui sécrète une hormone appelée

Topics: Diarrhea; Humans; Hypokalemia; Vasoactive Intestinal Peptide; Vipoma

To investigate the modulatory effect of recombinant-expressed vasoactive intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.. Forty-eight rats were randomized into six groups: normal control group (Control), model control group (TNBS), ethanol treatment group (ETOH), and VIP treatment groups with different dosage (rVIPa. Administration with 2 nmol rVIPa prevented TNBS-induced necrosis, hyperemia, swelling, inflammation,. rVIPa ameliorates TNBS-induced colonic injury and inflammation and effectively protected the intestinal mucosal barrier function in rats. The mechanism may be related to TLR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders.

Topics: Animals; Colon; Crohn Disease; Diarrhea; Disease Models, Animal; Gastrointestinal Agents; Humans; Intestinal Mucosa; Male; Necrosis; NF-kappa B; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Signal Transduction; Toll-Like Receptor 4; Treatment Outcome; Trinitrobenzenesulfonic Acid; Vasoactive Intestinal Peptide

Chronic watery diarrhoea can be a presentation of gastrointestinal disease itself or a less-evident systemic disease. A 17-month-old boy presented with intractable diarrhoea, failure to gain weight, refractory tachycardia and severe hypertension. The ability to recognise and make a quick diagnosis of secretory type of diarrhoea dictated the outcome of patients with this ailment. Catecholamine hypersecretion was considered with the additional clues of refractory tachycardia and hypertension, a well-recognised phenomenon of neuroblastic tumours. A neuroblastic tumour can lead to vasoactive intestinal peptide (VIP) overexpression, which may result in secretory diarrhoea. In this situation, measurements of plasma VIP enabled crucial diagnosis. Imaging studies were used to identify and localise a neuroblastic tumour. Subsequent removal of the tumour was curative and led to the resolution of the symptoms.

Topics: Adrenal Gland Neoplasms; Catecholamines; Diarrhea; Humans; Hypertension; Infant; Male; Neuroblastoma; Tachycardia; Treatment Outcome; Vasoactive Intestinal Peptide

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Diarrheal NB is quite rare and is not easy to diagnose in the early stage. Six cases of diarrheal NB in our hospital treated from 1996 to 2006 were retrospectively analyzed, including characteristics such as electrolyte imbalance, pathologic features, vasoactive intestinal peptide (VIP) immunohistochemical staining results, treatment, and prognosis. All patients were boys with 3-8 loose or watery stools each day and routine fecal tests were normal. Abdominal tumors were identified by B-ultrasound. Drugs were ineffective. Three patients underwent surgery, and the remaining three patients received surgery and chemotherapy. Diarrhea stopped after treatment in five patients. Two patients died due to intractable hypokalemia. The tumor was located in the adrenal gland in four patients, in the upper retroperitoneum in one patient, and in the presacral area in one patient. Pathologic findings were NB and ganglioneuroblastoma. Five patients were at clinical stage I-II, and one was at stage III. Four patients survived (followed-up for 6 mo to 4 years). Immunohistochemical staining for VIP was positive. Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely. Intractable diarrhea, hypokalemia, and dysplasia are the initial clinical manifestations. Increased VIP is characteristic of this disease. Potassium supplementation plays a vital role in the treatment procedure, especially preoperatively. The prognosis of diarrheal NB is good following appropriate treatment.

Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Biopsy; Child, Preschool; Diarrhea; Humans; Hypokalemia; Immunohistochemistry; Infant; Male; Neoplasm Staging; Neuroblastoma; Paraneoplastic Syndromes; Retroperitoneal Neoplasms; Retrospective Studies; Treatment Outcome; Vasoactive Intestinal Peptide

Recent studies have shown that mast cells play an important role in irritable bowel syndrome (IBS). We investigated the relationship between mast cells and the gut hormones substance P and vasoactive intestinal peptide (VIP) in irritable bowel syndrome with diarrhea (IBS-D).. Colonoscopic biopsies were performed on the rectal mucosa of 43 subjects (IBS-D patients: 22, healthy volunteers: 21) diagnosed according to the Rome III criteria. Mast cells, and substance P & VIP were evaluated by quantitative immunohistology and image analysis. Mast cells were counted as tryptase-positive cells in the lamina propria, and substance P and VIP levels were expressed as percentages of total areas of staining.. Mast cell counts were higher in IBS-D patients than healthy volunteers (9.6 ± 3.3 vs. 5.7 ± 2.5/high power field (HPF), p < 0.01). Substance P was also elevated (0.11 ± 0.08% vs. 0.03 ± 0.02 %, p < 0.01) while VIP was only high in women with IBS-D. Mast cell counts were positively correlated with levels of substance P & VIP in women but not men (women: r = 0.625, p < 0.01 for substance P and r = 0.651, p < 0.01 for VIP). However, mast cell counts were not correlated with IBS symptoms including abdominal pain.. Mast cells are activated leading to the raised levels of substance P & VIP in IBS-D patients. However, the correlation between mast cells and levels of substance P & VIP differs according to gender.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Cell Count; Diarrhea; Female; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Male; Mast Cells; Middle Aged; Rectum; Sex Factors; Substance P; Vasoactive Intestinal Peptide; Young Adult

Topics: Diarrhea; Female; Humans; Infant; Vasoactive Intestinal Peptide; Vipoma

Pancreatic neuroendocrine tumor (pNET) secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial.. A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0-100 pg/mL), and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL). There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR) subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable.. From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs.

Topics: Adult; Antineoplastic Agents, Hormonal; Calcitonin; Carcinoma, Neuroendocrine; Diarrhea; Humans; Male; Octreotide; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

To investigate the regulatory effects of Wei Chang An Pill (WCAP) on enzyme activity and gastrointestinal hormones in the small intestine of rats with compound diarrhea.. Forty Wistar rats were randomly divided into a control, diarrhea model, and WCAP high, medium, and low dose groups. The control group was not treated, and the model group was administered intragastric distilled water. The WCAP groups were given WCAP suspension, 80, 60 or 40 mg x kg(-1) x d(-1), for 4 days. Stool properties were observed. After the experiment, thymus and spleen indices were measured, and the activities of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), and disaccharidase (lactase) in the small intestinal mucous membrane, and levels of substance P (SP) and vasoactive peptide (VIP) in the colon were determined.. Compared with the control group, thymus and spleen indices were significantly decreased, LDH, MDH, and disaccharidase activity in the small intestine was decreased, and SP and VIP levels in the colon were significantly increased in the diarrhea model group. Compared with the model group, thymus and spleen indices were significantly increased, and LDH, MDH, and disaccharidase activity in the small intestine and SP and VIP levels in the colon were significantly decreased in the WCAP medium dose group.. The diarrhea model rats exhibited pathological changes including atrophy of the thymus and spleen, decreased enzyme activity in the small intestine, and gastrointestinal hormone disturbance. WCAP can increase the activity of intestinal digestive enzymes and regulate gastrointestinal hormones, thereby relieving diarrhea.

Topics: Animals; Colon; Diarrhea; Drugs, Chinese Herbal; Female; Humans; Intestine, Small; Rats; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

To explore the point specificity of eye-acupuncture and the mechanism of eye-acupuncture on diarrhea-predominant irritable bowel syndrome (D-IBS).. Forty male Wistar rats of SPF grade were randomly divided into a normal group, a model group, a eye-acupuncture point (AA) group and a non-point (NA) group. The D-IBS rat model was established with the combination methods of the chronic stress and binding limbs. The AA group was treated by acupuncture at "low energizer area", "large intestine area", "liver area" and "spleen area", and the NA group by acupuncture at 3 mm apart from the same points area mentioned above, and the normal group and the model group with no intervention. The rate of feces moisture content was detected. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA of aquaporin 8 (AQP 8) in colon. Protein expressions of the vasoactive intestinal peptide (VIP) and AQP 8 in colon were detected by SABC immunohistochemistry method.. Compared with normal group, the rate of feces moisture content at the 18th and 25th days, VIP protein in colon mucosa, myenteric nerve plexus and hypo-mucosa nerve plexus increased significantly (all P < 0.01), and AQP 8 mRNA in colon mucosa decreased significantly in model, AA and NA group (P < 0.05, P < 0.01); AQP 8 protein in colon mucosa decreased significantly in model group and NA group (both P < 0.01). Compared with model group, the rate of feces moisture content at the 25th day and VIP protein in colon mucosa decreased significantly (P < 0.01, P < 0.05), and AQP 8 mRNA and protein increased significantly (P < 0.05, P < 0.01) in AA group. Compared with AA group, the rate of feces moisture content at the 25th day and VIP protein in colon mucosa increased significantly (both P < 0.01), and AQP 8 mRNA and protein decreased significantly (both P < 0.01) in NA group.. Eye-acupuncture has a good therapeutic effect on D-IBS. It is suggested that one of the mechanism is relate to increase AQP 8 in colon tissue and restrain the expression of VIP. Non-point area of eye-acupuncture has no obviously therapeutic effect and so to illustrate the point specificity of eye-acupuncture.

Topics: Acupuncture Points; Acupuncture Therapy; Animals; Aquaporins; Colon; Diarrhea; Humans; Irritable Bowel Syndrome; Male; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

Topics: Adult; Diarrhea; Female; Focal Nodular Hyperplasia; Humans; Pancreatic Neoplasms; Pancreaticoduodenectomy; Paresis; Remission Induction; Vasoactive Intestinal Peptide; Vipoma

We aimed to evaluate the changes of nerve morphology and distribution of neurotransmitters and neuropeptides in the rectum of Shigella flexneri-infected patients and in the duodenum of Vibrio cholerae O1-infected patients. Nerve morphology was observed by transmission electron microscopy. Immunoreactivity of nerve growth factor (NGF), neurotransmitters and neuropeptides in tissues were studied by immunohistochemistry. Ultrastructural analysis of intestinal biopsy revealed persisting axons degeneration throughout the study period in all patients. Regeneration was already evident at the acute stage with marked increase at late convalescence. Both acute shigellosis and cholera were accompanied by increased expression of NGF and histamine and decreased expression of serotonin that was restored at convalescence. Immunoreactivity of vasoactive intestinal peptide (VIP) was increased during acute cholera, whereas in shigellosis VIP- and substance P-immunoreactive nerves appeared at early convalescence. Both shigellosis and cholera induced long-lasting degeneration of enteric neuronal axons, despite the presence of ongoing proliferation and regeneration processes. Neurotransmitters and neuropeptides may play differential roles in invasive and watery diarrhoea.

