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WDHA Syndrome

Updated : August 21, 2023





Background

WDHA (Watery Diarrhea, Hypokalemia, Achlorhydria) syndrome, also known as Verner-Morrison syndrome or pancreatic cholera, is a rare endocrine disorder characterized by the production of vasoactive intestinal polypeptide (VIP) by neuroendocrine tumors, usually originating from the pancreas. VIP is a hormone that regulates water and electrolyte balance in the body.

When produced in excess, it leads to watery diarrhea, low levels of potassium (hypokalemia), and decreased stomach acid production (achlorhydria). WDHA syndrome is most commonly associated with pancreatic neuroendocrine tumors called VIPomas. The condition typically presents with chronic watery diarrhea, electrolyte disturbances, and signs of dehydration. Prompt diagnosis and treatment are essential to manage symptoms and address the underlying tumor.

Epidemiology

  • Prevalence: WDHA syndrome is a rare condition, and the exact prevalence is not well-established in the literature.
  • Age: It can affect individuals of any age, but it is mostly diagnosed in adults.
  • Gender: There is no significant gender predilection, and both males and females can be affected.
  • Risk Factors: The primary risk factor for WDHA syndrome is the presence of a neuroendocrine tumor, particularly VIPoma, in the pancreas or other organs.

Anatomy

Pathophysiology

  • Neuroendocrine Tumors: WDHA syndrome, also known as Verner-Morrison syndrome, is typically associated with neuroendocrine tumors, particularly VIPomas. These tumors arise from the pancreatic islet cells or other organs and secrete vasoactive intestinal polypeptide (VIP).
  • VIP Overproduction: VIP is a hormone that plays a role in various physiological processes, including vasodilation, secretion, and motility of the gastrointestinal tract. In WDHA syndrome, excessive production of VIP by the neuroendocrine tumor leads to the characteristic symptoms.
  • Increased Intestinal Secretion: VIP acts on the intestinal epithelial cells, increasing chloride and water secretion into the lumen of the intestine. This results in chronic watery diarrhea, which is the hallmark symptom of WDHA syndrome.
  • Electrolyte Imbalance: The excessive loss of water and electrolytes in the diarrhea can lead to dehydration and electrolyte abnormalities, such as hypokalemia and metabolic acidosis.

Etiology

  • Neuroendocrine Tumors: WDHA syndrome is primarily associated with neuroendocrine tumors, particularly VIPomas. These tumors arise from the pancreatic islet cells or other sites in the body and secrete excessive amounts of vasoactive intestinal polypeptide (VIP).
  • VIPoma Mutation: In some cases, WDHA syndrome may be caused by a gene mutation in the VIPoma tumor cells, leading to uncontrolled production of VIP.
  • Sporadic Occurrence: WDHA syndrome can occur sporadically without any known underlying genetic or familial predisposition.
  • Other Neuroendocrine Tumors: Although VIPomas are the most common cause of WDHA syndrome, other neuroendocrine tumors, such as ganglioneuromas and ganglioneuroblastomas, can rarely produce VIP and result in similar clinical manifestations.

Genetics

Prognostic Factors

  • Tumor Stage: The stage of the underlying neuroendocrine tumor is an important prognostic factor. Early-stage tumors confined to the pancreas have a better prognosis compared to tumors that have spread to other organs or lymph nodes.
  • Tumor Grade: The grade of the neuroendocrine tumor, which reflects its cellular characteristics and aggressiveness, can influence the prognosis. Higher-grade tumors tend to have a poorer prognosis.
  • Metastasis: The presence of metastasis, particularly to distant organs such as the liver, significantly affects the prognosis of WDHA syndrome. Extensive metastatic disease is associated with a poorer outcome.
  • Tumor Resectability: The resectability of the neuroendocrine tumor is an important prognostic factor. Surgical removal of localized tumors offers better chances of long-term survival.
  • Response to Treatment: The response of the tumor to treatment modalities such as surgery, chemotherapy, and targeted therapies can impact the prognosis. Tumors that are more responsive to treatment may have a better prognosis.

