The recurring nature and worsening of the disease greatly affects quality of life. Left untreated, Graves’ disease can lead to severe complications, including heart problems and a potentially fatal condition known as thyroid storm.

Conventional treatments have changed little over the past 70 years and come with significant trade-offs. These treatments can result in an underactive thyroid or complete loss of thyroid function, typically requiring lifelong medication.

Graves’ disease can cause many different signs and symptoms throughout the body because thyroid hormones affect numerous bodily functions. These hormones control metabolism, heart rate, body temperature, brain development, and bone health. Since nearly every cell has thyroid hormone receptors, excessive hormone production can influence multiple body systems. Additionally, the thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Abs) responsible for overstimulating the thyroid can affect other tissues.

The presentation of these symptoms can vary depending on factors such as age, severity, and duration of the condition. For instance, older adults may experience more subtle or non-specific symptoms like fatigue, weight loss, or new-onset atrial fibrillation (a type of irregular heartbeat). Common signs and symptoms include the following:

• Bulging eyes with decreased blinking
• Thin hair or skin
• Tremors, particularly in the hand
• Muscle weakness (myopathy)
• Visible neck swelling due to an enlarged thyroid (goiter)
• Difficulty swallowing or voice changes
• Rapid, fluttering, or irregular heartbeat
• Shortness of breath (dyspnea)
• Restlessness or insomnia
• Accelerated reflex responses
• Rapid and intense mood changes
• Nervousness, anxiety, or irritability
• Accelerated bone maturation with decreased density and increased fracture risk
• Decreased cholesterol levels
• Frequent bowel movements or diarrhea
• Increased sensitivity to heat and excessive sweating
• Unintentional weight loss despite increased appetite
• Irregular menstrual cycles for women
• Decreased libido in men

Graves’ disease happens when the immune system makes antibodies that bind to receptors on the thyroid gland. These antibodies, known as TSH-R-Abs, mimic TSH and stimulate the gland to overproduce two key thyroid hormones: triiodothyronine (T3), the more potent and bioactive form, and thyroxine (T4), which can be converted to T3. This overproduction leads to decreased secretion of TSH from the pituitary gland, an increase in thyroid cell growth, and an enlarged thyroid gland.

The cause of Graves’ disease is complex. It involves a combination of genetic predisposition, immune dysregulation, gut health, nutritional factors, and environmental factors. Those with a family history of thyroid or other autoimmune conditions are at higher risk, suggesting genetics play a role. However, genetics alone do not determine who will develop the disease. Environmental factors can influence gene expression through a process called epigenetics.

Environmental Factors

Various environmental factors have been linked to Graves’ disease, including:

• Chronic stress
• Negative life experiences
• Radiation exposure
• Heavy metals
• Environmental toxins like some pesticides, polychlorinated biphenyls (PCBs), and Agent Orange
• Viruses such as Epstein-Barr, SARS-CoV-2, human immunodeficiency virus (HIV), and hepatitis C
• Bacterial infections, including Yersinia enterocolitica and Helicobacter pylori
• Medications, such as antibiotics, amiodarone used for heart rhythm disorders, and antivirals used to treat HIV, hepatitis C, and some cancers
• Iodine-containing contrast agents used for imaging
• Hormonal factors (particularly estrogen and progesterone)
• High-fat, high-sugar diet

Gut Health

Research has highlighted the important role of gut health in the development of Graves’ disease. The gut is home to trillions of microbes, collectively called the gut microbiome. These microbes play a major role in immune system regulation. Evidence supporting the microbiome’s role includes findings that antithyroid drugs can change the microbiota composition.

Gut bacteria can also influence the absorption of minerals important for thyroid function. Along with dysbiosis, a leaky gut can contribute to inflammation throughout the body and disrupt normal immune function. Over time, this heightened immune activity may lead to the development or worsening of autoimmune conditions, including Graves’ disease.

