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Physical Examination

• Medical history of the patient including any changes in symptoms or changes in health habits

• Complete physical examination including palpation (in order to identify any masses or enlargement of any organs

Laboratory Studies

• CBC (complete blood count)

  • number of red and white blood cells and number of platelets
  • amount of hemoglobin (oxygen) in the red blood cells
  • percentage of red blood cells in the blood sample (hematocrit)

• Biochemical analysis which may include:

  • Chromogranin A (CgA) - this glycoprotein is stored in neuroendocrine cells and is released into the blood circulation in the presence of carcinoid tumors even if it is dormant. Chromogranin A is elevated in almost all types of neuroendocrine tumors regardless of organ of origin. Highest levels tend to appear in metastatic disease of midgut tumors. The level of CgA may be used to predict prognosis of carcinoid tumor and may also be a reliable marker for follow-up after treatment.

  • Neuron-specific enolase (NSE) - this is an enzyme that is present in enterochromaffin-like cells. In general, measurable increases in the level of NSE can be detected with metastatic spread of neuroendocrine tumors to the liver.

  • Serotonin - elevated levels may be present in midgut tumors with accompanying carcinoid syndrome

  • 5HTP (5-Hydroxytryptophan) - a substance utilized in the production of serotonin and frequently elevated in the presence of tumors of the foregut.

  • ACTH (adrenocorticotropic hormone) - elevated in the presence of tumors of the foregut.

  • Noradrenaline - this hormone may be elevated in midgut tumors

  • Growth hormone - may be elevated in foregut tumors

  • Ki-67 - detection of this antigen in the blood is a strong indicator of the malignant activity of a carcinoid tumor.

  • Urine sample - following a 24 hour urine collection, an elevated presence of 5-HIAA (5-hydroxyindole acetic acid, which is a serotonin metabolite) indicates either the presence of a GI tumor or carcinoid syndrome. 5-HIAA tends to be significantly elevated in the presence of tumors of the midgut but only mildly elevated with tumors of the foregut. Elevated levels of 5-HIAA is indicative of above normal amounts of serotonin.

  • Pentagastrin Provocative Test may be performed if the test for levels of 5-HIAA in the urine is not conclusive. This test induces flushing as well as other symptoms of carcinoid syndrome as well as an elevation of circulating serotonin in people with carcinoid syndrome.

Tumor markers are rarely elevated in hindgut carcinoid tumors even after they have spread. This is one of the reasons why hindgut carcinoid tumors tend to be discovered at a later stage of development. Tumor markers are usually not utilized as predictors or indicators of the level of disease activity.

Diagnostic Imaging

Radiologically identifiable pancreatic endocrine tumors and carcinoid tumors require further investigation in patients with NETs. Imaging is performed to permit the identification and localization of the primary tumor and to determine whether the patient has metastatic disease. Delay in identifying the site of primary tumor involvement may lead to up to a 30% to 50% incidence of metastases.