Graves' Disease: Symptoms, Causes, and Treatment

Graves' disease is an autoimmune condition in which the immune system makes antibodies, called TSH-receptor antibodies or TRAb, that switch the thyroid gland on and make it produce too much thyroid hormone. It is the most common cause of an overactive thyroid (hyperthyroidism), causing about 6 to 8 in 10 cases in the United States, the United Kingdom and Australia. It is far more common in women, usually starts between the ages of 20 and 50, and often runs in families; smoking makes it, and especially its eye complications, more likely and more severe. Symptoms include weight loss with a normal appetite, a fast or pounding heartbeat, feeling hot and sweaty, shaky hands, anxiety and poor sleep, along with a smooth swelling of the whole thyroid (a goitre). About 2 in 5 people also develop thyroid eye disease, with gritty, swollen or bulging eyes and sometimes double vision. Diagnosis is a blood test showing a low TSH with a high free T4 or T3 and a positive TRAb. The three main treatments are anti-thyroid medicine (carbimazole or methimazole, sometimes propylthiouracil), radioactive iodine, and surgery to remove the thyroid; a beta blocker settles the heart rate and tremor while treatment takes effect.

In plain words

Graves' disease is an immune system problem. The immune system makes an antibody that switches the thyroid gland on too much. The thyroid then makes too much hormone. This speeds the body up. It is the top cause of an overactive thyroid. It is much more common in women. It often runs in families. Smoking makes it worse, especially for the eyes. Signs are weight loss, a fast heartbeat, feeling hot and sweaty, shaky hands, and feeling on edge. The thyroid may swell in the neck. About 2 in 5 people also get sore, puffy, or bulging eyes. A blood test finds it. It checks a hormone called TSH, the thyroid hormones, and a marker called TRAb. There are three main treatments: tablets that slow the thyroid, a drink of radioactive iodine, or surgery. A beta blocker tablet helps a fast heart while the main treatment works. Most people do well with treatment.

What is Graves' Disease: Symptoms, Causes, and Treatment?

Graves' disease is an autoimmune condition in which the immune system makes antibodies, called TSH-receptor antibodies or TRAb, that switch the thyroid gland on and make it produce too much thyroid hormone. It is the most common cause of an overactive thyroid (hyperthyroidism), causing about 6 to 8 in 10 cases in the United States, the United Kingdom and Australia. It is far more common in women, usually starts between the ages of 20 and 50, and often runs in families; smoking makes it, and especially its eye complications, more likely and more severe. Symptoms include weight loss with a normal appetite, a fast or pounding heartbeat, feeling hot and sweaty, shaky hands, anxiety and poor sleep, along with a smooth swelling of the whole thyroid (a goitre). About 2 in 5 people also develop thyroid eye disease, with gritty, swollen or bulging eyes and sometimes double vision. Diagnosis is a blood test showing a low TSH with a high free T4 or T3 and a positive TRAb. The three main treatments are anti-thyroid medicine (carbimazole or methimazole, sometimes propylthiouracil), radioactive iodine, and surgery to remove the thyroid; a beta blocker settles the heart rate and tremor while treatment takes effect.

Symptoms

Early symptoms

  • Weight loss with a normal or bigger appetite: Losing weight without trying because the body burns energy faster. (1) (2) (3)
  • A fast, pounding or irregular heartbeat: A resting pulse often above 100 beats per minute, palpitations, or an irregular rhythm called atrial fibrillation. (1) (2)
  • Feeling hot, sweating, and shaky: Being uncomfortably warm, sweating easily, a fine tremor of the hands, and feeling restless or anxious. (1) (3)
  • Poor sleep, tiredness and mood changes: Difficulty sleeping, tiredness, muscle weakness, irritability and mood swings. (1) (3)
  • A smooth swelling of the whole thyroid (goitre): In Graves' disease the whole gland enlarges evenly, sometimes with a soft rushing sound a doctor can hear over it. (1) (2)
  • Eye changes (thyroid eye disease): About 2 in 5 people with Graves' disease develop thyroid eye disease: gritty, watery or dry eyes, swelling of the eyelids, bulging of the eyes (proptosis), and sometimes double vision. It is a separate problem from the overactive thyroid and can start before, during or after it. (2) (1) (6)
  • Thick, reddened skin on the shins (rare): A small number of people, around 2 to 3 in 100, get raised, thickened, reddish skin over the shins or tops of the feet, called pretibial myxoedema or Graves' dermopathy. (1) (2)
  • Lighter or irregular periods and reduced fertility: In women, periods can become lighter or less regular and it can be harder to conceive. (2) (1)

