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Fatigue, brain fog, body aches, stomach problems, mood swings, and sleep problems are all common symptoms of a thyroid condition. However, these symptoms are also signs of a complicated and misunderstood immune condition known as Mast Cell Activation Syndrome (MCAS).
MCAS is also known as Mast Cell Activation Disease or Mast Cell Activation Disorder (MCAD). Evidence suggests that the risk of MCAS may be higher in people with autoimmune thyroid disease -- and that MCAS patients may have a higher risk of undiagnosed thyroid conditions. Ahead, a look at the complexities of MCAS and how it relates to autoimmune thyroid disease and hypothyroidism.
Human mast cells are white blood cells found throughout your body that function as part of your immune system, helping fight infection. Mast cells also play an essential role in allergic reactions.
Mast cells secrete various substances known as mediators, including histamine, heparin, leukotrienes, prostaglandins, and cytokines. These mediators are released as part of immune responses and allergic reactions. In a healthy person with a well-functioning immune system, the regular release of mediators causes temporary, mild symptoms.
The greatest concentration of human mast cells is on mucosal and skin surfaces that have exposure outside the body, where mast cells function as "sentinels" for the immune system, monitoring for allergens.
In Mast Cell Activation Syndrome (MCAS), your immune system does not function properly. As a result, human mast cells spontaneously release excessive amounts of chemicals and substances -- known as mast cell mediators -- into your body. One of the most common mediators is histamine, and this release causes a variety of symptoms often associated with an allergic response.
This spontaneous release is prompted by exposure to, in some cases, small amounts of trigger substances, which can include:
- Medications
- Insect and reptile venom
- Fragrances
- Food
- Alcohol
- Pollution
- Mold
- Chemicals
Excessive histamine release in MCAS can also be triggered by:
- Temperature extremes
- Infections
- Stress
- Changes in the gut microbiome
- Exercise
Periodic or mild responses to these triggers fall into the category of histamine intolerance. When the condition is chronic and severe, it's considered MCAS.
It's thought that people with MCAS have abnormally sensitive or hyperresponsive mast cells, and their immune system appears to be unable to tolerate a high mast cell burden. Experts do not have a clear understanding of the underlying cause of MCAS, as the condition does not appear to be caused by other diseases or related to specific allergies. MCAS patients tend to have many allergy symptoms, but laboratory tests do not confirm allergies to particular foods or substances. MCAS patients may also have a history of multiple episodes of unexplained anaphylaxis.
Symptoms of systemic mast cell activation and histamine intolerance are similar to common symptoms of an allergic response and can start at any age but usually begin in adulthood. The symptoms are broad, but a clinical picture of MCAS and histamine intolerance can include the following.
Signs and symptoms of mast cell activation syndrome:
- Skin: flushing of the face, itching, swelling, rash, hives
- Eyes: itching, dry eyes
- Nasal: congestion, runny nose, excessive mucus
- Respiratory: coughing, chest tightness, asthma-like symptoms, shortness of breath, wheezing, difficulty breathing
- Gastrointestinal: stomach cramps, bloating, indigestion, heartburn, nausea, vomiting, diarrhea, malabsorption
- Urinary: painful, frequent, urgent urination
- Cardiovascular: rapid fluctuations in blood pressure, fast heart rate, heart palpitations, weak pulse
- Neurological: headache, brain fog, difficulty concentrating, neuropathy (numbness and tingling in extremities), vertigo
- Hearing: tinnitus (ringing in the ears)
- Musculoskeletal: joint and muscle pain
- Sleep: insomnia
- Mental health: depression, anxiety
- Other: headache, fatigue, brain fog, frequent bruising, nosebleeds
MCAS can cause episodes of anaphylaxis in a subset of patients. Anaphylaxis is a life-threatening reaction that can include rapid swelling (especially of the face and airway), hives, a rapid drop in blood pressure, difficulty breathing, dizziness, fainting, and shock. Because these episodes are not typically the result of a specific allergic disease, they're known as idiopathic anaphylaxis.
MCAS is diagnosed when a patient does not test positive for any specific allergies and meets several diagnostic criteria:
- Repeat episodes of MCAS symptoms affecting more than one system (skin, gastrointestinal, cardiovascular, respiratory, etc.)