Topics: Adolescent; Adult; Biopsy; Cholera; Diarrhea; Dysentery, Bacillary; Enteric Nervous System; Histamine; Humans; Male; Middle Aged; Nerve Growth Factor; Neurons; Rectum; Serotonin; Substance P; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide; Vibrio cholerae O1; Young Adult

The watery diarrhoea, hypokalaemia and achlorhydria syndrome is a rare cause of secretory diarrhoea. In this case report, we highlight a young female with watery diarrhoea, hypokalaemia and achlorhydria syndrome as a consequence of a vasoactive intestinal peptide producing composite adrenal phaeochromocytoma-ganglioneuroma. She made a complete recovery after curative surgical resection.

Topics: Achlorhydria; Adrenal Gland Neoplasms; Diarrhea; Female; Ganglioneuroma; Humans; Hypokalemia; Pheochromocytoma; Vasoactive Intestinal Peptide; Young Adult

Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA) in 1958. VIPomas producing high amounts of vasoactive intestinal peptide (VIP) commonly originate from the pancreas. Typical symptoms play a momentous role in the diagnosis of VIPoma. Diarrhea may persist for years before the diagnosis. Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base metabolism disorders, which may cause chronic renal failure. Assessment of specific marker (VIP) offers high sensitivity in establishing the diagnosis. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogues. Treatment options include resection of the tumor, chemotherapy or the reduction of symptoms with somatostatin analogues. Early diagnosis and management may affect survival of patients favorably. VIPoma cases may be associated with multiple endocrine neoplasia type 1.

Topics: Achlorhydria; Aged; Biomarkers, Tumor; Diarrhea; Endosonography; Female; Humans; Hypokalemia; Immunohistochemistry; Magnetic Resonance Imaging; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

Neuroendocrine tumors are uncommon, including VIPoma that produces vasoactive intestinal polypeptide. We report a 45-year-old female presenting with a history of diarrhea lasting three months. An abdominal CAT scan showed a solid tumor in the body of the pancreas. A fine needle aspiration biopsy of the tumor was compatible with a neuroendocrine tumor. The patient was subjected to a partial pancreatectomy, excising a 4 cm diameter tumor. The pathological study was compatible with a neuroendocrine carcinoma. There was no regional lymph node involvement. During the postoperative period the results of serum vasoactive intestinal polypeptide were received. These were 815.9 pg/ml before surgery and normalized after the operation.

Topics: Carcinoma, Neuroendocrine; Diagnosis, Differential; Diarrhea; Female; Humans; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Watery diarrhoea, hypokalaemia and achlorhydria (WDHA) syndrome was caused by vasoactive intestinal polypeptide (VIP)-producing tumour. A 3-year-old Chinese girl with watery diarrhoea, abdominal distension and hypokalaemia due to a thoracic paraspinal VIP-secreting ganglioneuroma is reported. The girl coughed, fevering up to 39 degrees C after a flu-like episode. She had eight to ten abundant stools daily which is not improved by dietary treatment, resulting in an important weight loss. She weighed 6.8 kg (nl P50 at 6 months of age) and is 76 cm (nl P50 at 9 months of age) in height. Blood electrolytes showed 129 mmol/L sodium, 2.42 mmol/L potassium, 94 mmol/L chloride and 18.6 mmol/L bicarbonate; urinary catecholamines were normal. Computed tomography scan evidenced a left side paravertebral mass of 4 x 6 cm in the lower thoracic region leading to the blood determination of vasoactive intestinal polypeptide which amounted 830 pmol/L(normal < 25 pmol/L). Surgical removal showed a ganglioneuroma of 160 g and was associated with disappearance of the diarrhoea and normalization of VIP level below 20 pmol/L. Review of the 63 reported cases in children with WDHA showed that many of the cases presented with non-treatable watery diarrhoea, hypokalaemia. Achlorhydria is not necessarily part of the WDHA syndrome. The male to female ratio is 1:1.5. Ganglioneuroblastoma and ganglioneuroma are the commonest tumours. Location of the tumour is variable: abdomen, chest or neck. Abdominal distension, flushing, episodic hypertension and colonic dilatation, constipation and ataxia were the other associated features. Surgical resection is the treatment of choice of VIP-producing tumours.

Topics: Achlorhydria; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Humans; Hypokalemia; Thoracic Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; Vasoactive Intestinal Peptide; Weight Loss

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

Topics: Antineoplastic Agents, Hormonal; Diagnosis, Differential; Diarrhea; Female; Humans; Hypokalemia; Indium Radioisotopes; Irritable Bowel Syndrome; Liver; Liver Neoplasms; Middle Aged; Octreotide; Pancreatic Neoplasms; Radionuclide Imaging; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

To investigate the underlying mechanisms of Berberine-mediated antidiarrheal effects in thyroid hormone-induced diarrhea in rats, gastrointestinal peptides, such as motilin, gastrin, vasoactive intestinal peptide, and somatostatin from plasma and tissue of hyperthyroid diarrheic rats were measured using radioimmunoassay in healthy control, model, and treated model groups. The number and volume of goblet cells were also observed. Compared with healthy control, hyperthyroid diarrheic rats exhibited a significant reduction in body weight, and increase in plasma concentrations of tri-iodothyronine and free thyroxine along with the increase of wet stool. Both plasma motilin and gastrin were also elevated and reduced remarkably in Berberine-treated subgroup along with the body weight increased and wet stool reduced at the meantime. Significant changes in plasma vasoactive intestinal peptide and somatostatin were not seen. Gastrointestinal peptides trend in tissue samples were similar to those observed in plasma. Morphological data demonstrated an increase in number and/or volume of goblet cells to some extent in duodenum, jejunum, ileum, and colon, respectively and decreased by administration of Berberine. The possible underlying mechanisms of antidiarrheal effects of Berberine may be due in partially to the reduction of the number of goblet cells and the amount of mucous secretion through re-balancing gastrointestinal peptides.

Topics: Animals; Antidiarrheals; Berberine; Colon; Diarrhea; Duodenum; Gastrins; Gastrointestinal Hormones; Goblet Cells; Hyperthyroidism; Jejunum; Male; Motilin; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Somatostatin; Thyroid Hormones; Vasoactive Intestinal Peptide

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

We present an unusual case of a 52-year-old woman with severe, uncontrollable, refractory diarrhea attributable to pancreatic endocrine carcinoma (ECA) with markedly elevated serum vasoactive intestinal polypeptide (VIP) and calcitonin levels. After initial correction of fluid and electrolyte abnormalities, the patient was treated with high-dose octreotide. Shortly thereafter, due to the intractable nature of her diarrhea, she underwent cytoreductive hepatic surgery. The pancreatosplenectomy specimen showed a poorly differentiated ECA of the distal pancreas, immunoreactive for synaptophysin, CD56, and S100 protein, with morphologically similar hepatic and lymph node metastases. Postoperatively, her diarrhea improved, along with decline in serum VIP and calcitonin levels. Systemic chemotherapy with etoposide and cisplatin did not result in any radiographic and biochemical improvement. Having radiologically stable disease with depot-octreotide and short-acting octreotide (Sandostatin), she was subjected to peptide receptor radiotherapy with [177Lu-DOTA0,Tyr]octreotate (LuTate) that resulted in marked clinical and biochemical improvement, along with dramatic reduction in the number and size of hepatic metastases. In summary, this is a unique case of metastatic VIP- and calcitonin-secreting pancreatic ECA with dramatic sustained clinical, biochemical, and objective tumor response to peptide receptor radionuclide therapy.

Topics: Calcitonin; Combined Modality Therapy; Diarrhea; Female; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides, Cyclic; Radiopharmaceuticals; Vasoactive Intestinal Peptide

Pancreatic polypeptide (PP) islet cell tumors are usually not associated with a distinct clinical syndrome, although some reports suggest that they can cause a watery diarrhea syndrome similar to vasoactive intestinal polypeptide (VIP) cell tumors. We report the case of a young woman with an unusual presentation of a pancreatic neuroendocrine tumor mainly secreting PP. The patient developed a reversible hypokalemic rhabdomyolysis very likely secondary to the presence of the tumor. The myopathy resolved following the restoration of normokaliemia using potassium supplementation and a partial laparoscopic pancreasectomy. Isolated cases of hypokalemic rhabdomyolysis induced by intestinal diseases have been described in literature but these did not include gastroenteropancreatic neoplasms. We suggest that pancreatic neuroendocrine tumors should be added to the list of intestinal diseases capable of producing hypokalemic myopathy.

Topics: Adult; Diagnosis, Differential; Diarrhea; Female; Humans; Hypokalemia; Indium Radioisotopes; Neuroendocrine Tumors; Octreotide; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Radionuclide Imaging; Rhabdomyolysis; Tomography, X-Ray Computed; 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

In children, the watery diarrhoea-hypokalemia-achlorhydria (WDHA) syndrome is uncommon and usually due to a neuroblastic tumour hypersecreting the vasoactive intestinal peptide (VIP). We report a case of WDHA syndrome secondary to hypersecretion of VIP that revealed a neuroblastoma in a 13-month-old girl. A secretory diarrhoea, characterised by the persistence of diarrhoea despite the cessation of oral feeding, led to the search of a neuroblastic tumour in the patient. The serum concentration of VIP decreased to normal values soon after the surgical excision of the tumour.

