Individuals with Zollinger Ellison syndrome exhibit the following signs and symptoms:

• Pain in the abdomen is present in about 75% of the cases
• Diarrhea is experienced by 73% of individuals with ZES
• Weakness
• Nausea accompanied by vomiting
• Acid reflux and heartburn
• Weight loss
• Anemia due to gastrointestinal bleeding
• Loss of appetite
• Discomfort in the upper abdomen characterized by burning sensation and aches

• Weight Loss

  The presence of weight loss especially with abdominal pain, diarrhea, or heartburn is an important clue suggesting the presence of gastrinoma. [ncbi.nlm.nih.gov]

  Symptoms Symptoms of ZES include abdominal pain, diarrhea, unintended weight loss, anemia, gastrointestinal bleeding, loss of appetite, heart burn due to acid reflux, discomfort in the upper abdomen with pain and gnawing. [symptoma.com]

  […] unintended weight loss Nausea and vomiting Steatorrhea (increased levels of fats within the stool) Get useful, helpful and relevant health + wellness information enews More health news + info [my.clevelandclinic.org]

• Fatigue

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019 [patientslikeme.com]

  It presents a range of unpleasant symptoms, including: Stabbing abdominal pain, due to the ulcers Fatigue and weakness Nausea, vomiting and diarrhoea Weight loss, due to a lessened ability to eat food and to the cancerous tumours, if present. [irishhealth.com]

  The symptoms of ZES include signs of peptic ulcers: gnawing, burning pain in the abdomen; diarrhea; nausea; vomiting; fatigue; weakness; weight loss; and bleeding. [nursinglink.monster.com]

  Symptoms Abdominal pain Diarrhea Nausea Weakness Fatigue Weight loss Burning sensation in the abdomen Diagnosis During a general examination, the doctor will ask the patient about their family’s medical history whether they have suffered from any of the [bookinghealth.com]

• Diarrhea

  These results demonstrate that abdominal pain, diarrhea, and heartburn are the most common presenting symptoms in ZES and that heartburn and diarrhea are more common than previously reported. [ncbi.nlm.nih.gov]

  […] you have severe abdominal pain that does not go away, especially if it occurs with diarrhea. [nlm.nih.gov]

  Abdominal Pain Most common symptom, typically felt in the epigastric area and may mimic PUD Pancreatitis, which may cause abdominal pain and malabsorption, may occur concomitantly with ZES Diarrhea Occurs secondary to malabsorption that results from [specialty.mims.com]

  […] health care provider: Call your provider if severe, persistent abdominal pain occurs, especially if it occurs with diarrhea. [endocrinesurgery.ucla.edu]

• Abdominal Pain

  Most cases present with abdominal pain due to peptic ulceration and chronic diarrhoea not responding to general measures. The symptom complex is initially confused with other more common diseases, which lead to a delay in diagnosis. [ncbi.nlm.nih.gov]

  pain, malabsorption and chronic watery diarrhea Abdominal Pain Most common symptom, typically felt in the epigastric area and may mimic PUD Pancreatitis, which may cause abdominal pain and malabsorption, may occur concomitantly with ZES Diarrhea Occurs [specialty.mims.com]

  These medicines also relieve abdominal pain and diarrhea. Surgery to remove a single gastrinoma may be done if the tumors have not spread to other organs. Surgery on the stomach (gastrectomy) to control acid production is rarely needed. [nlm.nih.gov]

  When to Contact a Medical Professional Call your health care provider if you have severe abdominal pain that does not go away, especially if it occurs with diarrhea. [account.allinahealth.org]

• Vomiting

  Persistent severe vomiting in pregnancy may be caused by underlying disease and should be investigated. A patient with intractable vomiting associated with abdominal pain and dental enamel erosion in two pregnancies had a gastrinoma. [ncbi.nlm.nih.gov]

  Other common digestive symptoms include nausea, vomiting, bleeding in the digestive tract characterized by blood vomiting or bloody diarrhea and unintentional weight loss. [phaa.com]

  Call your provider if you have any signs of intestinal bleeding, such as black or tarry stool, blood in the stool, or vomiting of blood. [urmc.rochester.edu]

• Nausea

  […] loss Decreased appetite Anemia When to see a doctor See your doctor if you have a persistent, burning, aching or gnawing pain in your upper abdomen, especially if you've also been experiencing nausea, vomiting and diarrhea. [fortishealthcare.com]

  A 28-year-old woman was admitted for further evaluation of epigastric soreness, heartburn, nausea, vomiting, diarrhea, and a significant weight loss. [ncbi.nlm.nih.gov]

