Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (pancreatic NETs or PNETs) account for less than 5% of all pancreatic tumors. They may be benign or malignant and they tend to grow slower than exocrine tumors. They develop from the abnormal growth of endocrine (hormone-producing) cells in the pancreas called islet cells. This is why these tumors are sometimes referred to as “islet cell tumors.”

The prognosis of these neuroendocrine tumors is often much better than for pancreatic adenocarcinoma with good cure rates depending on the type of tumor. There is an association of neuroendocrine tumors with genetic mutations which can cause several members of the same family to have these types of tumors. The rarity of these tumors makes the care of these patients challenging and a multidisciplinary approach by experts in the field is important for patients to obtain the best care and treatment possible. The Multidisciplinary Endocrine Tumor Program at the University of Michigan is composed of endocrinologists, endocrine surgeons, radiologists, nuclear medicine specialists and oncologists who specialize in the diagnosis and treatment of these rare pancreatic endocrine tumors.

Types of pancreatic neuroendocrine tumors:

Insulinoma

Insulin is produced by beta cells which are organized into islands of cells in the pancreas. The primary function of insulin is to regulate the metabolism and storage of sugar in the body. Insulinomas are neuroendocrine tumors which produce insulin and are the most common type of functional neuroendocrine tumors. As these tumors grow they produce large amounts of insulin which can cause low blood sugar. When the blood sugar gets too low patients can experience symptoms which include dizziness, confusion, abnormal behavior and even loss of consciousness. Several tests are required to confirm the diagnosis of an insulinoma because there are several other reasons for low blood sugar. Once the diagnosis is confirmed with blood tests, imaging studies such as CT scan or ultrasound are used to localize the tumor. The primary treatment is surgical removal of the insulinoma which provides excellent cure rates.

Gastrinoma

A gastrinoma is a neuroendocrine tumor which produces the hormone gastrin. The function of gastrin is to stimulate the stomach to produce acid to aid in the digestion of food. Normally when there is enough acid in the stomach to digest a meal the production of gastrin is turned down and the stomach acid level slowly returns to a level needed for an empty stomach. Gastrinomas continuously produce gastrin which leads to very high levels of stomach acid which can then lead to ulcer formation in the stomach and small intestine (also called Zollinger-Ellison Syndrome). Patients may complain of abdominal pain from these ulcers which may improve with antacid medications. Blood tests to measure the level of gastrin can be falsely elevated if patients are taking antacid medications during the test and these should be discontinued prior to testing. After the diagnosis of gastrinoma is confirmed with blood tests, imaging studies including CT scan and ultrasound can help to localize the tumor prior to surgical removal.

Glucagonoma

The alpha cells of the pancreas produce the hormone glucagon which acts to counter the effects of insulin. Normally when a person has not eaten for several hours, the blood sugar drops and glucagon is released. This causes breakdown of sugar stored in the form of glucagon which quickly brings the blood sugar back up to normal. Glucagonomas continuously produce glucagon which can cause continuously elevated blood sugar and symptoms typically seen with diabetes. Surgical removal of the tumor is the primary treatment after imaging studies are completed.

VIPoma

Vasoactive intestinal polypeptide (VIP) is a hormone produced in the pancreas and in other locations throughout the body. Neuroendocrine tumors called VIPomas will cause symptoms including profuse watery diarrhea, dehydration and electrolyte disturbances. These tumors are extremely rare and blood tests and imaging studies are needed to confirm the diagnosis. Patients are treated with medication to decrease symptoms and often require intravenous fluid to treat dehydration before proceeding to surgery.

Non-functional neuroendocrine tumors

Some tumors that arise from endocrine cells of the pancreas do not produce hormones and therefore do not produce any of the symptoms which are described above. These types of tumors are often detected incidentally on CT scan or other imaging studies obtained to work-up another medical problem. Some of these tumors may grow quite large and cause upper abdominal discomfort as they compress surrounding structures. The challenge in the diagnosis of these types of tumors is to distinguish them from pancreatic adenocarcinoma which has a worse prognosis. Surgery is the primary treatment for non-functional neuroendocrine tumors after blood tests and imaging studies are complete.

Treatment of pancreatic neuroendocrine tumors

The treatment of pancreatic neuroendocrine tumors requires a multidisciplinary approach with medical, surgical, oncologic and radiological treatments. Medical management is often used to control symptoms caused by tumor hormone production until surgical resection is undertaken. Chemotherapy and radiation therapy is aimed at decreasing recurrence rates and controlling symptoms in patients with metastatic or unresectable tumors. The Multidisciplinary Endocrine Tumor Program at the University of Michigan is composed of endocrinologists, endocrine surgeons, radiologists, nuclear medicine specialists and oncologists who specialize in all aspects of diagnosis and treatment of pancreatic endocrine tumors. For additional information, visit Endocrine Surgery at the University of Michigan.