Zollinger-Ellison syndrome (ZES) is a condition characterized by a combination of gastroesophageal reflux disease, severe peptic ulcer disease, and chronic diarrhea. It is caused by a gastrin-secreting tumor in either the pancreas or duodenum, which leads to excessive stimulation of the acid-secreting cells in the stomach. This results in increased production of gastric acid.
The initial description of Zollinger-Ellison syndrome can be traced back to a case series published in 1955 by Dr. Edwin H. Ellison and Robert M. Zollinger. The two cases presented in the series exhibited ulcers in the upper jejunum and abnormally high gastric acid production that did not respond to conventional medical and surgical treatments, including gastrectomy.
Further investigation revealed the presence of non-beta cell islet tumors in the pancreas, which were responsible for the excessive secretion of gastrin and the associated symptoms of ZES. This seminal case series generated significant interest and paved the way for subsequent studies that established the link between gastrinomas and Zollinger-Ellison syndrome.
Epidemiology
Zollinger-Ellison syndrome is often challenging to diagnose early due to the increased use of proton pump inhibitors in modern times. It is worth noting that ZES is relatively rare, occurring in only 1% of patients with peptic ulcer disease. However, a report suggests that approximately 25% to 30% of individuals with ZES also have multiple endocrine neoplasia type 1 (MEN1).
In cases where ZES coexists with MEN1, hypersecretion of gastric acid can be attributed to hypercalcemia caused by the abnormal functioning of these cells. Interestingly, there is a higher prevalence of ZES among females compared to males, and this syndrome can affect individuals across all age groups.
Anatomy
Pathophysiology
The secretion of gastric acid is normally regulated by negative feedback mechanisms, which involve somatostatin release by gastric D cells. This feedback system helps maintain gastric acid homeostasis and ensures an appropriate pH level in the stomach. However, in the presence of a gastrinoma this delicate balance is disrupted. Gastrinoma leads to an unopposed release of gastrin, resulting in excessive gastric acid secretion.
The excess gastrin secretion caused by gastrinoma has detrimental effects, particularly in the post-bulbar regions of the duodenum. Gastrin stimulates the enterochromaffin-like and parietal cells, increasing gastric acid production. This acid production, combined with the trophic effect of gastrin, contributes to the development of severe peptic ulcer disease in the affected areas.
The duodenal ulcers that arise from ZES tend to be more prominent and refractory to treatment than ulcers caused by other factors. The most common symptoms associated with Zollinger-Ellison syndrome primarily result from the excess gastrin secretion from the gastrinoma. These symptoms include chronic diarrhea, abdominal pain, and heartburn.
Etiology
Zollinger-Ellison syndrome has a specific etiology centered around the presence of gastrin-secreting tumors known as gastrinomas. These gastrinomas are functional neuroendocrine tumors that typically arise in the duodenum or pancreas. In rare cases, they can also occur in other locations, such as the lymph nodes or liver. Gastrinomas results in the excessive secretion of gastrin.
The uncontrolled gastrin release disrupts the normal feedback mechanisms that regulate gastric acid secretion. This leads to increased acid production by the parietal cells in the stomach, resulting in hyperacidity. The elevated levels of gastric acid cause severe peptic ulcer disease, primarily in the post-bulbar regions of the duodenum.
The etiology of ZES is predominantly sporadic, but approximately 30% of patients with ZES are associated with multiple endocrine neoplasia type 1 (MEN1), a genetic disorder characterized by the development of tumors in various endocrine glands. In MEN1-related ZES cases, gastrinomas are often found with hyperplastic cells or tumors in the pituitary, parathyroid, and pancreatic islet cells.
Genetics
Prognostic Factors
The prognosis of Zollinger-Ellison syndrome is closely tied to the presence and stage of gastrinomas. Gastrinomas, the tumors responsible for ZES, have a variable malignancy rate ranging from 60% to 90%, with the potential to metastasize to lymph nodes, liver, or other distant organs.
