Graves' disease is an autoimmune disorder where the immune system attacks the thyroid gland causing it to make more thyroid hormones than your body needs. The thyroid is a small, butterfly-shaped gland in the front of your neck that produces hormones to help regulate how your body uses energy.

With Graves' disease, the extra thyroid hormones can cause many bodily functions to speed up or become dysregulated. Thyroid hormones have wide-reaching effects throughout the body. So, signs and symptoms of Graves' disease can impact the whole body and include weight loss, fast or irregular heart rhythms, bulging eyes, fatigue, heat sensitivity, sleep disturbances, anxiety, and changes in bowel functions and menstruation.

Four out of five cases of hyperthyroidism in the United States are caused by Graves' disease. While this condition may affect anyone, it is most common among women and people younger than 40. Approximately 3% of women and 0.5% of men will develop Graves' disease during their lifetime. Overall, Graves' disease affects around 1 in 100 Americans.

A functional medicine approach to Graves' disease addresses potential sources of immune system triggers while working to balance thyroid function to control symptoms.

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What is Graves' Disease?

The thyroid gland is a small butterfly-shaped gland located in the front of your neck. It produces thyroid hormones that help to influence the way that the body uses energy and regulate many important bodily functions. Thyroid hormones travel throughout the body in the blood and influence body temperature, heart rate, growth, energy production, and brain health. Hyperthyroidism is a condition that results when the thyroid gland becomes overactive and produces too much thyroid hormone.

Graves' disease is an autoimmune disorder where the immune system mistakenly targets the thyroid gland, causing it to make more thyroid hormones than your body needs. Graves' disease is the leading cause of hyperthyroidism in the United States.

Symptoms of Graves' Disease

The extra thyroid hormones produced when the immune system attacks the thyroid gland in Graves' disease can cause many bodily functions to speed up and become dysregulated. Since thyroid hormones have wide-reaching effects throughout the body, signs and symptoms of Graves' disease can impact the whole body.

Common signs and symptoms of Graves' disease include:

• weight loss
• increased appetite and hunger
• fast or irregular heart rhythms
• tremors
• thick red skin on shins or feet (Graves' dermopathy)
• fatigue
• muscle weakness
• heat sensitivity, hot flashes, and sweating
• sleep disturbances and insomnia
• anxiety and irritability
• changes in bowel habits like frequent stools, loose stool, or diarrhea
• changes in the menstrual cycle
• reduced sex drive
• reduced bone density and osteoporosis
• bulging eyes (Graves' ophthalmopathy)

When too high levels of thyroid hormones are released into the blood, your metabolism speeds up, causing the body to burn through energy and nutrients too quickly. This can result in malnutrition and a wide range of problems.

Around 30% of people with Graves' disease have eye involvement, usually in the form of Graves' ophthalmopathy. This condition results from inflammation and a buildup of certain carbohydrates in the muscles and tissues around the eyes. It leads to symptoms such as:

• eye bulging
• pressure behind the eyes
• a gritty sensation in the eyes
• light sensitivity
• vision changes

Symptoms of Thyroid Storm

Thyroid storm (accelerated hyperthyroidism or thyrotoxic crisis) is a rare but serious complication of Graves' disease. In this condition, a sudden and drastic increase in thyroid hormones causes an increase in metabolism. This can result in

• fever
• sweating
• vomiting
• diarrhea
• delirium
• severe weakness
• seizures
• irregular heartbeat
• yellow skin and eyes (jaundice)
• severe low blood pressure
• coma without appropriate care

What Causes Graves' Disease?

Thyroid function is normally regulated to stay within a range that allows the body to keep metabolism and other functions balanced. This balance is orchestrated by a complex interplay of signals coordinated by the brain and interacting with several nutrients and other hormones.

The hypothalamus in the brain is responsible for managing hunger, thirst, sleep, hormones, and body temperature and monitors the level of thyroid hormone in the blood. When it detects the need for increasing metabolism and energy, it releases thyroid releasing hormone (TRH) to signal the pituitary gland at the base of your brain to release thyroid stimulating hormone (TSH), also known as thyrotropin.