Serious or emergency symptoms

  • A sudden, severe flare (thyroid storm): Thyroid storm is a rare, life-threatening surge of an overactive thyroid, with a high fever, a very fast or irregular heartbeat, agitation, confusion or reduced consciousness, and vomiting or diarrhoea. It is usually set off by an infection, surgery, injury, childbirth, or stopping anti-thyroid medicine. Call the emergency services now: 911 in the United States, 999 in the United Kingdom, or 000 in Australia. Thyroid storm needs intensive hospital treatment. (1) (3)
  • Sudden severe sore throat, mouth ulcers or fever on anti-thyroid medicine: Carbimazole, methimazole and propylthiouracil can rarely cause a sharp drop in infection-fighting white blood cells (agranulocytosis). A severe sore throat, mouth ulcers or a high fever can be the first sign. Do not take the next dose, get urgent medical care the same day, and ask for an urgent blood count. Do not wait for a routine appointment. (1) (4)
  • New or fast-changing eye pain, double vision or reduced vision: In active thyroid eye disease, severe or increasing eye pain, new double vision, a change in colour vision, or loss of vision can mean the optic nerve is under pressure. This is sight-threatening. Seek same-day assessment by an eye specialist or an emergency department. Do not wait for a routine ophthalmology appointment. (6) (1)

Causes

Primary causes

  • An autoimmune antibody that switches the thyroid on: In Graves' disease the immune system makes an antibody, the TSH-receptor antibody (TRAb, also called thyroid-stimulating immunoglobulin), that binds the same switch on thyroid cells that the body's own TSH normally uses. This drives the whole gland to make too much hormone and to enlarge. (1) (2)
  • Inherited tendency: Graves' disease often runs in families. Having a close relative with Graves' disease, Hashimoto's disease or another autoimmune condition raises your risk. Genes set the tendency; something else usually triggers the disease. (1) (2)
  • Smoking: Smoking raises the chance of developing Graves' disease and strongly raises the risk and severity of thyroid eye disease. Stopping smoking is one of the most useful things a person with Graves' can do. (1) (2)

Contributing factors

  • Pregnancy and the months after birth: Changes in the immune system around pregnancy can bring on Graves' disease or make it flare, often in the first year after delivery. (2) (1)
  • Stress and major life events: Severe stress is reported as a trigger in some people, on top of the inherited tendency. (2) (5)
  • A large iodine load or certain medicines: A big dose of iodine, for example from a scan contrast dye or the heart drug amiodarone, can trigger or worsen an overactive thyroid in someone prone to it. (1) (5)
  • Other autoimmune conditions: Type 1 diabetes, coeliac disease, vitiligo, pernicious anaemia and rheumatoid arthritis are all more common in people with Graves' disease and their relatives. (1) (5)

Risk factors

Being a woman

The lifetime chance of Graves' disease is roughly 3 in 100 for women and about 0.5 in 100 for men. (1)

Age 20 to 50

Graves' disease most often starts in early to middle adult life, though it can occur at any age including in children. (1) (2)

Family history of thyroid or autoimmune disease

A close relative with Graves' disease, Hashimoto's disease or another autoimmune condition raises your risk. (1) (2)

Smoking

Smoking raises the risk of Graves' disease and, especially, of moderate to severe thyroid eye disease. (1) (2)

Recent pregnancy

The year after giving birth carries a higher risk of the condition appearing or flaring. (2) (1)

Another autoimmune condition

Having type 1 diabetes, coeliac disease or another autoimmune disease increases the risk. (1) (5)

Diagnosis

Graves' disease is diagnosed with blood tests, sometimes with a scan or ultrasound. A low or undetectable thyroid-stimulating hormone (TSH) with a high free thyroxine (free T4) or triiodothyronine (T3) confirms an overactive thyroid. The test that points specifically to Graves' disease is the TSH-receptor antibody (TRAb, also called TSI), which is very accurate: it is raised in almost everyone with Graves' disease and rarely in other causes. If the antibody is positive and there is a smooth goitre, or eye changes, no further test is usually needed. If the picture is unclear, a radioactive-iodine uptake scan shows the whole gland taking up iodine strongly in Graves' disease, and a thyroid ultrasound shows an enlarged gland with increased blood flow. This approach is used in United States guidance from the American Thyroid Association, United Kingdom guidance from the NHS and NICE, and Australian guidance from the RACGP.

