Neuroendocrine tumors are formed from cells in the neuroendocrine system that link your endocrine or hormonal system with your nervous system. One type of neuroendocrine tumor that most commonly forms in the gastrointestinal tract or lungs is a carcinoid tumor, also known as a well-differentiated neuroendocrine tumor. 

Sometimes, these types of tumors can secrete chemicals into the bloodstream that result in carcinoid syndrome. This complex syndrome can have a variety of symptoms and impacts depending on the types of chemicals released from the tumor. These can include polypeptides, prostaglandins, and biogenic amines.

Although carcinoid syndrome is rare, the impacts can be significant. A comprehensive management approach incorporates a holistic and patient-centered approach to address symptoms and improve quality of life. A combination of surgery, medications, nutritional, and lifestyle practices can be tailored to each individual to potentially alleviate the symptoms of carcinoid syndrome.

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What is Carcinoid Syndrome?

Your endocrine and nervous systems are in close communication with each other to help carry out essential processes in your body. You have neuroendocrine cells that help to coordinate this interaction to monitor signals, make hormones, and trigger hormone release. 

Neuroendocrine tumors can form if these neuroendocrine cells divide and multiply uncontrollably. These tumors are relatively rare, affecting about 5 in 100,000 people. 

One type of neuroendocrine tumor is known as a well-differentiated neuroendocrine tumor or carcinoid tumor. In some cases, these tumors can produce excess chemicals that have symptoms of carcinoid syndrome. This is a rare syndrome that impacts fewer than 10% of people with neuroendocrine tumors.

Carcinoid tumors that cause carcinoid syndrome most commonly form in the gastrointestinal tract or lungs. Your liver typically inactivates the biologically active substances produced by these tumors, but if neuroendocrine tumors metastasize or spread to the liver, these products can directly enter into the bloodstream or are not inactivated due to impaired liver function, resulting in symptoms of carcinoid syndrome. In other cases, carcinoid syndrome occurs due to primary tumors in the gastrointestinal tract with metastases to local lymph nodes, ovarian tumors, or bronchial carcinoid tumors, which release bioactive amines directly into the bloodstream. 

When these bioactive chemicals get into the bloodstream, they can cause a variety of symptoms of carcinoid syndrome. The most common and often earliest symptom of carcinoid syndrome is uncomfortable flushing of the head and neck. Carcinoid syndrome can also cause gastrointestinal symptoms like abdominal cramping, explosive diarrhea, and greasy or fatty bowel movements with a bad smell; edema or swelling of the feet and legs; palpitations; dizziness or lightheadedness; wheezing and shortness of breath; decreased libido and erectile dysfunction; the skin rash and other symptoms of pellagra; and yellowing of the skin and whites of the eyes (jaundice).

Some complications of carcinoid syndrome can be life-threatening, including carcinoid heart disease that can lead to heart failure and mesenteric fibrosis when inflammation and scarring of the mesentery occurs, causing scarring of the fold of tissue that attaches your intestines to the wall of your abdomen. In rare cases, a carcinoid crisis can occur due to surgery, other medical procedures, or traumatic events. This is an emergency that causes significant changes in blood pressure, including low blood pressure (hypotension), shortness of breath, confusion, and severe flushing.

Diagnosis of Carcinoid Syndrome

Diagnosing carcinoid syndrome is done by evaluating clinical symptoms, measuring biochemical markers, and using imaging studies to look for neuroendocrine tumors and metastasis. If carcinoid syndrome is suspected based on symptoms and clinical presentation, initial testing for biochemical markers is carried out. If these results suggest carcinoid syndrome, this is followed by imaging studies and endoscopic studies to help localize the tumor(s).

The initial diagnostic test is usually a twenty-four-hour urine test measuring 5-HIAA. Serotonin is the chemical most commonly secreted by carcinoid tumors, and 5-HIAA is the end product of serotonin metabolism used as a marker of this production. Blood levels are also sometimes measured but are not as validated as urine studies. 

If these biomarkers are elevated, imaging studies are usually carried out to pinpoint the specific location of the carcinoid tumor. Computerized tomography (CT) scan, ultrasound (US), or magnetic resonance imaging (MRI) are often used to look for tumors and metastasis to the liver. Scans that use radioactive dye to locate neuroendocrine tumors can also be used. Functional PET imaging with 68-Ga dotatate is preferred to find small tumors since it has increased sensitivity compared to indium-111 pentetreotide (Octreoscan).

