Neuroendocrine Tumor Symptoms and Delayed Diagnosis

This page is for people who have, or may have, a neuroendocrine tumor of the gut, and their families. It covers the symptoms, the tests and scans used to find these tumors, and questions for your care team.

Neuroendocrine tumors, often shortened to NETs, start in cells of the diffuse neuroendocrine system. Those cells sit scattered through the gut, the lungs and other organs. They sense what is happening around them and release hormones in response.

NCI puts the worldwide age-adjusted incidence at about 2 per 100,000 people. NETs make up roughly 0.5 percent of all newly diagnosed cancers. The typical age at diagnosis is about 61.

These tumors are rare, so ask questions if symptoms do not go away.

Flushing and diarrhea are linked with these tumors. That cluster is called carcinoid syndrome. NCI states it occurs in fewer than 20 percent of patients with neuroendocrine tumors.

NCI lists these symptoms:

• Redness or warmth in the face and neck.
• Belly pain, bloating and diarrhea.
• Wheezing or other trouble breathing.
• A fast heartbeat.

Carcinoid heart disease is a complication, described below.

Get emergency care right away (call 911) for sudden severe flushing with trouble breathing, a racing heart or a big blood pressure change.

NCI says carcinoid syndrome symptoms occur when the tumor has spread to the liver.

This complication is under-recognized. NCI reports that carcinoid heart disease develops in more than one-third of patients with carcinoid syndrome.

NCI says severe carcinoid heart disease is linked to lower survival. If carcinoid syndrome is confirmed, ask whether an echocardiogram (an ultrasound of the heart) has been done and how often it will be repeated.

Most NETs do not cause carcinoid syndrome. What they cause depends on where they are and what they block or bleed.

NCI lists symptoms by site. In the small intestine: belly pain, weight loss with no known cause, tiredness, bloating, diarrhea, nausea and vomiting. In the rectum: blood in the stool, rectal pain and constipation. Stomach and appendix tumors often cause no early symptoms. Many of these symptoms have common causes, so only tests can tell.

Two patterns deserve a second look:

• Belly symptoms that keep getting worse or do not go away.
• Flushing with diarrhea that has no clear cause.

Neither proves anything. Both are worth telling your doctor about. Our page on cancer symptoms covers how to describe a pattern so it is taken seriously.

If a NET is suspected, two biochemical tests come up. Both have known weaknesses, and knowing them changes how you read a result.

The first is a 24-hour urine collection for 5-hydroxyindoleacetic acid, shortened to 5-HIAA. It is a breakdown product of serotonin. NCI puts its specificity (how rarely it gives a false alarm) at approximately 88 percent, but reports sensitivity (how often it catches a tumor) as low as 35 percent. A specificity of 88 percent means a positive result usually means something. A sensitivity of 35 percent means a normal result misses a great many tumors.

The test takes 24 hours of urine collection. Ask your team about any food or drug rules beforehand.

The second is plasma chromogranin A, or CgA. NCI says plasma CgA appears to be a better marker than urinary 5-HIAA.

One false-positive cause is worth knowing before your blood is drawn. Proton pump inhibitors, the common acid-reducing drugs, raise CgA. Tell whoever orders the test if you take one.

NCI says more than 70 percent of these tumors carry several subtypes of somatostatin receptors.

NCI says receptor-based imaging, such as octreotide scanning, is effective for this reason. Other imaging includes CT, MRI and PET scans.

The practical question is direct. If a NET is suspected and a standard CT is normal, ask whether somatostatin receptor imaging is indicated.

NCI's prognostic factors are the site of origin, the size of the primary tumor, and how far the disease extends.

NCI says high Ki-67 and p53 levels, high urinary 5-HIAA, and carcinoid heart disease point to a poorer outlook.

• Which specific site did my tumor start in, and what size was it?
• What is the Ki-67 index on my pathology report?
• Has somatostatin receptor imaging been done, and if not, why not?
• Was my chromogranin A drawn while I was taking a proton pump inhibitor?
• If I have carcinoid syndrome, when is my echocardiogram, and who repeats it?
• Is there a neuroendocrine tumor center where my case could be reviewed?

That last question is worth pressing. These tumors are uncommon enough that experience varies a great deal between centers. Our page on getting a second opinion covers how to arrange one, and metastatic cancer explains what spread does and does not mean.

• NCI PDQ on GI neuroendocrine tumors, for doctors
• NCI PDQ on GI neuroendocrine tumors, for patients