Topics: Diagnosis, Differential; Diarrhea; Female; Humans; Infant; Neuroblastoma; Vasoactive Intestinal Peptide; Vipoma

The mechanisms underlying intestinal secretion in rotavirus diarrhoea remain to be established. We previously reported that rotavirus evokes intestinal fluid and electrolyte secretion by activation of the enteric nervous system. We now report that antagonists for the 5-hydroxytryptamine 3 receptor (5-HT(3)) and vasoactive intestinal peptide (VIP) receptor, but not antagonists for 5-hydroxytryptamine 4 receptor or the muscarinic receptor, attenuate rotavirus induced diarrhoea.. Neurotransmitter antagonists were administered to wild-type or neurokinin 1 receptor knockout mice infected with homologous (EDIM) or heterologous (RRV) rotavirus.. While RRV infected mice had diarrhoea for 3.3 (0.2) days (95% confidence interval (CI) 3.04-3.56), the 5-HT(3) receptor antagonist (granisetron) and the VIP receptor antagonist (4Cl-D-Phe(6),Leu(17))-VIP both reduced the total number of days of RRV induced diarrhoea to 2.1 (0.3) (95% CI 1.31-2.9) (p<0.01). EDIM infected mice treated with granisetron had a significantly shorter duration of diarrhoea (5.6 (0.4) days) compared with untreated mice (8.0 (0.4) days; p<0.01). Experiments with neurokinin 1 receptor antagonists suggest that this receptor may possibly be involved in the secretory response to rotavirus. On the other hand, rotavirus diarrhoea was not attenuated in the neurokinin 1 receptor knockout mice.. Our results suggest that the neurotransmitters serotonin and VIP are involved in rotavirus diarrhoea; observations that could imply new principles for treatment of this disease with significant global impact.

Topics: Animals; Antidiarrheals; Diarrhea; Granisetron; Mice; Mice, Inbred BALB C; Mice, Knockout; Muscarinic Antagonists; Receptors, Muscarinic; Rotavirus Infections; Serotonin; Serotonin Antagonists; Tachykinins; Vasoactive Intestinal Peptide

The presence of rare paraneoplastic syndromes, the opsoclonus-myoclonus-ataxia syndrome (OMA), presumably caused by antineuronal antibody production, and diarrhea, caused by vasoactive intestinal peptide (VIP) secreted by neuroblastoma, may strongly signal the presence of neuroblastoma. The authors describe a child who presented with both syndromes concurrently; this has never been described previously in the same patient. However, diagnosis of neuroblastoma was delayed by a workup focused on the prolonged diarrhea rather than the ataxia. The diarrhea resolved after tumor resection, whereas OMA required further therapy. Increased awareness of VIP-secretory diarrhea, especially in an ataxic child, might contribute to an earlier diagnosis of neuroblastoma.

Topics: Adrenal Gland Neoplasms; Ataxia; Diarrhea; Female; Ganglioneuroblastoma; Humans; Infant; Lymphatic Metastasis; Paraneoplastic Syndromes, Nervous System; Vasoactive Intestinal Peptide

Topics: Adrenal Gland Neoplasms; Ataxia; Diarrhea; Ganglioneuroblastoma; Humans; Paraneoplastic Syndromes, Nervous System; Vasoactive Intestinal Peptide

To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls.. We studied 34 patients with IBS and 15 subjects without gastrointestinal symptoms. The predominant bowel pattern in the IBS patients was constipation in 17 patients (IBS-C) and diarrhoea in 17 patients (IBS-D). With radioimmunoassay, the levels of vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and peptide YY (PYY) were analysed in biopsies from the descending colon and ascending colon obtained during colonoscopy.. The IBS patients had lower levels of PYY in the descending colon than the controls, but the levels in the ascending colon did not differ. The NPY levels were lower in IBS-D than in IBS-C, both in the ascending colon and in the descending colon. Low levels of VIP were more common in IBS patients, but mean levels did not differ between groups. No group differences were observed for substance P. The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY.. IBS patients demonstrate lower levels of PYY in the descending colon than controls. Colonic NPY levels differ between IBS subgroups based on the predominant bowel pattern. These findings may reflect the pathophysiology of IBS and the symptom variation within the IBS population.

Topics: Adult; Aged; Biopsy; Case-Control Studies; Colon; Colonic Diseases, Functional; Constipation; Diarrhea; Female; Humans; Male; Middle Aged; Neuropeptide Y; Peptide YY; Substance P; Vasoactive Intestinal Peptide

Ganglioneuromas (GNs) are neural crest cell-derived tumors and rarely occur in the adrenal gland. There are presently no markers that can reliably distinguish benign and malignant neuroendocrine tumors. Here we describe a 63-year-old woman who developed sudden chest pain and hypertension combined with increased stool frequency. An incidental adrenal mass 5 cm in size with a bright signal on T2-weighted magnetic resonance imaging was discovered. Biochemical evaluation and (131)I-metaiodobenzylguanidine (MIBG) scintigraphy were negative. Histopathological examination revealed a mature adrenal GN. Neuroblastoma, the immature form of a GN, is known for deletions on chromosomal locus 1p36, and adrenal tumors frequently show allele loss on 17p. To further elucidate the histo- and pathogenesis of adrenal GN, we performed loss of heterozygosity studies on chromosomal loci 1p34-36 and 17p13 (the p53 gene locus) after careful microdissection of tumor and normal tissue. We did not detect allelic losses at these loci with the informative polymorphic markers used, suggesting that these loci are not involved in tumorigenesis. In addition, immunohistochemical investigation of the GN was positive for vasoactive intestinal peptide, a hormone commonly expressed in ganglion cells. We suggest that in our patient with an adrenal GN, the combination of biochemical, scintigraphic, molecular, immunohistochemical, and histopathological findings are all consistent with the benign morphology of this tumor.

Topics: Adrenal Gland Neoplasms; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 17; Diarrhea; Female; Ganglioneuroma; Humans; Hypertension; Immunoenzyme Techniques; Loss of Heterozygosity; Magnetic Resonance Imaging; Middle Aged; Vasoactive Intestinal Peptide

Paraneoplastic syndromes are frequently associated with various types of malignant tumors but are fairly rare in the course of hepatocellular carcinoma (HCC). We describe the clinical case of a 76 year old man with chronic hepatitis C infection related to liver disease who had suffered for several months from chronic runny but blood and mucus-free diarrhea, together with progressive weight loss and flushing of the face. Serological tests made on admission confirmed the chronic liver disease and showed an increase of serum levels of some neuroendocrine hormones, i.e. 5-hydroxytryptamine and vasoattive intestinal peptide. Ultrasound and CT scans led to the diagnosis of HCC. The diarrhea and the increase in some neuroendocrine hormones were therefore interpreted as expression of a paraneoplastic-like neuroendocrine syndrome that had preceded the onset of HCC by some months. The patient died a few months after the diagnosis of HCC, from total portal vein thrombosis and consequent liver and renal failure. This clinical report draws the attention to the possibility of paraneoplastic syndrome expression before the clinical onset of HCC and to the role that neuroendocrine hormones may have on the growth and spread of HCC.

Topics: Aged; Carcinoma, Hepatocellular; Diarrhea; Hepatitis C, Chronic; Humans; Liver Neoplasms; Male; Paraneoplastic Syndromes; Radiography, Abdominal; Serotonin; Time Factors; Tissue Polypeptide Antigen; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide

The study was performed on 20 piglets of both sexes. The control group consisted of 10 healthy piglets, the experimental, group included 10 piglets with symptoms of gastroenteritis. All the animals were subjected to euthanasia at the age of 21 or 35 days (weaning), or 7 days after weaning, and immunohistochemical and histopathological examinations were performed on all of them. Immunohistochemical examinations of the experimental piglets included additional tests made on five piglets with gastroenteritis, characterized by poor general condition. Histopathological examinations of the pancreas revealed retrogressive changes, which might result from hemodynamic disorders. Changes in the localization of SOM and VIP found in the pancreas suggested inhibition of pancreatic enzyme synthesis in piglets with diarrhea. The co-localization of GAL and dopamine beta-hydroxylase (D beta H--a key enzyme of the noradrenaline synthesis pathway) in perivascular nerve fibers could lead to considerable vasospasms in the pancreas, resulting in deeper hypoxia of the organ. Immunohistochemical and histopathological examinations confirmed the results of biochemical analyses, indicating failure of the pancreatic exocrine function in piglets with gastroenteritis.

Topics: Animals; Case-Control Studies; Diarrhea; Dopamine beta-Hydroxylase; Female; Galanin; Gastroenteritis; Immunohistochemistry; Male; Metabolic Diseases; Pancreas; Somatostatin; Swine; Swine Diseases; Vasoactive Intestinal Peptide

The syndrome of watery diarrhea associated with hypokalemia and achlorhydria was originally described in 1958. Subsequently, this syndrome was shown to be caused by a neuroendocrine tumor secreting vasoactive intestinal peptide (VIP), and such tumors are almost always pancreatic in origin. We describe the case of a 78-year-old woman with gradual onset of hypokalemia, watery diarrhea, and weight loss. After a left adrenal mass was discovered, the patient chose medical therapy over surgical intervention. Initially her condition responded, then gradually became refractory to medical therapy. She had elevated levels of VIP, pancreatic polypeptide, dopamine, and vanillylmandelic acid. Subsequently, the patient underwent surgical excision of the mass that was found to be a VIP-producing pheochromocytoma. After surgery her diarrhea subsided, and her electrolytes and affected neuroendocrine hormone levels normalized.

Topics: Adrenal Gland Neoplasms; Aged; Diarrhea; Female; Humans; Hypokalemia; Pheochromocytoma; Vasoactive Intestinal Peptide

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) activate two shared receptors, VPAC1 and VPAC2. Activation of VPAC1 has been implicated in elevating glucose output, whereas activation of VPAC2 may be involved in insulin secretion. A hypothesis that a VPAC2-selective agonist would enhance glucose disposal by stimulating insulin secretion without causing increased hepatic glucose production was tested using a novel selective agonist of VPAC2. This agonist, BAY 55-9837, was generated through site-directed mutagenesis based on sequence alignments of PACAP, VIP, and related analogs. The peptide bound to VPAC2 with a dissociation constant (K(d)) of 0.65 nmol/l and displayed >100-fold selectivity over VPAC1. BAY 55-9837 stimulated glucose-dependent insulin secretion in isolated rat and human pancreatic islets, increased insulin synthesis in purified rat islets, and caused a dose-dependent increase in plasma insulin levels in fasted rats, with a half-maximal stimulatory concentration of 3 pmol/kg. Continuous intravenous or subcutaneous infusion of the peptide reduced the glucose area under the curve following an intraperitoneal glucose tolerance test. The peptide had effects on intestinal water retention and mean arterial blood pressure in rats, but only at much higher doses. BAY 55-9837 may be a useful therapy for the treatment of type 2 diabetes.