  Common symptoms are diarrhea, nausea, vomiting and abdominal pain. The disease is rare and usually affects people between the age of 30 and 50 years. [phaa.com]

  […] loss Decreased appetite When to see a doctor See your doctor if you have a persistent, burning, aching or gnawing pain in your upper abdomen, especially if you've also been experiencing nausea, vomiting and diarrhea. [mayoclinic.org]

• Chronic Diarrhea

  Abstract Zollinger-Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. [ncbi.nlm.nih.gov]

  Patients with gastrinomas suffer from heart burn, chronic diarrhea, gastric or duodenal ulcers. (so-called Zollinger-Ellison syndrome). These symptoms result from an extremely hyper-acidic stomach. [carcinoids.de]

  Most ZES patients present with symptoms of acid reflux (52%-56%) and peptic ulcer disease (73%-98%), while other common symptoms include chronic diarrhea (60%-75%) and weight loss (7%-53%) [3, 4]. [hindawi.com]

  To the Editor: In July 2003, a 43-year-old man presented for workup of chronic painless diarrhea of 3 years' duration. Passing 3 to 5 watery stools per day without pathologic admixtures, he had lost 3 kg of weight. [amjmed.com]

  […] watery diarrhea Abdominal Pain Most common symptom, typically felt in the epigastric area and may mimic PUD Pancreatitis, which may cause abdominal pain and malabsorption, may occur concomitantly with ZES Diarrhea Occurs secondary to malabsorption that [specialty.mims.com]

• Flushing

  Evaluate existence and repercussion of flushing episodes (history, clinical, heart rate and blood pressure measurement during flush). Preoperative hydration and electrolyte correction is necessary based on the laboratory investigations. [accessanesthesiology.mhmedical.com]

• Hypopigmented Macule

  macules 0007449 Diarrhea Watery stool 0002014 Hypoglycemia Low blood sugar 0001943 Insulinoma 0012197 Pancreatic islet cell adenoma 0008261 Parathyroid adenoma 0002897 Pituitary adenoma Noncancerous tumor in pituitary gland 0002893 Prolactinoma 0040278 [rarediseases.info.nih.gov]

• Axillary Freckling

  Physical examination was remarkable for cutaneous findings (axillary freckling and multiple café-au-lait spots) as well as neurofibromas (dermal, plexiform). A diagnosis of NF1 was confirmed. [ncbi.nlm.nih.gov]

A complete medical history will be gathered and the signs and symptoms studied. If a family history of MEN I exist then the chances of ZES will be higher. In addition, the following diagnostic tests will be done in order to draw an appropriate conclusion:

• Blood tests will be done to analyze the levels of serum gastrin. Elevated levels of gastrin are indicative of presence of tumors in the pancreas or duodenum. Although clinical conditions like primary hypochlorhydria and achlorhydria can elicit a false positive result in gastrin test [4]. This can also result from various other conditions, and therefore a fasting serum gastrin will yield appropriate results and is considered to be the best screening test for ZES. 
• An endoscopy of the upper gastrointestinal tract is carried out to conduct biopsy of the tumors in the pancreas and duodenum.
• Imaging studies such as CT scan and MRI of the abdomen would also be required. These are useful tools for localizing the tumor and evaluation of metastatic disease. These imaging modalities can survey patients presenting with ZES to diagnosed profound neoplasms in MEN 1 [5].
• Endoscopic ultrasound is also a useful diagnostic procedure required to spot the exact location of the tumor. Individuals will be asked to fast the night before the test.
• Surgery in the face of a negative imaging result may confirm the presence of gastrinoma tumors in almost 98% of patients with classic ZES signs, 7% of liver metastasis are incidentally found during early surgery preventing late complications and delay in treatment [6].

• Ovarian Mass

  Imaging studies demonstrated a normal liver and pancreas but a large cystic right ovarian mass. [ncbi.nlm.nih.gov]

• Gastrin Increased

  In 97%-99% of gastrinoma patients, an increase in serum gastrin post secretin (Delta secretin) or post calcium (Delta calcium) occurred. [ncbi.nlm.nih.gov]

  Aim(s): To investigate whether a higher dose of secretin would lead to higher serum gastrin increases, resulting in better sensitivity and specificity of the secretin stimulation test to identify Zollinger-Ellison patients. [enets.org]

  The tumors that occur with Zollinger-Ellison syndrome are made up of cells that secrete large amounts of the hormone gastrin. Increased gastrin makes the stomach produce far too much acid. [mayoclinic.org]