Nutritional Factors

Nutritional deficiencies may contribute to the development or worsening of Graves’ disease. The increased metabolism associated with the condition raises the body’s demand for various nutrients, which can lead to deficiencies. Additionally, hyperthyroidism can cause the body to break down both muscle and fat. Potential deficiencies include:

• Vitamins: A, B1, B6, B12, C, and D
• Minerals: Magnesium, selenium, and zinc
• Other essential nutrients: Protein, essential fatty acids, choline, and Coenzyme Q10.

In addition to these potential deficiencies, other nutritional factors play a role in Graves’ disease, such as:

• Iodine: While iodine is essential for thyroid function, excess can trigger or exacerbate autoimmune thyroid conditions in susceptible individuals.
• Salt: Research has shown a potential link between high salt intake and autoimmune diseases. High salt levels can stimulate the production and activation of Th17 immune cells, which are associated with inflammation and autoimmune processes.
• Gluten: Found in wheat, barley, rye, and contaminated oats, gluten is the autoimmune trigger in celiac disease, which often co-occurs with Graves’ disease. Studies also suggest a link between Graves’ disease and non-celiac gluten sensitivity. Eliminating gluten may benefit some individuals with Graves’ disease by reducing inflammation and intestinal permeability.

Vaccine-Induced Graves’ Disease

Numerous case reports and case series have linked vaccines to the onset or relapse of Graves’ disease. In a recent review of 62 cases of COVID-19 vaccine-induced Graves’ disease, 76 percent were new-onset cases, and 24 percent were relapsed cases. In reports regarding the COVID-19 vaccines, the new-onset Graves’ disease cases often occurred within days, and the vast majority emerged within four weeks of vaccination. These instances were seen with the first and subsequent doses of the vaccine and with various types of it.

The induction of autoimmune thyroid disease has been reported with other vaccines, such as influenza vaccines, prior to the COVID-19 vaccine rollout.

Proposed mechanisms for vaccine-induced autoimmunity include:

• Molecular mimicry/cross-reactivity: This occurs when components of the vaccine resemble human proteins, causing the immune system to attack both.
• Immune system upregulation: Vaccines can overstimulate the immune system to produce pro-inflammatory cytokines, which may contribute to autoimmune responses.
• Autoantibody generation: Vaccines may trigger the production of autoantibodies in susceptible individuals.
• ASIA syndrome: Vaccines often include adjuvants, substances that enhance the body’s immune response. Examples of adjuvants include aluminum salts, polyethylene glycol, and polysorbate 80. Some vaccines, like mRNA vaccines, use lipid nanoparticles as a delivery system, which may have some immunostimulatory properties. A proposed and controversial condition called autoimmune/inflammatory syndrome induced by adjuvants (ASIA) suggests that these components may trigger autoimmunity in some individuals.

Graves’ disease is one of several causes of hyperthyroidism. While it is a distinct condition and does not have subtypes, Graves’ disease can manifest in various ways, affecting different parts of the body. The TSH-R-Abs that bind to receptors on the thyroid gland can interact with similar receptors in other tissues, particularly in the eyes and skin. This phenomenon, known as molecular mimicry, explains why Graves’ disease can manifest outside the thyroid.

The primary types of manifestations include:

• Thyrotoxicosis: This is the most common manifestation of Graves’ disease and refers to an excess of thyroid hormones in the body, presenting with symptoms such as rapid heartbeat, weight loss, and anxiety.
• Graves’ orbitopathy or ophthalmopathy (GO): In some patients, Graves’ disease affects the eyes, causing symptoms like bulging eyes (exophthalmos), dryness, irritation, and, in severe cases, vision problems. This condition can also include the “thyroid stare,” where the eyes appear more prominent.
• Graves’ dermopathy: This is a less common manifestation in which the skin, usually on the shins and feet, becomes thick, red, and rough. It is also known as pretibial myxedema.
• Thyroid acropachy: In this rare form, swelling and clubbing of the fingers and toes occur.

