Biochemical tests for functional pancreatic NETs

In contrast to general biochemical tumor markers, such as CgA, other biochemical substances, particularly those secreted by pancreatic NETs, are specific to the type of tumor. Biochemical tests that target these secreted products are often the most useful diagnostic markers and may have prognostic significance.1

Insulinoma: A classic history of hyperinsulinemic-hypoglycemic syndrome is a reliable diagnostic indicator. The standard 72-hour fasting test should be used to measure glucose and insulin levels, and can be used to exclude all differential diagnoses of insulinoma except for very rare conditions. Measurement of proinsulin and C-peptide levels may also be helpful.1-3

One important note: Insulin levels are increasingly being measured by immunochemiluminescent assays or specific immunoradiometric assays that do not cross-react with proinsulin. These assays result in lower insulin values that will not compare accurately with results from radioimmunoassays.3

Gastrinoma: Diagnosis often begins with determination of fasting serum gastrin levels and gastric pH, with proton pump inhibitor (PPI) therapy stopped at least 1 week prior to testing. Over repeated testing, <0.5% of patients with Zollinger-Ellison syndrome (ZES) will have all normal values.1,2 PPI withdrawal should be performed with care by a group familiar with establishing the diagnosis of ZES because abrupt withdrawal in patients with ZES potentially can lead to serious consequences.3

Glucagonoma: Diagnosis can be made where plasma glucagon levels are increased to 500 to 1000 pg/mL (normal range <50 pg/mL) in the presence of symptoms, including glucose intolerance, weight loss, and erythematous rash.4

VIPoma: Diagnosis is based on elevated levels (>200 pg/mL) of plasma vasoactive intestinal peptide (VIP) in patient with large-volume secretory diarrhea (>700 mL/d).4,5

Somatostatinoma: These tumors can cause a clinical syndrome characterized by diabetes mellitus, gallbladder disease, diarrhea, weight loss, anemia, and steatorrhea. When these symptoms are present, along with a pancreatic mass, diagnosis can be confirmed by elevated plasma somatostatin levels.4

Other rare types of pancreatic NETs similarly can be diagnosed biochemically by the presence of elevated serum levels of specific hormones they secrete. These include GHRHomas (growth hormone and growth hormone-releasing factor) and ACTHomas (adrenocorticotropic hormone).4

As with other NETs, preliminary biochemical results for pancreatic NETs should be confirmed histologically. Immunohistochemical analysis is often needed to diagnose pancreatic NET subtypes by identifying cell markers present in the secretory granules, cytosol, or cellular membrane.5 Additionally, patients diagnosed with a pancreatic NET should be screened for MEN-1 syndrome, which includes measuring serum parathyroid hormone and prolactin levels.2

Click here for for more information on each of these types of pancreatic NETs and their syndromes.