TSH, free T4 and T3

A low TSH with a high free T4 or T3 confirms an overactive thyroid. (1) (3)

TSH-receptor antibody (TRAb or TSI)

A positive result confirms Graves' disease as the cause. It is highly accurate and often removes the need for a scan. (1)

Radioactive-iodine uptake scan

Used when the cause is unclear. In Graves' disease the whole gland takes up iodine strongly and evenly. (1) (2)

Thyroid ultrasound

Shows an enlarged gland with increased blood flow and any nodules. (1) (2)

Treatment

Medication options

Anti-thyroid medicine

Carbimazole and methimazole (methimazole is carbimazole's active form) block the thyroid from making new hormone and are usually the first treatment for Graves' disease, especially with milder disease or active eye disease. In the United Kingdom carbimazole is typically started at about 20 mg a day; thyroid blood tests return to normal over roughly 4 to 6 weeks and people feel better within 2 to 4 weeks. The course usually lasts 12 to 18 months, after which about 3 to 5 in 10 people stay well without further treatment. Propylthiouracil is a third option, kept for the first three months of pregnancy, for thyroid storm, and for people who cannot take the others, because it carries a higher risk of serious liver injury. (1) (4) (3) (2)

Beta blocker

A beta blocker such as propranolol or atenolol quickly eases a fast heartbeat, palpitations, tremor and anxiety while the anti-thyroid treatment takes effect. It does not lower thyroid hormone or treat the cause. (1) (3)

Radioactive iodine

A single drink or capsule of radioactive iodine is taken up by the overactive thyroid and gradually destroys it over weeks to months. It is a common definitive treatment for Graves' disease in adults who are not pregnant. (1) (2) (3)

Surgery (thyroidectomy)

Removing all or most of the thyroid quickly and reliably cures the overactive thyroid. It is chosen for a large goitre, a suspicious nodule, moderate to severe eye disease, when other treatments cannot be used, or by preference. (1) (2) (3)

Lifestyle and self-care

  • Stop smoking: This is the single most useful self-care step in Graves' disease. Smoking makes thyroid eye disease more likely and more severe and makes treatment less effective. Quit-smoking services can help; in Australia call Quitline on 13 7848. (1) (2)
  • Care for your eyes: For mild thyroid eye disease, use lubricating drops, wear sunglasses outdoors, and sleep with the head of the bed raised. A specialist may suggest a selenium supplement for mild, active eye disease. Report any new eye pain, double vision or change in vision urgently. (6) (1)
  • Take medicine as prescribed and keep blood tests: The anti-thyroid dose is guided by regular thyroid blood tests. Missing doses or tests can let the overactive thyroid rebound. (4) (1)
  • Avoid extra iodine and flag your thyroid before scans: Do not take kelp, seaweed or high-dose iodine supplements. Tell any doctor arranging a contrast scan, or considering amiodarone, that you have Graves' disease. (1) (5)
  • Plan pregnancy with your specialist: If you might become pregnant, discuss the safest treatment first. The choice of anti-thyroid medicine changes in pregnancy, and antibody levels are checked because they can affect the baby's thyroid. (1) (2)

Always discuss dosing and treatment changes with your own prescriber.

Possible complications

  • Heart problems: An untreated overactive thyroid raises the risk of atrial fibrillation, which itself raises the risk of stroke, and can cause a strained, overworked heart and heart failure. These usually improve once the thyroid is controlled. (1) (5)
  • Thinning bones (osteoporosis): Excess thyroid hormone speeds up bone loss, raising the risk of osteoporosis and fractures, particularly in women after the menopause. (1) (5)
  • Sight-threatening thyroid eye disease: In a minority, thyroid eye disease becomes severe, with pressure on the optic nerve or exposure of the cornea, which can permanently harm vision if not treated quickly with steroids, other medicines such as teprotumumab, orbital radiotherapy or surgery. (6) (1)
  • Pregnancy and baby problems: Poorly controlled Graves' in pregnancy raises the risk of miscarriage, pre-eclampsia, premature birth and low birth weight, and the antibodies can cross the placenta and briefly affect the baby's thyroid. (1) (2)
  • Thyroid storm, and the long-term outlook: Thyroid storm is a rare, life-threatening surge that needs emergency treatment. Overall the outlook is good. Living with Graves' disease usually means a period of tablet treatment, a choice at some point about radioactive iodine or surgery, and then, for most people, a daily levothyroxine tablet once the thyroid becomes underactive, with lifelong thyroid blood-test monitoring. Graves' can relapse after a course of medicine, so ongoing follow-up matters. (1) (2)

When to see a doctor

Routine follow-up

  • Book an appointment if you have symptoms such as unexplained weight loss, a fast or pounding heartbeat, feeling hot and sweaty, shaky hands or anxiety for more than a week or two, so a thyroid blood test can be done. (3) (2)
  • See your doctor if you have Graves' disease and symptoms return or change, or if you notice new eye symptoms such as bulging, grittiness, swelling or double vision, so you can be referred to an eye specialist. (6) (2)
  • Contact your specialist promptly if you have Graves' disease and are pregnant or planning a pregnancy, because treatment and antibody monitoring need to be reviewed. (1) (2)