Clinical History

CLINICAL HISTORY

Age Group: WDHA syndrome can occur in individuals of any age, but it is mostly diagnosed in middle-aged adults.

 

Physical Examination

PHYSICAL EXAMINATION

Vital Signs:

  • Blood pressure: Hypotension may be present in some cases.
  • Heart rate: Tachycardia (rapid heart rate) may be observed.

Abdominal Examination:

  • Abdominal tenderness: Palpation of the abdomen may reveal tenderness.
  • Mass or organ enlargement: In cases of underlying pancreatic neuroendocrine tumors, an abdominal mass or enlargement of the pancreas may be detected.

Signs of Dehydration:

  • Dry mucous membranes: The examiner may note dryness of the oral mucosa or decreased tear production.
  • Decreased skin turgor: Skin may appear less elastic or show decreased recoil when pinched.

Neurological Examination:

  • Weakness: Patients may exhibit generalized weakness or muscle fatigue.
  • Reflexes: Hyperactive or brisk deep tendon reflexes may be observed.

Age group

Associated comorbidity

Associated Comorbidity or Activity: WDHA syndrome is associated with neuroendocrine tumors, specifically pancreatic neuroendocrine tumors (also known as VIPomas).

These tumors secrete vasoactive intestinal peptide (VIP), leading to the characteristic symptoms of the syndrome. There are no specific comorbidities or activities associated with WDHA syndrome.

Associated activity

Acuity of presentation

Acuity of Presentation:

The presentation of WDHA syndrome can vary. Patients typically experience watery diarrhea, which may be chronic or intermittent. Other common symptoms include abdominal cramping, flushing, weakness, and weight loss. The severity and acuity of symptoms can vary among individuals.

Differential Diagnoses

DIFFERENTIAL DIAGNOSIS

Other Causes of Watery Diarrhea:

  • Infections: Viral gastroenteritis, bacterial enterocolitis, parasitic infections.
  • Inflammatory Bowel Disease (IBD): Crohn’s disease, ulcerative colitis.
  • Malabsorption syndromes: Celiac disease, lactose intolerance, pancreatic insufficiency.

Other Causes of Hypokalemia:

  • Renal causes: Renal tubular acidosis, renal potassium wasting syndromes.
  • Gastrointestinal losses: Diarrhea, vomiting, laxative abuse.
  • Endocrine disorders: Hyperaldosteronism, Cushing’s syndrome.

Other Causes of Achlorhydria:

  • Autoimmune gastritis.
  • Pernicious anemia.
  • Medications that inhibit gastric acid secretion.
  • Pancreatic Neuroendocrine Tumors (PNETs):
  • Insulinoma: Excessive insulin secretion leading to hypoglycemia.
  • Gastrinoma (Zollinger-Ellison syndrome): Excessive gastrin secretion causing gastric acid hypersecretion.
  • VIPoma: Excessive vasoactive intestinal peptide (VIP) secretion leading to watery diarrhea.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

TREATMENT PARADIGM

Modification of Environment:

  • Fluid and electrolyte replacement: Oral or intravenous fluids to correct dehydration and electrolyte imbalances.
  • Nutritional support: Adequate calorie intake and supplementation of specific nutrients if necessary.

Administration of Pharmaceutical Agents:

  • Somatostatin analogs: Octreotide or lanreotide to reduce hormone secretion and alleviate symptoms.
  • Proton pump inhibitors: To reduce gastric acid secretion in cases of achlorhydria.
  • Antidiarrheal agents: Such as loperamide to control diarrhea.

Intervention with Procedures:

  • Surgical resection: In cases of pancreatic neuroendocrine tumors (PNETs), surgical removal may be considered if feasible and indicated.
  • Endoscopic procedures: Endoscopic evaluation, biopsy, or tumor ablation techniques may be performed for diagnostic and therapeutic purposes.