If lung or bronchial neuroendocrine tumors are suspected, bronchoscopy with biopsy can be performed. Similarly, some gastrointestinal neuroendocrine tumors may be assessed using upper or lower endoscopy or ultrasound-guided biopsy for examining cells under the microscope. 

There are many challenges in identifying carcinoid syndrome. These types of neuroendocrine tumors can be difficult to locate and recognize since they often result in nonspecific symptoms and a variable course of the disease.

Functional Medicine Lab Testing

Personalized diagnostics in functional medicine can help rule out differential diagnoses, tailor individualized treatment plans, and identify imbalances that can be addressed to improve quality of life. Functional medicine testing helps to uncover deeper insights into individual health status that guide a personalized treatment plan.

Although the specificity of measuring serotonin in the blood alone has not been shown to be consistently reliable, elevated levels of blood serotonin may indicate carcinoid syndrome. Histamine is another marker that can be released from carcinoid tumors as well as from mast cells that can be measured in the blood or urine. In addition, tryptase may be added to evaluate for mastocytosis or mast cell activation syndrome (MCAS).

Since carcinoid syndrome often presents with vague or nonspecific symptoms, it can often mimic other conditions that need to be assessed. Functional medicine testing and a thorough clinical assessment can help identify a range of differential diagnoses, including gastrointestinal motility disorders like gastroparesis, celiac disease, acute urticaria, or angioedema. 

Celiac disease can mimic some of the symptoms of carcinoid syndrome, such as diarrhea and steatorrhea or fat in the stool. Celiac antibody testing can be used to check for antibodies to t-TG2, endomysial, and deamidated gliadin peptide. Specialty functional medicine testing like the LRA Gluten Hypersensitivity Block by ELISA / ACT Biotechnologies and Genova Diagnostics’ Celiac Profile (IgG & IgA) can detect antibodies to gluten proteins (while eating gluten) that suggest celiac disease. 

In addition to these specific disorders, an imbalance in the microbes within the gut (dysbiosis) can lead to hormonal imbalances and elevated levels of systemic inflammation that can mimic and worsen symptoms of carcinoid syndrome. The GI-MAP + Zonulin from Diagnostic Solutions measures the balance of microbes in the gut along with markers of inflammation, immune function (secretory IgA), and leaky gut (zonulin). This can provide insights into factors that may be contributing to symptoms like flushing, hormone imbalances, and diarrhea that can guide an individualized treatment approach. 

Further hormone testing can provide insights into how your body synthesizes, metabolizes, and eliminates hormones. This can help evaluate conditions that can cause similar symptoms, such as hot flashes. For example, the DUTCH Plus test by Precision Analytical uses salivary and urinary samples to measure the metabolites of sex and adrenal hormones to help identify imbalances in hormone metabolism and stress responses that can also cause hot flashes and flushing. 

Micronutrient testing, such as a panel offered by SpectraCell Laboratories, analyzes 31 vitamins, minerals, and other nutrients to determine nutritional deficiencies that can occur with chronic diarrhea in carcinoid syndrome. In particular, deficiencies in vitamin D and vitamin B12 are common in people with neuroendocrine tumors of the midgut.

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Conventional Treatment Approaches

The conventional approach to managing carcinoid syndrome symptoms involves addressing the underlying tumor. This is often accomplished with surgical removal or debulking of the neuroendocrine tumor and any accessible metastases. 

If the neuroendocrine tumor causing carcinoid syndrome is large or has spread and cannot be completely removed with surgery, other treatments may be used. Medical management with injectable somatostatin analogs like octreotide and lanreotide are used to inhibit the release of most of the gastrointestinal, endocrine hormones to stop the body from making too many hormones. This can help to reduce symptoms like diarrhea and flushing and may also slow the growth of the tumor. Somatostatin analogs provide relief of symptoms in about 50% to 70% of patients and improvements in biochemical markers in 40% to 60% of patients. They commonly cause side effects such as nausea, bloating, biliary sludge and gallstones, and pancreatic malabsorption that results in fatty stools. Pancreatic enzymes can help reduce some of these impacts. 

If patients do not respond to or cannot tolerate a somatostatin analog, interferon-alpha can be used. This medication causes cell cycle arrest in tumor cells, stimulates T-cells, and inhibits the angiogenesis of tumor cells, causing the tumor to start to die.

Systemic chemotherapy, such as the mTOR inhibitor everolimus, is sometimes used to improve symptoms and target tumor cells. Other targeted therapies, like peptide receptor radioligand therapy, may be used to deliver targeted radiation to neuroendocrine tumors that have somatostatin receptors.

