vasoactive-intestinal-peptide and Adenoma--Islet-Cell

Vasoactive intestinal polypeptide (VIP)-secreting tumors of the pancreas represent a rare subtype of pancreatic islet cell tumors with an estimated incidence of 0.2 to 0.5 per million per year. We provide data on a relatively large series of patients with VIP-secreting tumors and review current literature regarding this specific entity.. A retrospective review was performed of all patients with VIP-secreting tumors of the pancreas treated from 1977 to 1992 at our institution. Presenting signs, symptoms, mode of diagnosis, extent of disease, surgical resectability, tumor size, treatments, hormone levels, and survival were assessed.. Eighteen patients were identified, 9 male and 9 female. Ages ranged from 23 to 74 years (mean 51 years). Secretory diarrhea was the most common symptom, occurring in 16 of 18 patients (89%). The most common tumor location was the tail of the pancreas (9 patients). Fourteen patients (78%) had liver metastasis at diagnosis. Curative resections were attempted in only 5 patients (28%). The mean survival was 3.6 years with the longest disease-free survival being 15 years and longest overall survival 15 years.. VIP-secreting tumors are extremely rare entities and usually metastatic at the time of diagnosis. Despite advanced disease, these patients can have extended survival.

Topics: Adenoma, Islet Cell; Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide

Although neoplasms that produce gut regulatory peptides and amines can be found throughout the gastroenteropancreatic axis (excluding carcinoids), the vast majority of these lesions are found within the pancreas. Recognition of the various clinical syndromes produced by the secretions of these tumors, the development of sensitive and specific radioimmunoassays for the elaborated peptides, and development of more effective localization techniques have contributed to earlier diagnosis and marked improvement in patient care. Treatment is directed toward medical management to correct the metabolic disturbances produced by the excessive amounts of gut regulatory peptides, followed by localization and extirpation of tumor. In the presence of unresectable tumor or metastases, palliative treatment directed at reducing peptide secretion or preventing its effects by surgery, chemotherapy, hormonal therapy, and hepatic-artery embolization can produce long-term remission of symptoms. Because the majority of these tumors are malignant, the ultimate goal in successful patient management is the early detection and surgical excision of the islet cell tumor before metastases occur.

Topics: Adenoma, Islet Cell; Humans; Pancreatic Neoplasms; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

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 3 year old Chinese girl with watery diarrhoea, abdominal distension and hypokalaemia due to a thoracic paraspinal vasoactive intestinal peptide (VIP) secreting ganglioneuroma is reported. The pre-operative serum VIP was 314 pmol/l (normal less than 30). Her diarrhoea stopped after the removal of the tumour. The VIP was 14 pmol/l 6 months post-operatively. Review of the 19 reported cases in children with documented elevated serum VIP showed that many of the cases presented with watery diarrhoea for prolonged duration before the diagnosis was made. Earliest age of onset was 2 weeks of age. The male to female ratio was 9:10. Ganglioneuroma and ganglioneuroblastoma were the commonest tumours. Pancreatic non-beta cell hyperplasia and neurofibroma were also reported. Location of the tumour was variable: neck, chest or abdomen. Increased urinary catecholamine excretion was reported in 50% of the cases. Abdominal distension, flushing, episodic hypertension and failure to thrive were the other associated features.

Topics: Adenoma, Islet Cell; Child; Child, Preschool; Female; Ganglioneuroma; Humans; Soft Tissue Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Ganglioneuroma; Humans; Pancreatic Neoplasms; Peptide PHI; Protein Precursors; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Animals; Humans; Intestines; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Adult; Aged; Antineoplastic Agents; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Male; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

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

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

Gut peptide secreting tumours originate most commonly from the pancreatic Islets of Langerhans. Tumours at a variety of other sites have also been shown to synthesize and release these peptides, reflecting the wide distribution of the peptide secreting cells of the diffuse neuroendocrine system. Tumours such as the glucagonomas, insulinomas, VIPomas and gastrinomas are associated with characteristic clinical syndromes resulting from the effects of the peptide they secrete. The majority of the islet cell tumours in fact secrete a number of different peptides and many of these are present in several molecular forms, some of which may not be biologically active. This may explain the lack of clinical sequelae in association with tumours such as the somatostatinomas. The clinical features, methods of diagnosis, localisation and treatment of these tumours will be discussed.

Topics: Adenoma, Islet Cell; Bombesin; Bronchial Neoplasms; C-Peptide; Carcinoma, Small Cell; Diagnosis, Differential; Endocrine System Diseases; Erythema; Gastrointestinal Hormones; Glucagon; Glucagonoma; Humans; Insulin; Insulin Secretion; Insulinoma; Male; Neoplasms; Neurotensin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatinoma; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

As sensitive radioimmunoassays for the detection of polypeptide hormones are developed, the exciting discovery of a diffusely distributed system of interrelated endocrine cells has begun a new era of endocrinology. This system, although anatomically disassociated, is bound together by a number of common features such as its biosynthetic mechanism, histochemical and ultrastructural features, and embryologic origin (Table I). The most prominent feature, however, is their biosynthetic pathways for hormone production, from which the acronym APUD has been derived. These are the capacity for Amine Precursor Uptake such as DOPA and then subsequent Decarboxylation, resulting in the synthesis of bioactive amines or polypeptide hormones. Hyperplasias or neoplasms of these cells are defined as apudomas. In the last ten years a great deal of research has rapidly altered the original concepts of this system, especially in terms of its embryologic origin, physiologic interrelationships, classification, as well as the addition of many new APUD cell members. These will be reviewed, and the origin, diagnosis, and treatment of each recognized apudoma will be synthesized in light of its membership within the APUD system.

