All You Need To Know About Graves’ Disease

Graves’ disease is an autoimmune disorder that causes hyperthyroidism or an overactive thyroid. Although hyperthyroidism can be caused by other conditions, Graves’ disease is the most common.

In Graves’ disease, your body’s immune system becomes dysregulated and attacks your thyroid gland. In turn, this causes your thyroid to produce excess thyroid hormone, which normally regulates your metabolism. Essentially, the thyroid hormone regulates how quickly the cells in your body work. 

If you have too much thyroid hormone, it increases the rate at which your cells work. So, a problem with your thyroid gland can have a huge impact on your whole body. 

Graves’ disease primarily affects the thyroid gland but also affects other organs, such as the eyes and the skin. 

Because thyroid hormones have an influence over many bodily functions, you may experience symptoms ranging from tremors to diarrhea, to heat intolerance. 

Anyone can develop Graves’ disease, but women are more likely to be affected than men. 

In fact, women are approximately four times more likely to be diagnosed with Graves’ disease than males. 

Graves’ disease is most common in people between the ages of 20 and 50 years. 

Treatment options for Graves’ disease focus on controlling the symptoms and reducing thyroid hormone production.

Other related conditions

Statistics

  • Hyperthyroidism affects between 1% and 3% of people¹ in the US. Graves’ disease is the most common form of hyperthyroidism and accounts for around 60–80%² of hyperthyroidism cases. 

  • Graves’ disease is more common in women. If you’re a woman, you’re on average around four times³ more likely to be diagnosed with Graves’ disease than if you’re a man. 

  • Graves’ disease is most common² in people between the ages of 20 and 50 years. 

  • Around 30% of people,⁴ or nearly one in three people, with Graves’ disease, develop Graves’ ophthalmopathy. 

  • Graves dermopathy occurs in about 2–3%² of people with Graves’ disease.

  1. Hyperthyroidism (2016)

  2. Graves disease (2022)

  3. Epidemiology, management and outcomes of Graves’ disease—real life data (2017)

  4. Graves’ disease | National Institute of Diabetes and Digestive and Kidney Diseases

Symptoms

When you have Graves’ disease, you can have any combination of the following symptoms:

Swollen neck

One of the first symptoms that you may notice if you have Graves’ disease is that you have a swollen neck in the area where your thyroid gland is found. This is termed a goiter. Developing a goiter that you can see and feel is more common¹ if you’re under the age of 60 years. 

Eye problems

The eye changes associated with Graves’ disease are called Graves’ ophthalmopathy. Around 30% of people² or nearly one in three people with Graves’ disease develop Graves’ ophthalmopathy.

Graves’ ophthalmopathy is caused when your body’s immune system attacks the tissues and muscles surrounding your eyes. These tissues and muscles then become swollen and cause your eyes to bulge, and give your eyelids the appearance of being retracted.

If you’re experiencing these symptoms, you may also find that your eyes become gritty, reddened, and sensitive to light. Some people experience double vision or decreased vision. You may also experience a feeling of pressure in or around your eyes. 

You may develop Graves’ ophthalmopathy³ at the same time that other symptoms appear, or you may notice that your eyes are bulging before any other symptoms develop. 

Some people develop Graves’ ophthalmopathy only after they’ve begun treatment for their Graves’ disease, but this is rare.

Weakness and muscle fatigue

Weakness and muscle fatigue result from thyrotoxic myopathy, which occurs when there are raised levels of thyroid hormone in the blood, as occurs with Graves’ disease. 

Fatigue can occur in the muscles around your shoulders and hips, and you may find it harder to exercise, and generally feel tired. You may also notice that your muscles are becoming visibly less bulky. 

Thyrotoxic myopathy may follow a chronic or more acute path. In chronic cases, it takes around six months for symptoms to become noticeable, while in acute thyroid myopathy, symptoms can occur within days and can include severe muscle pain and cramps as well as weakness. 

Skin changes

Changes in your skin are also an associated symptom of  Graves’ disease. These occur in about 2–3%¹ of people with Graves’ disease. The skin changes caused by Graves’ disease are referred to as Graves’ dermopathy, and it is a painless condition. 

You may notice that your skin becomes thickened and red. It may develop a dimpled appearance, similar to the skin of an orange, and can become difficult to pinch. 

