What is carcinoid syndrome?

Carcinoid syndrome is a rare condition with a set of symptoms that are caused by an underlying carcinoid tumor. Carcinoid tumors are cancerous growths of neuroendocrine tissue that can secrete various substances - as many as 40 different types - into the bloodstream. The main chemicals secreted by carcinoid tumors include serotonin, histamine, tachykinins, kallikreins and prostaglandins.

Carcinoid syndrome occurs in about 10% of people with carcinoid tumors, typically in people with more advanced tumors. [1]  Carcinoid tumors are very rare and generally slow to grow and develop, but most commonly develop in the intestine or lungs. In particular, the majority of carcinoid tumors originate in the jejunum, ileum and caecum.

Bloodstream

The flow of blood within the blood vessels of the circulatory system.

Caecum

A pouch at the beginning of the large intestine that receives digested food from the small intestine.

Histamine

A type of compound found in all body cells. It has several roles in the body, being released by the tissues as an inflammatory response to an allergic reaction and playing a role in the function of nerves and the gut. In addition, the compound can be found in certain foods, such as cheese and wine, which when consumed can potentially induce allergic reactions.

Ileum

The final section of the small intestine.

Jejunum

The middle part of the small intestine.

Prostaglandins

A group of chemicals acting as hormones in the body.

Serotonin

A chemical messenger within the brain that is thought to play a role in mood and behavior. Many antidepressant medications act by increasing the amount of serotonin in the brain.

Neuroendocrine

The system comprising the nerves and glands that collectively secrete hormones into the bloodstream.

Carcinoid tumor

A rare tumor that begins in hormone-producing cells of various organs. About 80% of carcinoid tumors grow in the appendix and small bowel, but they can also develop in the pancreas, lungs, stomach, ovaries, kidneys or testicles.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Causes

Carcinoid syndrome is associated with the development of carcinoid tumors, which cause high levels of certain chemicals to be released into the bloodstream. The cause of carcinoid tumors is not fully understood, but they may run in families.

Bloodstream

The flow of blood within the blood vessels of the circulatory system.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Risk factors

For carcinoid syndrome, the risk factors may include:

Neurofibromatosis

An inherited condition in which neurofibromas (benign tumors) form from the layer that encloses nerve fibers (sometimes called nerve fiber sheaths).

Tuberous sclerosis

A rare genetic disease that causes tumors to grow in the brain and other organs and causes a combination of symptoms that may include seizures, intellectual disability, behavioral problems, and kidney disease.

von Hippel-Lindau syndrome

An inherited condition characterized by the formation of tumors and fluid-filled sacs (cysts), arising from newly formed blood vessels, throughout the body.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Types

Typical carcinoid syndrome

This is the most common form of carcinoid syndrome. It is most often caused by carcinoid tumors that have spread (metastasized) to the liver. It is characterized by brief periods of hot flushing, diarrhea, coughing, wheezing and shortness of breath. The flushing tends to be light pink to deep red and is commonly triggered by stress, alcohol, exercise and certain foods. Typical carcinoid syndrome is frequently linked to excess serotonin levels.

Atypical carcinoid syndrome

This is a rare form that is characterized by extended periods of hot flushing, headache and shortness of breath. The flushing tends to be deep purple, may last for hours, and can be followed by increased blood flow to the limbs and trunk. The flushing is not brought on by food.

Headache

Pain across the face, eye, ears and other head or neck areas. Can be a dull ache, stabbing or throbbing pain.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Serotonin

A chemical messenger within the brain that is thought to play a role in mood and behavior. Many antidepressant medications act by increasing the amount of serotonin in the brain.

Stress

The word ‘stress’ can have a variety of meanings, but generally describes the physical and mental responses of the body to a demand placed upon it. Often used to describe conditions where the demand is high or unable to be resolved and creates anxiety and tension.