Topics: Adenoma, Islet Cell; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Endocrine Glands; Humans; Neural Crest; Neuroblastoma; Paraganglioma; Pheochromocytoma; Pituitary Neoplasms; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

The three new endocrine pancreatic tumour syndromes dealt with in this chapter--glucagonomas, VIPomas and somatostatinomas--are not common. Nonetheless, the patients are potentially curable by tumour resection and therefore wider knowledge of the clinical picture is of considerable importance. It is possible that there are still further, presently unrecognized, clinical syndromes waiting in the wings and studies are currently under way to try to ascertain the effects of elevated PP. Early tumour diagnosis depends firstly on clinical acumen but the easy availability of a reliable radioimmunoassay service is of considerable importance as this allows the physician to screen likely patients and so detect cases at an early stage. Tumour localization is still a major problem and requires expert radiological assistance. The dramatic effectiveness of the cytotoxic agent streptozotocin illustrates the great potential of chemotherapy and it may be expected that further drugs of this nature will be discovered, especially as it is now possible to establish isolated tumour strains for mass drug screening. These tumours have shown the effect of long continued peptide elevation and given valuable insight into the physiological role of the respective regulatory peptides.

Topics: Adenoma, Islet Cell; Gastrointestinal Hormones; Glucagon; Humans; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Somatostatin; Vasoactive Intestinal Peptide

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

Gastrointestinal hormones (GI hormones) have received growing interest in endocrinology, gastroenterology and neuroendocrinology. Because of new methodological techniques, they can be measured in plasma and therefore be related to different pathophysiological conditions. In childhood, our present knowledge is as yet limited to the physiological rôle of gastrin at different ages and in some diseases (gastrinoma; Verner-Morrison syndrome) caused by humoral dysfunction. The present review relates the clinical important GI hormones to chemically classified families. The diagnostic value of determining endogenous hormone concentration in plasma and the validity of function tests carried out by administration of exogenous hormones are pointed out. Particular emphasis is given to the trophic action of GI hormones in the development and function of the gastrointestinal tract during childhood. More speculatively, GI hormones are involved in the complex function of the central nervous system, thus making food intake a trophotropic action in a broader sense.

Topics: Adenoma, Islet Cell; Bombesin; Ceruletide; Child; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Motilin; Neurotensin; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Female; Gastrins; Humans; Insulin; Insulin Secretion; Male; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

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

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

Topics: Adenoma, Islet Cell; Cholecystokinin; Gastric Juice; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Neoplasms; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Peptides; Precancerous Conditions; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

Topics: 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

Hypercalcitoninemia in gastroenteropancreatic tumors associated with calcitonin immunoreactivity is rare.. We report here two patients in whom pancreatic neuroendocrine tumors both contained and secreted immunoreactive calcitonin. Both patients experienced elevated basal calcitonin immunoreactivity.. The peak responses of immunoreactive calcitonin occurred 5 minutes after pentagastrin administration in these two patients and were 30% and 180% above basal concentrations corresponding to peak increments of 0.39 and 8.78 ng/ml, respectively. The immunoreactive calcitonin response to pentagastrin in these two patients was not significantly different from that seen among five patients with medullary carcinoma of the thyroid gland.. It does not appear that immunoreactive calcitonin responses to pentagastrin stimulation will discriminate between patients with medullary carcinoma of the thyroid gland and those with nonfamilial, gastroenteropancreatic neuroendocrine tumors that express calcitonin immunoreactivity. In patients with secretory diarrhea and/or flushing, an elevated level of immunoreactive calcitonin, in the absence of a thyroid mass in the neck, may herald the presence of a gastroenteropancreatic neuroendocrine tumor.

Topics: Adenoma, Islet Cell; Aged; Calcitonin; Female; Humans; Liver Neoplasms; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Pentagastrin; Stomach Neoplasms; Thyroid Neoplasms; Vasoactive Intestinal Peptide

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Bombesin; Calcitonin; Carcinoid Tumor; Carcinoma, Small Cell; Chromatography, Gel; Corticotropin-Releasing Hormone; Gastrin-Releasing Peptide; Gastrins; Humans; Hypothalamus; Lung Neoplasms; Neoplasms; Neuroblastoma; Pancreatic Neoplasms; Peptides; Pheochromocytoma; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

To examine the possible in vivo significance of the immunomodulatory effects of vasoactive intestinal polypeptide described in vitro, several parameters of peripheral blood lymphocyte function were studied in a patient with a pancreatic endocrine tumor and high circulating levels of vasoactive intestinal polypeptide. There was no imbalance of the circulating lymphocyte subpopulations, and the in vitro responses of the patient's lymphocytes to mitogens were normal. However, there was an increased number (32%) of peripheral lymphocytes expressing interleukin 2 receptor. Serum immunoglobulin M levels were higher than in controls, and the patient's lymphocytes exhibited a spontaneous in vitro immunoglobulin M production higher than normal. Comparable increases in both interleukin 2 receptor expression and immunoglobulin M production were induced in vitro in normal peripheral lymphocyte cultures by the addition of vasoactive intestinal polypeptide concentrations similar to that detected in the patient's plasma. These findings indicate that a modulatory effect of vasoactive intestinal polypeptide on lymphocyte activation and immunoglobulin synthesis may be operating in vivo. They also suggest that vasoactive intestinal polypeptide does not mediate major defects in peripheral blood lymphocyte function in vivo.

Topics: Adenoma, Islet Cell; Adjuvants, Immunologic; Epitopes; Female; Humans; Immunoglobulin M; Leukocyte Count; Lymphocytes; Middle Aged; Pancreatic Neoplasms; Protein Binding; Receptors, Interleukin-2; Vasoactive Intestinal Peptide; Vipoma

We describe a case of a tumour of the sigmoid colon with hepatic metastases in a patient with previously documented ulcerative colitis. A diagnosis of metastatic vipoma was made on the basis of high plasma levels of vasoactive intestinal polypeptide (VIP). Profuse diarrhoea and profound metabolic upset were corrected by the use of a somatostatin analogue SMS 201-995, whilst conventional cytotoxic therapy produced a significant tumour response with return of the plasma VIP level to normal.