Phase of Management:

  • Acute management: Focuses on stabilizing the patient, correcting fluid, and electrolyte imbalances, and controlling symptoms.
  • Long-term management: Involves regular monitoring, surveillance for tumor recurrence, and appropriate follow-up care based on the underlying cause.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

WDHA syndrome.ncbi.nlm.nih.gov

WDHA Syndrome

Updated : August 21, 2023




WDHA (Watery Diarrhea, Hypokalemia, Achlorhydria) syndrome, also known as Verner-Morrison syndrome or pancreatic cholera, is a rare endocrine disorder characterized by the production of vasoactive intestinal polypeptide (VIP) by neuroendocrine tumors, usually originating from the pancreas. VIP is a hormone that regulates water and electrolyte balance in the body.

When produced in excess, it leads to watery diarrhea, low levels of potassium (hypokalemia), and decreased stomach acid production (achlorhydria). WDHA syndrome is most commonly associated with pancreatic neuroendocrine tumors called VIPomas. The condition typically presents with chronic watery diarrhea, electrolyte disturbances, and signs of dehydration. Prompt diagnosis and treatment are essential to manage symptoms and address the underlying tumor.

  • Prevalence: WDHA syndrome is a rare condition, and the exact prevalence is not well-established in the literature.
  • Age: It can affect individuals of any age, but it is mostly diagnosed in adults.
  • Gender: There is no significant gender predilection, and both males and females can be affected.
  • Risk Factors: The primary risk factor for WDHA syndrome is the presence of a neuroendocrine tumor, particularly VIPoma, in the pancreas or other organs.
  • Neuroendocrine Tumors: WDHA syndrome, also known as Verner-Morrison syndrome, is typically associated with neuroendocrine tumors, particularly VIPomas. These tumors arise from the pancreatic islet cells or other organs and secrete vasoactive intestinal polypeptide (VIP).
  • VIP Overproduction: VIP is a hormone that plays a role in various physiological processes, including vasodilation, secretion, and motility of the gastrointestinal tract. In WDHA syndrome, excessive production of VIP by the neuroendocrine tumor leads to the characteristic symptoms.
  • Increased Intestinal Secretion: VIP acts on the intestinal epithelial cells, increasing chloride and water secretion into the lumen of the intestine. This results in chronic watery diarrhea, which is the hallmark symptom of WDHA syndrome.
  • Electrolyte Imbalance: The excessive loss of water and electrolytes in the diarrhea can lead to dehydration and electrolyte abnormalities, such as hypokalemia and metabolic acidosis.
  • Neuroendocrine Tumors: WDHA syndrome is primarily associated with neuroendocrine tumors, particularly VIPomas. These tumors arise from the pancreatic islet cells or other sites in the body and secrete excessive amounts of vasoactive intestinal polypeptide (VIP).
  • VIPoma Mutation: In some cases, WDHA syndrome may be caused by a gene mutation in the VIPoma tumor cells, leading to uncontrolled production of VIP.
  • Sporadic Occurrence: WDHA syndrome can occur sporadically without any known underlying genetic or familial predisposition.
  • Other Neuroendocrine Tumors: Although VIPomas are the most common cause of WDHA syndrome, other neuroendocrine tumors, such as ganglioneuromas and ganglioneuroblastomas, can rarely produce VIP and result in similar clinical manifestations.
  • Tumor Stage: The stage of the underlying neuroendocrine tumor is an important prognostic factor. Early-stage tumors confined to the pancreas have a better prognosis compared to tumors that have spread to other organs or lymph nodes.
  • Tumor Grade: The grade of the neuroendocrine tumor, which reflects its cellular characteristics and aggressiveness, can influence the prognosis. Higher-grade tumors tend to have a poorer prognosis.
  • Metastasis: The presence of metastasis, particularly to distant organs such as the liver, significantly affects the prognosis of WDHA syndrome. Extensive metastatic disease is associated with a poorer outcome.
  • Tumor Resectability: The resectability of the neuroendocrine tumor is an important prognostic factor. Surgical removal of localized tumors offers better chances of long-term survival.
  • Response to Treatment: The response of the tumor to treatment modalities such as surgery, chemotherapy, and targeted therapies can impact the prognosis. Tumors that are more responsive to treatment may have a better prognosis.

