Graves' Disease

What Graves' disease is

The thyroid, a butterfly-shaped gland at the front of the neck, is normally controlled by thyroid-stimulating hormone (TSH) from the pituitary. In Graves' disease, the immune system makes TSH receptor antibodies (TRAb) that mimic TSH. They switch the gland on constantly, so it grows (a diffuse goiter) and pours out thyroid hormone regardless of the body's needs. The pituitary responds by shutting TSH down to almost zero.

The same antibodies can also act on tissue behind the eyes and in the skin, which explains the eye and shin changes that are unique to Graves' disease.

Graves' disease vs hyperthyroidism

Hyperthyroidism means an overactive thyroid from any cause. Graves' disease is one cause, responsible for most cases. Others include toxic multinodular goiter, a single overactive nodule, and thyroiditis, a temporary leak of hormone from an inflamed gland, such as postpartum thyroiditis. The cause matters because treatment differs.

Graves' disease symptoms

From too much thyroid hormone

• Weight loss despite a good or increased appetite
• Fast or pounding heartbeat (palpitations), sometimes an irregular rhythm
• Fine tremor of the hands
• Feeling hot, sweating, and warm, moist skin
• Anxiety, irritability, poor sleep and restlessness
• More frequent, looser bowel movements
• Muscle weakness, especially climbing stairs or rising from a chair
• Tiredness
• Lighter or less frequent periods, and reduced fertility
• Thin, fine hair

Older adults often have fewer of these classic symptoms and may present mainly with atrial fibrillation, weight loss or tiredness ("apathetic hyperthyroidism").

Specific to Graves' disease

• Diffuse goiter: a smooth, painless swelling across the front of the neck. A doctor may hear a whooshing sound (bruit) over it.
• Graves' eye disease (orbitopathy): see below.
• Pretibial myxedema: thickened, orange-peel, reddish skin over the shins. Uncommon, nearly always with eye disease.
• Thyroid acropachy: clubbing and swelling of the fingers. Rare.

Graves' disease and the eyes

About 25 to 50% of people with Graves' disease have some eye involvement, usually mild. Inflammation and swelling of the muscles and fat behind the eye push it forward.

• Gritty, dry or watering eyes and light sensitivity
• A staring look from upper eyelid retraction
• Bulging eyes (proptosis), which can affect one side more than the other
• Puffy eyelids and red eyes
• Double vision, especially looking up or to the side
• Rarely, pressure on the optic nerve with loss of vision, which is an emergency

Smoking is the strongest preventable risk factor: it makes eye disease more likely, more severe and less responsive to treatment. Moderate to severe cases need an eye specialist. Treatments include lubricating drops, selenium for mild active disease, steroids, teprotumumab and other targeted medicines, radiotherapy and, later, surgery. More detail is on our thyroid eye disease page.

Causes and risk factors

Graves' disease results from a mix of genes and triggers:

• Female sex and age 20 to 50
• Family history of Graves' or Hashimoto's thyroiditis
• Other autoimmune conditions, such as type 1 diabetes, rheumatoid arthritis, vitiligo and celiac disease
• Smoking
• The year after pregnancy
• Major stress, some infections, and certain medicines (for example some immune therapies) may trigger onset

Diagnosis

1. Blood tests: a low TSH with high free T4 and/or T3 confirms hyperthyroidism.
2. TSH receptor antibodies (TRAb or TSI): positive in the vast majority of people with Graves' disease and the simplest way to confirm the cause.
3. Radioactive iodine uptake scan: shows diffuse, high uptake in Graves' disease, compared with patchy uptake in nodules and low uptake in thyroiditis. Used when antibodies are negative or the picture is unclear. Not done in pregnancy.
4. Thyroid ultrasound: shows an enlarged gland with increased blood flow, and checks any nodules.
5. Other tests: an ECG if the heart rate is fast or irregular, and sometimes liver tests and a blood count before starting treatment.

Graves' disease treatment

Symptom control

Beta-blockers such as propranolol or atenolol slow the heart and reduce tremor, sweating and anxiety within hours to days, while other treatments take effect.

The three main treatments

In the US, antithyroid medicine is now the most common first choice, with RAI or surgery if the disease relapses or does not respond. After RAI or surgery, a daily levothyroxine tablet replaces the thyroid hormone, and hypothyroidism is easily treated with regular blood tests.

Pregnancy

Graves' disease needs careful planning in pregnancy. Uncontrolled hyperthyroidism raises the risk of miscarriage, preterm birth and preeclampsia, and TRAb can cross the placenta and affect the baby's thyroid. Propylthiouracil is usually used in the first trimester and methimazole after that. Tell your doctor as soon as you know you are pregnant.

Complications if untreated

• Atrial fibrillation and other heart rhythm problems, raising stroke risk, and in time heart failure
• Osteoporosis from accelerated bone loss
• Thyroid storm: a life-threatening surge, often triggered by infection, surgery or stopping treatment
• Severe eye disease and vision loss
• Pregnancy complications

Living with Graves' disease

With treatment, most people return to normal health and energy within a few months. Regular thyroid blood tests are needed, every 4 to 6 weeks at first and then less often, and lifelong if you have had RAI or surgery. Stop smoking, ideally before RAI. Weight often rises once hormone levels normalize, so adjust eating habits as the appetite settles.

Frequently asked questions

What is the main cause of Graves' disease?

Graves' disease is autoimmune. The immune system makes antibodies that bind to the TSH receptor on thyroid cells and switch them on continuously. Why this starts is not fully known, but genes, female sex, smoking, pregnancy and stress all play a part.

What are the first signs of Graves' disease?

Common early signs are a racing heart, shaky hands, weight loss despite eating well, feeling hot and sweaty, anxiety or irritability, poor sleep and looser bowels. Some people first notice a swollen neck or gritty, staring eyes. Symptoms usually build over weeks to months.

Can Graves' disease go away on its own?

Occasionally it remits, but it is rarely left untreated because of the risks to the heart, bones and eyes. After 12 to 18 months of antithyroid medicine, about a third to a half of people stay in remission when the medicine is stopped. Others relapse and need definitive treatment.

Does Graves' disease affect the eyes?

In about a quarter to a half of people, yes. Symptoms range from dryness, grittiness and a staring look to bulging eyes and double vision. Most cases are mild. Smoking makes eye disease worse. Sudden vision changes or color vision loss need emergency care.

Is Graves' disease the same as hyperthyroidism?

Graves' disease is the most common cause of hyperthyroidism, but they are not the same thing. Hyperthyroidism means an overactive thyroid from any cause. Graves' disease is autoimmune and can also affect the eyes and skin, which other causes do not.

Can you live a normal life with Graves' disease?

Yes. Once thyroid levels are controlled, most people feel well, work, exercise and have healthy pregnancies with proper monitoring. Many end up taking a daily thyroid hormone tablet after radioactive iodine or surgery, with regular blood tests to keep the dose right.