What is Carcinoid Syndrome?
Carcinoid syndrome is a collection of symptoms brought about by the release of various substances such as polypeptides, biogenic amines, and prostaglandins, into the body. These substances usually come from a type of tumor known as a well-differentiated neuroendocrine tumor. These particular tumors were once called carcinoid tumors and originate from certain cells, named enterochromaffin cells, that can be found all over the body. Interestingly, only about 10% of these neuroendocrine tumors lead to carcinoid syndrome.
What Causes Carcinoid Syndrome?
Carcinoid syndrome typically happens because of a certain type of tumor, called neuroendocrine tumors, that develop in the middle part of the gut and then spread to the liver. Although it’s less common, these tumors can also start in the front or back part of the gut and lead to carcinoid syndrome.
These neuroendocrine tumors generally start in the digestive tract (accounting for 70% of cases), and the respiratory tract (25% of cases). In very rare cases, these tumors can begin in other parts like the ovaries, testicles, and kidneys.
Risk Factors and Frequency for Carcinoid Syndrome
Neuroendocrine tumors are relatively uncommon. Only about 10% of these tumors result in a condition known as carcinoid syndrome. According to information gathered by the Surveillance, Epidemiology, and End Results (SEER) program, the rate of nonpancreatic neuroendocrine tumors is 4.7 for every 100,000 people. Over time, these numbers have been increasing. Since 1973 to 2004, the rate of neuroendocrine tumors, which includes both nonpancreatic and pancreatic types, has increased from 1.09 to 5.25 per 100,000 people. This increase may be due to an uptick in various tests, including endoscopic and radio-imaging studies. However, the rate of these tumors can vary depending on gender and race. For example, recent data shows that black males have a higher rate of neuroendocrine tumors compared to Caucasians (6.46 versus 4.6 per 100,000). The occurrence of these tumors is nearly equal in males and females, with a slightly higher incidence in males. Generally, the median age for diagnosis of neuroendocrine tumors is between 55 and 60.
Signs and Symptoms of Carcinoid Syndrome
Carcinoid syndrome is a condition caused by certain types of tumors that release excessive amounts of hormones into the body, leading to a variety of symptoms. Some common symptoms can include reactions caused by specific biological compounds leading to skin flushing and wheezing, digestive issues such as diarrhea and malabsorption, skin problems due to niacin deficiency (pellagra), heart problems, fatigue, and in some cases, mental confusion. This condition often presents in different ways, details of which are shared below:
- Flushing: The most common symptom, found in around 85% of people. The upper body skin, such as the face, neck, and upper trunk, changes color to a salmon pink or dark red shade, which can last from seconds to half an hour. It can happen randomly, or be triggered by activities like eating, alcohol consumption, physical or emotional stress.
- Diarrhea: Occurs in approximately 80% of people. It is described as explosive and non-bloody, and can happen multiple times a day. Diarrhea is often chronic and sometimes comes with abdominal cramps.
- Cardiac issues: Affects 60% to 70% of people. Signs and symptoms of heart failure or valvular disease can be presented, usually affecting the right side of the heart.
- Bronchospasm: Less common, and occurs in 10% to 20% of patients. It comes with wheezing and breathlessness linked with flushing episodes.
- Purplish rash: Occurs in the later stages of the disease due to extended vasodilation.
- Other symptoms: These can include skin condition (pellagra), muscle wasting, and blockage in the ureter due to fibrosis in the retroperitoneal area.
- Atypical symptoms: These are caused by neuroendocrine tumors in the stomach and lungs. They may lead to patchy skin flushing with itching, and severe, long-lasting flushing episodes related to mental changes like anxiety and tremors.
Testing for Carcinoid Syndrome
If your doctor suspects you might have carcinoid syndrome, they will first carry out specific tests for biochemical markers – substances in your body that can indicate the condition. After that, they might use various imaging techniques or procedures to locate any tumors.
The initial diagnostic test is usually a 24-hour urine test, which checks for a product called 5-HIAA. This substance is what remains after your body has processed serotonin. This test is usually quite reliable, with a 90% accuracy rate. However, certain foods and medicines can cause a false positive result – that means, they can make the test suggest you have carcinoid syndrome when you don’t. These substances include certain foods that are high in an amino acid called tryptophan, such as bananas, pineapples, plums, kiwis, avocados, eggplants, pecans, and walnuts. Also, various medications can also lead to a false positive result. To ensure the test is accurate, you should avoid these foods and medicines for at least 24 hours before and during the urine collection. This 5-HIAA test can be used to monitor the progression of the disease and your response to treatment.