In addition to the potential causes mentioned previously, these factors increase the likelihood of developing Graves’ disease:

• Sex: Females are up to 10 times more likely than males to develop the disease.
• Age: While Graves’ disease can occur at any age, it is more frequent between 30 and 60 years of age.
• Ethnicity: African Americans have an increased incidence.
• Family history: Having relatives with Graves’ disease increases the risk. It is estimated that genetic factors account for 60 percent to 80 percent, with environmental factors contributing the remainder.
• Autoimmunity: Having one autoimmune disorder increases the risk of developing others. One study found that about 17 percent of those with Graves’ disease have at least one associated autoimmune condition, such as vitiligo, rheumatoid arthritis, celiac disease, or Type 1 diabetes.
• Smoking: Using products containing nicotine, such as cigarettes, increases the risk of developing Graves’ disease and its recurrence. Smokers with Graves’ disease are also more likely to develop GO compared to nonsmokers with the condition.

Diagnosing Graves’ disease involves a multistep process.

If antibodies are negative or nodules are present, imaging may be necessary. An ultrasound, which does not require radiation exposure, is one option. Alternatively, a thyroid scintigraphy, also known as a radioactive iodine uptake test or gamma scan, can help distinguish Graves’ disease. This test involves swallowing a small amount of radioactive iodine and using a special camera to see how much iodine the thyroid absorbs. In Graves’ disease, the thyroid typically appears brighter because it absorbs more iodine than usual.

Comprehensive Functional Medicine Assessment

While conventional practitioners focus on confirming Graves’ disease, functional medicine practitioners take a broader approach. They conduct a thorough assessment to find root causes and factors contributing to the autoimmune process. This involves exploring gut health as well as environmental and nutritional factors.

This comprehensive assessment may include additional tests tailored to each patient’s unique history and symptoms. Not all of these will be necessary for every patient, but they may include:

• Comprehensive stool analysis
• Hormone panel
• Chronic infection screening
• Micronutrient testing
• Vitamin D testing
• Celiac disease screening
• Food sensitivity testing
• Organic acid testing
• Environmental toxin testing
• Heavy metal testing

Graves’ disease, if left untreated or poorly managed, can lead to several serious complications, including:

• Thyroid storm: This is a severe, life-threatening form of thyrotoxicosis characterized by extremely high thyroid hormone levels. It can cause high fever, rapid heart rate, dehydration, and even organ failure, and requires immediate medical attention.
• Cardiovascular issues: Graves’ disease can lead to serious heart problems, including atrial fibrillation, high blood pressure, and, in severe cases, heart failure.
• Bone problems: Long-term untreated hyperthyroidism can lead to osteoporosis, increasing the risk of fractures.
• Eye problems (Graves’ orbitopathy): GO affects about 40 percent of people with Graves’ disease. In severe complications, it can double vision and vision loss.
• Thyrotoxic myopathy: Excessive thyroid hormone levels can cause thyrotoxic myopathy, a condition characterized by significant muscle weakness and wasting. This condition involves abnormal cellular metabolism of potassium and can generally be resolved with supplemental potassium.
• Pregnancy complications: Graves’ disease during pregnancy presents risks for both mother and baby. Women may experience an increased risk of pregnancy loss, premature birth, preeclampsia (high blood pressure), and thyroid storm. The baby may experience low birth weight, restricted growth, and potential developmental issues. Ideally, women should receive treatment and have their thyroid function normalized before becoming pregnant.
• Goiter complications: While a goiter is a common symptom, severe enlargement can cause difficulty swallowing or breathing.
• Mental health issues: Graves’ disease often comes with mental health disorders, such as anxiety, depression, and cognitive impairment. These issues may continue even after thyroid levels are treated and normalized.
• Long-term thyroid function changes: Interestingly, Graves’ disease and Hashimoto’s thyroiditis (hypothyroid) can occur together, though this is rare. More commonly, 15 percent to 20 percent of cases shift from Graves’ disease to Hashimoto’s thyroiditis at some point after treatment.
• Pancytopenia: Graves’ disease has been linked to pernicious anemia, an autoimmune vitamin B12 deficiency. In rare cases, this can lead to pancytopenia, a reduction in red and white blood cells and platelets, causing severe anemia and other complications. Additionally, antithyroid drugs used to treat Graves’ disease can also cause pancytopenia as a rare side effect. Treatment with vitamin B12 can resolve pancytopenia caused by pernicious anemia.

