Celiac disease and non-celiac gluten sensitivity (NCGS) have become increasingly prevalent in recent years, affecting millions worldwide (48). In the United States, 1% of the population has been diagnosed with celiac disease, while NCGS is estimated to affect up to 6% of the population. Beyond their well-known digestive symptoms, emerging research suggests a connection between these conditions and thyroid health. In functional medicine, understanding the intricate relationship between gluten-related disorders and thyroid function allows for personalized treatment strategies, emphasizing a holistic approach to overall well-being.
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Understanding the Connection Between Thyroid Health and Gluten-Related Disorders
Celiac disease and NCGS are two distinct but related conditions characterized by adverse reactions to gluten, a protein found in grains such as wheat, barley, and rye. Celiac disease is an autoimmune disorder in which the ingestion of gluten triggers an immune response that involves the production of antibodies, particularly anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. These antibodies target the lining of the small intestine, leading to inflammation and damage to the intestinal villi, which can lead to nutrient malabsorption (58, 7). NCGS, on the other hand, lacks the autoimmune response seen in celiac disease. Individuals with NCGS experience similar symptoms after consuming gluten without the same damage to the small intestine (24).
Interestingly, both celiac disease and NCGS have been linked to a higher risk of thyroid conditions (1, 3, 34). The thyroid is a butterfly-shaped gland in the neck responsible for regulating metabolism, energy production, and various physiological processes throughout the body. The thyroid gland produces two main hormones: thyroxine (T4) and triiodothyronine (T3). The release and regulation of T3 and T4 are primarily controlled by the thyroid-stimulating hormone (TSH), which is produced by the pituitary gland located in the brain. Hypothyroidism occurs when the thyroid gland doesn't produce enough thyroid hormones. Hyperthyroidism, on the other hand, results from an overproduction of hormones. Autoimmune thyroid conditions can also occur in which the immune system mistakenly attacks the thyroid gland, leading to inflammation, damage, and dysfunction. The two primary autoimmune thyroid conditions are Hashimoto thyroiditis and Graves’ disease, responsible for 90% of cases of hypothyroidism and 80% of cases of hyperthyroidism.
Celiac Disease, Gluten Sensitivity, and Their Impact on Thyroid Health
The connection between celiac disease, NCGS, and thyroid dysfunction involves various mechanisms, highlighting the complex relationships between the immune system, the gut, and the thyroid gland. Gluten refers to a group of proteins, consisting of two main groups of proteins: glutenins and gliadins. When gluten is ingested, the human digestive system is only capable of breaking it down partially in the small intestine. In individuals with gluten sensitivity or celiac disease, these incompletely digested peptides, including gliadin fragments, can be recognized as foreign substances by the immune system (36). Thyroid tissue contains proteins that may share structural similarities with components of gluten. When antibodies generated against gluten proteins encounter these thyroid proteins, they may mistakenly recognize them as foreign, and an immune response against the thyroid tissue is initiated, a concept known as molecular mimicry. This can lead to chronic inflammation and damage to the thyroid gland, contributing to the development or exacerbation of autoimmune thyroid conditions. (1)
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The gastrointestinal tract should serve as a physical barrier separating the body from the contents of the digestive tract. This barrier plays a crucial role in preventing harmful substances, such as pathogens and toxins, from entering the bloodstream. In both celiac disease and NCGS, the ingestion of gluten can trigger the release of zonulin, a protein that modulates the tight junctions between cells in the intestinal lining. An increase in zonulin production can promote intestinal permeability, often referred to as "leaky gut”, allowing the entry of unwanted substances into the bloodstream that lead to the immune system increasing inflammatory responses (7, 28, 85). This heightened inflammatory state is significant in the context of thyroid health because increases in inflammation and oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and antioxidants, have been linked to various thyroid diseases. Notably, the thyroid gland, in its natural synthesis of thyroid hormones, produces ROS. This heightened metabolic activity renders the thyroid particularly susceptible to damage from oxidative stress (44).
The immune response triggered by gluten ingestion in celiac disease may lead to inflammation and damage to the small intestine, reducing the surface area available for nutrient absorption (5). This malabsorption can result in insufficient absorption of essential nutrients crucial for thyroid function. Nutrients that play important roles in thyroid hormone production and metabolism, immune system regulation, and antioxidant protection include iodine, selenium, zinc, iron, and vitamin D (37, 66).