Skin changes usually occur² over the front of your shin and may extend onto the tops of your feet, called pretibial myxedema. Interestingly, it’s very rare that other areas of your skin are affected by this condition. 

You most often³ develop pretibial myxedema if you have Graves’ ophthalmopathy.

Swelling of your fingers and/or toes

In some cases, people with Graves’ disease develop swelling of their fingers and toes, as well as changes to the nails. This is called thyroid acropachy and is relatively rare.³ 

During Graves’ disease, new bone growth occurs in your fingers and toes. This causes swelling of the tissue surrounding your finger and toe bones as well as swelling at the base of your nails.

Weight loss

Unintended weight loss, despite having a normal or increased appetite, is common in people with Graves’ disease.

Heat intolerance

If you have Graves’ disease, you may feel hot regularly and notice that you become irritable or distressed in warmer surroundings. 

Increased sweating

Another symptom of Graves’ disease is increased sweating. You may notice that you’re sweating more than usual and that your skin frequently feels warm and moist. 

Tremor

If you have Graves’ disease you may notice that you have a fine tremor in your hands or fingers. In some cases, this becomes significant enough that your shaky hands interfere with your ability to do fine work and other people notice your shaking. 

Anxiety and nervousness

One recognized medical cause of anxiety is an overactive thyroid. Graves’ disease can trigger feelings of anxiety, nervousness, and irritability. This is particularly noticeable if you’re not usually an anxious person. 

Other people may comment on your personality changes before you notice them. Sometimes the anxiety is severe enough to trigger full-blown panic attacks. 

Insomnia

Insomnia, sleep disturbances, and difficulty sleeping can all be symptoms of Graves’ disease. Sleep disturbances are often exacerbated by heat intolerance and anxiety.

Palpitations

It’s common to feel as though your heart is racing or that it’s beating irregularly if your thyroid is overactive. 

In some people, especially older people,¹ Graves’ disease may trigger a heart arrhythmia called atrial fibrillation, which is characterized by a rapid, irregular heartbeat. 

Diarrhea

Graves’ disease can lead to diarrhea or frequent bowel movements. Your stool may become looser than usual or you may need to go to the toilet more often than is usual.

Menstrual changes

Your thyroid hormone helps regulate all the cells in your body, including your reproductive system. Therefore, if you are female and have Graves’ disease, you may have fewer or lighter periods than usual (called oligomenorrhea). Sometimes your periods disappear completely (called amenorrhea).

Loss of libido

Graves’ disease can cause loss of libido in both men and women and can lead to erectile dysfunction in men. 

Hair loss

An overactive thyroid can cause hair loss and hair thinning.

  1. Graves disease (2022)

  2. Graves’ disease | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  3. Hyperthyroidism (2016)

Causes

Graves’ disease is caused by a dysregulation of your body’s immune system. However, it’s unknown what causes this dysregulation. 

Normally, the release of thyroid hormone is triggered by a hormone called thyroid-stimulating hormone (TSH). TSH is secreted by a small gland in your brain called the pituitary gland. 

With Graves’ disease, your immune system creates an antibody called thyrotropin receptor antibody (TRAb) that mimics TSH and stimulates an overproduction of thyroid hormone. 

Although it’s not known what causes the malfunction in your body’s immune system, certain triggers that can put you at higher risk of developing Graves’ disease have been identified. 

Risk factors¹ for developing Graves’ disease include:

Family history

A family history of Graves’ disease is a known risk factor for developing the condition. 

If a close relative has Graves’ disease or other autoimmune thyroid disorders such as Hashimoto’s thyroiditis (underactive thyroid), your likelihood of developing Graves’ disease increases. 

This suggests that Graves’ disease has a genetic component.

Gender

Women are more likely to develop Graves’ disease than men. It’s thought that sex hormones and genes related to the X-chromosome may act as triggers for developing Graves’ disease. 

Emotional or psychological stress

Stressful life events can act as a trigger for developing Graves’ disease among people already at risk. 

Smoking

Smoking is a known risk for developing Graves’ disease. Smokers who have Graves’ disease are also more likely to develop Graves’ ophthalmopathy. 

Pregnancy 

Pregnancy or recent childbirth may increase the risk of developing Graves’ disease. 

Other autoimmune disorders

If you have another immune disorder such as rheumatoid arthritis or type 1 diabetes, you’re more likely to develop Graves’ disease.