Pancreatic gastrinomas, comprising approximately 50% of cases, have a higher incidence of metastasis (50%) than duodenal gastrinomas, where the liver is affected in about 10%. Liver metastasis significantly impacts overall survival, with pancreatic gastrinomas generally having lower long-term survival rates than duodenal gastrinomas.
Notably, patients with liver metastases show a 10-year survival rate of around 15% following surgical intervention, while those without liver metastases exhibit a remarkable 20-year survival rate of 95%. This finding highlights the significant influence of liver involvement on prognosis in ZES.
Clinical History
Clinical History
Zollinger-Ellison syndrome is a rare condition characterized by the development of gastrin-secreting tumors called gastrinomas in the pancreas or duodenum. The clinical history of a patient with ZES typically involves a range of gastrointestinal symptoms and complications. Patients may report recurrent and severe episodes of abdominal pain, often accompanied by burning or gnawing sensations in the upper abdomen. These symptoms are often resistant to standard acid-suppressing medications.
Additionally, patients may present with chronic diarrhea, which can be watery and voluminous. Weight loss, malabsorption, and nutrient deficiencies may be evident due to excessive gastric acid secretion and impaired digestion. Peptic ulcers are common, particularly in the stomach and duodenum, and may result in complications such as bleeding, perforation, or gastric outlet obstruction.
Gastroesophageal reflux disease may also be present, leading to symptoms such as heartburn and regurgitation. Furthermore, in some cases, patients may have a history of multiple endocrine neoplasia type 1 (MEN1), as ZES can be associated with this inherited condition. The clinical history of a patient with ZES thus encompasses a combination of gastrointestinal symptoms, associated complications, and relevant familial or personal medical history.
Physical Examination
Physical Examination
ZES can cause recurrent or persistent abdominal pain, typically located in the upper abdomen. In some cases, a palpable abdominal mass may be detected during the examination. This mass could be associated with the gastrinoma itself or related to any metastatic spread of the tumor. ZES often leads to the development of multiple peptic ulcers in the stomach or duodenum.
The physical examination may indicate the presence of these ulcers, which could manifest as epigastric tenderness or, in severe cases, signs of gastrointestinal bleeding. In rare instances, patients with ZES may exhibit specific skin lesions known as necrolytic migratory erythema (NME). These lesions typically appear as red, well-defined, and migrating patches.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential Diagnoses
Autoimmune Gastritis
Gastric Outlet Obstruction
Renal Insufficiency
Short Bowel Syndrome
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Prior to the discovery of H2-receptor antagonists and proton pump inhibitors, total gastrectomy was often the only viable treatment option for Zollinger-Ellison syndrome. However, the management approach has shifted with the advent of H2-receptor antagonists and PPIs. The dosage of PPIs, such as intravenous pantoprazole or oral omeprazole, must be carefully adjusted to normalize basal acid output levels, particularly in individuals who have undergone prior surgery, to reduce acid secretion.
In cases where PPIs are poorly tolerated, an H2-receptor antagonist may be considered an alternative. For patients with ZES and multiple endocrine neoplasia type 1, who often have multiple tumors and a low likelihood of cure, surgical gastrinoma resection is typically reserved for tumors larger than 2 cm in size. Surgical exploration is an option in sporadic gastrinomas due to the significant risk of tumor metastasis to the liver, lymph nodes, and distant organs.
In cases of advanced ZES, a multidisciplinary approach involving interprofessional rounds is necessary to explore non-surgical treatment options. These may include chemotherapy with sunitinib and everolimus, somatostatin analogs, interferon therapy, radioembolization, chemoembolization, and radiofrequency ablation. These alternative therapies aim to target and manage the disease progression in patients with advanced ZES.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
Future Trends
Media Gallary
References
News
Vaping’s ‘95% Safer’ Claim Debated for Youth Health
Posted on
News
Google DeepMind’s AI Revolutionizes the Search for Disease Genes
Posted on
News
Mosquitoes Pose New Challenge to Public Health
Posted on
News
3D-Printed e3-skin Redefines Wearable Health Monitoring
Zollinger-Ellison syndrome (ZES) is a condition characterized by a combination of gastroesophageal reflux disease, severe peptic ulcer disease, and chronic diarrhea. It is caused by a gastrin-secreting tumor in either the pancreas or duodenum, which leads to excessive stimulation of the acid-secreting cells in the stomach. This results in increased production of gastric acid.
