Zollinger-Ellison syndrome, what it is, symptoms and treatment

Zollinger-Ellison syndrome - what is it?
This pathology is a clinical manifestation of gastrinoma, which is a hormonally active tumor.

A number of tumor variants develop aggressively with the formation of metastases. The tumor produces an excessive amount of gastrin, thereby forcing the gastric mucosa to respond to this by producing a large amount of secretion, which causes ulcers, vomiting, and diarrhea. In some cases, the pathology develops so rapidly that the need for surgery arises in less than a day.

In the 50s of the 20th century, the pathology was considered a gastric ulcer, which occurs with diarrhea. There was also excessive production of juice by the stomach, as well as a high level of gastrin in the blood.

The cause of the pathology was considered:

Serious eating disorders;
Excessive alcohol consumption;
Stress.

Only then did they find out that the pathology was initiated by a tumor of a neuroendocrine nature, which, as a rule, is localized in the gastrointestinal tract.

The described syndrome is a rather rare pathology, found in 1 person in 1,000,000. Even in those who suffer from stomach ulcers, the pathology occurs in about 1%.

Most people susceptible to pathology are men 40-55 years old.

Causes of pathology

Tumor cells produce the hormonal substance gastrin, which, in turn, provokes the stomach to produce hydrochloric acid in excessive quantities.

Almost 80% of tumor cases occur in the duodenum, the rest are localized in the pancreas.

The cause of the tumor is a genetic mutation.

Neoplasia of the gastrin-producing type can also be localized in other organs, for example, in the lungs, and their manifestations can be a described pathology.

Ménétrier's disease

Ménétrier described two types of disorders associated with polypoid growths in the stomach, which he tried to associate with gastric carcinoma [10].

The first (called “polyadenomes polypeux”) consists of multiple non-confluent gastric polyps, which are currently classified as hyperplastic polyps [11].
The second (which he called Ménétrier's polyadenomatosis, or multiple sheet-like adenomas) is a new type associated with foveal hyperplasia and should by law bear his name [8].

Who is at particular risk?

It is difficult to predict the development of pathology. However, by studying nepotism, one can assume its genetic roots even in cases where the symptoms were subtle or were mistaken for the manifestation of other diseases. The pathology of the hereditary form is in most cases localized in the duodenum.

If we talk about those who were affected by the pathology by accident, then it is necessary to note its localization in the pancreas.

Hereditary neoplasms can develop as multiple tumors. The pathology is milder and oncological gastrinoma is less common. However, surgical intervention does not provide a complete cure for this form.

Diagnostics

X-ray and endoscopic examination reveal an ulcer that does not differ from that of a normal duodenal ulcer. The main laboratory criterion for Zollinger-Ellison syndrome is hypergastrinemia (the gastrin content in the blood is increased to 1000 pg/ml or more, whereas in ordinary peptic ulcer disease it does not exceed the upper limit of normal - 100 pg/ml).

The tumor itself is detected using ultrasound, computed tomography, and selective abdominal angiography. The most informative method is selective abdominal angiography with taking blood from the pancreatic veins and determining gastrin in it.

However, it is quite difficult to establish the localization of gastrinoma. In approximately half of patients with clinically and laboratory confirmed Zollinger-Ellison syndrome, the tumor cannot be found during surgery. Selective angiography can detect gastrinoma in 50%, CT - in 30%, and ultrasound - in 20% of cases.

Symptomatic manifestations

Pathology can manifest itself in various manifestations:

Ulcers of the stomach and duodenum;
Constant intense pain in the upper abdomen;
Copious, semi-formed or watery stools;
Prolonged heartburn and belching;
Narrowing of the esophagus;
Gastrointestinal bleeding, etc.

With the oncological nature of the pathology, a decrease in the patient’s weight is observed, and a significant decrease.

Superior vena cava syndrome (SVVC)

Symptoms of the disease

SZE causes severe abdominal pain, which usually has an atypical localization. Patients often suffer from reflux, in which stomach contents back up into the esophagus. Stomach acid causes inflammation of the mucous membranes and heartburn. A common consequence of reflux is inflammation of the larynx. Half of the patients suffer from diarrhea.

All this leads to loss of electrolytes and vitamins. Some patients experience vomiting of blood.

In addition, speaking about the symptoms of Zollinger-Ellison Syndrome , it should be noted that an excess of gastric juice inactivates lipases. Since these enzymes support digestion, the absorption of fats in the small intestine is disrupted, and they enter the large intestine, resulting in fatty changes in the consistency of stool. Sometimes the pH level in the blood increases. In rare cases, the production of parathyroid hormones increases.