TSH acts directly on the thyroid, stimulating it to produce and release thyroid hormones, including:

• T4, a storage form of thyroid hormone that circulates throughout the blood and is stored in tissues for when it is needed
• T3, the active form of thyroid hormone

Autoimmunity

In Graves' disease, the immune system mistakenly produces antibodies that target the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, where TSH normally binds to stimulate the production and release of thyroid hormones. These autoantibodies (thyroid stimulating hormone receptor antibody (TSHR Ab), also known as thyrotropin receptor antibody (TRAb)) mimic TSH from the pituitary gland and activate the TSHR receptor on cells in the thyroid. This leads to an overactive thyroid gland, hyperplasia or growth of the gland (goiter), and increased thyroid hormone secretion.

The TSHR autoantibodies also act on receptors on the surface of cells in tissues surrounding the orbits where the eyes sit, leading to inflammation, edema, and fibrosis, creating Graves' ophthalmopathy.

Some main factors contributing to autoimmunity and the development of Graves' disease include genetics, imbalances in gut health, nutrition, infections, and environmental exposures.

Genetics

Several immune-related genes increase the susceptibility to developing Graves' disease. Environmental or epigenetic factors interact with this genetic susceptibility to influence whether someone develops this condition.

People with other autoimmune diseases, such as type 1 diabetes, celiac disease, or rheumatoid arthritis, also have an increased risk of developing Graves' disease.

Environmental Factors

There are several environmental factors associated with developing the autoimmunity which underlies Graves' disease, such as:

• endocrine disrupting chemicals
• heavy metals
• smoking
• emotional or physical stress
• radiation exposure
• viral or bacterial infections

Past or ongoing exposures to heavy metals (mercury, arsenic, cadmium), solvents, plastics, or pesticides contribute to imbalanced gut bacteria (dysbiosis), inflammation, and autoimmunity. They harm the body's detoxification, digestive, nervous, and endocrine systems. Certain chemicals such as fluoride and bromine in municipal water supplies, flame retardants, and some baked goods can directly compete with iodine in the thyroid gland, impacting its functioning.

Smoking is related to an increased risk of Graves' hyperthyroidism, worsening of Graves' ophthalmopathy, and relapse.

Emotional and physical stress is implicated in the onset of Graves' disease and impacts treatment success. When stress hormones like cortisol and catecholamines are chronically elevated, they can affect the immune system and contribute to the development of autoimmunity.

External radiation also impacts the thyroid gland and can lead to Graves' disease. For example, Graves' may occur after radioiodine treatment of toxic goiter.

Viruses like herpes simplex virus (HSV), rubella, mumps, and Epstein–Barr (EBV) activate the immune system and may trigger autoimmune thyroid disease. Some pathogens, like Yersinia enterocolitica and Helicobacter pylori, can mimic parts of your own tissues and lead to cross-reactivity that triggers autoimmunity.

Gut Health

The digestive tract is a primary barrier to the outside world and a critical immune system mediator. The health of the gut and microbiome has a significant impact on the immune system and inflammation.

Imbalances in intestinal microbes (dysbiosis) and a leaky gut barrier are major risk factors for autoimmunity. The microbiome can become imbalanced, and the gut lining can become damaged and leaky from chronic exposures to toxicants, inflammatory foods such as gluten or lectins, and chronic stress. When the barrier becomes ineffective, substances can enter the body and trigger inflammation and autoimmune responses, contributing to Graves' disease risk.

Functional Medicine Labs to Test for Root Cause of Graves' Disease

Functional medicine testing can diagnose Graves' disease and help to identify the underlying causes. This includes assessing the functioning of the thyroid, measuring autoantibodies, looking at radioactive iodine uptake or thyroid nodules, and evaluating factors that play a role in immune system function to uncover the causes of the autoimmunity leading to Graves' disease.

Thyroid Function and Autoantibodies

To assess the state of thyroid function, a complete Thyroid Panel including thyroid-stimulating hormone (TSH), T3 (free and total), T4 (free and total), and reverse T3 should be assessed using functional medicine ranges.

• TSH measures how the pituitary gland in the brain is communicating with the thyroid and is indicative of hyperthyroidism when decreased.
• Free T4 measures the bioavailable or unbound thyroid hormone and is a marker of increased thyroid function when elevated.
• In the peripheral tissues, T4 is converted to T3. An elevated level of T3 can indicate increased thyroid function.
• In addition, thyroid antibody testing for thyrotropin receptor antibody (TRAb) can help diagnose Graves' disease.
• Some patients with Graves' will also develop Thyroid Peroxidase (TPO) antibodies or antithyroglobulin antibodies, although typically, these antibodies are more commonly associated with Hashimoto's hypothyroidism.