Seek emergency care

  • Call the emergency services now, 911 in the United States, 999 in the United Kingdom or 000 in Australia, if a person with Graves' disease has a high fever with a very fast or irregular heartbeat and becomes agitated, confused or hard to rouse. This may be thyroid storm. (1) (3)
  • Seek same-day care, and ask for a blood count, if you are taking carbimazole, methimazole or propylthiouracil and develop a severe sore throat, mouth ulcers or a high fever. (4) (1)
  • Get same-day assessment by an eye specialist or emergency department if you have thyroid eye disease and develop severe or worsening eye pain, new double vision, a change in colour vision, or any loss of vision. (6) (1)

Frequently asked questions

What is Graves' disease?

It is an autoimmune condition in which antibodies switch the thyroid gland on, making it overactive. It is the most common cause of an overactive thyroid, and it can also cause thyroid eye disease. It is more common in women and often runs in families. (1) (2)

What are the symptoms of Graves' disease?

Weight loss with a normal appetite, a fast or pounding heartbeat, feeling hot and sweaty, shaky hands, anxiety, poor sleep, and a smooth swelling of the thyroid. About 2 in 5 people also get gritty, swollen or bulging eyes, and rarely thickened skin on the shins. (1) (2) (3)

How is Graves' disease diagnosed?

With blood tests. A low TSH with a high free T4 or T3 confirms an overactive thyroid, and a positive TSH-receptor antibody (TRAb) confirms that Graves' disease is the cause. A radioactive-iodine scan or ultrasound is used only if the cause is unclear. (1) (3)

What are the treatment options?

Three main treatments: anti-thyroid medicine (carbimazole or methimazole, sometimes propylthiouracil), radioactive iodine, and surgery to remove the thyroid. A beta blocker is often added early to settle the heart rate and tremor. The best choice depends on how severe the disease is, whether there is eye disease, your age, and whether you are or may become pregnant. (1) (2) (3)

Can Graves' disease be cured?

A course of anti-thyroid medicine puts about 3 to 5 in 10 people into lasting remission, but it can relapse. Radioactive iodine and surgery reliably stop the overactivity but usually leave the thyroid underactive, so most people end up taking a daily levothyroxine tablet for life. With treatment, the condition is well controlled. (1) (2)

Why does smoking matter so much in Graves' disease?

Smoking makes Graves' disease more likely, makes thyroid eye disease much more likely and more severe, and makes treatments for the eyes work less well. Stopping smoking is the single most useful self-care step. (1) (2)

What is thyroid eye disease and how is it treated?

Thyroid eye disease, or Graves' ophthalmopathy, is swelling and inflammation of the tissues around the eyes. About 2 in 5 people with Graves' get it. Mild cases are managed with lubricating drops, sunglasses, sleeping propped up, stopping smoking, and sometimes selenium. Moderate to severe active disease is treated by an eye specialist with steroids, teprotumumab, orbital radiotherapy or surgery. Sudden eye pain, double vision or vision loss needs same-day care. (6) (1)

Is radioactive iodine safe for my eyes?

Radioactive iodine can make thyroid eye disease appear or worsen, especially in smokers and when eye disease is already active. In that situation doctors often choose anti-thyroid medicine or surgery instead, or give a short course of steroids alongside the radioactive iodine. (1) (6)

Can I have a baby if I have Graves' disease?

Yes, with planning and specialist care. Uncontrolled Graves' raises risks for mother and baby. Propylthiouracil is generally used in the first three months of pregnancy and carbimazole or methimazole after that, and antibody levels are checked because they can briefly affect the baby's thyroid. (1) (2)

Which anti-thyroid medicine warning signs should I act on?

Get urgent same-day medical care, and hold the next dose until a doctor has reviewed you, if you get a severe sore throat, mouth ulcers or a high fever (possible low white blood cell count), or yellow skin or eyes, dark urine or severe tummy pain (possible liver injury). Ask for an urgent blood test. Do not wait for a routine appointment. (4) (1)

References

  1. StatPearls / NCBI Bookshelf — Graves Disease source 1
  2. healthdirect (Australia) — Graves' disease source 2
  3. NHS — Overactive thyroid (hyperthyroidism) source 3
  4. NHS — Carbimazole (medicine for an overactive thyroid) source 4
  5. MedlinePlus (US National Library of Medicine) — Graves' disease source 5
  6. Cleveland Clinic — Graves' eye disease (thyroid eye disease) source 6
  7. American Thyroid Association — Graves' Disease (patient information) source 7