Diagnostic measures

The presence of pathology can be determined by observing a multiple increase in the level of gastrin in the blood.

When performing an endoscopic ultrasound examination, you can see the tumor, but only part of it, because it is located in the wall of the duodenum.

Computed tomography and magnetic resonance imaging examinations are clearer in terms of sensitivity. The degree of this sensitivity determines the size of the tumor. In any case, it must be detected for further monitoring of development.

The effectiveness of angiography and PET is associated with a good blood supply to the tumor. The final diagnosis is announced after examination of the biopsy specimen.

As practice shows, 2/3 of tumors are not malignant; therefore, there are no metastases. Sporadic tumors are aggressive, but this is not typical for multiple endocrine neoplasia.

Pancreatic cancers usually metastasize. They can cause damage to the liver and lymph nodes of the peritoneal cavity.

Tumors of the duodenum most often affect bones, usually flat ones.

The possibility of metastases depends on the size of the tumor focus; they can cause increased pathology.

Zollinger-Ellison syndrome is a disease in which a gastrinoma, a tumor that produces gastrin, appears in the pancreas, duodenum, or other organs. Gastrin is a hormone that regulates the production of gastric juice. As a result, excessive production of gastrin and increased secretion of gastric juice (hydrochloric acid) causes ulcers of the gastrointestinal mucosa.

Zollinger-Ellison syndrome is quite rare, somewhat more common in men than in women. The disease usually develops between the ages of 20 and 50 years.

Treatment for Zollinger-Ellison syndrome involves taking medications to reduce stomach acid production and, in some cases, removing the gastrinoma.

Synonyms Russian

Gastrinoma, GE syndrome.

English synonyms

Zollinger-Ellison Syndrome, ZES.

Symptoms

The symptoms of Zollinger-Ellison syndrome are similar to those of a peptic ulcer, with the exception of diarrhea, which is usually not observed with a peptic ulcer:

aching, “gnawing” pain, burning in the upper abdomen;
diarrhea;
heartburn (a feeling of discomfort and burning behind the sternum), nausea and vomiting;
bleeding from the gastrointestinal tract;
loss of appetite, weight loss;
anemia;
weakness, fatigue.

General information about the disease

Zollinger-Ellison syndrome is a disease in which a gastrinoma, a tumor that produces gastrin, appears in the pancreas, duodenum, or other organs. It occurs quite rarely, more often in men. As a rule, the disease develops between the ages of 20 and 50 years.

Gastrinoma in 80-90% of cases appears in the pancreas or duodenum. In other cases, the tumor can form in the spleen, other parts of the intestines, in the stomach, in the lymph node, in the liver, in the kidneys or in the ovary.

The pancreas is an organ located under the stomach that produces various digestive enzymes, including gastrin. The duodenum is the upper part of the small intestine, connected to the stomach.

The exact causes of tumor formation have not yet been established. The appearance of this disease is associated with multiple endocrine neoplasia (MEN), a group of hereditary syndromes caused by tumors or hyperplasia (overgrowth) of several glands of the endocrine system. Those suffering from MEN may also develop a thyroid tumor. About 25% of gastrinomas are associated with multiple endocrine neoplasia. Men suffer from MEN more often than women.

Normally, gastrin stimulates the production of hydrochloric acid in the stomach (the main component of gastric juice). It is produced in the gastric mucosa and pancreatic cells. Formed from cells that produce gastrin, the tumor releases this hormone into the blood. This leads to increased production of gastric juice, consisting of hydrochloric acid, which causes ulceration (deep inflammatory defect) of the intestinal mucosa.

Ulcers in Zollinger-Elisson syndrome are multiple, located in atypical places - at the border of the duodenum and jejunum, less often in the stomach. In a quarter of patients, ulcers are not detected.

About half of gastrinomas become cancerous over time. And although they grow slowly, the cancer can metastasize (spread beyond the primary site). Most often, gastrinomas metastasize to the lymph nodes and liver.

Over time, the tumor replaces healthy pancreatic tissue, which leads to a decrease in the production of digestive enzymes and, as a result, to insufficient digestion of fats. As a result, the patient develops diarrhea. Over time, insufficient absorption of nutrients leads to weight loss, decreased hemoglobin levels in the blood, and anemia.

Gatrinoma can lead to the following complications:

ulcerative bleeding;
penetration – penetration of an ulcer into surrounding organs and tissues;
tumor metastasis to vital organs.

Who is at risk?

People suffering from multiple endocrine neoplasia;
relatives of persons suffering from Zollinger-Ellison syndrome.