Gut Health

Since dysbiosis, leaky gut, and inflammation are key factors in developing autoimmunity, like Graves' disease, assessing gut health can help provide targeted interventions. A Comprehensive Stool Test measures amounts of healthy and unbalanced gut bacteria (dysbiosis), inflammatory markers, leaky gut, parasites, and yeast to assess the state of the gut and guide treatment aimed at restoring balance.

Additional testing for gluten sensitivity or celiac disease with Genova Diagnostics' Celiac Profile and the evaluation of the leaky gut marker, zonulin, can also help to guide treatment.

Food sensitivities can contribute to increased intestinal permeability, inflammation, and autoimmunity. ELISA testing can identify food sensitivities in individuals.

Pathogens

Since bacterial and viral pathogens can trigger autoimmunity leading to Graves' disease, testing can help target interventions to illuminate infections.

For example, stool antigen testing for H. pylori can help evaluate whether this pathogen is contributing to Graves' disease and can provide insights into antibiotic resistance genes to guide treatment protocols.

The EBV Panel from Immunosciences Lab measures antibodies to various components of the Epstien-Barr virus. This virus triggers autoimmunity due to molecular mimicry or cross-reactivity between EBV antigens and human tissue proteins.

Micronutrient Testing

A Cellular Micronutrient Assay can measure nutrients that support thyroid health, including Vitamin D, iron, iodine, zinc, and selenium.

Factors that Influence Detoxification

Methylation, detoxification capacity, and glutathione production can be assessed with specialized labs. They are all useful for understanding an individual's genetic susceptibilities and detoxification capacity, which contribute to autoimmunity risk. These tests help pinpoint areas in the body that can be supported to bring the body and hormones back into balance.

Other Lab Test to Check

Radioactive Iodine Uptake (Raiu)

RAIU uses a small dose of radioactive iodine (I-131) to look at how much iodine the thyroid takes up and in what pattern. A high iodine uptake is indicative of Graves' disease.

Ultrasound (Us)

US of the thyroid can help rule out other possible causes of an overactive thyroid. This type of imaging uses high-frequency sound waves to see if the thyroid is enlarged. It can look for nodules on the thyroid, which occur in a toxic multinodular goiter, another form of hyperthyroidism. These nodules stimulate the thyroid without using TSH, overriding the system and causing an overactive thyroid.

Conventional Treatment for Graves' Disease

There are three main conventional approaches for the treatment of Graves' disease:

• anti-thyroid drugs
• radioactive iodine
• surgical thyroidectomy

Anti-thyroid drugs like propylthiouracil (PTU) and methimazole (MMI) interfere with the production of thyroid hormones by blocking the thyroid's use of iodine to produce hormones. They require careful monitoring for side effects and to avoid overcorrection and hypothyroidism.

Large doses of radioactive iodine (I-131) are sometimes used in hyperthyroidism to destroy thyroid gland cells permanently. After the thyroid gland is destroyed, synthetic thyroid medication is used to replace normal hormone levels.

In some cases, partial thyroidectomy or surgical removal of part of the thyroid gland is used. After the surgery, treatment is generally needed to supply the body with normal amounts of thyroid hormones.

Functional Medicine Treatment for Graves' Disease

Rebalance The Gut

Since the gut microbiome has such a significant impact on the immune system and dysbiosis is closely related to the development of Graves' disease, maintaining diverse and balanced bacteria in the gut can help tame autoimmunity.

Restoring equilibrium in the gut microbiota is critical for repairing the mucosal barrier and halting excess inflammation and autoimmunity that can harm thyroid function. The best way to restore the microbiome is by eating a variety of real whole foods and incorporating probiotic-rich foods, like kimchi and sauerkraut that contain naturally-occurring probiotics and prebiotic-rich foods, like artichokes and garlic that nourish healthy bacteria.

Probiotics containing Bifidobacterium longum bacteria have been shown to improve thyroid function in Graves' disease by helping to balance the gut-thyroid axis.

Address Pathogens

Treating pathogens and infections like H. pylori, parasites, or viruses like EBV can also help rebalance the microbiome and tame autoimmunity.

