Neuroendocrine Tumors (NET)

Carcinoid tumors, the most common type of gastro-entero-pancreatic neuroendocrine (GEP NE) tumor, tend to yield vague symptoms, and are often misdiagnosed as other disorders, such as irritable bowel syndrome. Also complicating diagnosis is the tumors' wide variance in onset. For carcinoid tumors of the cervix, for example, the average age of onset is 39 years; of the small intestine, 63 years; and of the rectum, 66 years. As a result, a correct diagnosis of carcinoid disease may be delayed anywhere from 2 to 20 years. (An analysis in the Surveillance, Epidemiology, and End Results [SEER] program showed that 45% of people with GEP NE tumors had metastases when they were first diagnosed.)

A diagnosis of GEP NE tumors may be based on the following:

• Clinical symptoms
• Tests that measure hormones, biochemical tumor markers and other markers in the body
• Imaging tests, such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and somatostatin receptor scintigraphy (SRS).

 

Markers for GEP NE tumors

The following markers may help identify specific GEP NE tumors:

• Carcinoid tumors/carcinoid syndrome:
  • Circulating tumor markers for carcinoid tumors include chromogranin A, serotonin and tachykinins (e.g., substance P and neuropeptide A). Other markers include adrenocorticotropic hormone (ACTH), corticotropin releasing factor (CRF) and growth hormone-releasing hormone (GHRH), which are mostly associated with tumors of the foregut.
  • Significantly elevated levels of serotonin or its metabolites, especially increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), are observed in patients with carcinoid syndrome. Measurement of 5-HIAA is the most commonly used diagnostic test for this syndrome, with a sensitivity of 73% and a specificity of 100%. Elevated levels of substance P and chromogranin A also may be observed.
  • Flush provocation is the stimulatory test used for diagnosis; it is done through pentagastrin stimulation or alcohol ingestion. The amount of neuropeptide K is measured every 5 minutes for 30 minutes. CT, MRI, ultrasonography, and somatostatin receptor scintigraphy may be used for tumor localization.
• Gastrinomas (Zollinger-Ellison syndrome):
  • A diagnosis is made based on the findings of an elevated serum gastrin level coupled with high basal acid output. The diagnosis may be further established by using secretin infusion testing to measure the level of gastrin every 5 minutes for 30 minutes. Chromogranin A is an excellent tumor marker as well.
  • Tumor localization may be based on CT, MRI, ultrasonography, somatostatin receptor scintigraphy, and endoscopic ultrasonography. Antral and duodenal tumours, along with recurrent ulcer disease, may be observed using gastroscopy.
• Insulinomas (hypoglycemic syndrome):
  Serum insulin and pro-insulin are important tumor markers in making a diagnosis, along with a fasting (48 to 72 hours) blood glucose. A serum insulin-to-blood-glucose ratio of greater than 5.4 is indicative of insulinoma. Histopathology shows argyrophil staining and synaptophysin immunohistochemistry. Imaging techniques include CT with simultaneous angiography and endoscopic ultrasonography. The latter procedure may reveal liver metastases.
• VIPomas (Verner-Morrison syndrome):
  Diagnosis is based on elevated plasma levels of vasoactive intestinal peptide (VIP). The VIP molecule is very unstable, and careful preparation with protease inhibitors is essential. Histopathology shows argyrophil staining chromogranin A and VIP. Localization of the tumor can be achieved using somatostatin receptor scintigraphy, CT angiography, MRI, or endoscopic ultrasonography.

 

Testing methods

The following are available testing methods to diagnose and monitor GEP NE tumors. While the tests are effective, more accurate and simpler techniques still are needed.9

• Chromogranin A (CgA) Testing, a fast, easy blood test for testing all major types of GEP NE tumors
• 5-HIAA Testing, a reliable, 24-hour urine test that is specific to carcinoid tumors. With this test, 5-hydroxyindoleacetic acid (5-HIAA) is measured in the urine. 5-HIAA is a metabolite of serotonin, a natural chemical messenger that is overproduced in people with GEP NE tumors

OctreoScan® Somatostatin Receptor Scintigraphy (SRS) Testing, a highly accurate and versatile imaging test for all of the body's systems

 

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