• Gastric Lesion

  They are widely used in gastroesophageal reflux disease, gastroduodenal ulcers, Zollinger-Ellison syndrome or prevention and treatment of NSAIDs induced gastric lesions. [unboundmedicine.com]

Removal of the tumor and suppression of excessive acid production are the basis of treatment regime. In many cases, if the tumors are successfully removed then acid suppressing medications would rarely be required. The following methods are employed to treat ZES:

• Surgical procedures to selectively remove the gastrinoma are carried out [7]. If the tumor has spread to other parts of the body then decision to remove a single large tumor is taken. If liver is the site, then major part of the organ is removed to control the spread of the cancer.
• Chemotherapy is employed following surgery to arrest the growth of the other tumors.
• Medications like lanzoprazole can suppress the excessive acid in the stomach may be given to heal ulcers that have developed in the intestine and stomach [8]. However, proton pump inhibitors like lanzoprazole can cause lethal rebound acid hypersecretion state if abruptly discontinued among ZES patients [9]. For this reason, pantoprazole as an alternative may be taken as a long term maintenance with a high safety profile of up to 3 consecutive years of use [10].

The long-term prognosis of ZES is good. Medications to suppress the excessive acid production usually work well to relieve the symptoms. 

Complications

Timely diagnosis of the disease is necessary to prevent the onset of various secondary complications. The various complications of ZES include the following:

• The tumors metastasize to neighboring glands and organs like the liver [2]
• Severe diarrhea accompanied by weight loss
• Intestinal bleeding and development of perforation in the stomach due to ulcers
• Failure to locate the tumors during surgery
• Symptomatic hypomagnesemia with proton pump inhibitor overuse to treat ZES [3]

Tumors usually located in the pancreas or the small intestine call for the development of ZES. These tumors are producing the hormone gastrin and are termed as gastrinomas. Gastrinomas can appear as single tumors or as a group. Of the total tumors that develop, about 60% of them are malignant in nature. As a result of this, the cancer spreads to the neighboring sites and affects the lymph nodes and the liver.

ZES can also be caused as secondary condition to individuals suffering from multiple endocrine neoplasia type 1 (MEN 1). In such individuals, in addition to pancreas, tumors develop in the endocrine system as well.

It has been estimated that ZES occurs in about 0.1 to 1% individuals of the US. Due to improvised treatment profile of the disease condition, there has been a significant decrease in its morbidity and mortality rates. Due to this, as low as 5% of the individuals suffering from ZES develop complications.

The excessive production of acid by the gastrin hormone causes the levels of acid to increase. As a result of large quantity of acid, gastrointestinal mucosal ulceration develops. Due to this, individuals with ZES suffer from diarrhea and malabsorption. Causation of malabsorption in individuals affected by ZES actually occurs due to multiple factors. These are the following:

• Precipitation of bile salts
• Inactivation of enzymes of the pancreas
• Damage to the mucosa by excessive acid secretion

It has been estimated that 75% cases of ZES is sporadic in nature; while the rest 25% occur as a secondary complication to MEN I.

So far there are no guidelines to prevent ZES. However, it is suggested that if individuals have a family history of MEN 1 then they should get tested for ZES. Genetic counseling and genetic testing of family members with history of MEN 1 is advised.

Zollinger Ellison syndrome (ZES) is characterized by increased production of the hormone gastrin. It is a disease of the gastrointestinal system, wherein presence of tumors stimulates production of excessive gastrin causing increased formation of acid in the stomach [1]. The overproduction of acid in turn leads to development of peptic ulcers. It is a rare disease condition and affects individuals in the age group of 30 to 50 years.

Definition

Zollinger Ellison syndrome (ZES) is characterized by excessive production of acid in the stomach due to tumors in the pancreas and duodenum. This is a rare disease condition and usually strikes individuals in age group of 30 to 50 years.

Cause

Development of a kind of tumors is the major cause of ZES. However, this disease can also present as a secondary complication to MEN 1.

Symptoms

Symptoms of ZES include abdominal pain, diarrhea, unintended weight loss, anemia, gastrointestinal bleeding, loss of appetite, heart burn due to acid reflux, discomfort in the upper abdomen with pain and gnawing.

Diagnosis

Blood tests and fasting serum gastrin tests are the primary diagnostic tools employed for detecting ZES. In addition to these, imaging studies such as CT scan and MRI are done for localizing the tumors. Endoscopic ultrasound is also necessary to spot the exact position of the tumor. Biopsy of the tumor is also carried out to study its nature.

Treatment

Treatment of ZES includes surgical removal of tumors followed by chemotherapy. Acid suppressing medications are given to suppress the excess acid production in the stomach. 

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