What happens if you don’t treat your Graves’ disease?

Untreated hyperthyroidism² can have unpleasant long-term consequences. Some of the main complications of untreated Graves’ disease include:

  • Heart problems such as irregular heartbeats, palpitations, and heart failure

  • Thinning of your bones (osteoporosis)

  • Muscle weakness

  • Menstrual irregularities

  • Pregnancy complications.

A serious complication of Graves’ disease is thyrotoxicosis or thyroid storm. This happens when the amount of thyroid hormone produced by your body becomes dangerously high. 

A thyroid storm is dangerous and potentially life-threatening and should be treated immediately. 

Signs and symptoms of a thyroid storm include:

  • Very rapid heart rate

  • High fever

  • Agitation and confusion

  • Diarrhea

  • Decreased level of consciousness.

  1. Hyperthyroidism (2016)

  2. Hyperthyroidism (Overactive thyroid) | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Treatments

Three main treatment options for managing Graves’ disease are available: antithyroid medication, radioactive iodine therapy, and surgery. 

Initially, treatment may be aimed at getting the symptoms of your Graves’ disease under control. This is especially the case if your symptoms are severe. The next step would be to reduce thyroid hormone production.

Step one: Controlling symptoms

Beta-blockers

Beta-blockers are drugs that block the effects of thyroid hormone on many tissues in the body. They’re effective at controlling many of the symptoms of thyrotoxicosis.¹ 

Beta-blockers aren’t a permanent cure for Graves’ disease but do help control the symptoms and are often used in conjunction with other treatment modalities. The most common beta-blocker used is propranolol (Brand names: Inderal, InnoPran XL).

You should not take beta-blockers if you have asthma because they can trigger asthma attacks. 

Step two: Reducing thyroid hormone production

Antithyroid drugs

Antithyroid drugs available in the US include methimazole and propylthiouracil. Both of these medications inhibit thyroid hormone synthesis in the thyroid gland.

Methimazole is usually the drug of choice² for Graves’ disease because it has fewer side effects than propylthiouracil and is less toxic to the liver. It also has a slightly quicker onset of action and can be taken as a once-a-day dose. 

On the other hand, propylthiouracil needs to be taken three times a day.

If you’re pregnant, propylthiouracil is preferable to methimazole in the first trimester of pregnancy. Methimazole is teratogenic³and can cause birth defects if it’s taken during the first trimester. After the first trimester, it’s considered safe to change over to methimazole.

After beginning antithyroid medication, it takes a few weeks to months for thyroid hormone levels to return to normal ranges. Unfortunately, you have a high chance of relapsing if you stop treatment. 

Antithyroid drugs are often used before treatment with radioactive iodine or before surgery. 

Side effects associated with methimazole and propylthiouracil can include:

  • Allergic reactions, skin rashes, and itching

  • Low white cell count (neutropenia), which can be life-threatening

  • Liver failure.

If you’re taking methimazole or propylthiouracil for Graves’ disease and experience any of the following symptoms, you should seek medical care immediately as you may be experiencing a side effect to the medication:

  • Fatigue or weakness

  • Dull pain in your stomach

  • Loss of appetite

  • Skin rash, itching, or easy bruising

  • Yellowing of your skin or the whites of your eyes

  • Fever, chills, or constant sore throat.

Radioactive iodine therapy

Radioactive iodine therapy is a common treatment for Graves’ disease.  Although radioactive iodine therapy may seem scary, it’s far safer and simpler than it sounds.

Radioactive iodine works by destroying the cells within the thyroid that secrete thyroid hormone and is ingested either as a capsule or liquid. Once absorbed, it’s taken up by thyroid cells, which it then starts to destroy. Other body tissues don’t take up radioactive iodine, so the treatment is concentrated on the problem areas.

The major complication with radioactive iodine is that it can worsen moderate to severe Graves’ ophthalmopathy, so this treatment option should be avoided if you have moderate to severe eye symptoms. It can be used in conjunction with steroids if you have mild eye symptoms. Radioactive iodine therapy should not be considered if you are pregnant, planning a pregnancy, or breastfeeding. 

After treatment with radioactive iodine, you often develop hypothyroidism (an underactive thyroid) because you have effectively killed off most of your thyroid hormone-producing cells. Fortunately, this can easily be treated with daily replacement thyroid hormone. 