Topics: Amino Acid Sequence; Animals; Blood Pressure; Cells, Cultured; Diabetes Mellitus, Type 2; Diarrhea; Glucose; Heart Rate; Hormones; Humans; Injections, Intravenous; Injections, Subcutaneous; Insulin; Insulin Secretion; Islets of Langerhans; Molecular Sequence Data; Peptide Fragments; Rats; Rats, Wistar; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide

A 42-year-old woman presented with a 4-year history of worsening diarrhoea that was watery, profuse and confirmed to be secretory in nature. She had tested positive for phenolphthalein on urinary laxative screening but continued to deny laxative usage. Her vasoactive intestinal polypeptide (VIP) level was subsequently found to be markedly elevated. Despite a normal abdominal ultrasound, a computed tomography scan revealed a 5-cm pancreatic tail mass. Octreotide scanning was used to exclude metastatic disease and she went on to have surgical removal of a localized pancreatic vasoactive intestinal polypeptide-oma which resulted in the complete resolution of her diarrhoea.

Topics: Adult; Diagnosis, Differential; Diarrhea; Female; Humans; Pancreatectomy; Pancreatic Neoplasms; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

The enteric nervous system in the small intestine of cattle during Schistosoma bovis infection was studied by histological stains and immunohistochemical methods. Lesions due to migration of schistosoma eggs were located mainly in the mucous and the submucous layer overlaying the submucous vascular arcades. Granulomas destroyed ganglia, neurons, nerves fibre strands and nerve fibres. Ganglia situated within or near granulomas were infiltrated by mast cells, eosinophils, lymphocytes, globule leukocytes, neutrophils and macrophages. Mast cells were in close contact with degenerating neuronal perikarya. Whereas vasoactive intestinal peptide-like immunoreactivity in the nerves and neurons in the ganglia within and around granulomas was increased, the neurofilament-like immunoreactivity was reduced. Compared to the myenteric and external submucous plexuses, the internal submucous and mucous plexuses were the most damaged. These changes imply reduced functional capacity in the nervous tissue which might cause reduced motility, malabsorption and partly account for the loss of body weight and condition and failure to thrive which occur in schistosomosis. Biotinylated affinity purified swine anti-rabbit and mouse anti-rabbit immunoglobulins reacted nonspecifically with a subset of mast cells. The reaction revealed many mast cells in early forming granulomas and around schistosome egg tracts and infiltration of mast cells into the ganglia of intestinal nerve plexuses. The observation shows a localized, Type I hypersensitivity reaction suggesting for the release of mast cell-derived chemical mediators in the intestinal reaction to trap or evict S. bovis eggs and to cause diarrhoea.

Topics: Animals; Cattle; Cattle Diseases; Diarrhea; Enteric Nervous System; Immunohistochemistry; Intestine, Small; Male; Mast Cells; Mice; Neurofilament Proteins; Random Allocation; Schistosoma; Schistosomiasis; Vasoactive Intestinal Peptide

Muscle-stripped piglet colon was used to evaluate changes in short-circuit current (I(sc)) as an indicator of anion secretion. Mucosal exposure to Escherichia coli heat-stable (STa) or heat-labile enterotoxins (LT) stimulated I(sc) by 32 +/- 5 and 42 +/- 7 microA/cm(2), respectively. Enterotoxin-stimulated I(sc) was not significantly affected by either 4,4'-diaminostilbene-2, 2'-disulfonic acid or CdCl(2), inhibitors of Ca(2+)-activated Cl(-) channels and ClC-2 channels, respectively. Alternatively, N-(4-methylphenylsulfonyl)-N'-(4-trifluoromethylphenyl)urea (DASU-02), a compound that inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl(-) secretion, reduced I(sc) by 29 +/- 7 and 34 +/- 11 microA/cm(2), respectively. Two additional diarylsulfonylurea (DASU)-based compounds were evaluated for their effects on enterotoxin-stimulated secretion. The rank order of potency for inhibition by these three closely related DASU structures was identical to that observed for human CFTR. The degree of inhibition by each of these compounds was similar for both STa and LT. The structure- and concentration-dependent inhibition shown indicates that CFTR mediates both STa- and LT-stimulated colonic secretion. Similar structure-dependent inhibitory effects were observed in forskolin-stimulated rat colonic epithelium. Thus DASUs compose a family of inhibitors that may be of therapeutic value for the symptomatic treatment of diarrhea resulting from a broad spectrum of causative agents across species.

Topics: Amiloride; Animals; Anions; Antineoplastic Agents; Benzofurans; Biological Transport; Bumetanide; Cadmium Chloride; Colon; Cystic Fibrosis Transmembrane Conductance Regulator; Diarrhea; Diuretics; Enterotoxins; In Vitro Techniques; Intestinal Mucosa; Phenylurea Compounds; Stilbenes; Sulfonylurea Compounds; Swine; Tetrodotoxin; Urea; 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

Topics: Adrenal Gland Neoplasms; Child, Preschool; Diarrhea; Female; Ganglioneuroblastoma; Humans; Magnetic Resonance Imaging; Vasoactive Intestinal Peptide

Irinotecan--or CPT-11; 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptotheci n--is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is severe diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Cisplatin (CDDP; cis-diamminedichloroplatinum) and CPT-11 exhibit synergistic antitumor activity and have been used in combination-chemotherapy regimens. Single-agent chemotherapy with conventional doses of CDDP does not cause clinically relevant diarrhea.. To elucidate the mechanisms of induction of diarrhea by high-dose CPT-11 and to compare them with those of diarrhea induced by high-dose CDDP, we used histopathologic and immunohistochemical methods to examine the intestines of mice treated with either CPT-11, CDDP, or saline (control).. Male ICR mice were administered intraperitoneally either 100 mg/kg CPT-11 daily for 4 days, 10 mg/kg CDDP daily for 3 days, or phosphate-buffered saline (control) daily for 4 days (10 mice per group). Preliminary experiments indicated that diarrhea was induced in mice approximately 6 days after administration of CPT-11 or CDDP; therefore, in the experiments described, animals were killed 6 days after the first dose. Serial paraffin-embedded sections of the intestine were stained with hematoxylin-eosin, Grimelius (to identify endocrine cells), or high-iron diamine-alcian blue (stains sialomucin blue and sulfomucin brown-black). Immunohistochemical analyses were performed with the use of anti-proliferating cell nuclear antigen (anti-PCNA; to assay proliferation), anti-Le(y) (BM-1; indirect measure of apoptosis), and anti-synaptophysin antibodies (to identify the enteric nervous system and enterochromaffin cells). A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) method was used to detect DNA fragmentation in situ (i.e., apoptosis). The concentrations of two intestinally active secretogogues, plasma serotonin and vasoactive intestinal polypeptide, were also measured.. The levels of plasma intestinal hormones were similar in control, CPT-11, and CDDP groups. No active necrotic changes were observed in the intestines of CPT-11- and CDDP-treated mice, even though marked thinning of the intestinal walls was observed in both cases. The intestines of CPT-11-treated mice, but not those of control or CDDP-treated mice, were characterized by epithelial vacuolation of the ileum (associated with increased apoptosis as measured by BM-1 and TUNEL) and goblet-cell hyperplasia with excessive amount of sulfomucin in the cecum (suggesting induction of differentiation). By contrast, CDDP treatment of mice reduced the number of villi in the jejunum and destroyed crypt cells containing large Paneth (secretory) granules in the ileum.. CPT-11 may produce characteristic mucosal changes in the intestine by inducing apoptosis and cell differentiation. The observed changes are likely to cause malabsorption of water and electrolytes and hypersecretion of mucin. These structural and functional effects are probably the main causes of CPT-11-induced diarrhea. CDDP appears to cause diarrhea in mice by causing diffuse mucosal damage in the intestines.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Camptothecin; Cecum; Cisplatin; Diarrhea; Enzyme Inhibitors; Hyperplasia; Ileum; Intestinal Mucosa; Irinotecan; Male; Mice; Mucins; Proliferating Cell Nuclear Antigen; Serotonin; Topoisomerase I Inhibitors; Vasoactive Intestinal Peptide

Elevated plasma levels of vasoactive intestinal polypeptide (VIP) (as assessed by a radio-immunoassay), were found in 7/11 patients with AIDS or AIDS-related Complex (ARC), evaluated because of prolonged intractable diarrhea with either an infectious (6 cases) or a non-infectious (5 cases) etiology. Six subjects have been treated with the somatostatin analogue octreotide, which gave both a favourable clinical response and a significant reduction in plasma VIP concentrations. Evaluation of plasma VIP levels may provide a pathophysiological basis for explaining the efficacy of octreotide therapy in HIV-infected patients suffering from both infectious and non-infectious refractory diarrhea.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; Diarrhea; Homosexuality; Humans; Male; Octreotide; Substance Abuse, Intravenous; Time Factors; Vasoactive Intestinal Peptide

The opiate antidiarrhoeal drugs loperamide (0.6 mg kg-1, i.p.) or difenoxin (0.77 mg kg-1, s.c.), were administered in an anaesthetic mixture (pentobarbitone 60 mg kg-1) to rats. A length of jejunum (approx. 30 cm) was cannulated, washed and then perfused with iso-osmotic saline for 20 min. The perfusion commenced 50 min after drug administration and continued for 20 min. The perfusates were collected for analysis of fluid transport rates and antidiarrhoeal drug content. These doses of the antidiarrhoeals caused marked inhibition of intestinal fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide. However, neither of the antidiarrhoeal drugs were detected in the intestinal perfusates (< 0.5 ng by HPLC). The results indicate that loperamide and difenoxin have a different pharmacokinetic profile compared with that previously found for morphine under the same conditions.

Topics: Absorption; Animals; Antidiarrheals; Calibration; Castor Oil; Chromatography; Diarrhea; Diphenoxylate; Female; Intestinal Mucosa; Intestinal Secretions; Loperamide; Male; Narcotics; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

To evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide.. Three AIDS patients were evaluated for severe watery diarrhoea of 2-6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities. They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment.. A complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed. Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects.. Since no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed. Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5 pmol/l (values < 8.8 pmol/l in the control group). One patient received 50-100 micrograms octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values.. Although the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects. Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment.