Topics: Adenoma, Islet Cell; Adult; Antineoplastic Combined Chemotherapy Protocols; Colitis, Ulcerative; Colostomy; Combined Modality Therapy; Female; Humans; Liver Neoplasms; Octreotide; Pancreatic Neoplasms; Sigmoid Neoplasms; Streptozocin; Vasoactive Intestinal Peptide; Vipoma

Ten patients with metastatic pancreatic endocrine tumours were treated with the long-acting somatostatin analogue octreotide (SMS 201-995). Three patients showed no response, clinically or biochemically, and treatment was therefore withdrawn. The seven remaining patients continued treatment for a median period of 28 months (range 13-54 months). Treatment was initially effective, symptoms improved and the concentrations of tumour-related hormones were reduced. Worsening of symptoms and rising levels of tumour-related hormone concentrations occurred a median of 5 months (range 1-6 months) after the start of therapy and were initially reversed by increasing the dose of octreotide over a median of 10 months (range 6-16 months). However, after a median of 13 months (range 5-34 months) at the maximum dosage, symptoms recurred and were no longer responsive to a further increase in dosage of octreotide or other therapeutic measures. All patients died within a period of 5 months once this resistant phase of their illness had been reached.

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Liver Neoplasms; Octreotide; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide

A 58-year-old Taiwanese woman was admitted to Mackay Memorial Hospital for evaluation profuse watery diarrhea. She presented with watery diarrhea, hypokalemia, and hypochlorhydria, and had experienced these problems for 2 years prior to admission. A pancreatic tumor with liver metastasis was noted by the ultrasound, abdominal CT scanning, and angiography studies. Surgical exploration disclosed an ill-defined ovoid tumor in the body and tail of the pancreas measuring 8 x 3 x 3 cm. The immunohistochemistry study of the tumor for VIP-immunoreactivity (VIP: vasoactive intestinal polypeptide) was markedly positive, and also stained slightly positive for other peptides, including pancreatic polypeptide (PP), calcitonin, glucagon, and neuron-specific enolase (NSE). Postoperatively, the patient recovered immediately from her symptoms and there has been no evidence of recurrence during the past 8 months of follow-up.

Topics: Adenoma, Islet Cell; Female; Humans; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Vasoactive intestinal peptide-producing tumor tissue fragments obtained at surgery were maintained in short-term culture. Functional cellular integrity of vasoactive intestinal peptide-producing tumor tissue was reflected by progressive protein synthesis and the ability of tumor tissue to release vasoactive intestinal peptide when stimulated by the intracellular second messengers cyclic adenosine monophosphate and calcium. Studies with verapamil and ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid suggest that cyclic nucleotide- and ionophore A23187-mediated vasoactive intestinal peptide release are dependent, at least in part, upon the availability and transmembrane transport of extracellular calcium.

Topics: 1-Methyl-3-isobutylxanthine; Adenoma, Islet Cell; Calcimycin; Calcium; Cells, Cultured; Cyclic AMP; Egtazic Acid; Female; Humans; Immunohistochemistry; Leucine; Middle Aged; Pancreatic Neoplasms; Radioimmunoassay; Vasoactive Intestinal Peptide; Verapamil; Vipoma

This case report describes a patient with pancreatic cholera caused by a vasoactive intestinal polypeptide-producing pancreatic tumor. The case presents several unusual characteristics of this disease. The primary tumor was a mucinous adenocarcinoma of the pancreas. The serum vasoactive intestinal polypeptide level of 2400 pmol/L is the highest reported. At this vasoactive intestinal polypeptide level, the somatostatin analogue SMS 201-995 at doses up to 2 mg/24 h did not control the 21 L/24 h stool output. Fecal incontinence due to a manometrically documented hypotonic internal anal sphincter occurred. Using surgically created stomas, the segmental gastrointestinal fluid and sodium losses were shown to be greatest from the jejunum, whereas potassium losses from the colon and small intestine were equal. The cellular mechanism for the small intestinal potassium secretion is not known.

Topics: Adenoma, Islet Cell; Adult; Anal Canal; Chlorine; Female; Humans; Intestine, Small; Pancreatic Neoplasms; Potassium; Vasoactive Intestinal Peptide; Vipoma

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

A 35-yr-old woman presented with episodic secretory diarrhea. Plasma vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP) venous levels were elevated. An abdominal computerized tomographic scan showed an enlarged head of the pancreas but no discrete mass. Superselective abdominal arteriography also failed to localize the tumor. Transhepatic portal vein sampling for VIP and PP showed a large increase in VIP and PP in the veins draining the head of the pancreas, with the highest levels being found at the union of the posterior superior pancreaticoduodenal vein with the portal vein. Surgical exploration confirmed this tumor location and a 2 x 3 cm encapsulated benign tumor was enucleated from the posterior surface of the head of the pancreas. Postoperatively, VIP and PP levels decreased to normal and the diarrheal episodes ceased. This case report demonstrates the usefulness of transhepatic portal vein sampling in localization of VIPomas if other radiological modalities are not helpful.

Topics: Adenoma, Islet Cell; Adult; Blood Specimen Collection; Female; Humans; Pancreatic Neoplasms; Pancreatic Polypeptide; Portal Vein; Punctures; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Cardiovascular System; Hemodynamics; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones.

Topics: Adenoma, Islet Cell; Adult; Aged; Gastrins; Gastrointestinal Hemorrhage; Glucagon; Glucagonoma; Hormones; Humans; Insulinoma; Middle Aged; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Female; Humans; Pancreatic Neoplasms; Tears; Vasoactive Intestinal Peptide; Vipoma

This report describes a 7-year-old boy presenting with watery diarrhea, hypokalemia, and hypochlohydria associated with vasoactive intestinal polypeptide (VIP)-secreting ganglioneuromatosis involving the entire colon and rectum. The child's symptoms resolved following proctocolectomy, and the VIP levels returned to normal. Although 55 previous children have been reported with VIP-secreting tumors, this case is the first involving the entire colon and rectum.

