What is a gastrinoma?
A gastrinoma is a tumor that secretes the hormone gastrin. Normally gastrin is secreted by certain cells in the pancreas, duodenum and stomach. The hormone gastrin stimulates the stomach to produce gastric acid. A gastrinoma secretes large amounts of gastrin. This causes an oversecretion of stomach acid which has a wide range of effects on the stomach itself, and the neighboring regions of the esophagus and small intestine. It gives rise to a condition known as Zollinger-Ellison syndrome (ZES) which is marked by peptic ulcers and excessive gastric acid. Gastrinomas may be benign (non-cancerous) or malignant (cancerous) with the latter having serious and life threatening implications.
Gastrin secretion and regulation
The hormone gastrin is produced by the G cells in stomach, duodenum (first part of the small intestine) and the pancreas. Its secretion is controlled by various factors. The following stimulate gastrin secretion :
- stretching of the stomach wall due to the food that is eaten.
- proteins in the stomach.
- nerve input via the vagus nerve.
There are also several factors that inhibit gastrin secretion, such as :
- Acid in the stomach and duodenum.
- Other hormones like somastatin, secretin, VIP, GIP and calcitonin.
As food enters the stomach and stretches it, the stomach needs to utilize stomach acid for digestion. Along with the presence of protein and stimulation by the vagus nerve, gastrin is secreted. Gastrin acts on the parietal cells of the stomach to increase gastric acid secretion. This acid is necessary for chemical breakdown of food in the stomach. The partially digested food along with acid and enzymes, which is in a semi-fluid form known as gastric chyme, then enters the duodenum. This signals the gut that the stomach acid production can be reduced and initiates the inhibition of the gastrin.
The large amounts of gastrin released by the gastrinoma cause excessive stimulation of the parietal cells of the stomach. This in turn increase the size and activity of the acid-producing tissue of the stomach. Although the stomach has its own natural mucus barrier to prevent the gastric acid from making contact with the stomach wall, this may not be sufficient when there is excessive acid secretion. Furthermore the large quantity of acid may overwhelm the duodenum and also spill over into the esophagus. This contributes to severe ulceration of the upper gut wall.
Normally when acidic contents enter the duodenum, another hormone known as secretin is released. This induces the mass release of water and bicarbonate ions from the pancreas into the duodenum and from the duodenum wall itself. It serves to neutralize the acid. However, the larger than normal volume of water and bicarbonate ions can also lead to diarrhea. Therefore patients with gastrinoma experience both upper and lower gastrointestinal symptoms as a result of excess gastrin secretion.
Gastrinomas are more commonly found on the wall of the duodenum and may also occur in the pancreas. Majority of these tumors tend to occur within a triangular area demarcated by the bile ducts, latter two portions of the duodenum and the neck and body of the pancreas. Less commonly a gastrinoma can arise at other sites, some of which do not normally secrete the hormone gastrin. These areas may include the body of the stomach, jejunum (second part of the small intestine), lymph nodes around the pancreas, gallbladder, bile duct, spleen or ovary.
When the tumor originates at a specific site, it is known as a primary tumor. In malignant gastrinomas, some of the cells can lodge elsewhere in the body by directly infiltrating neighboring sites, traveling through the bloodstream or through the lymphatic system. These new tumors may produce gastrin as well and are known as secondary tumors. In this way, a gastrinoma may be located anywhere in the body although this is not common outside of the pancreas and duodenum.
Tumors occur for various reasons and is believed the be largely due to genetic factors. There may also be the impact of environmental factors such as cigarette smoking, radiation exposure and various toxic compounds with cancer-causing properties (carcinogens). However, a large number of tumors arise for no known cause (idiopathic).
A significant number of gastrinomas arise as part of multiple endocrine neoplasia (MEN) type I. In this syndrome, tumors occur at multiples sites in the body – in the endocrine glands and duodenum in particular. This means that a gastrinoma may also exist at the same time as other tumors in various other glands.
A gastrinoma may present in a similar way to peptic ulcer disease. These symptoms include :
- Abdominal pain, particularly in the upper middle region of the abdomen (epigastrium).
- Indigestion symptoms like nausea, belching and a bloated sensation.
- Appetite changes which may include an increase or decrease in appetite.
- Vomiting may sometimes occur and can be due to gastric outlet obstruction.
Complications of peptic ulcers are more likely to occur and may be severe when a gastrinoma is involved. These symptoms may include :
- Blood in the vomit (hematemesis) as a result of gastrointestinal bleeding.
- Blood in the stool which gives it a dark and tarry appearance.
- Signs of peritonitis due to a perforated ulcer.
- Heartburn from gastroesophageal reflux disease (GERD).
- Diarrhea due to excessive water and bicarbonate ion secretion into the duodenum.
- Vitamin B12 deficiency symptoms.
The clinical presentation of gastrinoma is largely the same as peptic ulcer disease and further investigations are necessary to confirm the diagnosis. There may be the suspicion of gastrinoma in patients with peptic ulcers who do not respond to conventional treatment, have recurrent episodes of peptic ulcers, a strong family history of ulcers or peptic ulcers that presents with diarrhea.
The three main tests to confirm a gastrinoma involves measuring the following :
- Gastrin levels in the blood during fasting.
- Gastric acid pH.
- Basal acid output.
Imaging studies may be helpful in isolating the site of the gastrinoma. These tests include :
- Computed tomography (CT) scan
- Magnetic resonance imaging (MRI)
- Somatostatin receptor scintigraphy (SRS)
Other tests like an upper gastrointestinal (GI) endoscopy may note multiple ulcers or very large ulcers (> 2 cm in diameter) in the stomach and duodenum. Although this does not confirm the presence of a gastrinoma, it should warrant further investigation.
A gastrinoma can be treated medically or surgically.
Medication for treating a gastrinoma, or its effects, includes the use of acid-suppressing drugs and anti-cancer drugs in the event of a malignant gastrinoma.
- Proton pump inhibitors (PPIs)
Surgery is usually necessary for the treatment of a gastrinoma.
- Resection (removal) of the tumor is conducted when the location can be clearly isolated.
- Laparotomy is indicated when the tumor cannot be localized as it allows the surgeon to explore the most likely area and resect the tumor once it is identified.
- Whipple pancreaticoduodenectomy is a surgical procedure where portions of the stomach, pancreas and duodenum are removed. These areas are also the most likely sites for a gastrinoma.