A neuroendocrine tumor is an abnormal growth that arises from the glands that produce these hormones. The tumor itself can also produce hormones on its own in high amounts and cause serious illness. Some neuroendocrine tumors impair quality of life by triggering uncomfortable symptoms, while others have the potential to be life-threatening.
Neuroendocrine tumors develop in many digestive organs, including the pancreas, liver, stomach, small intestine, appendix, large intestine, and rectum, as well as other areas in the abdomen. Physicians in the Center for Advanced Digestive Care at NewYork-Presbyterian/Weill Cornell Medical Center are highly skilled in the diagnosis and treatment of neuroendocrine tumors. They use the latest diagnostic tests and treatments to treat these tumors and restore quality of life to patients. When diagnosed and treated appropriately, the prognosis for most patients with neuroendocrine tumors is very good.
Types of Neuroendocrine Tumors
There are different types of neuroendocrine tumors. Some produce hormones, while others do not. Neuroendocrine tumors that grow without producing hormones are called "non-functioning tumors." Tumors that secrete hormones into the bloodstream are called "functional tumors."
Pancreatic Neuroendocrine Cancers
Pancreatic neuroendocrine cancers are uncommon and arise in the insulin-producing cells of the pancreas called islet cells. These tumors account for just five percent of pancreatic tumors and tend to be treatable, slow-growing tumors. (Most tumors found in the pancreas arise from ducts and are called adenocarcinomas — what is commonly known as pancreatic cancer — and are more challenging to treat.)
Functional pancreatic neuroendocrine tumors secrete hormones directly into the bloodstream and lead to dramatic hormone-related symptoms and metabolic imbalances. They tend be very small — only a few millimeters in size — when the patient experiences significant symptoms, and for this reason they often remain only in the pancreas. Types of functional pancreatic neuroendocrine tumors include:
- Insulinoma: A rare type of pancreatic tumor that produces excessive amounts of insulin, causing low blood sugar. Insulinomas are more common in women and are usually small (less than 2cm). More than 90 percent are benign. Insulinoma symptoms result from low blood sugar and may include faintness, weakness, trembling, heart palpitations, sweating, hunger, anxiety, headache, confusion, and dizziness. Some patients experience convulsions, loss of consciousness, or seizures.
- Gastrinoma: A tumor usually arising in the pancreas or duodenum (the first segment of the small intestine) that produces excessive levels of the hormone gastrin. Gastrin stimulates the stomach to secrete large amounts of acid, causing peptic ulcers. This condition is called Zollinger-Ellison syndrome. Most gastrinomas are malignant (cancerous). Symptoms include ulcers of the small intestine or stomach, diarrhea, stomach pain, bleeding, nausea, vomiting, weakness, fatigue, and unexplained weight loss or gain.
There are rare types of malignant functional pancreatic neuroendocrine tumors that are usually quite large by the time they are diagnosed. These include:
- VIPoma: This tumor produces excessive amounts of VIP (vasoactive intestinal polypeptide), a hormone which helps control the secretion and absorption of water in the intestines, leading to severe diarrhea, dehydration, weight loss, metabolic disturbances, and electrolyte imbalances. Patients may also experience muscular weakness, nausea, vomiting, and abdominal pain.
- Somatostatinoma: A somatostatinoma secretes excessive amounts of a hormone called somatostatin, a chemical that acts as a neurotransmitter. This tumor typically develops in the head of the pancreas and disrupts the production of a variety of hormones, leading to diabetes, gallstones, and an inability to digest fats. Patients may experience weight loss, poor digestion, diarrhea, and fat in the feces.
- Glucagonoma: This tumor produces excessive amounts of glucagon, a hormone that reduces insulin production, causing blood sugar to rise and diabetes to develop. Symptoms include weight loss, brownish red skin rash (which starts at the groin and moves to the buttocks, forearms, and legs), a bright red-orange tongue, and cracks at corners of mouth.
Most pancreatic islet cell tumors are non-functioning. Because they do not release any hormones into the blood that can cause symptoms, they grow silently for a long time before they are discovered, and are typically diagnosed at more advanced stages of disease — when the tumor becomes big enough to push against other structures. They may cause obstructive symptoms of the biliary tract or duodenum, bleeding into the gastrointestinal tract, or abdominal masses. Patients may also experience nausea, vomiting, abdominal pain, back pain, and jaundice (yellowing of the skin).
More than half of these non-functioning tumors are malignant (cancerous) at the time of diagnosis. They may account for as many as 60 percent of all neuroendocrine tumors of the pancreas.
Gastrointestinal Carcinoid Tumors
Neuroendocrine tumors arising outside the pancreas are most often carcinoid tumors, and represent the most common type of neuroendocrine cancer. Carcinoid tumors are considered a type of neuroendocrine tumor because they start in the hormone-producing cells of various organs — primarily the digestive tract. A carcinoid tumor can arise anywhere between the stomach and the rectum; the small intestine, appendix, and stomach are the most common sites.