Topics: Adenoma, Islet Cell; Child; Colonic Neoplasms; Ganglioneuroma; Humans; Male; Rectal Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Specific binding sites for 125I-labelled rat peptide-histidine-isoleucine (PHI) were identified on rat insulinoma-derived RINm5F cells. The concentrations of peptides producing half-maximal displacement of label were rat PHI, 0.36 +/- 0.14 nM, vasoactive intestinal polypeptide (VIP), 0.38 +/- 0.13 nM and secretin, approximately 0.2 microM. Glucagon and glucagon-like peptide-1(7-36)amide were without effect on binding. PHI and VIP produced dose-dependent increases in cAMP production in the cells that were significantly (P less than 0.05) above unstimulated rates for ligand concentrations between 10(-8) and 10(-6) M. Both PHI and VIP produced a small but significant (P less than 0.05) enhancement in the rate of release of immunoreactive insulin from the cells but the effect was not dose dependent.

Topics: Adenoma, Islet Cell; Adenylyl Cyclases; Animals; Cyclic AMP; Enzyme Activation; Insulin; Insulin Secretion; Insulinoma; Iodine Radioisotopes; Pancreatic Neoplasms; Peptide PHI; Rats; Receptors, Cell Surface; Receptors, Peptide; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Antineoplastic Agents; Female; Humans; Middle Aged; Octreotide; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

A case of multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I (MEN I) is reported. The patient was a 41-year-old woman who had a past history of thyroid cancer (papillary carcinoma) and hyperparathyroidism due to parathyroid adenoma. Later, a nonfunctional pituitary tumor and five nonfunctional pancreatic tumors were found simultaneously and the patient was finally diagnosed as having MEN I. Following surgical enucleation, the pancreatic tumors were histopathologically diagnosed as benign islet cell tumors. One of them (tumor 3) exhibited a solid nodular pattern while the others showed gyriform patterns. They were divided histochemically and immunohistochemically into three types: two (tumors 1 and 2) produced a single hormone (glucagon), one (tumor 3) produced five (insulin, glucagon, somatostatin, gastrin and pancreatic polypeptide) and the remaining two (tumors 4 and 5) produced two (glucagon and pancreatic polypeptide). Electron microscopically, three types of endosecretory granules were found in the tumor cells of tumor 3 but only one type was found in tumor 4. However, in the tumor 4 extract, glucagon, pancreatic polypeptide, C-peptide, somatostatin, vasoactive intestinal peptide and growth hormone releasing factor were detected by radioimmunoassay. These findings suggest that these pancreatic tumors were both multicellular and multihormonal.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Female; Gastrins; Glucagon; Growth Hormone-Releasing Hormone; Humans; Immunohistochemistry; Insulin; Microscopy, Electron; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Somatostatin; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Adult; Female; Ganglioneuroma; Humans; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Retroperitoneal Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Two patients with severe secretory diarrhea due to metastatic vasoactive intestinal peptidoma were treated with a synthetic somatostatin analogue in an attempt to control the patients' vasoactive intestinal peptide-related symptoms. In both patients, a good initial response to this treatment could be demonstrated; not only did diarrhea subside but there was also a dramatic fall in vasoactive intestinal peptide plasma levels. However, after 11 and 4 days respectively, diarrhea recurred accompanied by a rise in vasoactive intestinal peptide plasma levels. In fact, under treatment with the somatostatin analogue and with natural somatostatin, a significant rebound state was observed regarding diarrhea as well as vasoactive intestinal peptide levels, which caused considerable difficulty in the clinical management in 1 patient. This patient had to undergo surgery. In the second patient, the responsiveness to somatostatin analogue returned a few days after discontinuation of the treatment, lasting, however, for a short period only. The possible mechanism of this escape and rebound with somatostatin treatment is discussed.

Topics: Adenoma, Islet Cell; Antineoplastic Agents; Female; Humans; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Somatostatin; Time Factors; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Humans; Octreotide; Pancreatic Neoplasms; Receptors, Neurotransmitter; Receptors, Somatostatin; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

A 20-yr-old black woman presented in 1969 with headache, amenorrhea, hyperprolactinemia, hypogonadotropism, hypogonadism, and hypercalcemia due to a chromophobe adenoma. She received 5000 rads to the sella. One year later she was found to have hyperparathyroidism due to parathyroid adenoma and three and a half glands were removed. Thirteen years later she presented with 3 months of profuse watery diarrhea, hypokalemia, hypercalcemia, hyperchloremic metabolic acidosis, and a normal anion gap. A vasoactive intestinal polypeptide-producing tumor of the pancreas was found and successfully removed, after which hypercalcemia resolved. This is an unusual case of the multiple endocrine neoplasia syndrome, type 1, being associated with a vasoactive intestinal polypeptide-oma and pancreatic cholera.

Topics: Adenoma, Islet Cell; Adult; Female; Humans; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