The initial description of Zollinger-Ellison syndrome can be traced back to a case series published in 1955 by Dr. Edwin H. Ellison and Robert M. Zollinger. The two cases presented in the series exhibited ulcers in the upper jejunum and abnormally high gastric acid production that did not respond to conventional medical and surgical treatments, including gastrectomy.
Further investigation revealed the presence of non-beta cell islet tumors in the pancreas, which were responsible for the excessive secretion of gastrin and the associated symptoms of ZES. This seminal case series generated significant interest and paved the way for subsequent studies that established the link between gastrinomas and Zollinger-Ellison syndrome.
Zollinger-Ellison syndrome is often challenging to diagnose early due to the increased use of proton pump inhibitors in modern times. It is worth noting that ZES is relatively rare, occurring in only 1% of patients with peptic ulcer disease. However, a report suggests that approximately 25% to 30% of individuals with ZES also have multiple endocrine neoplasia type 1 (MEN1).
In cases where ZES coexists with MEN1, hypersecretion of gastric acid can be attributed to hypercalcemia caused by the abnormal functioning of these cells. Interestingly, there is a higher prevalence of ZES among females compared to males, and this syndrome can affect individuals across all age groups.
The secretion of gastric acid is normally regulated by negative feedback mechanisms, which involve somatostatin release by gastric D cells. This feedback system helps maintain gastric acid homeostasis and ensures an appropriate pH level in the stomach. However, in the presence of a gastrinoma this delicate balance is disrupted. Gastrinoma leads to an unopposed release of gastrin, resulting in excessive gastric acid secretion.
The excess gastrin secretion caused by gastrinoma has detrimental effects, particularly in the post-bulbar regions of the duodenum. Gastrin stimulates the enterochromaffin-like and parietal cells, increasing gastric acid production. This acid production, combined with the trophic effect of gastrin, contributes to the development of severe peptic ulcer disease in the affected areas.
The duodenal ulcers that arise from ZES tend to be more prominent and refractory to treatment than ulcers caused by other factors. The most common symptoms associated with Zollinger-Ellison syndrome primarily result from the excess gastrin secretion from the gastrinoma. These symptoms include chronic diarrhea, abdominal pain, and heartburn.
Zollinger-Ellison syndrome has a specific etiology centered around the presence of gastrin-secreting tumors known as gastrinomas. These gastrinomas are functional neuroendocrine tumors that typically arise in the duodenum or pancreas. In rare cases, they can also occur in other locations, such as the lymph nodes or liver. Gastrinomas results in the excessive secretion of gastrin.
The uncontrolled gastrin release disrupts the normal feedback mechanisms that regulate gastric acid secretion. This leads to increased acid production by the parietal cells in the stomach, resulting in hyperacidity. The elevated levels of gastric acid cause severe peptic ulcer disease, primarily in the post-bulbar regions of the duodenum.
The etiology of ZES is predominantly sporadic, but approximately 30% of patients with ZES are associated with multiple endocrine neoplasia type 1 (MEN1), a genetic disorder characterized by the development of tumors in various endocrine glands. In MEN1-related ZES cases, gastrinomas are often found with hyperplastic cells or tumors in the pituitary, parathyroid, and pancreatic islet cells.
The prognosis of Zollinger-Ellison syndrome is closely tied to the presence and stage of gastrinomas. Gastrinomas, the tumors responsible for ZES, have a variable malignancy rate ranging from 60% to 90%, with the potential to metastasize to lymph nodes, liver, or other distant organs.