CLINICAL HISTORY

Age Group: WDHA syndrome can occur in individuals of any age, but it is mostly diagnosed in middle-aged adults.

 

PHYSICAL EXAMINATION

Vital Signs:

  • Blood pressure: Hypotension may be present in some cases.
  • Heart rate: Tachycardia (rapid heart rate) may be observed.

Abdominal Examination:

  • Abdominal tenderness: Palpation of the abdomen may reveal tenderness.
  • Mass or organ enlargement: In cases of underlying pancreatic neuroendocrine tumors, an abdominal mass or enlargement of the pancreas may be detected.

Signs of Dehydration:

  • Dry mucous membranes: The examiner may note dryness of the oral mucosa or decreased tear production.
  • Decreased skin turgor: Skin may appear less elastic or show decreased recoil when pinched.

Neurological Examination:

  • Weakness: Patients may exhibit generalized weakness or muscle fatigue.
  • Reflexes: Hyperactive or brisk deep tendon reflexes may be observed.

Associated Comorbidity or Activity: WDHA syndrome is associated with neuroendocrine tumors, specifically pancreatic neuroendocrine tumors (also known as VIPomas).

These tumors secrete vasoactive intestinal peptide (VIP), leading to the characteristic symptoms of the syndrome. There are no specific comorbidities or activities associated with WDHA syndrome.

Acuity of Presentation:

The presentation of WDHA syndrome can vary. Patients typically experience watery diarrhea, which may be chronic or intermittent. Other common symptoms include abdominal cramping, flushing, weakness, and weight loss. The severity and acuity of symptoms can vary among individuals.

DIFFERENTIAL DIAGNOSIS

Other Causes of Watery Diarrhea:

  • Infections: Viral gastroenteritis, bacterial enterocolitis, parasitic infections.
  • Inflammatory Bowel Disease (IBD): Crohn’s disease, ulcerative colitis.
  • Malabsorption syndromes: Celiac disease, lactose intolerance, pancreatic insufficiency.

Other Causes of Hypokalemia:

  • Renal causes: Renal tubular acidosis, renal potassium wasting syndromes.
  • Gastrointestinal losses: Diarrhea, vomiting, laxative abuse.
  • Endocrine disorders: Hyperaldosteronism, Cushing’s syndrome.

Other Causes of Achlorhydria:

  • Autoimmune gastritis.
  • Pernicious anemia.
  • Medications that inhibit gastric acid secretion.
  • Pancreatic Neuroendocrine Tumors (PNETs):
  • Insulinoma: Excessive insulin secretion leading to hypoglycemia.
  • Gastrinoma (Zollinger-Ellison syndrome): Excessive gastrin secretion causing gastric acid hypersecretion.
  • VIPoma: Excessive vasoactive intestinal peptide (VIP) secretion leading to watery diarrhea.

TREATMENT PARADIGM

Modification of Environment:

  • Fluid and electrolyte replacement: Oral or intravenous fluids to correct dehydration and electrolyte imbalances.
  • Nutritional support: Adequate calorie intake and supplementation of specific nutrients if necessary.

Administration of Pharmaceutical Agents:

  • Somatostatin analogs: Octreotide or lanreotide to reduce hormone secretion and alleviate symptoms.
  • Proton pump inhibitors: To reduce gastric acid secretion in cases of achlorhydria.
  • Antidiarrheal agents: Such as loperamide to control diarrhea.

Intervention with Procedures:

  • Surgical resection: In cases of pancreatic neuroendocrine tumors (PNETs), surgical removal may be considered if feasible and indicated.
  • Endoscopic procedures: Endoscopic evaluation, biopsy, or tumor ablation techniques may be performed for diagnostic and therapeutic purposes.

Phase of Management:

  • Acute management: Focuses on stabilizing the patient, correcting fluid, and electrolyte imbalances, and controlling symptoms.
  • Long-term management: Involves regular monitoring, surveillance for tumor recurrence, and appropriate follow-up care based on the underlying cause.

WDHA syndrome.ncbi.nlm.nih.gov