The presence of peptide histidine-methionine (PHM)-like peptides has been determined in plasma and tumor specimens from patients with vasoactive intestinal peptide (VIP)-secreting tumors and the watery diarrhea syndrome. All patients had strikingly elevated plasma concentrations of PHM immunoreactivity (median, 1800; range, 500-6800 pmol/liter; n = 12), which were higher than those of VIP (median, 235; range, 50-580 pmol/liter). In patients with other endocrine and nonendocrine pancreatic tumors, plasma PHM concentrations were not significantly different from normal (median, 20; range, 5-60 pmol/liter; n = 28). Plasma samples from patients with diarrhea due to other illnesses also had PHM concentrations that were not significantly different from normal (median, 40; range, 10-80 pmol/liter; n = 23). The gel chromatographic profiles of plasma and tumor extracts from patients with VIP-secreting tumors revealed the presence of at least two molecular forms that reacted with an antiserum directed to the N-terminus of PHM (SY1). The later peak (Kav, 0.50-0.53) corresponded in position to synthetic PHM and also reacted with the PHM-specific antiserum (SY2). The earlier peak (Kav, 0.30-0.37), not reactive with antiserum SY2, corresponded to a large molecular form of PHM-like immunoreactivity previously identified as the predominant form in normal human stomach and plasma, though not in the rest of the intestinal tract. The neuroendocrine nature of the tumors was confirmed by the demonstration of immunostaining with a battery of antisera to neuroendocrine markers. Immunocytochemistry revealed the presence of both VIP and PHM in tumor cells. The presence of high circulating concentrations of PHM-like immunoreactivity in patients with VIP-secreting tumors, as measured with a PHM N-terminus-directed antiserum, SY1, suggests that use of this type of antiserum may provide valuable information in the diagnosis of such tumors. The contribution of the PHM-like peptides to the features of this syndrome is not known.

Topics: Adenoma, Islet Cell; Antibodies; Chromatography, Gel; Histocytochemistry; Humans; Immune Sera; Immunoenzyme Techniques; Pancreatic Neoplasms; Peptide PHI; Radioimmunoassay; Vasoactive Intestinal Peptide; Vipoma

The pathophysiological, biochemical, histological, ultrastructural, and immunohistochemical characters of a case of malignant pancreatic islet cell tumor with watery diarrhea syndrome were carefully investigated. Four hormones or mediators--somatostatin (SST), vasoactive intestinal peptide (VIP), serotonin, and prostaglandin E--were markedly elevated in the circulation. The diagnosis was further confirmed by exploratory laparotomy and autopsy. The contents of SST and VIP in tumor tissues were very high. Gel chromatography of tumor extract revealed single peaks for both SST and VIP. Immunohistochemical studies of tumor tissues showed numerous immunoreactive cells to anti-SST, moderate amount of VIP-positive cells, and a few hCG-, insulin-, and glucagon-positive cells. In conclusion, this is an unusual case of Verner-Morrison syndrome in which three kinds of bioactive hormones or mediators were simultaneously secreted; peptides, amine, and prostaglandin.

Topics: Adenoma, Islet Cell; Adult; Histocytochemistry; Hormones; Humans; Male; Pancreatic Neoplasms; Prostaglandins E; Serotonin; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

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: Adenoma, Islet Cell; Cholecystokinin; Female; Humans; Pancreatic Neoplasms; Secretin; Vasoactive Intestinal Peptide; Vipoma

Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed.

Topics: Adenoma, Islet Cell; Calcitonin; Histocytochemistry; Humans; Immunochemistry; Microscopy, Electron; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Peptide PHI; Protein Precursors; Radioimmunoassay; Staining and Labeling; Vasoactive Intestinal Peptide; Vipoma

A 43-yr-old-man with metastatic VIPoma in whom the conventional measures of surgery, chemotheraphy, and hepatic artery embolization ultimately failed to control his severe diarrhea, resulting from vasoactive intestinal polypeptide hypersecretion, was treated with a new long-acting somatostatin analogue, SMS 201-995, for 14 mo. SMS 201-995 not only controlled the diarrhea without side effects but appeared to have possibly induced a reduction in metastatic tumor size.

Topics: Adenoma, Islet Cell; Adult; Delayed-Action Preparations; Drug Evaluation; Humans; Liver Neoplasms; Male; Octreotide; Pancreatic Neoplasms; Somatostatin; Time Factors; Vasoactive Intestinal Peptide; Vipoma

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

A 30-year-old man presenting with watery diarrhea, hypokalemia, and hypochlorhydria (Verner-Morrison syndrome, WDHH syndrome) had raised plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin (SRIF), calcitonin, and gastrin, as well as high urinary excretion of vanillylmandelic acid. A right adrenal pheochromocytoma was found and excised. The neoplastic cell population was immunohistochemically shown to contain VIP, SRIF, and calcitonin. Gross, histologic, and immunohistochemical evaluation of the pancreas revealed no abnormalities, whereas a marked hyperplasia of the gastrin-producing cells of the gastric antral mucosa was demonstrated. Postoperatively, the patient recovered from his symptoms and the plasma hormone levels returned to normal values. The clinical and histogenetic implications of this most unusual tumor of neural crest derivatives are discussed.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Calcitonin; Gastrins; Histocytochemistry; Hormones, Ectopic; Humans; Immunoenzyme Techniques; Male; Pheochromocytoma; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

The pancreatic cholera syndrome is a serious and potentially fatal disease found in patients with endocrine pancreatic tumours and ganglioneuromas. Two patients with therapy-resistant pancreatic cholera syndrome were successfully treated with human leucocyte interferon given intramuscularly in a dose of 3 X 10(6)-6 X 10(6) IU per day. This produced a reduction in stool volume and plasma vasoactive intestinal polypeptide (VIP) within 3-5 days of the start of treatment. Tumour mass decreased in one of the patients after 3 months of treatment but some tumour tissue remained after 15 months' observation, although circulating concentrations of VIP are normal. The mechanisms of action of interferon are not known but a direct inhibition of tumour-cell hormone production and perhaps of tumour-cell proliferation might account for the rapid clinical response.

Topics: Adenoma, Islet Cell; Aged; Humans; Interferon Type I; Male; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

The effect of a synthetic somatostatin analog was studied in a patient with severe secretory diarrhea due to pancreatic cholera syndrome. Basal intestinal perfusion studies indicated an absence of water and sodium absorption, and active chloride secretion in the small bowel. Intravenous administration of the somatostatin analog (1 microgram/kg.h) changed zero net water movement to absorption (122 mL/30 cm of the jejunum per hour). Chloride secretion changed to absorption (5.0 to 7.9 meq/30 cm.h), and plasma vasoactive intestinal polypeptide concentration was reduced from 330 to 45 pmol/L (normal, less than 51). When the analog was given subcutaneously, 100 micrograms twice daily, stool weight decreased, and plasma vasoactive intestinal polypeptide concentration fell toward the normal range (67 pmol/L). Plasma concentration of pancreatic polypeptide was initially elevated and dropped during intravenous infusion of somatostatin analog but returned to baseline on maintenance therapy with the analog delivered subcutaneously. The patient has not had further diarrhea during 9 months of therapy.