Pancreatic gastrinomas, comprising approximately 50% of cases, have a higher incidence of metastasis (50%) than duodenal gastrinomas, where the liver is affected in about 10%. Liver metastasis significantly impacts overall survival, with pancreatic gastrinomas generally having lower long-term survival rates than duodenal gastrinomas.
Notably, patients with liver metastases show a 10-year survival rate of around 15% following surgical intervention, while those without liver metastases exhibit a remarkable 20-year survival rate of 95%. This finding highlights the significant influence of liver involvement on prognosis in ZES.
Clinical History
Zollinger-Ellison syndrome is a rare condition characterized by the development of gastrin-secreting tumors called gastrinomas in the pancreas or duodenum. The clinical history of a patient with ZES typically involves a range of gastrointestinal symptoms and complications. Patients may report recurrent and severe episodes of abdominal pain, often accompanied by burning or gnawing sensations in the upper abdomen. These symptoms are often resistant to standard acid-suppressing medications.
Additionally, patients may present with chronic diarrhea, which can be watery and voluminous. Weight loss, malabsorption, and nutrient deficiencies may be evident due to excessive gastric acid secretion and impaired digestion. Peptic ulcers are common, particularly in the stomach and duodenum, and may result in complications such as bleeding, perforation, or gastric outlet obstruction.
Gastroesophageal reflux disease may also be present, leading to symptoms such as heartburn and regurgitation. Furthermore, in some cases, patients may have a history of multiple endocrine neoplasia type 1 (MEN1), as ZES can be associated with this inherited condition. The clinical history of a patient with ZES thus encompasses a combination of gastrointestinal symptoms, associated complications, and relevant familial or personal medical history.
Physical Examination
ZES can cause recurrent or persistent abdominal pain, typically located in the upper abdomen. In some cases, a palpable abdominal mass may be detected during the examination. This mass could be associated with the gastrinoma itself or related to any metastatic spread of the tumor. ZES often leads to the development of multiple peptic ulcers in the stomach or duodenum.
The physical examination may indicate the presence of these ulcers, which could manifest as epigastric tenderness or, in severe cases, signs of gastrointestinal bleeding. In rare instances, patients with ZES may exhibit specific skin lesions known as necrolytic migratory erythema (NME). These lesions typically appear as red, well-defined, and migrating patches.
Differential Diagnoses
Autoimmune Gastritis
Gastric Outlet Obstruction
Renal Insufficiency
Short Bowel Syndrome
Prior to the discovery of H2-receptor antagonists and proton pump inhibitors, total gastrectomy was often the only viable treatment option for Zollinger-Ellison syndrome. However, the management approach has shifted with the advent of H2-receptor antagonists and PPIs. The dosage of PPIs, such as intravenous pantoprazole or oral omeprazole, must be carefully adjusted to normalize basal acid output levels, particularly in individuals who have undergone prior surgery, to reduce acid secretion.
In cases where PPIs are poorly tolerated, an H2-receptor antagonist may be considered an alternative. For patients with ZES and multiple endocrine neoplasia type 1, who often have multiple tumors and a low likelihood of cure, surgical gastrinoma resection is typically reserved for tumors larger than 2 cm in size. Surgical exploration is an option in sporadic gastrinomas due to the significant risk of tumor metastasis to the liver, lymph nodes, and distant organs.
In cases of advanced ZES, a multidisciplinary approach involving interprofessional rounds is necessary to explore non-surgical treatment options. These may include chemotherapy with sunitinib and everolimus, somatostatin analogs, interferon therapy, radioembolization, chemoembolization, and radiofrequency ablation. These alternative therapies aim to target and manage the disease progression in patients with advanced ZES.
medtigo
Zollinger-Ellison Syndrome(ZES)
Updated :
September 5, 2023
Zollinger-Ellison syndrome (ZES) is a condition characterized by a combination of gastroesophageal reflux disease, severe peptic ulcer disease, and chronic diarrhea. It is caused by a gastrin-secreting tumor in either the pancreas or duodenum, which leads to excessive stimulation of the acid-secreting cells in the stomach. This results in increased production of gastric acid.