Diagnostics

Zollinger-Ellison syndrome can be suspected if symptoms of a peptic ulcer are present if they do not go away after antiulcer therapy. In this case, the level of gastrin in the blood is determined. If its level increases significantly, studies are carried out aimed at identifying the tumor, determining its location and size.

Laboratory research:

Gastrin. The study involves measuring the level of the hormone gastrin in the blood. Elevated gastrin levels may indicate a tumor in the pancreas or duodenum. Before the study, you should stop taking medications that reduce the production of gastric juice. Gastrin levels can fluctuate, so to obtain more accurate results, the test can be performed several times on different days. Gastrin levels can also increase in chronic gastritis, B12 deficiency anemia and other diseases.
Measuring the acidity level of gastric juice. The technique involves inserting a probe into the stomach and then collecting gastric juice. Microprobes can also be inserted to directly measure the level of gastric acidity in the stomach. Zollinger-Elisson syndrome is characterized by a significant increase in the acidity of gastric juice.
Provocative test with secretin (a hormone involved in the regulation of the pancreas). The study consists of intravenous administration of a secretin solution. Normally, the level of gastrin in the blood decreases, but with Zollinger-Ellison syndrome, the level of gastrin paradoxically increases significantly.

Other research methods:

Endoscopy. The study involves a visual assessment of the gastric and intestinal mucosa to identify ulcers. To do this, a thin flexible tube with a camera is used, which is inserted into the patient's body through the throat. During an endoscopy, a biopsy may be performed - taking a tissue sample for subsequent examination under a microscope.
Ultrasound examination (ultrasound) of the abdominal cavity, computed tomography (CT) and magnetic resonance imaging (MRI) of the abdominal cavity. These studies are carried out to visualize the tumor and determine its location and size.

Treatment

In the treatment of Zollinger-Ellison syndrome, medications are used that reduce the production of gastric juice.

Surgical tumor removal is indicated for patients without metastases. It is possible in approximately 20% of patients with Zollinger-Ellison syndrome. For multiple endocrine neoplasia, surgical treatment is not performed.

When a tumor metastasizes, chemotherapy is used to destroy tumor cells, which makes it possible to reduce the size of the tumor and reduce gastrin levels.

If the tumor has metastasized to the liver, a liver transplant may be performed.

Prevention

Prevention of Zollinger-Ellison syndrome has not yet been developed.

Recommended tests

Gastrin

Literature

https://emedicine.medscape.com/article/183555-overview
Feldman, Friedman, Brandt. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 9 ed. Saunders. 2010. P. 2480.
Dan L. Longo, Dennis L. Kasper, J. Larry Jameson, Anthony S. Fauci, Harrison's principles of internal medicine (18th ed.). New York: McGraw-Hill Medical Publishing Division, 2011.
https://www.mayoclinic.com/health/zollinger-ellison-syndrome/DS00461

Treatment

A radical method of treating pathology is tumor removal. In this case, fiber-optic diaphanoscopy of the duodenum and lateral duodenotomy are performed. As a rule, metastases are detected at the time of surgery, which means that only 30% of patients can achieve a complete cure.

The effectiveness of removing a significant part of the stomach is low: the risk of rapid recurrence is quite high.

Several decades ago, the method of total gastrectomy was widely used. Now they resort to it if conservative treatment does not give positive results and the course of the ulcer is complicated.

For therapy, drugs that reduce the level of hydrochloric acid are used. Their use may be indicated for life, since the risk of relapse is high. The doses of drugs exceed the usual ones prescribed for a standard ulcer.

In case of oncology and it is impossible to perform surgery on the tumor, chemotherapy is used.

Treatment of Zollinger-Ellison Syndrome in Germany

In accordance with clinical recommendations, after passing the main stages of diagnosing gastrinoma , topical therapy is prescribed. In this case, complete healing is possible only if the tumor has not metastasized. Then one or more tumors are completely removed surgically. However, this does not exclude the occurrence of relapses, and the patient needs constant regular monitoring. Since surgery does not guarantee complete removal of all tumor cells, postoperative radiation is recommended.

In cases of tumor metastasis, surgery is performed to relieve symptoms, which can significantly prolong the patient's life. To improve the quality of life, pain relief and other symptomatic therapy are carried out.

Prognosis and prevention

The prognosis of the pathology depends on the histology of the neoplasm, its location and the presence of metastases. In most cases, the prognosis is relatively favorable. This is due to the slow growth of the tumor and the presence on the modern pharmaceutical market of a huge number of drugs that reduce gastric secretion.
The prognosis for 5-year survival depends on the patient’s initial health status, the treatment method used, and the presence of metastases in the internal organs. Death occurs when severe ulcerative lesions appear.