Conventional treatments for Graves’ disease include drugs to manage symptoms and methods to correct the hyperthyroid state. Each has advantages and disadvantages. These treatments may not help GO and do not stop the autoimmune process or address what is causing the disease.

1. Beta-Adrenergic Blockers

Beta blockers are used in moderate to severe cases or a thyroid storm to quickly reduce blood pressure and relieve some of the symptoms of hyperthyroidism like shaking, rapid heartbeat, and anxiety. These can be stopped once thyroid hormone levels are normalized.

2. Antithyroid Thionamide Drugs

Globally, antithyroid thionamide drugs (ATDs) are the preferred initial treatment for Graves’ disease for 12 to 18 months. These drugs prevent thyroid hormone production. Methimazole (MMI or MMZ) is generally the preferred ATD. Propylthiouracil (PTU), another ATD, is preferred over MMI during the first trimester of pregnancy. However, PTU is not recommended for children and adolescents due to potential liver toxicity.

Some advantages of using ATDs include the following:

• They do not adversely affect GO.
• Low-dose MMI may be used long-term and is encouraged in cases likely to achieve remission.
• They have a lower risk of causing hypothyroidism compared to other treatments.

Unfortunately, ATD treatment requires frequent monitoring and strict compliance. There is also a high relapse rate and risk of adverse events. In addition to allergic reactions, potential adverse events include:

• Agranulocytosis (dangerously low white blood cell count, increasing susceptibility to infections)
• Liver toxicity
• Vasculitis (inflammation of the blood vessels, which can damage organs and tissues)
• Pancreatitis
• Hair loss
• Aplastic anemia (failure of the bone marrow to produce sufficient red blood cells, white blood cells, and platelets)
• Thrombocytopenia (low platelet count, leading to increased risk of bleeding and bruising)

Treating Graves’ disease during pregnancy requires careful consideration. Both MMI and PTU can cross the placenta and affect the baby’s thyroid function. These drugs can also cause birth defects, especially during Weeks 5 to 10 of pregnancy. It is recommended that TSH-R-Abs be measured on all women with a history of autoimmune thyroid disease, including those who have had radiation or a thyroidectomy. Additionally, thyroid hormone levels should be monitored during pregnancy to help balance the treatment for the mother with the safety of the baby.

3. Radioactive Iodine

Radioactive iodine (RAI) may be used under the following circumstances:

• Hyperthyroidism is not resolved after taking ATDs for 12 to 18 months.
• Thyrotoxicosis recurs.
• The patient exhibits poor compliance in taking ATDs.
• ATDs cause side effects.

RAI destroys the thyroid gland, creating a hypothyroid state that requires taking thyroid hormones permanently. It is effective but slow-acting. Administered orally as a capsule or solution, it is suitable for outpatient treatment. Due to its high affinity, the thyroid quickly absorbs most of the radioactive iodine.

RAI is not recommended for:

• Active GO
• Increased risk of GO, such as in smokers
• Nodular goiter with suspected thyroid cancer
• Pregnancy
• Breastfeeding

It is recommended to defer RAI for three months after breastfeeding and to postpone pregnancy for 12 months.

Potential adverse events include:

• Severe thyrotoxicosis or thyroid storm
• Sialadenitis (inflammation of the salivary glands)
• Painful radiation thyroiditis
• Increased risk of certain cancers
• Negative impacts on female fertility and earlier menopause

4. Thyroidectomy

Surgery to remove some or all of the thyroid is a permanent way to stop thyroid hormone production. It quickly controls the overactive thyroid without radiation, usually without worsening GO. However, it results in permanent hypothyroidism, which requires taking thyroid hormones for life.