A glycoprotein called Chromogranin A, which is secreted by neuroendocrine tumors – the type of tumors involved in carcinoid syndrome – might also be tested for. Some conditions and certain medications can also affect levels of Chromogranin A in the body. This marker is useful for monitoring the disease but isn’t so good at diagnosing it.
Some other tests are not recommended or not available in certain places, including the US, because they’re not reliable enough, or because they’ve not been validated yet.
If these initial tests indicate that you might have carcinoid syndrome, your doctor will then use imaging techniques or procedures to locate any tumors. They might use a computerized tomography (CT) scan or magnetic resonance imaging (MRI), and sometimes a type of imaging called somatostatin receptor scintigraphy. CT scans of your abdomen, as well as your liver, are usually the first choice. Some doctors may prefer using an MRI scan rather than a CT scan as they’re more sensitive at identifying liver metastases – secondary malignant growths that started in the liver.
A few other imaging techniques and procedures are used for more specific tasks, like checking for bronchial neuroendocrine tumors – tumors in the air passages of your lungs – with a procedure called bronchoscopy with biopsy. Depending on the imaging results, various other procedures might be necessary to get a tissue sample for further study.
Treatment Options for Carcinoid Syndrome
There are several ways to treat carcinoid syndrome, a condition caused by certain types of cancerous tumors. These include particular medications, treatments aimed specifically at the liver, surgery for early-stage cases, and chemotherapy for certain advanced cases.
In some situations, surgeons can remove the primary tumor as well as any tumor growth that has spread to the nearby lymph nodes and liver. This can help to lessen the effect of the disease on the body.
Two drugs, octreotide and lanreotide, are commonly used as part of the medical treatment for carcinoid syndrome. Both drugs work in similar ways, and can help to control symptoms like flushing and diarrhea by blocking certain hormones that are usually found in high levels in patients with this condition.
Both octreotide and lanreotide provide relief from symptoms in around half to three-quarters of patients, and biochemical responses (meaning, a decrease in the level of certain substances in the body that are associated with the disease) in about 40% to 60% of patients. However, these drugs can have side effects such as nausea, abdominal bloating, and steatorrhea (a type of diarrhea caused by too much fat in the stool). Before beginning treatment with these drugs, patients should be aware that they can cause gallbladder problems.
Surgery can sometimes cure carcinoid syndrome, especially in patients who are diagnosed at an early stage. For patients with tumors that can be removed with surgery, the operation can lead to an improvement in symptoms. Even in advanced stages, surgical methods can help to alleviate symptoms and improve quality of life. For example, patients with tumors that have spread to the liver might benefit from a procedure that blocks off the blood supply to the tumors, causing them to shrink.
If other treatments don’t work, there are other options:
1. Higher or more frequent doses of octreotide or lanreotide can be tried.
2. Telotristat, a medicine taken by mouth that interferes with a certain chemical process in the body, might be used together with octreotide or lanreotide to control diarrhea.
3. Interferon, a type of protein that can help the immune system fight cancer, might be used in patients who don’t respond to octreotide or lanreotide.
4. Antidiarrheal medications (medicines that help control diarrhea) can also be used.
5. Certain types of chemotherapy might be used.
6. Another treatment option involves using radiation to target tumors.
Under certain conditions, patients with carcinoid syndrome can experience a severe condition called carcinoid crisis, which involves episodes of severe flushing, difficulties with breathing, and low blood pressure. It can be provoked by various factors such as certain medications, surgery, and the death of tumor cells. To prevent a carcinoid crisis, part of the care plan can involve taking octreotide if certain substances in the urine are found to be elevated.
For those with significant increases in certain body chemicals or physical signs of carcinoid heart disease, or those who are preparing for major surgery, an echocardiogram (an ultrasound of the heart) might be recommended. This is a test that uses sound waves to produce images of your heart, which allows your doctor to see how your heart is functioning.
What else can Carcinoid Syndrome be?
Carcinoid syndrome can show up with different symptoms, which means it can be confused with several other medical conditions. When a doctor is trying to diagnose carcinoid syndrome, they have to consider these other conditions, which include:
- Irritable bowel syndrome
- Disorders affecting the movement of the stomach and intestines
- Celiac disease
- Anaphylaxis, a severe allergic reaction
- Acute urticaria, a type of hives
- Angioedema, swelling beneath the skin
- Ogilvie syndrome, a disorder affecting the intestines
Doctors need to keep these possibilities in mind and use appropriate tests to make an accurate diagnosis.
