Watery Diarrhea, Hypokalemia, And Achlorhydria Research Articles

Etiology, Assessment and Management of WDHA (Watery Diarrhea, Hypokalemia, and Achlorhydria) and VIPoma

The syndrome of watery diarrhoea, hypokalemia, and achlorhydria (WDHA syndrome) is an uncommon disorder marked by severe, watery diarrhoea caused by non–beta pancreatic islet cell oversecretion of vasoactive intestinal peptide (VIP). The onset of the disease is gradual, and diagnosis is often months or years later. Long-term dehydration, electrolyte and acid-base abnormalities, and chronic renal failure are all linked to morbidity. Pancreatic endocrine tumours are extremely rare, with less than 10 incidences per million people. VIPomas are uncommon tumours that affect between 0.05 and 2.0 percent of people. The most prevalent symptom is diarrhoea, which affects at least 89 percent of patients. VIPoma is treated with a combination of medicine and surgery The goal of first medical treatment is to reduce symptoms and restore fluids and electrolytes as quickly as possible

A 45-Year-Old Female with Hypokalemic Rhabdomyolysis due to VIP-Producing Composite Pheochromocytoma

The watery diarrhea, hypokalemia and achlorhydria (WHDA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing extra-pancreatic tumors is rare. We report on a 45-year-old woman who suffered from persistent secretory diarrhea for six years and who was admitted to hospital with complaints of muscular weakness and myalgia. Biochemical testing revealed pronounced rhabdomyolysis due to severe hypokalemia. Gastrointestinal evaluation of long-standing diarrhea including endoscopy of the upper and lower gastrointestinal tract and the small intestine did not show any pathologies. An abdominal computed tomography scan revealed a mass of 4 × 5 cm in the left adrenal gland demonstrating a strong uptake in the 123I-labelled metaiodobenzylguanidine scintigraphy. Plasma levels of chromogranin A, calcitonin, parathormone, basal renin and most prominently VIP were increased in line with a increased 24 hour urinary secretion of noradrenaline, dopamine, normetanephrine and vanillymandelic acid. A WDHA (watery diarrhea, hypokalaemia, achlorhydria) syndrome with hypokalemic rhabdomyolysis due to a VIP-producing adrenal tumor was diagnosed that was removed surgically. The histological evaluation demonstrated a composite pheochromocytoma. Diarrhea stopped immediately after surgery together with a normalization of laboratory parameters. In conclusion, this case report focuses on the rare clinical presentation of secretory diarrhea and electrolyte disturbances in combination with hypokalemic rhabdomyolysis which was caused by a VIP-producing composite pheochromocytoma.

Verner-Morrison syndrome: a case study

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.

Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma

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.

Hypokalemic Rhabdomyolysis due to WDHA Syndrome Caused by VIP-producing Composite Pheochromocytoma: A Case in Neurofibromatosis Type 1

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.

WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome: clinical features, diagnosis, and treatment.

WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome is an unusual paraneoplastic condition caused by excess vasoactive intestinal polypeptide (VIP) secreted by certain tumors. The onset of the syndrome is insidious, and diagnosis is usually delayed by months to years. Morbidity and mortality from untreated WDHA syndrome are related to long-standing dehydration and electrolyte and acid-base disturbances resulting in chronic renal failure. Diagnosis requires documentation of large volumes of secretory diarrhea, elevated serum VIP levels, and localization of the VIP-secreting tumor. Treatment includes correction of volume, electrolyte, and metabolic abnormalities, pharmacotherapy to decrease gastrointestinal secretion and increase absorption, and ultimately surgical resection or debulking of the vipoma.

Multiple-hormone gene expression in ganglioneuroblastoma with watery diarrhea, hypokalemia, and achlorhydria syndrome

It has been reported that vasoactive intestinal peptide (VIP)-producing tumors accompanied by watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome often produce multiple hormones biochemically and immunohistochemically. The authors examined the distribution of several peptides--VIP, peptide histidine methionine (PHM), neuropeptide Y (NPY), methionine-enkephalin (M-EK), somatostatin (SS), substance-P (Sub-P), corticotropin-releasing hormone, and tyrosine hydroxylase--with immunohistochemical studies and an in situ hybridization method in three ganglioneuroblastomas with WDHA syndrome. All patients had an extremely elevated plasma level of VIP. Peptides examined immunohistochemically in the tumor were all detectable in ganglionic cells and some neurites. The coexistence of those peptides was observed with serial section staining. The presence of messenger RNA of VIP/PHM-27, NPY, and SS was detectable in the cytoplasm of the tumor cells with the in situ hybridization. It was shown that multiple genes of peptides are expressed simultaneously and translated to proteins in those tumors.