In addition to general surgical risks, thyroidectomy can result in:

• Laryngeal nerve injury, with consequential voice changes or hoarseness
• Hypoparathyroidism (low calcium levels due to damaged parathyroid glands)
• Hypocalcemia (temporary or permanent low blood calcium causing muscle cramps or tingling)

Managing Graves’ disease involves more than just medical treatment; mindset and stress management can play a role in the course of the disease. Stress can trigger Graves’ disease and worsen its symptoms. Although specific studies on epigenetics and Graves’ disease are limited, research on other autoimmune conditions provides useful insights. These studies show that stress can change how genes are expressed, which can have long-term effects on the body’s stress response.

Over half a century ago, Dr. Hans Selye’s pioneering research revealed the detrimental effects of stress on health. His work demonstrated how chronic stress can lead to hormonal imbalances and glandular disturbances, laying the foundation for our understanding of how stress affects the body. Selye showed that prolonged stress could lead to what he termed “diseases of adaptation.”

Recent research has built upon Selye’s work, finding that people with Graves’ disease often experience a high number of stressful life events before their diagnosis. When the body experiences stress, it activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to several changes that can exacerbate Graves’ disease, such as:

• Reduced production of TSH
• Release of stress hormones (glucocorticoids and catecholamines)
• Increased production of inflammatory cytokines

While stressful events may be uncontrollable, how we respond to stress is controllable and stress is largely about perception. Our mindset and interpretation of events are crucial in determining our stress response. In a small study of patients with stress-induced Graves’ disease, simply reducing stress led to remission without the need for antithyroid drugs.

Other research shows that people with a positive emotional style—being happy, lively, and calm—tend to have better health. This style is more about a positive mindset than just temporary feelings. Developing this positive emotional style could include practices like gratitude journaling, reframing negative thoughts, or regularly doing activities that bring joy and relaxation.

Thus, whether it is yoga, prayer, meditation, breathing practices, therapy, or exercise, it is important for those with Graves’ disease or at risk of it to find an effective stress-reduction technique. Being actively engaged in care is also associated with better health outcomes. Active engagement might include getting educated about the condition, asking questions during medical appointments, adhering to treatment plans, and making informed decisions in partnership with health care providers.

Natural or functional medicine approaches to Graves’ disease complement conventional treatments and go deeper into addressing the root causes that trigger the condition. This approach focuses on reducing inflammation and oxidative stress, restoring immune system balance, and suppressing the autoimmune process while preserving the thyroid.

Natural Supplements and Botanicals

Graves’ disease can be a serious condition that requires careful management. Therefore, it is essential to work with an integrative or functional medicine practitioner skilled in supplementation. He or she can determine which supplements, forms, and dosages are appropriate for your individual case. The following are some natural supplements that have been shown to reduce hyperthyroidism or its symptoms in Graves’ disease:

• L-carnitine: Research shows that L-carnitine can reduce and prevent symptoms of hyperthyroidism and increase bone mineral density. It works by inhibiting the entry of T3 and T4 into the cell nuclei and is useful in thyroid storm or when a lower dose of MMI is required. High doses may cause stomach upset or diarrhea. These results are not applicable to acetyl-L-carnitine, D-carnitine, or DL-carnitine.
• Selenium: Selenium supplementation may help achieve remission and enhance the effectiveness of ATDs. When combined with L-carnitine, one pilot study found that selenium reduced symptoms of hyperthyroidism and improved quality of life.
• Lemon balm (Melissa officinalis): Lemon balm extract can help manage hyperthyroidism by reducing thyroid hormone levels. In animal studies, it decreased oxidative stress and improved thyroid gland structure.
• Coenzyme Q10 (CoQ10): This potent anti-inflammatory agent and antioxidant is often low in people with hyperthyroidism. Preclinical research and small studies suggest proper supplementation can restore optimal levels and improve cardiac function within one week in those with hyperthyroidism.