Wheezing

Breathing with a whistling or rattling sound in the chest.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Signs and symptoms

In the early stages of the carcinoid tumor's development, there are usually no visible symptoms, because the liver clears away the substances that the tumor produces and secretes. However, once the tumor has spread to the liver, the liver is no longer able to remove the chemical products and they circulate freely throughout the body. As the chemicals circulate, they may start to cause the onset of various symptoms.

There may not be any symptoms associated with carcinoid syndrome. When symptoms do occur, they may vary depending on the site of the carcinoid tumor and the substances being secreted into the bloodstream.

Most common symptoms

Episodic flushing

Episodic flushing is the main sign of carcinoid syndrome. It usually appears suddenly and lasts for 20-30 seconds. It primarily appears on the face, neck and upper cheeks. More severe flushes are associated with a fall in blood pressure and rise in pulse rate. The flushing is associated with the release of histamine.

Flushing symptoms may be worsened with physical exertion, stress or drinking alcohol, or be associated with dietary triggers, such as eating aged cheese, salted or pickled meats or other foods high in tyramine.

Diarrhea

Diarrhea is a very common symptom of carcinoid syndrome. Episodes of diarrhea may occur several times a day, cause dehydration, and interfere with daily life.

Bronchospasms and wheezing

Breathing problems are a common symptom of carcinoid syndrome that may be mistaken for asthma. They are caused by the constriction of blood vessels, which makes it difficult to breathe.

Other symptoms

Some less common symptoms of carcinoid syndrome may include:

Blood pressure

The pressure the blood places on the walls of the arteries, largely mirroring the contraction of the heart, and consisting of two readings. The higher reading is systolic blood pressure, when the heart contracts, and the lower is diastolic blood pressure, when the heart is relaxed.

Bloodstream

The flow of blood within the blood vessels of the circulatory system.

Dehydration

The state of insufficient hydration; excessive loss of water; requiring more water in order to function normally.

Histamine

A type of compound found in all body cells. It has several roles in the body, being released by the tissues as an inflammatory response to an allergic reaction and playing a role in the function of nerves and the gut. In addition, the compound can be found in certain foods, such as cheese and wine, which when consumed can potentially induce allergic reactions.

Hypotension

Low blood pressure.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Stress

The word ‘stress’ can have a variety of meanings, but generally describes the physical and mental responses of the body to a demand placed upon it. Often used to describe conditions where the demand is high or unable to be resolved and creates anxiety and tension.

Telangiectasia

Small dilated blood vessels with a distinct appearance on the skin or mucous membranes. Also called spider veins.

Tryptophan

An important amino acid found in a range of foods including meats, seeds, nuts, eggs and dairy products. Bananas are rich in tryptophan.

Tyramine

A compound found in some cheeses and other foods. It can cause high blood pressure in people taking certain antidepressant medications.

Carcinoid tumor

A rare tumor that begins in hormone-producing cells of various organs. About 80% of carcinoid tumors grow in the appendix and small bowel, but they can also develop in the pancreas, lungs, stomach, ovaries, kidneys or testicles.

Peripheral edema

An abnormal swelling of the limbs, such as swelling of the ankles, caused by a pooling of fluid.

Niacin

A water-soluble vitamin, which is essential for the breakdown and use of nutrients in the body. It supports the health of the skin, nervous and digestive systems and sex hormones. Known as vitamin B3 or niacin.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Methods for diagnosis

There is often a delay in the diagnosis of carcinoid syndrome because the initial symptoms can be vague and occur sporadically. However, early diagnosis is very important in improving the outcome for people with the condition.

Blood and urine tests

In healthy people, only around 1% of dietary tryptophan is converted to serotonin, whereas in people with carcinoid syndrome, a much greater proportion - up to 70% - of dietary tryptophan is converted to serotonin. The serotonin is then broken down into a compound called 5-hydroxyindoleacetic acid (5-HIAAA).

