vasoactive-intestinal-peptide and Achlorhydria

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

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

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

Topics: 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

A 68-year-old woman with an 11-day history of sudden abdominal pain and severe watery diarrhea was transferred to our hospital due to an exacerbation of renal function despite hydration. After treatment for dehydration and acidemia was provided in our intensive care unit, patient's renal function improved. Contrast-enhanced abdominal computed tomography was finally performed, revealing a hypervascular pancreatic mass with multiple hepatic masses. This imaging finding along with her clinical symptoms indicated watery diarrhea hypokalemia achlorhydria (WDHA) syndrome caused by a pancreatic VIPoma. Somatostatin analog was administered immediately leading to the improvement of her diarrhea and her general condition. As a result, endoscopic ultrasonography-guided fine-needle aspiration could be performed. Consequently, she was diagnosed with a pancreatic neuroendocrine tumor. She then underwent surgical resection of the pancreatic tumor and liver metastasis. As revealed in the immunohistochemical analysis of the excised tumor tissue, VIP was highly expressed, resulting in the final diagnosis of pancreatic VIPoma. Therefore, the immediate use of a somatostatin analog is crucial for improving the patient's general condition and achieving a definitive diagnosis pathologically when a patient is suspected of having a pancreatic VIPoma.

Topics: Achlorhydria; Aged; Female; Hormones; Humans; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Vipoma

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

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

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

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

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: Achlorhydria; Diarrhea; Humans; Hypokalemia; Pancreatic Neoplasms; 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

Activation of adenylate cyclase (AC) by PGE2, histamine and gastrointestinal hormones was studied in parietal cell-free gastric biopsy specimens from the corpus of patients with proven high gastrin achlorhydria. PGE2, somatostatin, VIP, pentagastrin and secretin activated AC in a concentration-dependent manner both in normal and in atrophic mucosa. Histamine activated AC only in normal gastric mucosa, being entirely ineffective in mucosa devoid of parietal cells. The results indicate that histamine-sensitive AC disappears in patients with achlorhydria, probably due to their loss of parietal cells. Enzyme activity in response to somatostatin, VIP, pentagastrin, secretin and PGE2 remains unchanged in these patients indicating AC localization in nonparietal cells, e.g. chief or mucous cells.

Topics: Achlorhydria; Adenylyl Cyclases; Adult; Aged; Dinoprostone; Enzyme Activation; Female; Gastric Mucosa; Gastrointestinal Hormones; Histamine; Humans; Middle Aged; Pentagastrin; Prostaglandins E; Somatostatin; Vasoactive Intestinal Peptide

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

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

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

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

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

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

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

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

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

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

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

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

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

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