Gastrointestinal Neuroendocrine Tumors: Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (also known as Islet cell carcinoma) are a type of neuroendocrine tumor found in the pancreas. Only 5 percent of pancreatic tumors arise in the islet cells. (The vast majority of tumors found in the pancreas are adenocarcinoma, which is more commonly referred to as pancreatic cancer. For more information, visit the Pancreatic Cancer section on our Web site.)

Some pancreatic neuroendocrine tumors are functional, which means they produce excess hormones that can lead to a variety of hormone-related symptoms. (Nonfunctional tumors do not produce hormones.) There are several types of functional pancreatic neuroendocrine tumors, described below.

  • Insulinomas

    This type of tumor produces too much or too little insulin, a hormone that regulates blood sugar (glucose). Insulinomas can cause low blood sugar, which leads to symptoms such as dizziness and light-headedness.

  • Glucagonomas

    These tumors may interfere with the production of glucose in the blood, causing an elevation of blood sugar and diabetes. Rarely, glucaganomas can cause a skin rash when they become advanced.

  • Somatostatinomas

    These tumors disrupt the production of a variety of hormones, leading to diabetes, gallstones, and an inability to digest fats.

  • Gastrinomas

    This type of tumor increases the production of gastrin, a stomach acid that aids in digestion and can lead to the formation of stomach ulcers.

  • VIPomas

    This type of tumor disrupts the production of vasoactive intestinal peptide (VIP), which helps control the secretion and absorption of water in the intestines. VIPomas can cause severe diarrhea.

  • GRFomas

    These tumors produce excessive amounts of growth hormone release factor, which can lead to sudden growth of the hands and feet (acromegaly).

  • ACTHoma

    These tumors produce excessive amounts of the hormone ACTH. Too much ACTH increases the production of steroids, which can lead to weight gain, depression, easy bruising, increased risk of infection, and darkened skin.

Risk Factors

There are few known risk factors for pancreatic neuroendocrine tumor. However, a family history of multiple endocrine neoplasia type 1 (MEN1) syndrome — a rare genetic disorder that can cause the parathyroid glands, pituitary gland, and pancreas to produce too many hormones — may increase a person's risk for a pancreatic neuroendocrine tumor.

Symptoms

Depending on the hormones produced by the tumor, pancreatic neuroendocrine tumors can cause a variety of symptoms, including:

  • diabetes
  • hypoglycemia (low blood sugar)
  • gallstones
  • stomach ulcers
  • severe diarrhea
  • sudden growth of the hands and feet (acromegaly)

Diagnosis

Many pancreatic neuroendocrine tumors are found through imaging studies performed for other health issues.

If an pancreatic neuroendocrine tumor is suspected, and if patients have any of the symptoms described above, blood and urine tests may be performed to look for abnormal amounts of hormones and other substances (peptides) produced by the tumor, including chromogranin A (a protein commonly found in many carcinoid tumors), serotonin, and 5HIAA (a byproduct of serotonin).

Imaging tests also may be performed to determine the exact location and size of the tumor, if it has spread to other organs, and whether it can be removed with surgery.

  • Endoscopic Ultrasound

    The doctor may insert an endoscope — a thin, flexible tube attached to a small ultrasound probe — through the mouth into the stomach or intestines. The ultrasound probe bounces sound waves off the walls of the stomach or intestines.

  • Biopsy

    A small sample of the tumor may be obtained for examination under a microscope through a technique called fine-needle aspiration.

  • MRI and Triphasic CT Scanning

    MRI or triphasic CT scanning, which provides images during three different phases of blood flow through the liver, provide a more accurate diagnosis than routine CT. These tests are often used to determine whether the tumor has spread to the liver or nearby lymph nodes. Sometimes a dye is injected into the organ to help provide better detail.

  • OctreoScan (Somatostatin Receptor Scintigraphy) Imaging

    Most neuroendocrine tumors absorb large amounts of somatostatin, a substance that suppresses the hormones involved in growth, metabolism, and digestion. Patients suspected of having a neuroendocrine tumor receive an injection of octreotide, a synthetic form of somatostatin that is attached to a radioactive substance. Radiation-sensitive imaging tests reveal how much octreotide has been absorbed, indicating the presence and size of a tumor. Tumors that absorb octreotide may be treated with octreotide therapy (described below in the Treatment section).

Treatment

Treatment of pancreatic neuroendocrine tumors may include a combination of surgery, hormone therapy, radiation therapy, and chemotherapy.

  • Surgery

    Surgical removal of the tumor is considered the most effective treatment for islet cell tumors. Tumors that have not spread beyond the pancreas (localized tumors) may be removed along with a small portion of healthy tissue surrounding the tumor. This procedure is much less extensive than the type of surgery used to treat adenocarcinoma of the pancreas.

  • Hormone Therapy

    Patients with functional pancreatic neuroendocrine tumors that cannot be surgically removed may benefit from monthly injections of octreotide, a synthetic hormone that controls hormone-related symptoms and may have the potential to slow tumor growth.

  • Radiation Therapy and Chemotherapy

    Chemotherapy is usually reserved for patients whose pancreatic neuroendocrine tumors begin to grow during treatment with octreotide, or if a patient has symptoms from the tumor that are not well controlled by octreotide. In addition, chemotherapy may be used to treat tumors that contain fast-growing (undifferentiated) cells.

    External-beam radiation therapy, which delivers radiation from a machine outside of the body, is typically only used to treat patients with pancreatic neuroendocrine tumors that are causing symptoms such as pain, particularly when they have metastasized to the bone.

  • MIBG Radiolabeled Therapy

    Some pancreatic neuroendocrine tumors absorb a hormone called norepinephrine. These tumors may respond to a nuclear medicine technique called MIBG radiolabeled therapy. In this treatment, the patient is given an intravenous dose of MIBG, a protein that is similar to norepinephrine and is attached to a radioactive substance. The MIBG is absorbed by the tumor, permitting the radioactive substance to selectively destroy tumor cells.

  • Investigational Approaches

    Researchers at Memorial Sloan Kettering are exploring new treatment approaches using a mouse model that exhibits pancreatic neuroendocrine tumors. This model will be used to conduct early-stage testing of new drug therapies and targeted antibody-based treatments. The pancreatic neuroendocrine tumor model also will be used to test a new class of drugs that may have the potential to block the production of a protein called cathepsin proteases, which are thought to promote the growth of pancreatic neuroendocrine tumors.