Zollinger Ellison Syndrome

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

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].

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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10. Metz DC, Comer GM, Soffer E, Forsmark CE, Cryer B, Chey W, Pisegna JR. Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions. Aliment Pharmacol Ther. 2006; 23(3):437-44