The initial description of Zollinger-Ellison syndrome can be traced back to a case series published in 1955 by Dr. Edwin H. Ellison and Robert M. Zollinger. The two cases presented in the series exhibited ulcers in the upper jejunum and abnormally high gastric acid production that did not respond to conventional medical and surgical treatments, including gastrectomy.
Further investigation revealed the presence of non-beta cell islet tumors in the pancreas, which were responsible for the excessive secretion of gastrin and the associated symptoms of ZES. This seminal case series generated significant interest and paved the way for subsequent studies that established the link between gastrinomas and Zollinger-Ellison syndrome.
Zollinger-Ellison syndrome is often challenging to diagnose early due to the increased use of proton pump inhibitors in modern times. It is worth noting that ZES is relatively rare, occurring in only 1% of patients with peptic ulcer disease. However, a report suggests that approximately 25% to 30% of individuals with ZES also have multiple endocrine neoplasia type 1 (MEN1).
In cases where ZES coexists with MEN1, hypersecretion of gastric acid can be attributed to hypercalcemia caused by the abnormal functioning of these cells. Interestingly, there is a higher prevalence of ZES among females compared to males, and this syndrome can affect individuals across all age groups.
The secretion of gastric acid is normally regulated by negative feedback mechanisms, which involve somatostatin release by gastric D cells. This feedback system helps maintain gastric acid homeostasis and ensures an appropriate pH level in the stomach. However, in the presence of a gastrinoma this delicate balance is disrupted. Gastrinoma leads to an unopposed release of gastrin, resulting in excessive gastric acid secretion.
The excess gastrin secretion caused by gastrinoma has detrimental effects, particularly in the post-bulbar regions of the duodenum. Gastrin stimulates the enterochromaffin-like and parietal cells, increasing gastric acid production. This acid production, combined with the trophic effect of gastrin, contributes to the development of severe peptic ulcer disease in the affected areas.
The duodenal ulcers that arise from ZES tend to be more prominent and refractory to treatment than ulcers caused by other factors. The most common symptoms associated with Zollinger-Ellison syndrome primarily result from the excess gastrin secretion from the gastrinoma. These symptoms include chronic diarrhea, abdominal pain, and heartburn.
Zollinger-Ellison syndrome has a specific etiology centered around the presence of gastrin-secreting tumors known as gastrinomas. These gastrinomas are functional neuroendocrine tumors that typically arise in the duodenum or pancreas. In rare cases, they can also occur in other locations, such as the lymph nodes or liver. Gastrinomas results in the excessive secretion of gastrin.
The uncontrolled gastrin release disrupts the normal feedback mechanisms that regulate gastric acid secretion. This leads to increased acid production by the parietal cells in the stomach, resulting in hyperacidity. The elevated levels of gastric acid cause severe peptic ulcer disease, primarily in the post-bulbar regions of the duodenum.
The etiology of ZES is predominantly sporadic, but approximately 30% of patients with ZES are associated with multiple endocrine neoplasia type 1 (MEN1), a genetic disorder characterized by the development of tumors in various endocrine glands. In MEN1-related ZES cases, gastrinomas are often found with hyperplastic cells or tumors in the pituitary, parathyroid, and pancreatic islet cells.
The prognosis of Zollinger-Ellison syndrome is closely tied to the presence and stage of gastrinomas. Gastrinomas, the tumors responsible for ZES, have a variable malignancy rate ranging from 60% to 90%, with the potential to metastasize to lymph nodes, liver, or other distant organs.
Pancreatic gastrinomas, comprising approximately 50% of cases, have a higher incidence of metastasis (50%) than duodenal gastrinomas, where the liver is affected in about 10%. Liver metastasis significantly impacts overall survival, with pancreatic gastrinomas generally having lower long-term survival rates than duodenal gastrinomas.
Notably, patients with liver metastases show a 10-year survival rate of around 15% following surgical intervention, while those without liver metastases exhibit a remarkable 20-year survival rate of 95%. This finding highlights the significant influence of liver involvement on prognosis in ZES.