Because carcinoid tumors generally grow slowly over many years, patients typically don't experience symptoms — such as diarrhea, skin flushing, and difficulty breathing — until they are quite advanced. The tumor might be discovered through a test for an unrelated disease or condition. These tumors can occur as part of certain genetic disorders — such as multiple endocrine neoplasia type 1 (MEN I) and neurofibromatosis type 1 (NF1, or von Recklinghausen disease), a disorder affecting the nervous system. Carcinoid tumors account for nearly half of all small intestine cancers.
The symptoms a person develops from a gastrointestinal carcinoid tumor often depend on where it is located. In ten percent of patients, carcinoid tumors release enough hormone-like substances into the bloodstream to cause symptoms known as "carcinoid syndrome," which is characterized by facial flushing, severe diarrhea, wheezing, and fast heartbeat. Over a long period of time, these hormone-like substances can damage heart valves, causing shortness of breath, weakness, and heart murmur. They may also cause weight gain, weakness, high blood sugar or diabetes, and increased body and facial hair.
Diagnosis of Neuroendocrine Tumors
In addition to a physical examination, endocrine oncologists at the Center for Advanced Digestive Care may use the following tests to diagnose an endocrine tumor:
The doctor may take samples of blood, urine, and stool to check for abnormal levels of hormones, glucose levels, and other substances.
To confirm a diagnosis, a small sample of the tumor is sometimes obtained for examination under a microscope using either a thin needle (fine-needle aspiration biopsy) or a wider needle (core biopsy). Sometimes, doctors will suggest a biopsy in which the tumor and possibly other tissues in the area are removed by surgery, most often done under general anesthesia.
In some cases, the doctor may evaluate a patient's central nervous system (brain and spinal cord function) by testing reflexes, motor and sensory skills, balance, and coordination.
Imaging tests can help to confirm a diagnosis and determine the exact location and size of a tumor, including whether there has been spread to other organs and whether the tumor(s) can be surgically removed. Doctors may use one or more of these tests:
Treatment of Neuroendocrine Tumors
The treatment of a neuroendocrine tumor depends on the type of tumor, its size and location, whether it is benign or malignant, whether the cancer has spread, and the patient's overall health. The Center for Advanced Digestive Care assesses each patient to create a personalized plan of care for neuroendocrine tumor treatment. Our multidisciplinary team of endocrine specialists works with patients to determine the best approach. Treatment may consist of one or more of the following therapies:
Surgical removal of the tumor is the first treatment for many neuroendocrine tumors. We specialize in image-guided minimally invasive surgical approaches that reduce the length of inpatient hospital stays, result in less physical trauma, and help patients resume normal activities as soon as possible.
Hormone therapy may be given to help stop the tumor from growing, or to relieve symptoms caused by the tumor by lowering the levels of hormones in the body. Patients with gastrointestinal carcinoid tumors that cannot be surgically removed may benefit from injections of a synthetic hormone which controls hormone-related symptoms and may have the potential to slow tumor growth.
Systemic chemotherapy, delivered through the bloodstream, employs drugs to kill cancer cells. For patients with gastrointestinal carcinoid tumors, chemotherapy is usually reserved for patients whose tumors begin to grow during treatment with a synthetic hormone. In addition, chemotherapy may be used to treat advanced neuroendocrine tumors that contain fast-growing cells.
Liver Tumor Embolization
Embolization is a localized approach to destroying liver tumors that may be used to treat gastrointestinal carcinoid tumors that spread to the liver. Embolization uses image guidance, such as CT or ultrasound, to inject tiny particles through a small tube (catheter) threaded into the hepatic artery. The particles block the flow of blood to the tumor, depriving it of the nutrients and oxygen it needs to survive. Embolization may be used alone or in combination with surgery.
Some patients with neuroendocrine tumors benefit from radiation therapy, which uses a type of energy called ionizing radiation to kill cancer cells and shrink tumors. The goal is to kill as many cancer cells as possible without harming healthy tissue.
Most pancreatic tumors contain receptors for the hormone somatostatin. These tumors may therefore respond to a nuclear medicine technique called radiolabeled therapy, which selectively destroys tumor cells with radioactivity attached to a molecule that binds to somatostatin receptors.
Immunotherapy is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to bolster, target, or restore the ability of the immune system to recognize and destroy cancer cells.
This treatment targets faulty genes or proteins that contribute to cancer growth and development. Early results of clinical trials with targeted drugs for the treatment of neuroendocrine tumors are promising, but additional research is needed to confirm their effectiveness.
NewYork-Presbyterian Hospital has established a clinical trials network to ensure that patients have access to medicines and therapies that are on the cutting edge. Clinical trials take place under the most stringent guidelines, and those who participate benefit from closely supervised monitoring. Patients are encouraged to speak with their doctors about current clinical trials for neuroendocrine tumors when making their treatment plan decisions. For more information, visit Clinical Trials.