Carcinoid Syndrome

What causes carcinoid syndrome

Neuroendocrine tumors (formerly called carcinoid tumors) arise from hormone-producing cells, most commonly in the small intestine, appendix, rectum and lungs. Some release serotonin, histamine, tachykinins, kallikrein and prostaglandins.

Normally, hormones from gut tumors travel to the liver first and are broken down. Carcinoid syndrome develops when the substances reach the general circulation, which happens mainly when:

• the tumor has spread to the liver, so hormones from liver deposits flow straight into the bloodstream (most common)
• the tumor is outside the gut's drainage to the liver, such as in the lungs or ovaries

Only about 10 to 20% of people with NETs develop carcinoid syndrome.

Symptoms

• Flushing (most common): sudden warmth and redness of the face, neck and upper chest, lasting from 30 seconds to several minutes. Some tumors cause longer, purple-red flushes. Over time, permanent redness and visible vessels can develop.
• Diarrhea: frequent, watery stools, often with cramping, from serotonin speeding the gut.
• Wheezing: asthma-like episodes during flushing.
• Fast heartbeat and blood pressure changes during episodes.
• Abdominal pain from the tumor or bowel narrowing caused by scarring.
• Pellagra: tumors divert tryptophan to make serotonin, which can cause niacin deficiency with rash, diarrhea and confusion.

Can carcinoid syndrome symptoms fluctuate?

Yes. Symptoms often come in episodes and vary over days to months. Common triggers include alcohol, large meals, spicy food, foods high in tyramine such as aged cheese, stress, exercise, and pressure on the liver or tumor. Symptoms may also worsen as tumors grow, or improve with treatment. A sudden change should be reported to your care team.

Carcinoid heart disease

Long-term exposure to serotonin causes fibrous plaques on the heart valves on the right side, mainly the tricuspid and pulmonary valves. They thicken and leak, leading to right-sided heart failure with leg swelling, fluid in the belly and tiredness. It affects a significant minority of people with carcinoid syndrome. Regular echocardiograms and checking the blood marker NT-proBNP help detect it. Valve replacement surgery may be needed. See tricuspid valve disease.

Carcinoid crisis

A sudden, massive release of hormones can cause severe flushing, low or high blood pressure, irregular heartbeat, wheezing and confusion. It can be triggered by anesthesia, surgery, biopsies, tumor treatments or certain medicines. It is life-threatening and is prevented by giving octreotide before and during procedures.

Diagnosis

1. 5-HIAA test: a 24-hour urine collection or blood test measuring the breakdown product of serotonin. Some foods (bananas, avocados, pineapples, walnuts, tomatoes, eggplant, plums, kiwi) and medicines can falsely raise it, so follow preparation instructions.
2. Chromogranin A: a blood marker of NETs; less specific.
3. Imaging: CT or MRI of the abdomen and liver, and a somatostatin receptor PET scan (such as Ga-68 DOTATATE) that lights up NET cells and shows spread.
4. Biopsy: usually of a liver deposit, to confirm the diagnosis and tumor grade (Ki-67).
5. Echocardiogram: to check for carcinoid heart disease.

Other causes of flushing and diarrhea, such as menopause, rosacea, mastocytosis, medullary thyroid cancer, pheochromocytoma and medicines, are considered.

Treatment

Controlling symptoms

• Somatostatin analogs: octreotide or lanreotide injections, usually monthly long-acting forms, reduce hormone release and control flushing and diarrhea in most people. They also slow tumor growth.
• Telotristat ethyl: a tablet that blocks serotonin production, added for diarrhea not controlled by somatostatin analogs.
• Antidiarrheals such as loperamide, and pancreatic enzymes if fat malabsorption occurs (a side effect of somatostatin analogs).
• Niacin supplements to prevent pellagra.
• Avoiding triggers: alcohol, large meals and foods that provoke symptoms.

Treating the tumor

• Surgery to remove the primary tumor and, where possible, liver metastases.
• Liver-directed therapy: embolization, radioembolization or ablation.
• Peptide receptor radionuclide therapy (PRRT): lutetium-177 DOTATATE, a targeted radioactive treatment for somatostatin receptor-positive tumors.
• Targeted therapy: everolimus and other drugs.
• Chemotherapy for faster-growing tumors.

Outlook

Many NETs grow slowly, and people with carcinoid syndrome can live for many years with treatment, often a decade or more. Outlook depends on tumor grade, extent of spread and whether carcinoid heart disease develops. Care at a specialist NET center is recommended.

Frequently asked questions

What are the main symptoms of carcinoid syndrome?

The main symptoms are episodes of flushing of the face and upper chest and frequent watery diarrhea. Others include wheezing, a racing heart, belly cramps and, over time, heart valve problems. Symptoms often come and go and can be triggered by alcohol, stress or certain foods.

Can symptoms of carcinoid syndrome fluctuate over time?

Yes. Symptoms often vary from day to day and month to month, flaring with triggers such as alcohol, large or spicy meals, aged cheese, stress and exercise. They may worsen as tumors grow and improve with treatment. Tell your doctor about any lasting change.

Is carcinoid syndrome cancer?

Carcinoid syndrome is a set of symptoms caused by a neuroendocrine tumor, which is a type of cancer. Most NETs that cause carcinoid syndrome have spread to the liver, but many grow slowly and can be controlled for years with treatment.

What foods should you avoid with carcinoid syndrome?

Common triggers include alcohol, large meals, spicy foods, and foods high in amines such as aged cheese, cured meats and some fermented products. Triggers vary, so a food diary helps. Before a 5-HIAA test, avoid serotonin-rich foods such as bananas, avocados, pineapple, walnuts and tomatoes.

What is carcinoid crisis?

Carcinoid crisis is a sudden, severe release of tumor hormones causing extreme flushing, blood pressure swings, irregular heartbeat and breathing difficulty. It can occur during surgery or procedures and is life-threatening. It is prevented and treated with octreotide given by IV.