Carcinoid syndrome

Neuroendocrine tumors (NETs) are rare, slow-growing neoplasms that develop from neuroendocrine cells, which are hormone-producing cells found throughout the body.

Research shows that about 10 percent of these NETs result in a condition called carcinoid syndrome. Carcinoid syndrome occurs when active peptides and amines are released into the bloodstream by tumors of the gastrointestinal (GI) tract, the liver and a few other organs.

Neuroendocrine tumors of the appendix, small intestine, cecum and colon that metastasize to the liver will more often lead to carcinoid syndrome than tumors that originate elsewhere.

Carcinoid syndrome symptoms

The most common symptom of carcinoid syndrome is flushing of the face, which occurs in about 85 percent of patients with this disease. The face, neck and upper torso may become warm and dark pink to red in color for as little as 30 seconds to as long as 30 minutes.

Diarrhea and wheezing are also hallmark symptoms of carcinoid syndrome.

Stress, alcohol, certain foods and heavy exercise may exacerbate these and other symptoms, which include:

• Extreme diarrhea, which may lead to malabsorption of nutrients
• Angiomas (dilated blood vessels)
• Bronchial spasms
• Rapid heartbeat
• Quick decreases in blood pressure (hypotension)
• Changes in weight
• Dehydration
• Muscle and joint pain
• Peptic ulcers

Over time, damage to the valves of your heart can occur, causing difficulty catching your breath, weakness and fatigue or a heart murmur. In serious cases, this can lead to congestive heart failure.

Carcinoid syndrome causes

Research into the exact cause of carcinoid syndrome is ongoing. In most instances, it occurs when neuroendocrine cells that produce serotonin and other hormonal substances spread to the liver.

Carcinoid syndrome risk factors

Carcinoid syndrome is rare. Approximately 27 per 1 million Americans are diagnosed with neuroendocrine tumors annually, with about 10 percent of these patients developing carcinoid syndrome, according to the National Organization for Rare Disorders. While the incidence of most cancers has plateaued, the incidence of neuroendocrine tumors continues to go up. The most recent numbers reflect that over the last 40 years, the incidence has gone up sevenfold.

The following risk factors may increase the likelihood of developing a neuroendocrine tumor.

• Age: Though people of any age may develop a neuroendocrine tumor, it’s more likely to occur in middle age.
• Race: Although all races may be affected, African-Americans are slightly more likely than others to develop carcinoid syndrome.
• Family history: Having relatives with certain genetic conditions, such as multiple endocrine neoplasia type 1 (MEN 1), increases the risk.

Carcinoid syndrome diagnosis

If a patient is experiencing symptoms of carcinoid syndrome, the doctor will likely conduct a physical examination to rule out other causes. Additional testing may be necessary, such as:.

• 5-HIAA urine test measures the metabolism of serotonin in urine, which produces 5-HIAA. This level is higher in patients with carcinoid syndrome.
• Blood test looks for the presence of hormones and other substances released by neuroendocrine tumors.
• Tumor markers such as chromogranin A levels and others that might be relevant.
• Imaging tests help visualize the cancer to identify the tumor’s location and find out whether it has metastasized. These include a computed tomography (CT) scan, magnetic resonance imaging (MRI) and a specialized positron emission tomography (PET) scan for neuroendocrine tumors.
• Endoscopy or bronchoscopy each uses a thin, lighted tube with a camera on the end to peer inside the body. An endoscopy looks at the GI tract and a bronchoscopy checks out the lungs. Endoscopic ultrasound may facilitate location and sampling of these tumors. 
• Biopsy involves removing a small tissue sample to be examined under a microscope to confirm the diagnosis.

Carcinoid syndrome treatment

Treatment for carcinoid syndrome often involves the surgical removal of the primary tumor and debulking the metastatic burden when deemed feasible.

If surgery isn’t an option, the patient may undergo one of the following treatments:

• Hormone therapy
• Immunotherapy
• Radiation therapy
• Chemotherapy
• Targeted treatment

Treatment of carcinoid syndrome involves managing its symptoms and may include one or more of the following:

• Anti-diarrheal medications to treat extreme diarrhea as a result of carcinoid syndrome, includingImodium^® (loperamide), Lomotil^® (diphenoxylate-atropine) or Xermelo^® (telotristat ethyl)
• Changes to diet and/or medications, including avoiding certain foods that are high in serotonin or that trigger its release and stopping medications that may affect adrenaline or amine levels (patients should never stop taking medication without a doctor’s direction)
• Peptide receptor radionuclide therapy (PRRT), which involves the injection of a radioactive substance that binds with the cells of the tumor, to shrink it and decrease symptoms
• Somatostatin analogs (SSA) to prevent the production of serotonin and other hormones that cause carcinoid syndrome, thereby reducing symptoms; these include Sandostatin^® (octreotide), Somatuline Depot^® (lanreotide) and the Bynfezia Pen^®, which delivers octreotide in short-acting doses

Carcinoid syndrome survival rates

Because carcinoid syndrome occurs with neuroendocrine tumors, the survival rate depends on the extent of the tumor. Rates are categorized based on whether the cancer is:

• Localized, or hasn’t spread past its place of origin
• Regional, or has spread to nearby tissues and lymph nodes 
• Distant, or has metastasized farther to other areas of the body, such as the liver.

For gastrointestinal carcinoid tumors, the five-year survival rates are as follows, according to the American Cancer Society (ACS):

• Localized gastrointestinal carcinoid tumors: 97 percent
• Regional gastrointestinal carcinoid tumors: 96 percent
• Distant gastrointestinal carcinoid tumors: 68 percent

For lung carcinoid tumors, the ACS has five-year survival rates for:

• Localized lung carcinoid tumors: 98 percent
• Regional lung carcinoid tumors: 86 percent
• Distant lung carcinoid tumors: 55 percent