Topics: Acquired Immunodeficiency Syndrome; Adult; Diarrhea; Female; Humans; Male; Octreotide; Vasoactive Intestinal Peptide

This study examines the effects of endotoxin on intestinal water and electrolyte transport in adult male rats. Endotoxin (1.55 mg/kg, intravenously) reduced in vivo colonic saline absorption 61% in 1 hour. In vitro unidirectional and net 22Na and 36Cl fluxes showed that endotoxin significantly decreased net colonic 22Na absorption compared with control colons (0.3 +/- 1.7 vs. 4.8 +/- 1.1 microEq/h x cm2). Although endotoxin had no significant effect on basal short circuit current (Isc) and conductance, 3H-inulin flux studies suggested an increase in colonic permeability. Isc responses to the 5'-cyclic adenosine monophosphate (cAMP)-dependent secretagogues prostaglandin E2 (1 mumol/L) and vasoactive intestinal peptide (0.1 mumol/L) were diminished by 80% and 50%, respectively. However, cytosolic cAMP-dependent protein kinase activity under basal and stimulated (6 mumol/L 8-bromo-cAMP) conditions was not altered by endotoxin treatment. The Isc responses to 10 mumol/L bethanechol, a Ca(2+)-dependent agonist, were not effected by endotoxin treatment. It was concluded that endotoxin significantly affects colonic transport function and may contribute to the development of diarrhea in inflammatory bowel diseases.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Bethanechol; Bethanechol Compounds; Biological Transport; Chlorine; Colforsin; Colon; Diarrhea; Dinoprostone; Endotoxins; Ileum; Insulin; Jejunum; Male; Protein Kinases; Rats; Rats, Sprague-Dawley; Sodium; Theophylline; Vasoactive Intestinal Peptide; Water-Electrolyte Balance

By means of radioimmunoassay, the mucosal substance P (SP) and vasoactive intestinal polypeptide (VIP) concentration in distal ileum, transverse colon and sigmoid colon in 30 patients of chronic diarrhea with splenic weakness was determined and compared with that in 28 patients of chronic diarrhea without splenic weakness and in 15 controls without chronic diarrhea. In patients of chronic diarrhea with splenic weakness, the SP contents in the mucosa of distal ileum (120.95 +/- 90.70 pg/mg wet weight) was significantly increased compared with that in controls without diarrhea (47.86 +/- 35.49 pg/mg wet weight) and in chronic diarrhea without splenic weakness (52.50 +/- 42.49 pg/mg wet weight), P less than 0.01 and 0.01 less than P less than 0.05 respectively. The VIP contents of sigmoid mucosa in patients of chronic diarrhea with splenic weakness (510.63 +/- 265.22 pg/mg wet weight) was markedly increased in comparison of that in controls without chronic diarrhea (308.67 +/- 204.49 pg/mg wet weight), 0.01 less than P less than 0.05, and was not significantly augmented compared with that in chronic diarrhea without splenic weakness (398.97 +/- 240.80 pg/mg wet weight), but the tendency of increase was present. Our results suggested that the increased SP and VIP in patients of chronic diarrhea with splenic weakness might be closely related to the symptom of chronic diarrhea. According to the general function of VIP, the authors predicted that VIP might play a more important role in the pathogenetic action of chronic diarrhea with splenic weakness.

Topics: Adult; Chronic Disease; Diarrhea; Female; Humans; Intestinal Mucosa; Male; Splenic Diseases; Substance P; Vasoactive Intestinal Peptide

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Chromatography, Gel; Chronic Disease; Diarrhea; Female; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Radioimmunoassay; Vasoactive Intestinal Peptide

To investigate whether peptide YY (PYY) has a role in minimising fluid loss during diarrhoea, its effect on hypersecretion induced by vasoactive intestinal peptide (VIP) was studied in seven subjects with ileostomies. An isotonic electrolyte solution containing polyethylene glycol 4000 was infused directly into the duodenum and the effluent was collected for 40 min (baseline), then VIP was infused intravenously at 5 pmol.kg-1.min-1 for 500 min. PYY was infused intravenously at low doses (0.4 and 0.2 pmol.kg-1.min-1) for 100 min each during the continuous VIP infusion. Small-intestinal secretion was assessed by effluent weight and by polyethylene glycol dilution, which gave similar results. Plateau ileal output was 501 (SEM 33) ml/h during VIP infusion. PYY caused significant falls in secretion--to 404 (48) ml/h for the lower dose and to 323 (75) ml/h for the higher. It also prolonged small-bowel transit. These findings suggest that PYY is a natural inhibitor of diarrhoea and that its therapeutic potential merits investigation.

Topics: Diarrhea; Female; Gastrointestinal Transit; Humans; Ileostomy; Ileum; Infusions, Intravenous; Intestinal Absorption; Male; Middle Aged; Peptide YY; Peptides; Random Allocation; Stimulation, Chemical; Vasoactive Intestinal Peptide

Long-acting somatostatin analogues such as SMS 201-995 (Sandoz) are being evaluated in a wide range of clinical indications, including gut neuroendocrine tumours and acrogemaly. Long-term continuous SMS 201-995 treatment has achieved useful symptomatic improvement in diarrhoea in 4 patients with metastatic VIPomas who had relapsed following previous treatment. Clinical improvement has outlasted suppression of VIP secretion (suggesting an additional direct antisecretory action of SMS 201-995) and has occurred despite expansion of hepatic metastases. In 6 patients with tumours secreting gastrin and/or glucagon, secretion of these peptides was acutely inhibited by SMS 201-995. However, endocrine and clinical responses to chronic treatment have been less consistent. SMS 201-995 is active orally at doses of 4-8 mg and when given thrice-daily to 6 patients with active acromegaly, suppressed mean 24-h growth hormone levels by 51-88%. Despite significantly reduced plasma insulin concentrations, glucose tolerance did not deteriorate. SMS 201-995 was also effective in suppressing thyroid-stimulating hormone (TSH) and thyroid hormone secretion in a patient with mild thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. In all cases SMS 201-995 treatment has been well tolerated and has few side-effects.

Topics: Acromegaly; Adenoma; Adult; Aged; Diarrhea; Female; Gastrointestinal Neoplasms; Glucagonoma; Growth Hormone; Humans; Hyperthyroidism; Liver Neoplasms; Male; Middle Aged; Neoplasms, Glandular and Epithelial; Octreotide; Pancreatic Neoplasms; Pituitary Neoplasms; Somatostatin; Streptozocin; Thyrotropin; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

A 40 year old woman presented with a 10 year history of watery diarrhoea and an acute quadriparesis. On clinical examination there was severe muscle weakness and a nodule was palpable in the thyroid gland. Biochemical testing revealed a hypokalaemia at 1.6 mmol/l. Plasma levels of VIP were raised at 202 pmol/l. CT scanning demonstrated a mass in the area of the left adrenal gland, and isotope scanning of the thyroid gland showed a 'cold' nodule. The plasma catecholamines and calcitonin were elevated. The patient also presented with psychiatric symptoms, and the relevance of these to her condition has been discussed. At operation a left adrenal tumour was removed. Post-operatively the patient's symptoms disappeared and the plasma hormone levels returned to normal values. Histological examination of the tumour revealed a well differentiated phaeochromocytoma which contained VIP and calcitonin. The thyroid nodule was excised and showed histological features of autoimmune thyroid disease. It is suggested that in all cases of the WDHA syndrome where the tumour is in an extra-pancreatic site patients should be screened for phaeochromocytoma.

Topics: Adrenal Gland Neoplasms; Adult; Calcitonin; Diarrhea; Epinephrine; Female; Humans; Norepinephrine; Pheochromocytoma; Thyroiditis, Autoimmune; Vasoactive Intestinal Peptide

The effect of oral lidamidine hydrochloride and subcutaneous long acting somatostatin analogue, SMS 201-995, on stool output and salt and water transport in the small intestine was investigated in a patient with gross secretory diarrhoea caused by a vasoactive intestinal polypeptide (VIP) secreting tumour in the liver. Transport in the jejunum and ileum were assessed by steady state perfusion techniques. Under basal conditions, the patient was absorbing fluid and electrolytes from the jejunum and ileum, but at rates that were abnormally low. Lidamidine had no effect on either intestinal transport or stool frequency and output. SMS 201-995 increased intestinal absorption in the jejunum and ileum, reduced plasma VIP concentrations, daily stool frequency and weight, and enabled the patient to resume a normal diet without oral or intravenous fluid and electrolyte supplements. After two months of treatment, medical control was becoming increasingly difficult and stool output had risen again to 2 litres per day. Surgical resection, fortunately, was possible and led to resolution of symptoms and normal plasma VIP concentrations.

Topics: Adult; Biological Transport; Body Fluids; Diarrhea; Electrolytes; Humans; Intestinal Absorption; Liver Neoplasms; Male; Octreotide; Phenylurea Compounds; Somatostatin; Vasoactive Intestinal Peptide

A 44-year-old woman with hepatocellular carcinoma presented with intractable watery diarrhea and her condition was evaluated angiographically. Surgical ablation of the tumor resulted in complete resolution of the diarrhea. The tumor cells of the hepatocellular carcinoma were found to contain vasoactive intestinal polypeptide, gastrin, and prostaglandinlike immunoactivity. To our knowledge, this is the first report of such an association.

Topics: Adult; Carcinoma, Hepatocellular; Diarrhea; Dinoprostone; Female; Gastrins; Histocytochemistry; Humans; Liver Neoplasms; Paraneoplastic Endocrine Syndromes; Prostaglandins E; Radiography; Vasoactive Intestinal Peptide

Pancreatic islet cell tumors that secrete one or several polypeptide hormones have been suspected and diagnosed secondary to their systemic manifestations. This case report details the diagnosis and treatment of an 62-year-old man with a large pancreatic islet cell tumor without symptoms in whom the mass was found as a direct result of blunt trauma to the abdomen. The tumor contained high concentrations of both vasoactive intestinal polypeptide (VIP) and somatostatin. A discussion of VIP-containing tumors is included.