<b>INHIBITORY EFFECTS OF ACUTE AND CHRONIC TREATMENTS WITH ADRENOCORTICOTROPIN-RELEASING HORMONE ON THE LEYDIG CELLS OF THE RAT </b><b>TESTIS </b>

Totally 180 tumor tissue extracts of neuroendocrine tumors were examined for the production of vasoactive intestinal polypeptide (YIP), peptide histidine-methionine (PHM), glucagon, growth hormone-releasing hormone (GRH) and secretin. Twenty-two tumors were obtained from patients with the watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome, 4 were from patients with the glucagonoma syndrome and 2 were from the ectopic GRH syndrome. YIP, PHM, glucagon and GRH were frequently produced by neuroendocrine tumors, but secretin was not. When a large amount of peptides are produced and their plasma levels are enormously elevated, hormonal syndromes are developed

A Case of the Watery Diarrhea-Hypokalemia-Achlorhydria Syndrome: Successful Preoperative Treatment of Watery Diarrhea with a Somatostatin Analogue

A 35-year-old man presenting with severe watery diarrhea was diagnosed as having the watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome with the elevation of plasma vasoactive intestinal peptide (VIP) level. Imaging diagnostic techniques revealed a hypervascular tumor at the tail of the pancreas as well as a solitary liver metastasis. During the patient's stay in hospital, he developed acute renal failure probably due to persistent dehydration and severe hypokalemia. Although these complications improved with artificial dialyses, severe watery diarrhea continued, which made it difficult to achieve surgical resection of the tumor. A new long-acting and potent somatostatin analogue, SMS 201-995 (Sandoz Ltd, Basel, Switzerland), was tested and was shown to be effective; after a few hours of subcutaneous injection of this agent, the watery diarrhea disappeared, which in turn improved the patient's hypokalemia, hypercalcemia and metabolic acidosis. Three weeks later, distal pancreatectomy with splenectomy and hepatic lobectomy were successfully performed, and the patient resumed his normal life. The somatostatin analogue has been reported to be useful in the long-term treatment of patients with inoperable WDHA syndrome. The present case demonstrated that short-term administration of this agent is also useful for improving the condition of WDHA patients at the preoperative stage.

Vasoactive Intestinal Peptide—Secreting Tumor Appearing as Growth Failure

Neural crest tumors are a known cause of intractable watery diarrhea in children. Although high levels of catecholamines and their metabolites were previously thought to be the causative agents, vasoactive intestinal peptide (VIP) has recently been implicated as the mediator of such diarrhea. In adults, high levels of VIP were found in association with the syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA), with the majority suffering from pancreatic islet cell tumors.1 We report a case of VIP-secreting ganglioneuroma in a 7-year-old boy in whom the predominant clinical picture was growth failure with intermittent secretory diarrhea and soiling. In previously reported pediatric cases, diarrhea, failure to thrive, wasting, and anorexia were the predominant symptoms.2-5Our patient is unique in that short stature with severe growth failure was a dominant feature in the absence of weight loss, malabsorption, or ill health. A growth spurt of 10 cm in the

Retrospective study of 77 pancreatic endocrine tumors using the immunoperoxidase method.

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.

Radiologic and pathologic characteristics of the WDHA syndrome

A case of a non-beta islet cell tumor of the pancreas that produced the WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome is presented. An enlarged body-tail region of the pancreas is demonstrated on transaxial views; multiple fluid-filled loops of small and large bowel are also noted. The angiography of the tumor is similar to other non-beta islet cell lesions consisting of a large hypervascular mass with hypertrophied feeding vessels and a persistent, dense capillary stain. The demonstration of elevated levels of vasoactive intestinal polypeptide in both tumor and plasma and the ultrastructural description of endocrine granules may help to explain the pathophysiology in this case.