Newly Diagnosed With a Neuroendocrine Tumor: First Steps

This page is for people just diagnosed with a neuroendocrine tumor (NET) and those helping them. It explains where NETs start, hormone-related symptoms, the tests and scans used, the main treatments, and when to get help sooner.

Neuroendocrine tumors, or NETs, start in a scattered set of hormone-making cells. Those cells sit all over the body. NCI calls these tumors rare and slow-growing.

You may see the older word carcinoid on your report. It means the same family of tumors.

The scale is small. Worldwide, about 2 people per 100,000 are diagnosed each year. NETs make up about 0.5 percent of all new cancers. The average age at diagnosis is 61.4.

NCI groups them by the part of the embryonic gut they came from:

• Foregut, up to 25 percent of cases. Lung, thymus, stomach, or upper duodenum.
• Midgut, up to 50 percent. Small intestine, appendix, or proximal colon.
• Hindgut, about 15 percent. Distal colon or rectum.

Other sites include the gallbladder, kidney, liver, pancreas, ovary, and testis.

Site matters. NCI says that in general, people with NETs of the appendix and rectum live longer than people with tumors of the stomach, small intestine, and colon. NETs in the small intestine, even small ones, are more likely to spread than tumors in other sites.

One more fact worth knowing. NCI says another cancer occurs in roughly 29 percent of people with small intestinal NETs, at the same time or later. NCI notes this may be partly because slow-growing NETs are found while doctors look into other tumors. This figure comes from the National Cancer Institute’s “Gastrointestinal Neuroendocrine Tumors Treatment.”

A functional tumor makes hormones that cause symptoms. A nonfunctional one does not.

In the pancreas, NCI names five functional types. They are gastrinoma, insulinoma, glucagonoma, somatostatinoma, and VIPoma. VIPoma is also called Verner-Morrison syndrome. About 15 percent of islet cell tumors are nonfunctional. Those look much like ordinary pancreatic cancer.

Two of these have distinctive pictures. Zollinger-Ellison syndrome comes from a gastrinoma. It means stubborn peptic ulcers, diarrhea, and high stomach acid. NCI notes it causes under 1 percent of all peptic ulcer disease. Of gastrinomas, 15 to 35 percent are linked to MEN1 syndrome, and up to half are malignant. One test for gastrinoma is a serum gastrin level 10 times normal or above 500 pg/mL. Insulinomas are the opposite. They are far more often benign than malignant.

MEN1 is multiple endocrine neoplasia type 1. It is inherited, and it causes tumors of the pituitary, parathyroid, and endocrine pancreas. If it applies to you, there may be several pancreatic tumors. Ask your team whether MEN1 testing applies to you.

Carcinoid syndrome hits fewer than 20 percent of people with NETs. It starts when vasoactive amines, hormone-like substances the tumor makes, reach the bloodstream. The result is flushing, belly pain and diarrhea, tight airways, and heart disease. This figure is also from the National Cancer Institute’s “Gastrointestinal Neuroendocrine Tumors Treatment.”

There is a reason it usually signals liver spread. The liver normally breaks these substances down. So the syndrome rarely appears without liver metastases. Exceptions include lung and ovarian primaries, pelvic or retroperitoneal spread, and wide bone spread.

Carcinoid heart disease develops in more than one third of those with the syndrome. Scarring thickens the heart valves. The tricuspid and pulmonic valves are hit harder than the mitral and aortic. That causes leaking valves, a narrowed pulmonary valve, and irregular heart rhythms. NCI links severe carcinoid heart disease to shorter survival.

If you have flushing or diarrhea, ask your team whether you need a heart check, such as an echocardiogram.

24-hour urinary 5-HIAA. This measures a breakdown product of serotonin. Specificity (how rarely it flags people without the tumor) is about 88 percent. Sensitivity (how often it catches the tumor) is reported as low as 35 percent. Prep matters: laboratories instruct patients to leave out serotonin-rich foods such as bananas, tomatoes, and eggplant before the collection, because eating them can push the result up on its own. The lab or your care team will give you the list that applies to your test.