- Diagnostic workup that shows elevated levels of mediators – i.e., histamine, tryptase, or prostaglandins -- during MCAS episodes (or during a challenge test conducted by a physician)
- Improvement of symptoms after antihistamine medications and mast cell stabilizer drugs
Diagnosis can be a long process, however, and many MCAS patients need to consult several doctors over a lengthy period before a differential diagnosis is made.
While there is no cure for MCAS, there are treatment recommendations that can successfully achieve a therapeutic response.
Your first line of defense in managing MCAS is to actively avoid any identifiable triggers that will trigger any systemic mast cell activation. It can be helpful to keep a detailed food and drink diary while also keeping track of other known triggers, including hydration, stress, temperature, infections, and exercise.
After that, there's no one-size-fits-all treatment for MCAS. Apart from avoiding specific triggers resulting in mediator release, the recommended treatment usually starts with antihistamine medications. Other medications are added as needed, based on symptoms and response to treatment. The success of medicines depends on the individual response of each patient.
Antihistamines
Since histamine is one of the primary mediators released by activated mast cells, taking an antihistamine drug can block and prevent histamine from affecting your body.
Second-generation H1 antihistamines, such as loratadine (Claritin), cetirizine ( Zyrtec), fexofenadine (Allegra), and levocetirizine (Xyzal), are frequently recommended when itching and gastrointestinal problems are chief symptoms. First-generation antihistamines like diphenhydramine (Benadryl), chlorpheniramine (Chlortrimeton), doxepin (Sinequan), or clemastine (Tavist) can be used. Second-generation antihistamines are preferred, however, because they are non-sedating.
An H2 antihistamine such as famotidine (Pepcid, Zantac 360) is recommended when gastrointestinal symptoms are predominant.
Proton pump inhibitors (PPIs)
PPIs may be recommended when gastroesophageal reflux (GERD) is the main symptom. PPIs include drugs like esomeprazole (Nexium), lansoprazole (Prevacid), and omeprazole (Prilosec.)
Important Note: if you are taking PPIs and being treated for hypothyroidism, be aware that tablet forms of levothyroxine are significantly less effective when you are taking a PPI. The gel cap and liquid form of levothyroxine (Tirosint and Tirosint-SOL) were designed to be absorbed well by patients taking PPIs.
How To Maintain A Healthy Gut
Digestive issues like bloating, constipation, or gas can be resolved or improved with simple lifestyle changes
Mast cell stabilizers
Mast cell stabilizers are medications or supplements that help prevent the release of mast cell mediators. The primary mast cell stabilizer is cromolyn sodium (Gastrocom and Nasalcrom). This drug prevents mast cells from releasing too much histamine and minimizes Benzodiazepines, such as Lorazepam (Valium) and Clonazepam (Klonopin), which can act as mast cell stabilizers, and are sometimes prescribed when anxiety is a dominant symptom of MCAS.
Other mast cell stabilizers include:
- Quercetin – a supplement that helps reduce histamine release
- High dose vitamin C – which can help reduce histamine release
- Aspirin – which can help minimize prostaglandin release
Leukotriene Receptor Antagonists
Also known as antileukotrienes, leukotriene receptor antagonists include medications like zafirlukast (Accolate) and montelukast (Singulair) that can block the excessive release of leukotrienes. These drugs are often recommended if difficulty breathing or asthma-like reactions are key MCAS symptoms.
Corticosteroids
Steroid drugs are not commonly prescribed for MCAS but are sometimes given on a short-term basis to treat significant swelling, wheezing, or hives.
Epinephrine injections (EpiPen)
MCAS patients with a history of anaphylactic reactions are typically given an EpiPen, a self-injecting pen containing epinephrine, for emergency use.
Other drugs
In MCAS patients with a history of anaphylactic reactions, monoclonal antibody treatment with omalizumab (Xolair) is sometimes prescribed because it can help block mast cells from releasing various mediators and reduces the risk of life-threatening anaphylaxis.
