Gastrinoma Health Article

Definition

Gastrinomas are tumors associated with a rare gastroenterological disorder known as Zollinger-Ellison syndrome (ZES). They occur primarily in the pancreas and duodenum (beginning of the small intestine) and secrete large quantities of the hormone gastrin, triggering gastric acid production that produces ulcers. They may be malignant (cancerous) or benign.

Description

Gastrinomas are an integral part of the Zollinger-Ellison syndrome (ZES). In fact, ZES is also known as gastrinoma. This syndrome consists of ulcer disease in the upper gastrointestinal tract, marked increases in the secretion of gastric acid in the stomach, and tumors of the islet cells in the pancreas. The tumors produce large amounts of gastrin that are responsible for the characteristics of Zollinger-Ellison syndrome, namely severe ulcer disease. Although usually located within the pancreas, they may occur in other organs.

Gastrinomas may occur randomly and sporadically, or they may be inherited as part of a genetic condition called multiple endocrine neoplasia type 1 (MEN-1) syndrome. About half of persons with MEN-1 have gastrinomas, which tend to be more numerous and smaller than tumors in sporadic cases.

About half of ZES patients have multiple gastrinomas, which can vary in size from 1–20 mm. Gastrinomas found in the pancreas are usually much larger than duodenal gastrinomas. About two thirds of gastrinomas are malignant (cancerous). These usually grow slowly, but some may invade surrounding sites rapidly and metasta-size (spread) widely. Sometimes, gastrinomas are found only in the lymph nodes, and it is uncertain whether these malignancies have originated in the lymph nodes or have metastasized from a tumor not visible in the pancreas or duodenum.

There is some evidence that the more malignant form of gastrinomas is more frequent in larger pancreatic tumors, especially in females and in persons with a shorter disease symptom duration and higher serum gastrin levels.

Causes and symptoms

Most persons with gastrinomas secrete profound amounts of gastric acid, and almost all develop ulcers, mostly in the duodenum or stomach. Early in the course of the disease, symptoms are typical of peptic ulcers, however once the disease is established, the ulcers become more persistent and symptomatic, and may respond poorly to standard anti-ulcer therapy. Abdominal pain is the predominant symptom of ulcer disease. About 40% of patients have diarrhea as well. In some patients, diarrhea is the primary symptom of gastrinoma.

Diagnosis

Persons with gastrinomas have many of the same symptoms as persons with ulcers. Their levels of gastric acid, however, are usually far greater than those in common ulcer disease. Gastrinomas are usually diagnosed by a blood test that measures the level of gastrin in the blood. Patients with gastrinomas often have gastrin levels more than 200 pg/mL, which is 4–10 times higher than normal. Serum gastrin levels as high as 450,000 pg/mL have occurred.

When the serum gastrin test does not show these extremely high levels of gastrin, patients may be given certain foods or injections in an attempt to provoke a response that will help diagnose the condition. The most useful of these provocative tests is the secretin injection test (or secretin stimulation or provocative test), which will almost always produce a positive response in persons with gastrinomas but seldom in persons without them.

Surgically, gastrinomas are often difficult to locate, even with careful inspection. They may be missed in at least 10–20% of patients with ZES. Gastrinomas are sometimes found only because they have metastasized and produced symptoms related to the spread of malignancy. Such metastasis may be the most reliable indication of whether the gastrinoma is malignant or benign.

Diagnostic imaging techniques help locate the gastrinomas. The most sophisticated is an x-ray test called radionuclide octreotide scanning (also known as somatostatin receptor scintigraphy or 111In pentetreotide SPECT). A study by the National Institutes of Health (NIH) found this test to be superior to other imaging methods, such as computed tomography scan (CT) or magnetic resonance imaging (MRI), in pinpointing the location of tumors and guiding physicians in treatment.

Approximately half of all gastrinomas do not show up on imaging studies. Therefore, exploratory surgery is often recommended to try to locate and remove the tumors.

Treatment

Therapy for gastrinomas should be individualized, since patients tend to have varying degrees of disease and symptoms. Treatment is aimed at eliminating the over-production of gastric acid and removing the gastrin-producing tumors.

Drugs

Gastrinomas may not be easily treated by the standard anti-ulcer approaches. The medical treatment of choice is with drugs called proton pump inhibitors, such as omeprazole or lansoprazole, daily. These drugs are potent inhibitors of gastric acid. High doses of H-2 receptor antagonists may also reduce gastric acid secretion, improve symptoms, and induce ulcer healing. These drugs must be continued indefinitely, since even a brief discontinuation will cause ulcer recurrence. Antacids may provide some relief, but it is usually not longlasting or healing.