Diagnosing Thyroid Conditions in Patients with Celiac Disease and Gluten Sensitivity
Thyroid function should be assessed in all patients with celiac disease at the time of diagnosis and later in follow-up if clinical indications arise (9). Symptoms that indicate possible thyroid dysfunction include fatigue, weight changes, bowel changes, temperature sensitivity, skin and hair changes, mood changes, menstrual irregularities, swelling in the neck (goiter), heart rate changes, and sleep disturbances (35).
Traditionally, TSH is used to diagnose hypothyroidism and hyperthyroidism. However, TSH alone might miss about 7% of cases of thyroid dysfunction. During the initial phase of autoimmune thyroid disease, signs and symptoms of thyroid disease may be absent and TSH can fall within normal limits, but anti-TPO antibodies can be positive. Thyroid function can worsen over time in autoimmune thyroid conditions, so early recognition of this immune response can be beneficial (41).
A complete thyroid panel measures T4, T3, free T4, free T3, and thyroid antibodies in addition to TSH. The inclusion of these markers facilitates a thorough assessment of various aspects of thyroid health, including total thyroid hormone production, the efficiency of T4 conversion into T3, the availability of free or bioavailable hormones, and the potential presence of an autoimmune thyroid condition.
In patients with enlarged thyroids or palpable nodules, as well as patients with autoimmune thyroid diseases, thyroid imaging might be ordered. Several types of imaging studies are available to assess thyroid function, including ultrasound, computed tomography (CT), and uptake scans.
Additional Functional Medicine Labs to Consider
Functional medicine labs can be ordered in patients with gluten-related disorders to further assess nutrient status, gut health, and inflammation.
Comprehensive Stool Analysis
Dysbiosis, an imbalance in the gut microbiome composition, has been associated with celiac disease, NCGS, and autoimmune thyroid diseases. Genova's GI Effects is a stool test that provides detailed insights into various aspects of gastrointestinal function, including microbiome composition, digestive function, and inflammation.
Intestinal Permeability
Precision Point’s Advanced Intestinal Barrier Assessment evaluates three markers associated with intestinal barrier dysfunction. Zonulin is a protein that triggers tight junctions to open, low levels of diamine oxidase (DAO) relate to the thickness of the gut lining, and lipopolysaccharides (bacterial endotoxins) antibodies elevated with increased intestinal permeability.
Micronutrient Panel
SpectraCell’s Micronutrient Test measures 31 different vitamins, minerals, and nutrients to identify nutritional insufficiencies. By analyzing intracellular levels, it evaluates how well the body is absorbing and utilizing nutrients at the cellular level.
Inflammation & Oxidative Stress
Systemic inflammation can be seen as a consequence of poor gut health and can promote thyroid dysfunction (53, 54). C-reactive protein (CRP) is a commonly used marker to assess and monitor inflammation. The liver produces CRP in higher amounts in the presence of inflammation.
Precision Point’s Advanced Oxidative Stress test measures % Reduced glutathione, oxidized glutathione, and total glutathione. It also measures 8-OHdG, a modified nucleoside and a biomarker for oxidative damage to DNA, and F2-isoprostanes, prostaglandin-like compounds that are formed through the peroxidation of arachidonic acid. Glutathione is an important antioxidant. GSH is the reduced form of glutathione that neutralizes ROS, becoming oxidized to GSSG during the process of neutralization. Assessing the levels of reduced glutathione, oxidized glutathione, and total glutathione, along with calculating the GSH/GSSG ratio, provides a comprehensive understanding of the redox status within cells (57).
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The Role of Medication and Thyroid Hormone Replacement Therapy
The medication management of hyperthyroidism and hypothyroidism involves distinct approaches to address abnormal thyroid function. In hyperthyroidism, anti-thyroid medications like methimazole or propylthiouracil are commonly prescribed. Conversely, hypothyroidism is typically managed with thyroid hormone replacement therapy, most commonly using the medication levothyroxine. As a synthetic form of the thyroid hormone T4, levothyroxine aims to supplement deficient thyroid hormones. Regular follow-up appointments are necessary to monitor thyroid function and make adjustments as needed (38, 39).