The 5R’s Functional Medicine Approach

The 5R approach in functional medicine can be particularly beneficial in managing Graves’ disease. Even after RAI or thyroidectomy, most of these therapies can still benefit Graves’ disease and overall health. The steps involved in this approach include the following:

1. Remove: Treat infections, minimize exposure to toxins, and eliminate foods that cause inflammation, such as gluten, dairy, soy, ultra-processed foods, and sugars. Avoid factors that increase intestinal permeability, including alcohol, certain medications, and stressors. Avoid caffeine if it increases heart rate or anxiety.
2. Replace: Supplement digestive enzymes and essential nutrients that may be deficient. A broad-spectrum, high-potency multivitamin and mineral supplement can provide general nutritional support and antioxidants to combat oxidative stress. Balance hormones as indicated by testing. Because supplement quality can vary drastically, it’s important to ensure professional-grade quality or enlist a health care practitioner to help.
3. Reinoculate: Rebuild the gut microbiome with prebiotic and probiotic foods and supplementation based on stool analysis.
4. Repair: Use gut-healing nutrients like collagen peptides, glutamine, curcumin, zinc L-carnosine, vitamins A and D, and omega-3 fatty acids to protect and repair the gut lining and help reduce inflammation.
5. Rebalance: Make lifestyle modifications to reduce stress, prioritize sleep, increase movement, and improve work–life balance. Eat an anti-inflammatory, nutrient-dense diet rich in whole foods.

While there is no one-size-fits-all diet for Graves’ disease, anti-inflammatory diets such as the Paleo, autoimmune protocol (AIP), or Mediterranean diets may be helpful. What is inflammatory can vary by individual, so it is important to work with a nutrition professional to determine the best approach for you.

Focus on healthy fats like olive oil, avocados, and fatty fish like salmon. Avoid refined seed oils (like soybean, corn, and canola) and trans fats often found in processed foods.

While genetics plays a role in the development of Graves’ disease, other modifiable factors can trigger it. By addressing these factors, you can potentially lower your risk of triggering the condition. Even genetic predispositions can be influenced by epigenetic factors—environmental influences that can turn genes on and off—offering hope for prevention.

Here are some preventive measures to consider:

• Buy organic: Pesticides, herbicides, and some fertilizers used on conventionally grown crops have thyroid-disrupting properties. Widely used glyphosate, in particular, has been shown to disrupt the HPT axis by decreasing TSH concentrations and altering gene expression related to thyroid hormone transport and metabolism. It also alters gut microbiota.
• Avoid plastic containers: Bisphenol A (BPA), phthalates, and polybrominated diphenyl ethers (PBDEs) contaminate food through plastic containers and have thyroid-disrupting effects.
• Avoid other toxic chemicals: Brominated flame retardants and perfluorinated chemicals found in furniture, water-resistant clothing, and nonstick cookware have thyroid-disrupting effects.
• Invest in a good water filtration system: Water can be contaminated with perchlorate, nitrates, fluoride, and polychlorinated biphenyls (PCBs), which can disrupt thyroid function. Chlorinated water can also disrupt the gut microbiota.
• Consume omega-3 fatty acids: Consume foods rich in omega-3 fatty acids, or consider fish oil supplements. These have anti-inflammatory effects and may help prevent Graves’ disease in those exposed to endocrine disruptors.
• Maintain a healthy gut: A balanced gut microbiome and functional gut barrier play crucial roles in immune function and overall health. Eat a diverse, fiber-rich diet and consider probiotic foods or supplements to support gut health.
• Avoid smoking: Also avoid exposure to secondhand smoke.
• Moderate salt intake: Sodium is a necessary mineral, but high salt intake can drive inflammation and the autoimmune process. Avoid processed foods and use sea salt or Himalayan pink salt in moderation.
• Manage stress levels: Find healthy outlets for stress, such as yoga, meditation, qigong, or breathwork.