Surgery (thyroidectomy)

Thyroidectomy is the treatment of choice if you have any of the following;

  • A very large goiter (thyroid swelling)

  • Compression of the front of your throat because of the size of your goiter

  • Possible thyroid cancer as well as Graves’ disease

  • Nodules in your thyroid

  • Moderate to severe Graves’ ophthalmopathy

  • Not responding to other treatment modalities.

Before having surgery you need to take antithyroid drugs to get your thyroid hormone levels to within the normal range. You also need to take potassium iodine to decrease the blood supply to your thyroid. 

When surgery is completed by an experienced surgeon, the complication rate is low²(around 1–3% of patients). Possible complications include:

  • Damage to the small glands alongside your thyroid that control calcium levels in your blood (called the parathyroid glands)

  • Damage to the nerve that controls your vocal cords

  • Reaction to the anesthesia.

Once your thyroid has been removed, you will need to take daily replacement thyroid hormone. 

Clinical trials

The function of clinical trials is to look for new ways to prevent, diagnose, or treat diseases. Ongoing clinical trials ensure that the field of medicine is continually moving towards improved health outcomes. 

Volunteers for clinical trials help researchers and doctors advance healthcare. In the process, they may have the benefit of being exposed to cutting-edge new treatments for their Graves’ disease and Graves’ ophthalmopathy. 

Search for Graves’ disease clinical trials here. 

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014602/

  2. https://www.ncbi.nlm.nih.gov/books/NBK448195/#:~:text=Graves%E2%80%99%20disease%20is%20the%20most%20common%20cause%20of,disease%20is%20more%20common%20in%20women%20than%20men.

Treatment of Graves’ ophthalmopathy

Graves’ ophthalmopathy doesn’t usually respond to treatment for Graves’ disease and may require separate management. 

Mild eye symptoms can be treated with:

  • Lubricating eye drops and gels

  • Taping eyes shut at night to avoid damage to exposed areas of your eye

  • Cold compresses on your eye

  • Sleeping with your head raised to avoid extra eye congestion

  • Wearing sunglasses to reduce light sensitivity.

 More severe eye symptoms can be treated with:

  • Oral, intraorbital (into tissues around the eye), or intravenous corticosteroids 

  • Immunosuppressive medication

  • Ocular surgery.

Diagnosis

To make a diagnosis of Graves’ disease, your doctor needs to chat with you about your symptoms and family history, as well as examine you for signs of Graves’ disease. You will also need to undergo additional testing, including:

Blood tests

You will require blood tests to accurately diagnose Graves’ disease. Blood tests look at the levels of your thyroid hormones and your thyroid-stimulating hormone as well as your thyroid antibody levels. 

If your doctor is thinking of starting you on antithyroid drugs, you may need your white cell count measured as well as your baseline liver function.

Thyroid imaging

If the diagnosis of Graves’ disease is still unclear after your examination and blood tests, your doctor may request that you have an ultrasound scan or magnetic resonance imaging scan of your thyroid. This can help identify the presence of cysts or nodules within the thyroid.

Radioactive iodine uptake

Since your thyroid gland takes up iodine to make thyroid hormone, if you ingest a small amount of radioactive iodine, it can be visualized within the thyroid using a special scan. 

Assessing the rate at which your thyroid gland takes up the radioactive iodine can help to distinguish between Graves’ disease and other causes of hyperthyroidism.

Awareness

Raising awareness of Graves’ disease allows people to seek treatment earlier in the course of the disease. 

Several websites are dedicated to raising awareness of the signs and symptoms of Graves’ disease, along with other thyroid disorders. These include the thyroid awareness page by the American Association of Clinical Endocrinology and an information page by the American Thyroid Association.

Doctors & specialists

Graves’ disease is more than just a thyroid disorder; it involves numerous organs and systems. For this reason, it’s best managed by a multidisciplinary team. 

Specialists involved in your care if you have Graves’ disease could include:

  • An endocrinologist 

  • An ophthalmologist

  • A surgeon

  • A dermatologist

  • An ear, nose, and throat surgeon


Clinical trials for graves' disease

Actively recruiting
Proteomics and thyroid eye diseases
Wan Chai District (HK)
Actively recruiting
RCT of QoL study in RAI vs Surgery
Wan Chai District (HK)