During diagnostic screening for carcinoid syndrome, the altered metabolism of tryptophan typically results in abnormally high levels of 5-HIAAA in the urine and/or blood. When a urine test indicates normal 5-HIAAA levels in someone suspected of having carcinoid syndrome, a blood test may instead be used to confirm the diagnosis.

Imaging test

An octreoscan can be used to see hormone-producing tumors of the neuroendocrine system. In an octreoscan, a small amount of radioactive material and a hormone-like substance that is attracted to the carcinoid tumor is injected into a vein. After a few hours, a camera is used to detect where the material has been taken up.

The precise location of the tumor may be confirmed by using other imaging techniques such as X-ray, computerized tomography (CT) or magnetic resonance imaging (MRI) scans.

Endoscopy

An endoscopy may be performed to closely examine the digestive tract. This involves using an endoscope, which is an instrument with a small camera that allows the internal lining of the digestive tract to be viewed.

Biopsy

A biopsy may be used to clearly identify the type of tissue present in a suspected tumor and involves taking a small tissue sample from the tumor for laboratory testing.

Computerized tomography

A scan that uses X-rays to create a 3D image of the body. This can detect abnormalities more effectively than a simple X-ray can.

Digestive tract

The series of organs within the body that contribute to the digestion of food. It begins at the mouth and ends at the anus, and includes the stomach, small and large intestines as well as the pancreas, gallbladder and liver.

Hormone

A chemical substance secreted in one part of an organism and transported to another part of that organism, where it has a specific effect.

MRI

A type of imaging that uses a magnetic field and low-energy radio waves, instead of X-rays, to obtain images of organs.

Serotonin

A chemical messenger within the brain that is thought to play a role in mood and behavior. Many antidepressant medications act by increasing the amount of serotonin in the brain.

Tryptophan

An important amino acid found in a range of foods including meats, seeds, nuts, eggs and dairy products. Bananas are rich in tryptophan.

X-ray

A scan that uses ionizing radiation beams to create an image of the body’s internal structures.

Neuroendocrine

The system comprising the nerves and glands that collectively secrete hormones into the bloodstream.

Carcinoid tumor

A rare tumor that begins in hormone-producing cells of various organs. About 80% of carcinoid tumors grow in the appendix and small bowel, but they can also develop in the pancreas, lungs, stomach, ovaries, kidneys or testicles.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Types of treatment

Treatment will vary depending on the size of the tumor, its location and where it has spread.

Surgery

Surgery is typically the first choice of treatment for tumors, especially when they are found early and confined to a small area. Many small tumors can be completely removed with surgery, while larger tumors may require more extensive surgery. When the tumor is too large, or has spread too far, surgical removal may not be a viable option.

Medication

If the tumor cannot be removed through surgery, medication can help relieve symptoms.

The most commonly used drug is octreotide, which can help relieve symptoms in the majority of people and may also help to slow the tumor's growth.

Other medication may include:

  • Antihistamines, to treat the facial flushing;
  • Bronchodilators, to treat the wheezing and help ease breathing;
  • Alpha interferon, which may help ease some symptoms associated with carcinoid syndrome;
  • Steroids or theophylline, which may be prescribed for treatment of lung carcinoids;
  • Antidiarrheal therapy, which may include loperamide, and;
  • Diuretics, which may be used to increase urine output.

Ablation

Cancerous tissue can be destroyed by using targeted liquid nitrogen or high-energy radio waves that can be injected into the area of the tumor. Ablation therapy is useful when a tumor has already spread to the liver and surgery is no longer an option.

Hepatic artery embolization

This involves the insertion of a catheter through a needle near the groin and up the main artery that supplies the blood to the liver. Through the catheter, the blood supply to the tumor in the liver can be stopped.

Chemotherapy

Chemotherapy may be used when tumors cannot be removed with surgery. Chemotherapy medication can either be taken orally or by injection.

