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Symptoms of neuroendocrine tumors

Highly differentiated tumors

These tumors are often slow-growing and symptoms occur gradually, sometimes over years. Symptoms depend on the primary organ and the extent to which the tumor produces symptom-causing peptides. 

Metastatic symptoms are often the first manifestation. Even non-symptom causing primary tumors of 1–2 cm in diameter may cause extensive metastasis. A mesenterial metastasis from neuroendocrine intestinal and colon carcinomas can induce a fibrotic process around the metastasis, which by itself can cause significant symptoms from surrounding structures drawn into the fibrotic process (desmoplastic reaction). This can lead to ileus/subileus by traction on the bowel, hydronephrosis by stenosis of the ureter, or to thrombosis in intestinal blood vessels due to compression. 

CT scan of patient with neuroendocrine intestinal tumor. Click to enlarge the image. CT scan showing extensive liver metastasis originating from a small intestinal tumor. Click to enlarge the image.

Tumors in the intestines and upper part of the colon can cause "carcinoid syndrome", diarrhea, redness (most common in the face/upper body, not normally accompanied by a feeling of warmth), diarrhea, and difficulty breathing. In these patients, the valves on the right side of the heart may become fibrotic and damaged due to substances released by the tumor. Cardiac valve surgery may be indicated to prevent cardiac failure. Lung tumors can also cause similar hormonal symptoms.

Common symptoms are:

  • pain
  • weight loss   
  • lethargy
  • hormonal symptoms

Peptides produced by neuroendocrine tumors can, but not necessarily, cause symptoms. In the stomach-intestinal tract, the peptides do not cause symptoms until the tumor has spread outside the intestinal system, most often to the liver. This is because peptides which enter the bloodstream from tumors in the stomach-intestinal tract are usually degraded in the liver before they enter the systemic circulation.

Examples of peptides produced by neuroendocrine tumors and subsequent symptoms

Neuroendocrine tumor Peptide  Symptom
Pancreas Insulin Hypoglycemia
Gastrin Peptic ulcer (Zollinger Ellison's syndrome)
Glucagon Hyperglycemia, rash
VIP Intense diarrhea
Intestines Serotonin Diarrhea, flushing, dyspnoe (”carcinoid syndrome”)
Lungs Serotonin Diarrhea, flushing
Histamine Angioedema
 ACTH Cushing's syndrome

Poorly differentiated carcinomas

The most common symptom is pain, often combined with and reduced performace status.

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