When MCAS doesn't respond to the existing treatments, or patients only have a partial response, the condition is sometimes treated with drugs used for a more severe mast cell condition known as systemic mastocytosis. This involves using the tyrosine kinase inhibitor drug imatinib (Gleevec), or in some cases, interferon, and a chemotherapy drug cladribine (Leustatin, Mavenclad).
Mast cells can affect thyroid function, and thyroid function can affect the operation of mast cells. It's already well-established that mast cell activation is associated with various autoimmune diseases, including rheumatoid arthritis and multiple sclerosis.
While there's limited research on autoimmune thyroid disease and MCAS, we know that thyroid antibodies bind to the surface of mast cells, causing them to activate, suggesting that an increase in thyroid antibodies, consistent with autoimmune Hashimoto's thyroiditis, may increase the number of activated mast cells, which could increase the risk of MCAS.
Mast cells also synthesize and store the thyroid hormone triiodothyronine (T3), which has led experts to conclude that when mast cells are activated, along with other chemicals, they may also be releasing thyroid function in irregular ways.
Researchers also report that the number of mast cells increases when you're hypothyroid. Again, if you have more mast cells, you can be exposed to high amounts of histamine when they become activated.
There is also evidence that histamine controls the release of TSH. These findings raise the possibility that an underactive thyroid may increase the risk of histamine intolerance and MCAS.
Research has also reported that mast cells play a role in early thyroiditis and autoimmune thyroid disease and even develop some of the follicular variants of papillary thyroid cancer.
Many integrative physicians recommend complementing conventional treatment with the following interventions, which may be helpful if you have an oversensitivity to histamine or MCAS.
DAO supplementation
A deficiency of diamine oxidase (DAO), the enzyme responsible for breaking down histamine, is associated with MCAS. Supplementing with DAO may help break down excess histamine.
Focusing on gut health
Because a gut imbalance appears to contribute to a risk of MCAS, consider addressing conditions like leaky gut, small intestinal bacterial overgrowth SIBO, and other gastrointestinal imbalances with diet, probiotic therapy, and other treatment recommendations. (You may want to review the Paloma Health video presentation, How & Why to Keep Your Gut Microbiome Healthy.)
How To Maintain A Healthy Gut
Digestive issues like bloating, constipation, or gas can be resolved or improved with simple lifestyle changes
A low histamine diet
MCAS patients should consider following a low-histamine diet. You can't avoid histamine entirely, but you can reduce or eliminate foods and drinks that contain a high amount of histamine, those that trigger systemic mast cell activation and cause mast cells to release histamine, and those that block DAO.
When you're on a low histamine diet, you'll need to avoid foods and drinks that are high in histamine, that promote histamine release, or those that block DAO. These include:
- Aged cheeses
- Aged, cured, smoked meats
- Processed lunch meat
- Canned fish: including tuna, mackerel, anchovies
- Shellfish
- Fermented vegetables, including sauerkraut, kimchi, pickles, and pickled vegetables)
- Fermented dairy products, like yogurt, sour cream, buttermilk
- Yeast and yeast extract
- Certain fruits, including citrus, bananas, strawberries, papaya, pineapple, pears, tomatoes, tomatillos, olives, avocados, and dried fruits
- Tomato products, including spaghetti sauce and ketchup Vegetables, including spinach, white and red potatoes, and nightshade vegetables, including eggplant and peppers
- Beans and legumes: including chickpeas, peanuts
- Nuts: walnuts and cashews
- Chocolate
- Alcohol: especially red wine and beer
- Fermented beverages like kombucha, kefir,
- Teas, including black tea, mate tea, and green tea
- Citrus fruit juices
- Preservatives, especially benzoates and sulfites
- Fermented condiments like vinegar and soy sauce
- Fermented soy products
- Fermented bread, like sourdough
- Red spices like curry, chili powder, cayenne, red pepper, and paprika
A note from Paloma Health
MCAS, Hashimoto's thyroiditis, and hypothyroidism share similar symptoms. If optimal thyroid treatment does not resolve those symptoms, you may benefit from an evaluation for MCAS and treatment for mast cell activation if it's diagnosed. And, if you have MCAS, make sure that you periodically have a comprehensive thyroid evaluation to rule out the possibility that an underlying thyroid condition may be contributing to your condition.
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