Zollinger Ellison Syndrome: Causes, Symptoms, Treatments and Prognosis

What is Zollinger-Ellison Syndrome?

Zollinger-Ellison Syndrome (ZES) is a rarely occurring gastrointestinal disorder that causes excessive secretion of gastric acid from the stomach, which eventually leads to the formation of multiple recurrent gastric and duodenal ulcers. A patient with ZES presents with a chief complaint of abdominal pain due to the ulcer. These ulcers if left untreated can result in life-threatening complications such as hemorrhage, gastric outlet obstruction, cancer, intestinal perforation, peritonitis, septic shock, and even death. This condition is primarily diagnosed in middle-aged people between 30-60.

Ulcers Due To Zollinger-Ellison Syndrome

Ulcers Due To Zollinger-Ellison Syndrome. Image Courtesy of Wikipedia

What causes ZES?

ZES is caused by a tumor, i.e. a gastrinoma that primarily involves the stomach, duodenum, and the pancreas. This is a neuroendocrine tumor, which means the tumor arises from hormonal and neural cells. A gastrinoma can cause hypersecretion of gastric acid from the parietal cells in the stomach. A majority of the gastrinoma occurs sporadically, but in a minority of cases, ZES is associated with Multiple Endocrine Neoplasia type 1. MEN – is a group of neuroendocrine disorders involving the pancreas, parathyroid gland, and pituitary gland.

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Normally, there is a balance between the gastric acid and the protective mechanisms of the stomach lining, which prevents the gastric acid from eroding the gastric lining. These protective mechanisms include bicarbonate, which is a base that buffers the acid and mucus, which forms a barrier around the stomach lining that prevents the acid from destroying the mucosal layers of the stomach.

However, in patients with gastrinoma, the tumor causes increased gastric acid production via two major mechanisms. First of all, the gastrinoma secretes large quantities of gastrin, which in turn stimulates the parietal glands to secrete hydrogen ions that form Hydrochloric acid into the cavity of the stomach. Secondly, the elevated levels of gastrin act like a stimulant to parietal cells, resulting in hyperplasia of the parietal cells. Parietal cell hyperplasia consequentially further raises the gastric acid secretion.

This increase in levels of gastric acid overwhelms the protective barriers formed by the bicarbonate and mucus, resulting in multiple ulcers in the stomach, duodenum, and infrequently the jejunum.

Clinical Presentation Of ZES

Symptoms of ZES are mainly caused by multiple ulcers, which are present in the stomach, duodenum, or rarely the jejunum. These ulcers mimic the symptoms of peptic ulcer disease, causing abdominal pain, nausea, vomiting, diarrhea, decreased appetite, and malnourishment. The severity and range of symptoms can vary and are based on the location and number of gastrinomas. Gastrinomas can be present as an isolated tumor of the stomach, or multiple tumors involving the stomach, duodenum, and Israeli Artificial Micro Pancreas Could Make Insulin Injections Obsolete.

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How is ZES Diagnosed?

When a patient presents with recurrent multiple gastric ulcers that are not responding to the conventional treatment of peptic ulcers, a physician will order further tests to confirm a diagnosis of ZES. These tests follow a step-wise guideline that includes:

  1. Gastric acid pH: A pH that is lower than 2 of the gastric fluid warrants the need for further investigation. Additionally, a secretion level higher than 15 meq/hour raises the suspicion of ZES.
  2. Measurement of Fasting Serum Gastrin: If serum gastrin level is higher than 1000pg/ml, the diagnosis of Zollinger Ellison Syndrome is confirmed. But if serum gastrin level is lower than 1000pg/ml but high enough to cause suspicion, a provocation test with secretin or calcium is done.
  3. Secretin Provocation Test: If the gastrin level rises after the administration of exogenous secretin, the test is considered to be positive. A positive test implies Zollinger Ellison syndrome.
  4. Localization of tumor: Once ZES diagnosis is confirmed, it is essential to determine the location and stage of the gastrinomas. This is done via a CT scan of the abdomen.

Treatment of Zollinger Ellison Syndrome

Treatment is centered on reducing the detrimental effects of gastric acid on the mucosal linings of the stomach. For this, pharmacological therapy using proton pump inhibitors such as omeprazole, esomeprazole, pantoprazole, and H2-receptor antagonists such as ranitidine are prescribed for long-term.

In certain patients with severe symptoms despite treatment, multiple tumors, tumors with a high risk of malignancy, life-threatening complications, etc; surgery can be considered for tumor excision. Some patients may also receive chemotherapy for ZES treatment.

Complications

In most cases of ZES, the complications are mainly a consequence of untreated recurrent ulcers. These ulcers can cause hemorrhage in the upper gastrointestinal tract, resulting in severe anemia. A more acute and serious complication of these ulcers is perforation of the stomach lining, which causes leakage of the gastric contents into the peritoneal cavity leading to peritonitis, septic shock, and death.

In approximately half of the ZES patients, gastrinomas have the potential to metastasize to distant organs such as the liver, spleen, bones, and lymph nodes.

Prognosis

The prognosis of ZES is largely dependent on the nature of the tumors. In patients with a non-malignant type of ZES gastrinomas, the five-year survival rate is about 90%. However, in patients with malignant ZES gastrinomas, the survival rate is much lower with only a 25% cure rate even after surgery.

References

https://rarediseases.info.nih.gov/diseases/7918/zollinger-ellison-syndrome

 

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