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

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

Topics: Aged; Diarrhea; Female; Ganglioneuroma; Humans; Neoplasms, Multiple Primary; Pheochromocytoma; Vasoactive Intestinal Peptide

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

Topics: Acidosis; Adenoma, Islet Cell; Aged; Diarrhea; Drug Resistance; Female; Humans; Hypokalemia; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Motilin; Neurotensin; Octreotide; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide

Seven patients with gut and pancreatic endocrine tumours have been treated with a long acting somatostatin analogue (SMS 201-995), given as a twice daily subcutaneous injection. This produced dramatic improvement in their endocrine related symptoms, in association with a fall in circulating tumour peptides. One of these patients has now been treated for seven months with this analogue which has controlled his previously life threatening diarrhoea caused by a malignant VIP secreting tumour. He gives his own injections twice daily, and has returned to a full and active life. This is a promising agent both for acute treatment of peptide hypersecretion, and for the long term management of some patients who are unresponsive to other available therapy.

Topics: Adult; Aged; Diarrhea; Female; Gastrins; Glucagon; Humans; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptide PHI; Peptides; Somatostatin; Vasoactive Intestinal Peptide

Amelioration or cure of hypertension, hypercortisolism, diarrhea with steatorrhea, and massive proteinuria resulted from excision of a pheochromocytoma that contained immunoreactive ACTH, VIP, and somatostatin. Ectopic ACTH production by the tumor was clearly the cause of the hypercortisolism, and the possible involvement of VIP and somatostatin in the diarrhea and steatorrhea was considered. The response to tumor removal suggested that the mesangioproliferative glomerulonephritis shown on renal biopsy was also a paraneoplastic phenomenon.

Topics: Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Celiac Disease; Diarrhea; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Pheochromocytoma; Proteinuria; Somatostatin; 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; Contrast Media; Diarrhea; Diatrizoate; Humans; Iodine; Iopanoic Acid; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Prednisone; Vasoactive Intestinal Peptide; Vipoma

A 55-year-old woman presented with several protracted episodes of diarrhea; it was found to be secretory in origin. In the course of evaluating the diarrhea, an ultrasound of the abdomen was performed which disclosed a large right adrenal mass. Endocrinologic studies revealed elevated serum levels of gastrin, vasoactive intestinal polypeptide (VIP), catecholamines, and its metabolites. Surgery was performed successfully without any intraoperative complications, and postoperatively the patient was asymptomatic without further episodes of diarrhea. Histologically the tumor was a pheochromocytoma with neuroendocrine granules of vasoactive intestinal polypeptide and norepinephrine. To our knowledge, there have been six previously reported cases of pheochromocytoma secreting vasoactive intestinal polypeptide. In a patient with secretory diarrhea of unknown etiology, the adrenal glands as well as the pancreas should be examined by ultrasound and/or computerized tomography for the presence of a mass. Should an adrenal mass be discovered, it is necessary to evaluate the tumor for catecholamine production, despite the absence of clinical symptoms of a pheochromocytoma.

Topics: Adrenal Gland Neoplasms; Angiography; Diarrhea; Female; Humans; Microscopy, Electron; Middle Aged; Paraneoplastic Endocrine Syndromes; Pheochromocytoma; Tomography, X-Ray Computed; Ultrasonography; Vasoactive Intestinal Peptide

Topics: Diarrhea; Humans; Neoplasms; Vasoactive Intestinal Peptide

Topics: Diarrhea; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

The diagnosis of vasoactive intestinal poly-peptide-secreting tumor (VIPoma) was established in two boys on the basis of watery diarrhea with hypokalemia, elevated plasma levels of vasoactive intestinal polypeptide (VIP) (range of 55-94 pmol/L), and presence of a tumor of the left adrenal gland. Despite celiac angiography, VIP estimation in blood samples taken from different parts of the body, and exploratory laparotomy, localization of the tumor in one child in vivo was unsuccessful. In the other boy, computed tomography revealed a large tumor in the left adrenal gland. Following the removal of the tumor, diarrhea ceased, and 10 days after surgery, the plasma level of VIP was 5 pmol/L. Histologically, the tumors in the two boys were found to be ganglioneuromas. The diagnosis of VIPoma is simple but localization can be very difficult. Surgical removal of VIPoma is often rewarding.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Child; Chronic Disease; Dehydration; Diarrhea; Ganglioneuroma; Humans; Hypokalemia; Male; Tomography, X-Ray Computed; Vasoactive Intestinal Peptide; Vipoma

A case of a 12-month-old child with chronic water diarrhoea, weight loss, abdominal distension, hypokalaemia and hypochlorhydria, which were associated with a vasoactive intestinal peptide secreting ganglioneuroma, is reported. Removal of the tumour led to complete clinical and biochemical recovery. Measurement of vasoactive intestinal peptide levels should be included in the evaluation of chronic diarrhoea after the more common causes have been ruled out.

Topics: Adenoma, Islet Cell; Diarrhea; Female; Ganglioneuroma; Gastric Dilatation; Humans; Infant; Vasoactive Intestinal Peptide; Vipoma

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

Topics: Adenoma, Islet Cell; Body Water; Diarrhea; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

In 12 patients treated 2 to 58 months previously for medullary carcinoma of the thyroid, basal serum concentrations of calcitonin, gastrin, vasoactive intestinal polypeptide, glucagon, insulin, and pancreatic polypeptide were measured in search of any correlation between these and the clinical course of the disease. All patients had elevated serum calcitonin levels indicating present disease. One patient had increased serum concentrations of several hormones. Another had achlorhydria and high serum gastrin levels. No relationship between calcitonin and gastro-intestinal polypeptides was found in 11 patients. No correlations were found between serum levels of polypeptides and the occurrence of diarrhoea in 5 patients. It is concluded that gastro-intestinal polypeptides, which are produced by other apudomas, are not secreted in more than normal concentrations under basal conditions, by the majority of patients previously treated for medullary carcinoma of the thyroid.

Topics: Adolescent; Adult; Aged; Calcitonin; Carcinoma; Diarrhea; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Male; Middle Aged; Thyroid Neoplasms; Vasoactive Intestinal Peptide

To determine whether the antidiarrheal effect of loperamide is due to an effect on intestinal motor function or to an acceleration of the rate of absorption by the intestine (as has been suggested recently), we studied absorption during experimental diarrhea produced by the rapid intragastric infusion of electrolyte solution. In studies in which a 2700-ml bolus of electrolyte solution was infused into the stomach over 90 min, loperamide delayed the appearance of rectal effluent in each of 5 subjects and decreased the volume of rectal effluent from 1090 +/- 118 to 770 +/- 73 ml (p = 0.05). When intragastric infusion was continued for 5 h, producing steady-state total gut perfusion, the volume of effluent produced per unit time and the concentration of a nonabsorbable polyethylene glycol marker in rectal effluent was not different with or without loperamide, indicating that loperamide did not alter the rate of absorption by intestinal mucosal cells. Loperamide also had no effect during steady-state perfusion when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. Loperamide did substantially increase the intraluminal volume of the total gut, from 985 +/- 131 to 1764 +/- 195 ml (p less than 0.02). These results suggest that loperamide exerts its antidiarrheal effect by a change in the motor function of the intestine, which results in increased capacitance of the gut and a delay in the passage of fluid through the intestine. This change in motor function, rather than a change in the rate of absorption by intestinal mucosal cells, is responsible for the antidiarrheal effect of loperamide in our experimental diarrhea model.

Topics: Adult; Antidiarrheals; Diarrhea; Electrolytes; Gastrointestinal Motility; Humans; Intestinal Absorption; Loperamide; Male; Piperidines; Polyethylene Glycols; Vasoactive Intestinal Peptide

Peptide histidine isoleucine (PHI), first isolated from pig intestine, is distributed identically to vasoactive intestinal peptide (VIP) in all mammals. 42 patients with high plasma VIP secondary to VIPoma also had very high plasma PHI-like immunoreactivity, in a constant ratio to VIP. None of 125 patients with other endocrine tumours had high levels of either peptide. VIPoma tissue from 20 patients also contained PHI shown by immunocytochemistry to be produced by the same cell as VIP. Messenger RNA(mRNA) from one of these tumours contained the codes for VIP and a separate PHI-like sequence. Human PHI-like sequence differed from porcine PHI in only two aminoacid residues. A single cell thus produces two separate regulatory peptides with apparently similar potencies but different spectra of activity. In normal tissue the constant coproduction of two active neuropeptides by a single neuron provides further evidence against the doctrine of one neuron producing only one neurotransmitter.

Topics: Adenoma, Islet Cell; Base Sequence; Diarrhea; Genetic Code; Histocytochemistry; Humans; Intestinal Secretions; Intestine, Small; Pancreatic Neoplasms; Peptide PHI; Peptides; Radioimmunoassay; RNA, Messenger; RNA, Neoplasm; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Adult; Diarrhea; Humans; Male; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

We attempted to reproduce the diarrhea of pancreatic cholera syndrome with prolonged (10-hour) administration of vasoactive intestinal polypeptide (VIP) in five healthy nonfasting subjects. The polypeptide was given as a continuous intravenous infusion at a rate of 400 pmol per kilogram of body weight per hour. By two hours the plasma VIP concentration had risen from a normal basal value of 15.3 +/- 0.2 (mean +/- S.E.M.) to 129 +/- 40 pmol per liter--within the range found in patients with pancreatic cholera syndrome. In each subject profuse watery diarrhea developed within 4.3 +/- 0.8 hours (range, 2.0 to 6.3), and the mean stool weight at 10 hours was 2441 +/- 600 g (normal 24-hour stool weight, less than 200 to 250 g). The results of stool analysis were consistent with secretory diarrhea. Between the first and last stool, there were significant increases in fecal sodium and bicarbonate concentrations and in pH. The large fecal bicarbonate loss induced hyperchloremic metabolic acidosis, which is characteristic in patients with pancreatic cholera syndrome. Our study suggests that VIP is not merely a marker of pancreatic cholera, but is the mediator of watery diarrhea in this syndrome.