Clinical History
Zollinger-Ellison syndrome is a rare condition characterized by the development of gastrin-secreting tumors called gastrinomas in the pancreas or duodenum. The clinical history of a patient with ZES typically involves a range of gastrointestinal symptoms and complications. Patients may report recurrent and severe episodes of abdominal pain, often accompanied by burning or gnawing sensations in the upper abdomen. These symptoms are often resistant to standard acid-suppressing medications.
Additionally, patients may present with chronic diarrhea, which can be watery and voluminous. Weight loss, malabsorption, and nutrient deficiencies may be evident due to excessive gastric acid secretion and impaired digestion. Peptic ulcers are common, particularly in the stomach and duodenum, and may result in complications such as bleeding, perforation, or gastric outlet obstruction.
Gastroesophageal reflux disease may also be present, leading to symptoms such as heartburn and regurgitation. Furthermore, in some cases, patients may have a history of multiple endocrine neoplasia type 1 (MEN1), as ZES can be associated with this inherited condition. The clinical history of a patient with ZES thus encompasses a combination of gastrointestinal symptoms, associated complications, and relevant familial or personal medical history.
Physical Examination
ZES can cause recurrent or persistent abdominal pain, typically located in the upper abdomen. In some cases, a palpable abdominal mass may be detected during the examination. This mass could be associated with the gastrinoma itself or related to any metastatic spread of the tumor. ZES often leads to the development of multiple peptic ulcers in the stomach or duodenum.
The physical examination may indicate the presence of these ulcers, which could manifest as epigastric tenderness or, in severe cases, signs of gastrointestinal bleeding. In rare instances, patients with ZES may exhibit specific skin lesions known as necrolytic migratory erythema (NME). These lesions typically appear as red, well-defined, and migrating patches.
Differential Diagnoses
Autoimmune Gastritis
Gastric Outlet Obstruction
Renal Insufficiency
Short Bowel Syndrome
Prior to the discovery of H2-receptor antagonists and proton pump inhibitors, total gastrectomy was often the only viable treatment option for Zollinger-Ellison syndrome. However, the management approach has shifted with the advent of H2-receptor antagonists and PPIs. The dosage of PPIs, such as intravenous pantoprazole or oral omeprazole, must be carefully adjusted to normalize basal acid output levels, particularly in individuals who have undergone prior surgery, to reduce acid secretion.
In cases where PPIs are poorly tolerated, an H2-receptor antagonist may be considered an alternative. For patients with ZES and multiple endocrine neoplasia type 1, who often have multiple tumors and a low likelihood of cure, surgical gastrinoma resection is typically reserved for tumors larger than 2 cm in size. Surgical exploration is an option in sporadic gastrinomas due to the significant risk of tumor metastasis to the liver, lymph nodes, and distant organs.
In cases of advanced ZES, a multidisciplinary approach involving interprofessional rounds is necessary to explore non-surgical treatment options. These may include chemotherapy with sunitinib and everolimus, somatostatin analogs, interferon therapy, radioembolization, chemoembolization, and radiofrequency ablation. These alternative therapies aim to target and manage the disease progression in patients with advanced ZES.
Free CME credits
Both our subscription plans include Free CME/CPD AMA PRA Category 1 credits.
Digital Certificate PDF
On course completion, you will receive a full-sized presentation quality digital certificate.
medtigo Simulation
A dynamic medical simulation platform designed to train healthcare professionals and students to effectively run code situations through an immersive hands-on experience in a live, interactive 3D environment.
medtigo Points
medtigo points is our unique point redemption system created to award users for interacting on our site. These points can be redeemed for special discounts on the medtigo marketplace as well as towards the membership cost itself.
Community Forum post/reply = 5 points
*Redemption of points can occur only through the medtigo marketplace, courses, or simulation system. Money will not be credited to your bank account. 10 points = $1.
All Your Certificates in One Place
When you have your licenses, certificates and CMEs in one place, it's easier to track your career growth. You can easily share these with hospitals as well, using your medtigo app.