In addition to targeting and trying to reduce the neuroendocrine tumor(s) resulting in carcinoid syndrome, conventional treatments for carcinoid syndrome also aim to reduce and manage symptoms. For example, the oral tryptophan hydroxylase inhibitor telotristat can help reduce diarrhea when used in combination with somatostatin analogs. Conventional antidiarrheal drugs like loperamide, Lomotil, and cholestyramine are also added for symptom relief. If your carcinoid tumor secretes histamine, antihistamine medications may be used to help symptoms like hives and flushing.

Functional Medicine Approach to Carcinoid Syndrome

Functional medicine for carcinoid syndrome looks at the factors causing symptoms and addresses all parts of a person’s health. This patient-centered and holistic approach to neuroendocrine tumors allows for a personalized look at factors that impact an individual’s mind, body, and spiritual health. Utilizing targeted testing and looking at the root causes of imbalances can guide a unique management plan of care for each person’s needs.

For example, flushing is one of the most prominent symptoms of carcinoid syndrome and can be triggered or worsened by your nervous system’s reaction to physical or emotional stress. Regularly utilizing stress management practices like breath work can help calm the nervous system and activate your parasympathetic response. It can also be helpful to use cool compresses on your face or chest and to get fresh air to help cope with flushing. 

Mind-body modalities like mindfulness-based stress reduction can help reduce the anxiety and depression that many patients experience. Appropriate physical activity is also valuable for improving vascular tone and cardiac function to help reduce cardiovascular complications of carcinoid syndrome. 

If you have pancreatic exocrine insufficiency, pancreatic enzyme replacement therapy taken before and during eating can help break down fats. The amount of enzymes needed depends on the size of the meal or snack and the fat content it contains. This can also help improve the absorption of fat-soluble vitamins A, D, E, and K if deficiencies have been identified on micronutrient testing. 

Nutritional and Lifestyle Interventions in Functional Medicine

Certain dietary and lifestyle habits may worsen or precipitate the symptoms of carcinoid syndrome. Therefore, nutrition and lifestyle approaches can help manage hormonal imbalances and support the immune system. Overall, an anti-inflammatory diet that is balanced in fresh fruits and vegetables supports hormonal balance, gut health, and immune system function.

A diet for carcinoid syndrome is usually made up of several smaller meals that are rich in proteins like nuts, beans, lentils, and legumes and do not have too much fat at one time since large fatty meals can worsen symptoms. It can also be helpful to avoid foods that are high in tyramine, like aged cheeses, avocado, and many processed foods, as well as spicy foods. Cooked vegetables are easier to digest and better tolerated. 

Dietary amines can cause increased symptoms of carcinoid syndrome. Amines are formed when proteins break down in foods like meat, fish, and cheese as they age or mature. They are also found in fruits like tomatoes and bananas as they ripen, in pickled and fermented foods, and in spoiled foods, so these should be avoided for most people with carcinoid syndrome. Each person is unique with different triggers, so diet should be tailored to your needs.

People with carcinoid syndrome should avoid alcohol, which can trigger flushing and other symptoms since it also contains amines. 

It is essential that people with chronic diarrhea stay well-hydrated and maintain a proper balance of electrolytes. These minerals, like sodium, potassium, magnesium, and calcium, work together to preserve the function of crucial body functions like heart and muscle movement. 

Integrating Conventional and Functional Medicine Strategies

Given the complex nature of this disease, the nonspecificity of symptoms, and the heterogeneity of this disease, a multidisciplinary approach to care is crucial for the effective and efficient diagnosis and management of carcinoid syndrome. A collaborative healthcare approach for carcinoid syndrome may involve multiple specialists working together to care for the whole patient. 

Integrating treatments for carcinoid syndrome by bringing together both conventional and functional medicine strategies allows for the most effective and comprehensive care. Symptoms can most effectively be controlled when looking at them holistically. 

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A Functional Medicine Approach to Carcinoid Syndrome: Key Takeaways

Certain neuroendocrine tumors can release substances that cause symptoms like flushing, diarrhea, and wheezing. Together, this condition is known as carcinoid syndrome and can significantly impact a person’s functioning and quality of life.

Holistic management of carcinoid syndrome takes a multidisciplinary approach to identifying imbalances and supporting the immune system, hormones, and overall body. This way of dealing with carcinoid syndrome blends conventional, integrative, and functional medicine strategies to develop a personalized plan of care for each individual. Diet, lifestyle, and mind-body approaches help to address all aspects of a person’s needs to reduce symptoms and improve quality of life.