For patients with celiac disease or gluten sensitivity, additional considerations come into play. Some thyroid medications may contain gluten as an inactive ingredient. It is important for individuals with gluten-related disorders to carefully scrutinize medication labels and opt for gluten-free formulations (40). Moreover, celiac disease can impact absorption, potentially influencing the effectiveness of thyroid medications. Individuals with malabsorption issues may require higher doses of thyroid hormones or alternative formulations (23, 63). Regular monitoring of thyroid function and nutrient levels is essential for optimizing treatment outcomes (27, 61, 62).
Dietary Management and Nutritional Support
Therapeutic diets and strategic dietary recommendations play an important role in both managing celiac disease and NCGS as well as supporting optimal thyroid function. The cornerstone of treatment for celiac disease is a gluten-free diet, addressing the autoimmune response triggered by gluten. In patients with both celiac disease and NCGS, GF diets also help to modify the composition of the microbiome, reducing proinflammatory microorganisms (4). Switching to a GF diet can create difficulty in maintaining a balanced intake of both macro and micronutrients. GF diets have been observed to have lower intakes of fiber and important vitamins like D, B12, and folate, as well as minerals including iron, zinc, magnesium, and calcium. Furthermore, the quality of food choices is sometimes poor, resulting in higher intakes of saturated fats, and hydrogenated fats, as well as foods with higher glycemic loads (80). When switching to a GF diet, careful dietary planning and nutrient-conscious choices are necessary, emphasizing nutrient-dense whole foods, including fruits, vegetables, lean proteins, and gluten-free grains, like quinoa, to provide optimal nutrition.
In conjunction with gluten avoidance, incorporating specific nutrients can help to support thyroid function. Iodine, found in iodized salt, seaweed, and seafood, is critical for thyroid hormone synthesis, while selenium, abundant in Brazil nuts, seafood, and poultry, supports hormone conversion and acts as an antioxidant. Zinc, found in meat, nuts, seeds, and legumes, plays a role in hormone production and immune function (37, 47, 50, 81).
Incorporating prebiotics, and non-digestible fibers, promotes the growth of beneficial microorganisms in the gut. Sources of prebiotics include foods like garlic, onions, leeks, bananas, and asparagus. Probiotics, live beneficial bacteria, found in fermented foods like yogurt, kefir, sauerkraut, and kimchi, can also positively influence the gut microbiota. Diverse and plant-rich diets, such as the Mediterranean diet for example, have been associated with more favorable gut microbiome profiles (55). These diets emphasize fruits, vegetables, whole grains, and legumes, providing a variety of fibers and nutrients that support a healthy microbial balance.
Lifestyle Modifications and Stress Management
The World Health Organization (WHO) ranks physical inactivity as the 4th leading cause of mortality. More than 80% of adolescents and 27% of adults do not meet WHO’s recommended levels of physical activity. Sedentary behavior is associated with an increased risk of autoimmune diseases and worse thyroid function than in active individuals(64, 84). Exercise can positively modulate the microbiome in celiac disease and other chronic inflammatory diseases (22, 82). The WHO recommends at least 150 minutes of moderate-intensity aerobic activity per week, spread over at least three days, along with two or more sessions of resistance training per week.
The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that plays an important role in orchestrating the body’s response to stress and the regulation of various physiological processes. Under stress, the HPA axis is activated, ultimately resulting in the release of cortisol from the adrenal glands. Chronic stress, characterized by prolonged elevation of cortisol levels, can impact thyroid function. Stress is associated with adverse changes to gut health, including increased intestinal permeability and dysbiosis. Mind-body practices, like mindfulness, breathing, yoga, and biofeedback, stimulate the body’s parasympathetic nervous system to restore balance to the neuroendocrine system.
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Thyroid Health for Those with Celiac and Gluten Sensitivity: Final Thoughts
Managing celiac disease and gluten-related disorders should include a holistic, patient-centered approach in which the important relationship between the gut, immune system, and thyroid is considered. This comprehensive approach incorporates advanced testing to evaluate thyroid and gut health, dietary and lifestyle recommendations, and proper medication management.
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