An Individualized Anti-Inflammatory Diet

Diet has a significant influence on the microbiome and overall inflammation levels. Therefore, a nutrient-rich, anti-inflammatory organic diet tailored to an individual's sensitivities and needs can help balance inflammation and tame autoimmunity. Eliminating individual trigger foods, such as gluten and other grains, dairy, soy, processed sugars, and inflammatory fats and balancing the intake of micronutrients like vitamin A, zinc, vitamin D, omega-3 fatty acids, and selenium can help to counteract inflammation and prevent nutrient deficiencies.

While iodine is a mineral that the thyroid uses to make thyroid hormones, too high iodine intake, which can come from too much refined iodized salt in processed foods or excessive consumption of seaweeds, can negatively affect thyroid functioning.

Caffeine and alcohol can aggravate symptoms of Graves' disease, like anxiety and rapid heart rate, so they should be avoided.  

Manage Stress

High levels of chronic stress contribute to inflammation and autoimmunity. Finding balance via lifestyle practices like adequate quality sleep, stress management practices, and balanced movement can improve thyroid and overall health.

Restorative exercises such as yoga, walking, and Qi gong are generally more helpful for balancing inflammation than overly intense exercise. Spending calm time in nature can also reduce inflammation by providing exposure to natural sunlight to optimize vitamin D and contact with the earth.

Stop Smoking

Since smoking increases the risk of autoimmunity, Graves' thyroid disease, and Graves' ophthalmopathy, stopping or avoiding smoking is important for successful treatment.

Reduce Toxicity

Chemicals in plastics, pesticides, heavy metals, and other pollutants can disrupt thyroid function and gut microbes. You can reduce your exposure to these chemicals by using high-quality water and air filters, choosing organic produce, and assessing other exposures such as plastic use and metal dental amalgams.

Thyroid-Suppressing Supplements

Some supplements may suppress thyroid function and help reduce the overactive metabolism symptoms.

L-carnitine blocks the effects of thyroid hormones in many peripheral tissues so that it is not able to act. While L-carnitine does not impact thyroid hormone levels, it is effective in reversing and preventing many symptoms of hyperthyroidism, like an elevated heart rate, nervousness, and insomnia.

Selenium reduces inflammation and helps degrade oxidants that can damage the body. It has been shown to reduce autoantibodies in Graves' disease. It can also help to decrease eye complications associated with Grave's disease.

Herbs, including bugleweed and lemon balm, can reduce the symptoms of hyperthyroidism in Graves' disease by blocking TSH and lowering thyroid hormone production.

Common fenugreek seed, sevenlobed yam rhizome, Prunella vulgaris L, Gynostemma pentaphyllum, and Astragalus mongholicus Bunge are often used in Traditional Chinese Medicine. They show promise in reducing the growth and overstimulation of the thyroid and inhibiting the fibrotic changes that can occur around the eyes in Graves' disease.

Another phytonutrient that addresses the increased oxidative stress that occurs with overactive thyroid hormones is resveratrol.  

Summary

Graves' disease is the most common form of hyperthyroidism, or an overactive thyroid, in the United States. This autoimmune condition results when the body produces antibodies that target the TSH receptor, mimicking the binding of thyroid-stimulating hormone and causing the thyroid gland to overproduce hormones.

Thyroid hormones travel throughout the body, stimulating metabolism and influencing many bodily functions such as temperature and heart rate. Therefore, Graves' can cause a wide range of signs and symptoms, such as weight loss, increased appetite, rapid heart rate, anxiety, sweating, frequent bowel movements, sleep disturbances, and bulging eyes (Graves' ophthalmopathy).

Like many autoimmune conditions, Graves' disease is triggered by exposure to certain environmental factors in an individual with a genetic predisposition. Imbalances in the microbiome, a leaky gut barrier, stress, smoking, and certain types of infections can increase the risk of developing Graves'.

Blood tests can measure levels of thyroid hormones and the presence of antibodies. A low TSH indicates that the thyroid is producing too much hormone.

A functional medicine approach to Graves' disease aims to bring the thyroid back into balance and prevent complications. Functional laboratory testing can help uncover contributing factors like dysbiosis of gut bacteria. Dietary and lifestyle interventions can then target these causes of autoimmunity and excess inflammation to rebalance the gut, manage chronic stress, and bring the body back into balance.