Topics: Adenoma, Islet Cell; Aged; Feces; Female; Humans; Injections, Subcutaneous; Intestinal Absorption; Jejunum; Octreotide; Pancreatic Neoplasms; Pancreatic Polypeptide; Perfusion; Somatostatin; Vasoactive Intestinal Peptide; Vipoma; Water-Electrolyte Balance

A patient presenting clinically with the glucagonoma syndrome had high plasma glucagon levels (1920 ng/l) and at laparotomy, a pancreatic islet cell tumour was removed. The tumour was dispersed and placed in culture where it remained viable for 63 days. The tumour cells secreted immunoreactive (IR) glucagon at levels up to 2400 ng/l as detected by a C-terminal glucagon specific antibody and 85 400 ngequiv./l as measured by an N-terminal glucagon specific antibody. The difference between these two levels was attributed to the presence of different molecular forms of glucagon measured with the N-terminal specific antibody. IR insulin (up to 302 mU/l) and IR somatostatin (up to 2500 ng/l) were also detected. There was no direct or inverse correlation between different hormone levels. Small but significant levels of N-terminal and C-terminal vasoactive intestinal peptide (VIP) were detected in some cultures but there was no evidence of gastrin or ACTH. Glucagon and somatostatin secretion persisted for the duration of the culture (63 days) but insulin concentrations declined. Incubation of cultures with somatostatin (1 ng/ml) caused a 75% decrease in glucagon levels, while insulin (1000 mU/l) produced a 70% inhibition of somatostatin.

Topics: Adenoma, Islet Cell; Cells, Cultured; Female; Fluorescent Antibody Technique; Gastrins; Glucagon; Glucagonoma; Humans; Immunoenzyme Techniques; Insulin; Insulin Secretion; Kinetics; Middle Aged; Neurotensin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Adult; Aged; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Peptide PHI; Peptides; Protein Precursors; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Contrast Media; Diarrhea; Diatrizoate; Humans; Iodine; Iopanoic Acid; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Prednisone; Vasoactive Intestinal Peptide; Vipoma

The case history of a patient with an islet cell carcinoma, which produced both gastrin and vasoactive intestinal polypeptide (VIP), is presented. Although several examples have been observed of the combined production of these hormones by pancreatic endocrine tumors, few reports have related the clinical details of such cases. Resolution of diarrhea occurred in our patient after institution of nasogastric suction and cimetidine therapy, suggesting that gastric hypersecretion, rather than VIP activity, accounted for this problem. Chemotherapy with streptozotocin and 5-fluorouracil was highly effective in ameliorating clinical symptoms, diminishing serum levels of gastrin and VIP, and greatly reducing the bulk of metastatic disease in this case.

Topics: Adenoma, Islet Cell; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Gastrins; Humans; Middle Aged; Pancreatic Neoplasms; Streptozocin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Vipomas are tumours which secrete vasoactive intestinal peptide (VIP) and present with severe watery diarrhoea (the Verner and Morrison syndrome). The tumours are usually pancreatic in adults and originate in the sympathetic nervous system in children (neuroblastoma). The diagnosis is confirmed by the finding of raised plasma VIP. The treatment of choice is surgical excision of the tumour which leads to the regression of the watery diarrhoea.

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

Two patients with secretory diarrhea and signs and symptoms consistent with the Verner-Morrison syndrome and islet cell hyperplasia are described. Both patients responded well to subtotal pancreatectomies. The morphologic changes in the pancreata were characterized by proliferation of islets associated with periductal and interstitial fibrosis. Immunohistochemical stains demonstrated increased staining for serotonin in islet cells. A few islet cells also stained for vasoactive intestinal polypeptide. The significance of these results is discussed.

Topics: Adenoma, Islet Cell; Adult; Female; Histocytochemistry; Humans; Hyperplasia; Immunoenzyme Techniques; Islets of Langerhans; Male; Middle Aged; Pancreatic Neoplasms; Serotonin; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Alloxan; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; DNA Repair; Humans; Insulin; Islets of Langerhans; Molecular Weight; Pancreatic Neoplasms; Rats; Streptozocin; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Glucagon; Humans; Hyperplasia; Islets of Langerhans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Phosphopyruvate Hydratase; Serotonin; Somatostatin; Staining and Labeling; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

The biochemical characteristics of a pancreatic tumor from a patient with watery diarrhea, hypokalemia, hypochlorhydria, and steatorrhea is described Plasma concentrations of vasoactive intestinal peptide (VIP) were elevated 6-fold, those of neurotensin (NT) were elevated 10-fold, and those of pancreatic polypeptide (PP) were elevated 200-fold above the normal range. The pancreatic tumor removed was found to contain high concentrations of these peptides in a similar ratio to plasma. The tumor content of NT was 6 times higher than any previously reported, but no specific symptoms could be ascribed to NT. After removal of the tumor, plasma levels of VIP, NT, and PP returned to normal, and the diarrhea disappeared. Gel chromatography of plasma and tumor extracts indicated that all of the immunoreactive PP co-eluted with standard human PP. When the tumor extract was subjected to gel chromatography and high pressure liquid chromatography, two forms of VIP were detected, the major one resembling porcine VIP and a smaller more hydrophobic form detected by C- but not N-terminally directed VIP antisera. This smaller form was not present in normal ileum. Immunoreactive NT in plasma was predominantly an N-terminal fragment. High pressure liquid chromatography of the tumor extract revealed that approximately 75% of the NT immunoreactivity consisted of N-terminal fragments. In contrast, normal ileum contained only authentic NT-(1-13). Since N-terminal fragments of NT are thought to be biologically inactive, the nature of the immunoreactive NT should be determined before attempting to assign specific clinical symptoms to NT-secreting tumors.