Topics: Adenoma, Islet Cell; Adult; Diarrhea; Electrolytes; Feces; Flushing; Humans; Injections, Intravenous; Male; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

Topics: Acute Disease; Adult; Aged; Blood Glucose; Diarrhea; Female; Food; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Motilin; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

A three year old girl with severe watery diarrhoea and a vasoactive intestinal peptide, calcitonin, and catecholamine-secreting supra-renal ganglioneuroblastoma is reported. Steady-state perfusion studies showed the jejunum to be in a net secretory state with respect to water, sodium, and chloride at low concentrations (2 mmol/l) of glucose whereas higher concentrations (56 mmol/l) reversed secretion to absorption; transmural rectal potential difference was increased (lumen negative); Na+ absorption by the rectum was impaired and secretion of potassium and bicarbonate excessive. Motility studies showed prolonged, slowly propagated migrating motor complexes with abnormal runs of non-propagated contractions in the fasting state. During perfusion with glucose, no postprandial activity occurred. These results suggest that diarrhoea results from small intestinal secretion with impaired colonic function and that tumour products may have a direct effect on intestinal motility.

Topics: Adrenal Gland Neoplasms; Biological Transport; Calcitonin; Child; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Motility; Humans; Infant; Intestine, Small; Male; Norepinephrine; Rectum; Vasoactive Intestinal Peptide

Topics: Adrenal Gland Neoplasms; Child; Diagnosis, Differential; Diarrhea; Female; Ganglioneuroma; Growth Disorders; Humans; Male; Vasoactive Intestinal Peptide

A case of vasoactive intestinal polypeptide secreting ganglioneuroma associated with watery diarrhea and hypokalemia is presented. Diagnosis was delayed due to the presence of two parasitic infestations. After surgical removal of the tumor, the diarrhea resolved.

Topics: Adrenal Gland Neoplasms; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Giardiasis; Humans; Intestinal Diseases, Parasitic; Trichomonas Infections; Vasoactive Intestinal Peptide

This paper describes two children with diarrhea, hypokalemia, and VIP-secreting ganglioneuroblastomas, and includes further evidence that VIP is the cause of the loose stools among patients with such tumors. It suggests that the level of this peptide should be measured in pediatric patients with intractable diarrhea of unknown etiology. Clinicians have long recognized intractable diarrhea as an occasional feature of neuroblastoma, ganglioneuroblastoma or ganglioneuroma. Until recently catecholamine was thought to cause the frequent stools in some patients with these tumors. New radioimmunoassay methods, the identification of new hormones and hormone-like substances, and the discovery that some of the tumors which cause diarrhea secrete Vasoactive Intestinal Peptide (VIP), make it probable that this substance is responsible for the diarrhea in such patients.

Topics: Child, Preschool; Chronic Disease; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Infant; Male; Vasoactive Intestinal Peptide

Topics: Adrenal Gland Neoplasms; Celiac Disease; Child, Preschool; Chronic Disease; Cystic Fibrosis; Diagnosis, Differential; Diarrhea; Ganglioneuroma; Gastrointestinal Hormones; Humans; Male; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Animals; Diarrhea; Humans; Male; Pancreatic Neoplasms; Rabbits; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Diarrhea; Gastrointestinal Hormones; Humans; Male; Middle Aged; Pancreatic Neoplasms; 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

The concentration of vasoactive intestinal polypeptide (VIP) in plasma was measured in 22 children with neural crest tumours (NCT) during a 5-year period; the mean concentration of VIP in plasma was 22.5 pmol/l (interval 2.0-95.0 pmol/l). To establish a reference interval the plasma concentration of VIP was measured in 41 children without tumours; the mean concentration of VIP in plasma was 6.2 pmol/l (interval 0.5-19.0 pmol/l). Of the 22 children with NCT 16 had a plasma concentration of VIP within the normal range while 6 children (27%) had elevated plasma concentration of VIP between 28 and 95 pmol/l. Only one child, whose plasma concentration of VIP was 95 pmol/l had diarrhoea. Elevated plasma concentration of VIP in children with NCT but no diarrhoea has not previously been described. The urinary excretion of vanillylmandelic acid (VMA) was increased in 18 of the children with NCT (82%). In 2 of the children with normal excretion of VMA the concentration of VIP in plasma was elevated. Thus, the plasma concentration of VIP may be a supplement to VMA as a tumour marker in some cases of NCT.

Topics: Child; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Infant; Male; Neoplasms, Germ Cell and Embryonal; Neuroblastoma; Reference Values; Vasoactive Intestinal Peptide

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

The mechanisms by which bacterial enterotoxins cause secretory diarrheas have been well defined, and the definitions of such mechanisms have been important in developing a consistently successful therapeutic approach. The less common secretory diarrheas, caused by the interaction of hormones of tumor origin with the gut small intestinal mucosa have also been clearly defined, and their pathogenetic mechanisms are similar to those by which the cholera and E. coli enterotoxins cause secretory diarrhea. The mechanisms by which histamine and gastrin of tumor origin cause gastric hypersecretion are less clearly delineated; secretory diarrhea caused by both of these agents can be stopped by total gastrectomy without removal of the responsible tumor. The secretory diarrhea caused by villous adenomas of the colon, which does not appear to be related to a distally produced humoral agent, results in the same picture of hypokalemic acidosis that is characteristic of the nonbacterial secretory diarrheas originating in the small intestine and is cured by resection of the responsible tumor.

Topics: Adenoma; Antigens, Bacterial; Bacterial Toxins; Cholera; Cholera Toxin; Colonic Neoplasms; Diarrhea; Enterotoxins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fimbriae Proteins; Hormones, Ectopic; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Neoplasms, Hormone-Dependent; Prostaglandins; Vasoactive Intestinal Peptide; Water-Electrolyte Balance; Zollinger-Ellison Syndrome

A 1 1/2 year old child developed profuse watery diarrhoea, shown to be due to excessive plasma vasoactive intestinal peptide (VIP) levels, whilst on treatment for metastatic neuroblastoma. Because it was unresponsive to alternative treatment, an attempt was made to control the diarrhoea with a somatostatin infusion. The attempt failed despite the fact that serum VIP levels were substantially reduced. Possible reasons for failure are discussed and the importance of plasma VIP as a marker for maturation in neuroblastoma emphasised.

Topics: Diarrhea; Female; Gastrointestinal Hormones; Humans; Infant; Neoplasm Metastasis; Neuroblastoma; Somatostatin; Vasoactive Intestinal Peptide

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

During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.

Topics: Adult; Aged; Child; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Infant; Male; Middle Aged; Neural Crest; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

A female patient is described with a single pancreatic tumour producing vasoactive intestinal polypeptide (VIP), insulin, and pancreatic polypeptide. The initial presentation was with diarrhoea and hypokalaemia and a raised plasma VIP was demonstrated. Her symptoms improved with metoclopramide administration and absolute concentrations of 28 aminoacid (peak IV) VIP were found to have fallen. She then developed hypoglycaemia with hyperinsulinism. All symptoms resolved after surgical excision. This case emphasises the potential of these tumours to contain more than one endocrine cell type synthesising different biologically active peptides.

Topics: Apudoma; Diarrhea; Female; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Metoclopramide; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

Topics: Diarrhea; Female; Gastrointestinal Hormones; Humans; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

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; Dehydration; Diagnosis, Differential; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Animals; Chickens; Colon; Cyclic AMP; Diarrhea; Dose-Response Relationship, Drug; Epithelial Cells; Female; Gastrointestinal Hormones; Humans; In Vitro Techniques; Intestines; Isoproterenol; Male; Models, Biological; Prostaglandins E; Secretin; Species Specificity; Swine; Temperature; 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

A case of WDHA syndrome accompanied by a pancreatic tumor in a 44-year-old Japanese male is presented, the 6th case in Japan. Clinically, the patient suffered from unremitting watery diarrhea, hypokalemia and achlorhydria with marked anemia and jaundice. The patient died of emaciation, dehydration and bronchopenumonia, and an autopsy was performed. Autopsy examination revealed a hen's egg-sized tumor in the tail of the pancreas with metastases in liver, lungs and lymph nodes. In addition, bronchopneumonia and diabetic nephrosclerosis were present. Histologically, the tumor had the characteristics of an islet cell tumor, and histochemically the tumor cells were positive to Grimelius' stain which revealed non-B-islet cell features. Electron-microscopically, the tumor cells had electron dense round membrane-bounded granules resembling non-B-granules of pancreatic islet cells. With the immunoperoxidase procedure (PAP method), tumor cells nearly almost reacted to anti-vasoactive intestinal polypeptide (VIP) serum, which suggested that the tumor of the present case had the capability to produce VIP.

Topics: Achlorhydria; Adenoma, Islet Cell; Adult; Cytoplasmic Granules; Diarrhea; Humans; Hypokalemia; Male; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

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

A patient with water diarrhoea syndrome (WDS) is described. A pancreatic tumour was found containing many cells with immunoreactivity to enkephalin and neurotensin, a few with immunoreactivity to calcitonin but none to vasoactive intestinal peptide (VIP). High levels of calcitonin, neurotensin, VIP and pancreatic polypeptide (PP) were present in plasma as measured by radioimmunoassay. After removal of the tumour, the plasma levels of the first three peptides returned to normal and the WDS disappeared. On the other hand, plasma PP did not change. No specific symptoms could be attributed to the new spectrum of peptides found in the tumour. This is the first report of a pancreatic tumour containing high levels of neurotensin.

Topics: Aged; Calcitonin; Diarrhea; Endorphins; Enkephalins; Fluorescent Antibody Technique; Humans; Male; Neurotensin; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; 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: Body Weight; Child, Preschool; Diarrhea; Female; Gastrointestinal Hormones; Humans; Mediastinal Neoplasms; Neurofibroma; Vasoactive Intestinal Peptide

Topics: Adult; Catecholamines; Child; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Infant; Retroperitoneal Neoplasms; Vasoactive Intestinal Peptide

In a 2 1/2-year-old girl with persistent watery diarrhea a retroperitoneal tumour and lymph node composed of benign ganglioneuroma cells were found. The histological picture was compatible with an original metastasizing neuroblastoma which has passed through a stage of late maturation. Electron microscopy of the ganglioneuroma showed cytological evidence of increased secretory activity. The tumour contained large amounts of vasoactive intestinal polypeptide (VIP) and preoperative plasma concentration of this peptide was increased. Postoperatively the VIP concentration was normalized, and the diarrhea ceased. Analysis of catecholamine metabolites in urine was normal. The findings suggest that the watery diarrhea was due to the benign VIP-producing neural crest tumour.