In cases where the tumor has spread to the liver and surgery is not an option, a direct injection of the chemotherapeutic substance into the artery that supplies the liver can deliver a high dose of the medication directly to the liver, without having to expose the entire body to it.

Radiation

If the cancer has spread to the bones, radiation can prove effective in alleviating bone pain, but it is not very effective in reducing the size or further spread of the tumor.

Lifestyle changes

Lifestyle changes that can ease the symptoms of carcinoid syndrome include:

  • Avoiding triggers that cause flushing and other symptoms, such as foods high in tyramine. These can include (but are not limited to) cheeses, cured meats, fermented foods (such as kimchi or sauerkraut), pickles, sourdough, Vegemite, tap beers and other yeast products, chocolate, fava beans, fish sauce, shrimp paste, soy sauce, bananas, pineapples, coconuts, avocado and foods that have been left to age or left out of the refrigerator;
  • Avoiding large meals;
  • Avoiding alcohol, and;
  • Taking recommended dietary supplements to replace the nutrients lost from diarrhea.

Catheter

A thin, flexible tube inserted through a narrow opening into a body cavity for removing fluid.

Chemotherapy

A medication-based treatment, usually used in the treatment of cancers. There are numerous, different types of chemotherapy drugs that can be prescribed by a specialist. These can commonly be used alongside other cancer treatments such as surgery and radiotherapy.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Radiation

Energy that is emitted, such as heat, light, or energy in electromagnetic waves. Different types of radiation can be used to diagnose and treat disease.

Tyramine

A compound found in some cheeses and other foods. It can cause high blood pressure in people taking certain antidepressant medications.

Wheezing

Breathing with a whistling or rattling sound in the chest.

Groin

The area where the abdomen joins the thighs.

Octreotide

A medication used to treat severe watery diarrhea and sudden reddening of the face and neck caused by certain types of tumors, such as carcinoid tumors.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Potential complications

  • Bowel obstruction - cancer that spreads to the lymph nodes next to the small intestine can cause narrowing and kinking of the intestine, leading to a bowel obstruction;
  • Carcinoid heart disease - a heart valve problem that can cause the valves around your heart to thicken and not function properly;
  • Increased risk of falls from low blood pressure;
  • Bleeding into the digestive tract, and;
  • Carcinoid crisis - people with carcinoid syndrome may experience a carcinoid crisis, which can either occur without any apparent cause, or be induced by stress. The symptoms of a crisis may include severe hypertension or hypotension, irregular rapid heartbeat, wheezing, shortness of breath and prolonged flushing. A carcinoid crisis can prove life-threatening and requires careful medical attention.

Blood pressure

The pressure the blood places on the walls of the arteries, largely mirroring the contraction of the heart, and consisting of two readings. The higher reading is systolic blood pressure, when the heart contracts, and the lower is diastolic blood pressure, when the heart is relaxed.

Digestive tract

The series of organs within the body that contribute to the digestion of food. It begins at the mouth and ends at the anus, and includes the stomach, small and large intestines as well as the pancreas, gallbladder and liver.

Hypotension

Low blood pressure.

Stress

The word ‘stress’ can have a variety of meanings, but generally describes the physical and mental responses of the body to a demand placed upon it. Often used to describe conditions where the demand is high or unable to be resolved and creates anxiety and tension.

Wheezing

Breathing with a whistling or rattling sound in the chest.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Prognosis

The outlook for people with carcinoid syndrome depends on the size, spread and location of the underlying carcinoid tumors. New medication and therapies are helping to improve the outcome for people with carcinoid syndrome.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.

Prevention

Early detection of carcinoid tumors reduces the risk of developing carcinoid syndrome.

1. Modlin, Irvin M., Mark Kidd, Igor Latich, Michelle N. Zikusoka, and Michael D. Shapiro. “Current Status of Gastrointestinal Carcinoids.” Gastroenterology 128, no. 6 (May 2005): 1717–51.