To avoid the development of pathology, experts recommend following the following rules:

Healthy food,
visit a gastroenterologist regularly,
undergo an endoscopic examination of the gastrointestinal tract once a year,
fight bad habits,
avoid stress and conflict situations.

Preparing for your appointment

Although your symptoms may prompt you to visit your primary care doctor, you will most likely be referred to a doctor who specializes in diseases of the digestive system (gastroenterologist) to diagnose and treat Zollinger-Ellison syndrome. You can also see an oncologist, a doctor who specializes in treating cancer.

Here's some information to help you prepare for your appointment and know what to expect from your doctor.

What can you do

Be aware of any prior restrictions. When you make your appointment, tell your doctor's staff if you are taking any medications. Some acid-lowering drugs, such as proton pump inhibitors or H2 antagonists, may alter the results of some tests used to diagnose Zollinger-Ellison syndrome. However, do not stop taking these medications without consulting your doctor.
Write down any symptoms you experience, including any that may seem unrelated.
Write down key personal information, including any major stresses or recent life changes. Also write down what you know about your family's medical history.
Make a list of all the medications, vitamins, or supplements you take.
Write down questions to ask your doctor.

Questions to ask your doctor

For Zollinger-Ellison syndrome, some basic questions to ask include:

What is the most likely cause of my symptoms?
Are there any other explanations for my symptoms?
What tests are needed to confirm the diagnosis? How should I prepare for these tests?
What treatments are available for Zollinger-Ellison syndrome that you recommend for me?
Are there dietary restrictions I must follow?
How often do I need to return for follow-up appointments?
What is my prognosis?
Do I need to see a specialist?
Is there a generic alternative to the medicine you are prescribing me?
Are there any sites you recommend to learn more about Zollinger-Ellison syndrome?
Are there any other medical problems possible because I have Zollinger-Ellison syndrome?

What to expect from your doctor

Your doctor may ask you several questions, including:

When did you start experiencing symptoms?
Do you have symptoms all the time, or do they come and go?
How severe are your symptoms?
Will anything improve your symptoms?
Have you noticed something that is making your symptoms worse?
Have you ever been told you have a stomach ulcer? How was it diagnosed?
Have you or anyone in your family ever been diagnosed with multiple endocrine neoplasia type 1?
Have you or anyone in your family been diagnosed with parathyroid, thyroid or pituitary problems?
Have you ever been told that your blood calcium levels are high?

Share link:

Click to share on Twitter (Opens in new window)
Click here to share content on Facebook. (Opens in a new window)
Click to share on Telegram (Opens in new window)

Liked this:

Similar

Pathogenesis

The pathogenesis of Ménétrier's disease is not entirely understood, but may be mediated by transforming growth factor alpha (TGF-alpha). TGF-alpha increases gastric mucus production and inhibits acid secretion [12-14]. The level of TGF-alpha in the cells of the gastric mucosa in patients with Ménétrier's disease is significantly increased [12]. The role of TGF-alpha is further supported by a mouse study in which overproduction of TGF-alpha is associated with significant hyperplasia of gastric mucus-producing cells comparable to that found in humans with Ménétrier's disease [12]. These mice also had reduced basal and histamine-stimulated acid secretion, similar to that observed in humans with Ménétrier's disease [12,13,15]. TGF-alpha may exert its effect by binding to epidermal growth factor receptors. This was suggested based on a report of a patient who experienced clinical improvement after treatment with monoclonal antibodies directed against epidermal growth factor receptors [16]. A similar connection with cytomegolovirus infection is observed in the so-called childhood Ménétrier's disease. Its mechanism can also be realized through TGF-alpha [17]. However, during various types of inflammation and regenerative responses in the stomach, increases in foveal TGF-alpha may also be observed, demonstrating that these findings may be nonspecific [18]. In addition, this pathology may be an example of the incorrect use of the term Ménétrier's disease to other forms of hypertrophic gastropathy.

Diagnosis

The diagnosis of Ménétrier's disease is based on the identification of extreme foveal hyperplasia with glandular atrophy on biopsy in a patient with significant enlargement of the gastric folds observed on endoscopic examination or barium radiography. A full-thickness or loop biopsy is usually necessary [3,22]. Enlarged folds are limited to the body and fundus of the stomach. The folds are usually symmetrically enlarged, although asymmetrical "polypoid" enlargement may rarely occur.