Topics: Child, Preschool; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Vasoactive Intestinal Peptide

Topics: Brain Chemistry; Chromatography, Affinity; Chromatography, Gel; Colon; Diarrhea; Gastrointestinal Hormones; Humans; Molecular Weight; Pancreas; Pancreatic Neoplasms; Radioimmunoassay; Vasoactive Intestinal Peptide

Cyclic AMP accumulation in human colon adenocarcinoma cells in culture (HT-29) is known to be particularly sensitive to the stimulating action of vasoactive intestinal peptide (VIP). This property was exploited as a means of investigating the possible role of VIP as a humoral mediator in the watery diarrhoea syndrome. Our results showed that plasma from two patients with watery diarrhoea syndrome associated with ganglioneuroblastoma and pheochromocytoma strongly stimulated cyclic AMP accumulation in HT-29 cells, whereas plasma from normal subjects and patients with other diarrhoeal disorders had no effect. The stimulation induced by serial dilutions of plasma from patients paralleled the VIP-induced response. Preincubation of these plasmas with specific anti-VIP antibody prevented their stimulatory effects. Plasma sampled after the arrest of diarrhoea (spontaneous or after surgical resection of tumours) elicited AMP rise in HT-29 cells. Tumour extract stimulated cyclic AMP accumulation in HT-29 cells with a dose-response curve which was superimposable on the one obtained with standard VIP. The results lend support to the hypothesis that VIP is a humoral mediator in WDS and suggest that the diarrhoea is mediated through a VIP-induced accumulation of cyclic AMP in intestinal epithelial cells.

Topics: Adrenal Gland Neoplasms; Adult; Biological Assay; Child, Preschool; Diarrhea; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Male; Pheochromocytoma; Vasoactive Intestinal Peptide

Topics: Adult; Autonomic Nervous System Diseases; Child; Child, Preschool; Diarrhea; Ganglioneuroma; Humans; Infant; Intestines; Nervous System Neoplasms; 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

With the advent of radioimmunoassay and immunocytochemical methods, the peptides of the gastrointestinal tract have been identified and measured. Gastrinoma and insulinoma syndromes have been wall characterized. The pancreatic cholera syndrome and some of the evidence that the major manifestations of this disease may be mediated by vasoactive intestinal peptide have been re-examined. Pancreatic polypeptide seems to be an ideal peptide for study of vagal-cholinergic mechanisms that regulate hormone release; it also appears to be a tumor marker for several types of pancreatic endocrine tumors, particularly those of pancreatic cholera. Secretin and cholecystokinin are important regulators of pancreatic exocrine secretion and have been used to test pancreatic function, but there is little evidence that they account for clinical disease. Glucagon-secreting tumors produce a clinical syndrome of diabetes mellitus and distinctive skin lesions, which can be cured by tumor resection. Hormone-secreting tumors may provide insight into normal gut physiology.

Topics: Adenoma, Islet Cell; Animals; Apudoma; Cholecystokinin; Diarrhea; Dogs; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon; Hormones; Humans; Intestines; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Stomach; Stomach Neoplasms; Vasoactive Intestinal Peptide

A father and son each presented with severe watery diarrhea. The son was found to have a pancreatic islet-cell tumor associated with the pancreatic cholera syndrome, as well as a parathyroid adenoma. The father was found to have multiple islet-cell adenomas and the Zollinger-Ellison syndrome. Pancreatic tumor tissue from each patient contained detectable gastrin and vasoactive intestinal peptide; however, a much higher gastrin concentration was found in the tumor tissue from the father and a much higher vasoactive intestinal peptide content in the tumor tissue from the son. Thus, watery diarrhea may be mediated by different hormones in families having multiple endocrine neoplasia; the precise cause of the diarrheal syndrome should be defined to ensure the proper therapy.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Diarrhea; Endocrine System Diseases; Gastrins; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Parathyroid Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

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

Topics: Animals; Antibody Specificity; Diarrhea; Dogs; Gastrointestinal Hormones; Humans; Immune Sera; Rabbits; Radioimmunoassay; Vasoactive Intestinal Peptide

Topics: Cholera Toxin; Diarrhea; Gastrointestinal Hormones; Glucocorticoids; Humans; Infusions, Intra-Arterial; Vasoactive Intestinal Peptide; Water-Electrolyte Imbalance

Topics: Adenoma, Islet Cell; Animals; APUD Cells; Biliary Tract; Cholera; Dehydration; Diarrhea; Gastric Juice; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Hypokalemia; In Vitro Techniques; Kidney Diseases; Metabolism; Neurotransmitter Agents; Pancreatic Neoplasms; Respiration; 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

Two unusual cases of the watery diarrhea syndrome are presented. In one patient an adrenal medullary tumor, a pheochromocytoma that produced vasoactive intestinal polypeptide (VIP) was excised with total relief of symptoms. The second patient a 65-year-old man with abrupt onset of massive watery diarrhea that led to acidosis and coma was symptomatically controlled for one year on 10 mg/day of prednisone. Elevated levels of VIP returned to normal after prednisone therapy was started. A benign islet cell tumor not localized by angiography was removed by distal pancreatic resection. Tissue levels of VIP were markedly elevated. VIP is a humoral mediator of the water diarrhea syndrome. Both benign and malignant pancreatic and extrapancreatic tumors may cause the watery diarrhea syndrome. Steroids may cause symptomatic relief of the diarrhea by lowering peptide levels to normal. The term watery diarrhea syndrome may be more accurate than the pancreatic cholera syndrome.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Aged; Diarrhea; Female; Gastrointestinal Hormones; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pheochromocytoma; Prednisone; 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

A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea.

Topics: Aged; Cyclic AMP; Cyclic GMP; Diarrhea; Female; Humans; Jejunum; Vasoactive Intestinal Peptide

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

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

A 56-year-old man suffered unexplained watery diarrhoea for 5 years which ultimately produced quadraparesis due to serve potassium depletion. All investigations were negative until demonstration of elevated plasma vasoactive intestinal peptide (VIP) indicated the presence of a vipoma. Removal of the VIP-producing tumour tissue--an adrenal ganglioneuroma--resulted in complete cure. Plasma VIP measurement is thus a valuable diagnostic screen in such cases and can be used to predict prognosis and to guide further therapy.

Topics: Adrenal Gland Neoplasms; Diarrhea; Ganglioneuroma; Humans; Male; Middle Aged; 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: Diarrhea; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Male; Middle Aged; Pancreatic Neoplasms; Portal Vein; Vasoactive Intestinal Peptide

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

Topics: Brain Neoplasms; Calcitonin; Cholesterol; Diarrhea; Endocrine Glands; Gastrins; Gastrointestinal Hormones; Histamine Release; Humans; Hypercalcemia; Neoplasms; Nutrition Disorders; Pellagra; Peptides; Serum Albumin; Thyroid Hormones; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

Levels of vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay in plasma or tissue from thirty-five patients with watery diarrhoea, and in plasma of twenty-five normal controls. Plasma levels were between 0.6 and 11.0 ng/ml in thirty-one of the thirty-three patients in whom it was measured and too low to measure (less than 200 pg/ml) in the other two. Peptide levels were less than 200 pg/ml in twenty-three of the controls, but higher in the remaining two. All tissues from patients were "rich" in VIP (10 ng to 35 microgram per g). The aetiologic diagnoses included pancreatic islet-cell adenoma or adenocarcinoma, islet-cell hyperplasia, bronchogenic carcinoma, pheochromocytoma, ganglioneuroblastoma, medullary thyroid carcinoma, and retroperitoneal histiocytoma. The findings support the conclusions that: (1) VIP is a likely mediator of the water-diarrhoea syndrome; (2) the syndrome may result from a variety of tumours; (3) this or a related peptide hormone may be secreted by these tumours; and (4) these tumours may have a common embryonic origin.

Topics: Adrenal Gland Neoplasms; Adrenal Medulla; APUD Cells; Diarrhea; Gastrointestinal Hormones; Humans; Lung Neoplasms; Pancreatic Neoplasms; Radioimmunoassay; Thyroid Neoplasms; Vasoactive Intestinal Peptide

Topics: Achlorhydria; Adenoma, Islet Cell; Angiography; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Male; Middle Aged; Paraneoplastic Endocrine Syndromes; 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

Eighteen endocrine pancreatic tumors were examined for the occurrence of cells producing insulin, glucagon, gastrin, human pancreatic polypeptide (HPP), and vasoactive intestinal polypeptide (VIP) and for A1 cells. More than half of the tumors were mixed, i.e., they contained more than one type of hormone-producing cell. The clinical symptoms were attributable only to one of the hormones produced by the mixed tumors. Three of four tumors causing the watery diarrhea syndrome contained both VIP and HPP cells. In one such tumor there was a strong predominance of HPP cells; the serum HPP levels of this patient were a thousandfold elevated, whereas her VIP levels were within the normal range. Several lines of evidence point to HPP as a possible agent causing the watery diarrhea syndrome. In many of our patients, HPP cells hyperplasia was present in the extratumoral pancreas. Such hyperplasia may give rise to the raised serum HPP levels seen in many patients having endocrine pancreatic tumors.

Topics: Diarrhea; Humans; Pancreas; Pancreatic Neoplasms; Peptides; Vasoactive Intestinal Peptide

The WDHA syndrome characterized by watery diarrhea, hypokalemia, and achlorhydria is being diagnosed with increasing frequency. The diagnosis has been made to date only due to severe clinical symptomatology. In a review of the literature gastrin, secretin, glucagon, enteroglucagon, gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP), and prostaglandins have been variously suggested as a possible etiologic agent for this syndrome. A case of the WDHA syndrome is reported in which hormonal assays of the serum preoperatively and two years postoperatively and tumor for many of the proposed agents is performed. A discussion of possible cross-reactivity among these similary structured polypeptides in the radioimmunoassays systems is used to explain the multitude of possible hormonal agents presented in the literature. Standardization of the VIP assays will result in increasing diagnosis of this diseases state prior to its fulminant clinical presentation.

Topics: Achlorhydria; Adult; Diarrhea; Gastrointestinal Hormones; Humans; Hypokalemia; Male; Middle Aged; Vasoactive Intestinal Peptide

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

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