Topics: Adenoma, Islet Cell; Chromatography, Gel; Chromatography, High Pressure Liquid; Fluorescent Antibody Technique; Humans; Ileum; Male; Middle Aged; Neurotensin; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; 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

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Child; Child, Preschool; Chronic Disease; Female; Ganglioneuroma; Hormones, Ectopic; Humans; Male; Retroperitoneal Neoplasms; Vasoactive Intestinal Peptide; Vipoma

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

A typical pancreatic insulinoma is characterized by immunohistochemistry which reflects its histogenesis, morphology and hormonal activity.

Topics: Adenoma, Islet Cell; Glucagon; Humans; Insulin; Insulinoma; Microscopy, Electron; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide

A patient with an islet cell tumor presented initially with a supra-renal mass that histologically had an extensive clear cell component. Electron microscopic and immunocytochemical findings were essential to prove that the extrapancreatic mass with clear cells was an unusual metastatic manifestation of an islet cell tumor. Both the pancreatic and extrapancreatic tumor cells contained neurosecretory granules and produced vasoactive intestinal polypeptide and substance P. The clear cell morphology was due to the accumulation of lipid and glycogen and cytoplasmic swelling.

Topics: Adenoma, Islet Cell; Cytoplasmic Granules; Histocytochemistry; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Substance P; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Child; Ganglioneuroma; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenoma, Islet Cell; Gastrins; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Humans; Insulinoma; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

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

Topics: Adenoma, Islet Cell; Adult; Aged; Diabetes Mellitus; Diagnosis, Differential; Female; Glucagonoma; Humans; Insulinoma; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Skin Diseases; Somatostatinoma; Vasoactive Intestinal Peptide

The effects of somatostatin on diarrhea and on small intestinal flow of water and electrolytes (slow-marker perfusion technique) in a patient with pancreatic cholera are reported. Continuous intravenous infusion of somatostatin (8 micrograms/kg/hr) suppressed the diarrhea, but a rebound was observed after somatostatin. Infusion of somatostatin at the same dosage decreased the ileal fluid flow rate to within control values. This effect was mainly due to a sharp reduction in the rate fluid entered the jejunum, but was also due to a suppression of the abnormal water and electrolyte secretion in the proximal jejunum. Secretion in the rest of the small bowel remained unchanged. Somatostatin did not noticeably alter the high preinfusion plasma level of prostaglandin E1, but decreased the initially high plasma concentration of vasoactive intestinal peptide to normal values. These results suggest that long-acting somatostatin analogs could be of value in the symptomatic treatment of diarrhea in pancreatic cholera.

Topics: Adenoma, Islet Cell; Adult; Humans; Infusions, Parenteral; Intestine, Small; Male; Pancreatic Neoplasms; Prostaglandins E; Somatostatin; Vasoactive Intestinal Peptide; Vipoma; Water-Electrolyte Balance

Immunocytochemical stains for various pancreatic hormones were performed on 77 pancreatic endocrine tumors from 59 patients [17 with hypoglycemia, three with glucagonoma syndrome, 18 were Zollinger-Ellison syndrome, six with WDHA (watery, diarrhea, hypokalemia, and achlorhydria) syndrome and 15 without endocrine symptoms]. In all tumors that caused either hypoglycemia or glucagonoma syndrome, insulin and glucagon were respectively identified. On the other hand, only 10 tumors from 18 patients with Zollinger-Ellison syndrome were positive for gastrin, and only four of six patients with WDHA syndrome had a vasoactive intestinal peptides-positive tumor. Ten of 15 clinically silent tumors contained hormone-producing cells but without a consistent pattern. Ten neoplasms were negative for all hormones tested. Twenty-six tumors showed positively for more than one hormone and usually one cell type predominated. Four patients had multiple tumors which showed variation in the architecture and cellular composition. The tumors were classified into three major histopathologic groups: solid, gyriform, and glandular. The correlation between the pattern of growth and the hormonal production was generally poor. However, a pure gyriform pattern was often associated with insulin production, and glandular differentiation was commonly seen in tumors associated with Zollinger-Ellison syndrome. This study demonstrates the reliability of the immunocytochemical method for the specific identification of cell types in pancreatic endocrine tumors.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Child; Female; Gastrins; Glucagon; Hormones; Humans; Immunoenzyme Techniques; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Retrospective Studies; Somatostatin; Vasoactive Intestinal Peptide

This syndrome, also known under the initials W.D.H.A., is due to a single or multiple pancreatic tumour or to micropolyadenomatosis consisting of non-beta islet cells. Malignancy is found in about two-thirds of the cases. The other endocrine glands are rarely involved. The syndrome is more frequent in women than in men. It is characterized by liquid diarrhoea, marked hypokalaemia and absence of gastric hyperacidity. The tumour is mainly diagnosed by echotomography, computerized tomography and arteriography. It can also be located by staged collections of blood along the portal system for hormonal assays. The nature of the tumour can only be ascertained by demonstrating the presence of the responsible hormone, usually the "vaso-intestinal peptide". Treatment is primarily surgical. Adjuvant treatments include streptozotocine and embolization by superselective catherization in cases of hepatic matastases. The prognosis is sombre since in spite of the various treatments cure can only be achieved in 50% of the patients.