Plasma chromogranin A, or CgA. Very sensitive, but not specific. It also rises in pancreatic and small cell lung cancers. NCI calls it a better marker than urinary 5-HIAA. Its level tracks with how advanced the disease is.

One trap deserves emphasis. Proton pump inhibitors are common acid-reducing drugs. They cause false-positive CgA results. NCI notes this happens even at a low dose, taken briefly. Tell whoever orders the test if you take one.

Most NETs carry somatostatin receptors on their surface. NCI reports that more than 70 percent of gut and pancreatic NETs carry several subtypes. Subtype 2 and subtype 5 dominate.

Scans use that. A radiolabeled somatostatin analogue is injected, and receptor-rich tumors light up. Sensitivity of the octreotide scan is reported as high as 90 percent. Misses come from small tumors, technical problems, or too few receptors.

For bone, technetium-99m MDP scintigraphy is the main tool, with detection rates of 90 percent or higher. This figure is also from the National Cancer Institute’s “Gastrointestinal Neuroendocrine Tumors Treatment.”

One exception matters. Receptor imaging works less well for insulinomas. They often carry few somatostatin receptors.

Somatostatin analogues are an important treatment for symptoms. Octreotide was the first one used. NCI describes its benefit as limited to symptom relief. About 70 percent of patients see their diarrhea or flushing clear. Lanreotide is another long-acting somatostatin analogue. NCI says its effect on symptoms is similar, with 75 to 80 percent reporting less diarrhea and flushing.

Depot forms exist for both. Ask your team which one is right for you and how often it is given.

Four radionuclide conjugates are used most. They are iodine I 131-MIBG, indium In 111, yttrium Y 90, and lutetium Lu 177. The last three are bound to somatostatin analogues. That is how they find the tumor.

NCI calls 177Lu-octreotate the most promising advance here. The largest series reported covered 131 patients. Remission rates tracked with two things: high uptake on the scan beforehand, and limited tumor in the liver.

By contrast, median tumor response to 131I-MIBG is under 5 percent, though roughly 70 percent achieve tumor stability. These figures come from the National Cancer Institute’s “Gastrointestinal Neuroendocrine Tumors Treatment.”

For advanced pancreatic NETs, NCI lists several chemotherapy drugs that have shown anti-tumor effects. They include streptozocin, doxorubicin, fluorouracil, dacarbazine, and temozolomide.

NCI says the evidence that chemotherapy helps people live longer is weak or conflicting. NCI also lists targeted drugs, including sunitinib and everolimus, as having shown activity. Ask your team what is approved and right for you.

• Call 911 or go to an emergency department if intense flushing arrives together with wheezing, a racing heart, fainting, or confusion. NCI describes carcinoid crisis as profound flushing, big swings in blood pressure, wheezing, abnormal heart rhythms, and confusion or stupor. It can be brought on by anesthesia or a procedure. Wheezing that your usual inhaler will not touch also counts. Do not drive yourself.
• Call your care team right away, day or night, if diarrhea leaves you lightheaded when you stand, or you cannot hold fluids down.
• Call your care team right away if your ankles are swelling, or breathlessness lying flat or on stairs is new. NCI says carcinoid heart disease can affect the heart valves.
• Call your care team the same day if flushing episodes are becoming more frequent.

• Where did my tumor start, and is it well or poorly differentiated?
• What is my Ki-67 index, and what grade does that make it?
• Has somatostatin receptor imaging been done? Did the tumor light up?
• Was my chromogranin A drawn while I was taking a proton pump inhibitor?
• Do I need an echocardiogram to check my heart valves?
• Should I be tested for MEN1?

• https://www.cancer.gov/types/gi-neuroendocrine-tumors/hp/gi-neuroendocrine-treatment-pdq
• https://www.cancer.gov/types/pancreatic/hp/pnet-treatment-pdq