Topics: Adenoma, Islet Cell; Adult; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prognosis; Streptozocin; Vasoactive Intestinal Peptide; Vipoma

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

Topics: Adenoma, Islet Cell; Dactinomycin; Female; Humans; Indomethacin; Liver Neoplasms; Middle Aged; Pancreatic Neoplasms; Prednisolone; Vasoactive Intestinal Peptide; Vipoma

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

A 3 yr 11 mo-old girl showing classical symptoms of WDHA syndrome was transferred to our department of surgery. In preoperative examination, serum vasoactive intestinal peptide (VIP) was markedly elevated and pancreatic tumor was suspected. However, no tumor was found in the resected pancreas. Unfortunately, an unexpected adrenal tumor (ganglioneuroblastoma) was found in autopsy. The tumor was judged VIPO positive, immunohistochemically. This case was thought to be WDHA syndrome caused by VIPO-producing ganglioneuroblastoma (VIPoma).

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Child, Preschool; Female; Ganglioneuroma; Gastrointestinal Hormones; Humans; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

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

A case of pancreatic cholera (Verner-Morrison syndrome) associated with a pancreatic endocrine tumor and hepatic metastases is presented. VIP and HPP plasma levels, initially elevated, were accurately followed in various conditions: during corticosteroid therapy, after pancreatic tumor excision, during and after streptozotocin therapy (1.5 g/m2) by repeated intraarterial route). Only streptozotocin therapy resulted in a reduction of the stool volume with concomitant decrease in VIP plasma levels. However, the size of the hepatic metastases was unchanged and HPP plasma levels remained elevated. It is suggested that VIP represents the tumoral secretion and HPP a marker of the residual malignant tissue.

Topics: Adenoma, Islet Cell; Adult; Humans; Liver Neoplasms; Male; Outcome and Process Assessment, Health Care; Pancreatic Neoplasms; Streptozocin; Tissue Extracts; Vasoactive Intestinal Peptide; Vipoma

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

Topics: Adenoma, Islet Cell; Glucagon; Humans; Hyperinsulinism; Immunoenzyme Techniques; Insulin; Islets of Langerhans; Pancreatic Neoplasms; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

The Verner-Morrison syndrome has been described in 19 previous patients with ganglioneuroma and ganglioneuroblastoma but never neuroblastoma. Its occurrence following treatment of a neuroblastoma with chemotherapy with maturation of the tumor has only been reported on one previous occasion. Our case suggests that vasoactive intestinal polypeptide may be used not only as a diagnostic indicator for the presence of a neural crest tumor but also as a marker to monitor maturation of the tumor and indicate an improving prognosis.

Topics: Adenoma, Islet Cell; Female; Ganglioneuroma; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Infant; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Vasoactive Intestinal Peptide; Vipoma; Vulvar Neoplasms

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

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

A 61-year-old man with a malignant endocrine pancreatic tumour, so-called "non-functioning" islet cell tumour, is described. The tumour consisted of enterochromaffin-like cells with positive immunocytochemistry for gastrin, glucagon and VIP, but neither of these or other peptides were elevated in the circulation. Elevated serum levels of HCG-alpha and HCG-beta subunits were found. They seemed to be valuable tumour markers during cytotoxic therapy.

Topics: Adenoma, Islet Cell; Antineoplastic Agents; Chorionic Gonadotropin; Female; Gastrins; Glucagon; Humans; Middle Aged; Pancreatic Neoplasms; 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

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

A 51-year-old woman with a history of several years' watery diarrhoea caused by a vasoactive intestinal peptide (VIP) secreting tumour of the pancreas (VIPoma) is presented. Measured stool outputs ranged from 1000 to 2600 ml/24 h. S-K 2.5 mmol/I. The pancreatic VIPoma was localised by abdominal angiography and removed. The plasma concentration of vasoactive intestinal peptide was 80 pmol/l before and 5 pmol/I after the operation (normal under 30 pmol/I). The patient has been symptom-free for 15 months since surgery.

Topics: Adenoma, Islet Cell; Female; Gastrointestinal Hormones; Humans; Middle Aged; Pancreatic Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Insulinoma, glucagonoma, gastrinoma (Zollinger-Ellison syndrome), vipoma, somatostatinoma and a tumor that secretes human pancreatic polypeptide are the primary endocrine-secreting tumors of the pancreas. hormones are produced by specific tumor cell types and cause a variety of dramatic clinical pictures. Diagnosis often requires hormone assays. Computerized tomography may be helpful. Definitive surgical treatment is possible, but metastases may be present.

Topics: Adenoma, Islet Cell; Apudoma; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Digestive System Neoplasms; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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: 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

Topics: Adenoma, Islet Cell; Adult; Female; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Gastrointestinal Neoplasms; Glucagon; Growth Hormone-Releasing Hormone; Humans; Pancreatic Polypeptide; Peptide Biosynthesis; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

The case of an infant who developed refractory watery diarrhea at the age of 2 weeks is described. Diarrhea was secretory in type, stool weight on no oral intake was 400 to 600 gm daily. A vasoactive intestinal peptide (VIP)-producing tumor was suspected. At the age of 7 1/2 months an exploratory laparotomy revealed nonbeta islet cell hyperplasia of the pancreas. VIP levels were elevated in plasma and pancreatic tissue. After 95% pancreatectomy, plasma VIP level dropped to normal. Hypokalemia, described in adult patients with VIP-producing pancreatic tumors and refractory watery diarrhea, was not a significant problem in this infant. This is the first report on the association of refractory watery diarrhea with elevated levels of plasma VIP and pancreatic islet nonbeta cell hyperplasia in the pediatric age group.

Topics: Adenoma, Islet Cell; Chronic Disease; Diagnosis, Differential; Diarrhea, Infantile; Humans; Hyperplasia; Infant, Newborn; Infant, Newborn, Diseases; Islets of Langerhans; Male; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

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

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

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

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

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Intestinal Neoplasms; Motilin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

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

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

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

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

Topics: Adenoma, Islet Cell; Glucagon; Humans; Islets of Langerhans; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

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

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

Topics: Adenoma, Islet Cell; Antigens; Calcitonin; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; 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

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Hormones, Ectopic; Humans; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide

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

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

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

A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms.

Topics: Adenoma, Islet Cell; Female; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

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

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

Topics: Achlorhydria; 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