Graves' Disease

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Reviewed by Alexander Shifrin, MD, Director of Endocrine Surgery, CentraState Medical Center. Based on the 2016 ATA hyperthyroidism guideline and the 2022 update on Graves' disease and thyroid eye disease.

What is Graves' disease?

Graves' disease (called Basedow disease in Europe) is an autoimmune disorder and the most common cause of hyperthyroidism, an overactive thyroid. The immune system makes antibodies (thyrotropin receptor antibodies, or TRAb) that switch the thyroid on, so it makes too much thyroid hormone and the body's metabolism speeds up.

Graves' disease can cause hyperthyroidism, a goiter (enlarged thyroid), eye disease (thyroid eye disease, also called Graves' orbitopathy), and occasionally a skin change (dermopathy). Its course is unpredictable. It runs in families and is more common in women. More information: Graves' Disease Center.

What are the symptoms of hyperthyroidism?

Most people with hyperthyroidism have symptoms, usually one or more of the following:

• Anxiety, irritability, trouble sleeping
• Weakness, especially of the upper arms and thighs, making it hard to lift heavy items or climb stairs
• Tremor of the hands
• Sweating more than normal, trouble tolerating hot weather
• Rapid or irregular heartbeat
• Fatigue
• Weight loss despite a normal or increased appetite
• Frequent bowel movements
• Eye disease and, rarely, skin changes (specific to Graves' disease)

Some women have irregular periods or stop having periods, which can be linked to infertility. Men may develop enlarged or tender breasts or erectile dysfunction. These resolve when the hyperthyroidism is treated.

Who gets Graves' disease?

• It affects women about 4 to 6 times more often than men, and it most often starts between ages 20 and 50.
• About 1 to 5% of patients are children, most often between ages 11 and 14.
• It has a strong hereditary and genetic component.
• Smoking is weakly linked to Graves' disease, but strongly linked to Graves' eye disease. Smoking is the most important modifiable risk factor for thyroid eye disease, and quitting is advised.

How is hyperthyroidism diagnosed?

The best first test is a blood TSH. If the TSH is normal, hyperthyroidism is very unlikely. A low TSH with high free T4 and/or T3 confirms the diagnosis, and free T4 and T3 tell us how severe it is.

To find the cause (Graves' disease, toxic nodular goiter, or thyroiditis), one or more of these tests is used:

• TRAb (thyrotropin receptor antibody) blood test. Current tests are about 97% sensitive and 99% specific for Graves' disease.
• Radioactive iodine uptake and thyroid scan. This shows whether the whole gland is overactive (Graves' disease), or only nodules, or whether uptake is low (thyroiditis).
• Thyroid ultrasound with Doppler, which shows increased blood flow throughout the gland in Graves' disease and finds nodules. Dr. Shifrin performs thyroid ultrasound in the office.

A diagnosis of Graves' disease can also be made from the exam alone in a patient with a diffuse goiter, high thyroid hormone, and a suppressed TSH.

What are the treatment options?

There are three ways to treat the hyperthyroidism of Graves' disease. All three work. The best choice depends on your age, goiter size, eye disease, other conditions, plans for pregnancy, and personal preferences, and the decision should be shared between you and your doctors.

1. Antithyroid medication

Methimazole (MMI, Tapazole) blocks the thyroid from making hormone. It is the preferred drug for nearly every patient. Propylthiouracil (PTU) is used mainly in the first trimester of pregnancy and in thyroid storm, because it carries a higher risk of serious liver injury.

• Duration. The ATA suggests a course of about 12 to 18 months, then stopping if the TSH and TRAb are normal. Longer courses do not improve the chance of remission in most adults. Some patients with mild, stable disease can stay on a low dose of methimazole for years.
• Remission. Roughly 30 to 50% of patients stay in remission after stopping. A normal TRAb before stopping predicts a better chance. If TRAb stays high, relapse is likely (about 80 to 100% in the studies). Remission is less likely in men, smokers, and patients with large goiters.
• Monitoring. Blood counts and liver tests before starting, and thyroid tests every 2 to 4 weeks at first. Report fever, a sore throat, jaundice, dark urine, light stools, or a rash right away. Serious side effects (low white blood cell count, liver injury) are uncommon and mostly happen in the first months. Minor reactions such as a rash, hives, joint pain or stomach upset are more common.
• Beta-blockers (propranolol or atenolol) do not reduce thyroid hormone, but they control a racing heart, tremor, anxiety and heat intolerance while the treatment takes effect. They are stopped after hyperthyroidism is controlled.

2. Radioactive iodine (RAI)

Radioactive iodine, given as a capsule or liquid, concentrates in the thyroid and destroys much of the gland over about 6 weeks to 6 months. The goal is to make the thyroid underactive, so almost all patients need thyroid hormone pills for life afterward. A single dose (typically 10 to 15 mCi) is usually given; a second treatment is suggested if hyperthyroidism persists after 6 months.

• Success. Success depends on the dose given: in the studies cited by the guidelines, about 6 to 9 in 10 patients were cured with one treatment, the higher figure with higher doses. Retreatment is suggested if hyperthyroidism persists.
• Eye disease. RAI can cause new or worsening thyroid eye disease in 10 to 39% of patients with Graves' disease, usually mild and temporary. The risk is higher in smokers and in patients who already have eye disease. RAI is not recommended for patients with moderate to severe or sight-threatening eye disease. In patients with mild active eye disease, a short course of prednisone is given after RAI to protect the eyes.
• Not suitable for: pregnancy, breastfeeding, suspected thyroid cancer, patients who cannot follow radiation safety rules, and women planning pregnancy within about 6 months. A pregnancy test is required within 48 hours before treatment. RAI is generally avoided in young children.
• Safety. You receive written radiation-safety instructions. The long-term cancer risk is debated: studies disagree, and hyperthyroidism itself raises some risks.

3. Surgery: total thyroidectomy

When surgery is the treatment chosen, the ATA recommends total or near-total thyroidectomy (not partial removal). Total thyroidectomy has a nearly 0% chance of recurrent hyperthyroidism, versus about 8% at 5 years with subtotal removal. After surgery, you take levothyroxine (thyroid hormone) for life. The ATA strongly recommends that surgery be done by a high-volume thyroid surgeon, because complications are lower in experienced hands. Details below.

How do the three treatments compare?

Treatment choices are individual. Percentages are approximate and come from the guidelines and the studies they cite. In U.S. practice, antithyroid drugs are increasingly chosen first, and surgery is chosen first in a small minority.

When is surgery the best choice for Graves' disease?

Situations in which surgery is favored

• A suspicious or malignant thyroid nodule, or confirmed thyroid cancer, along with Graves' disease
• A large goiter or symptoms of pressure (trouble swallowing or breathing)
• Moderate to severe active thyroid eye disease (RAI is avoided; surgery or medication is used)
• Coexisting hyperparathyroidism, which can be treated in the same operation
• Low radioactive iodine uptake, which makes RAI less effective
• A woman planning pregnancy within about 6 months who wants to avoid antithyroid drugs
• Side effects of antithyroid drugs (low white cell count or liver injury), or relapse after a course of medication
• A child who does not respond to medication. RAI is avoided in young children (especially under age 5), so surgery is preferred.
• Pregnancy with hyperthyroidism that cannot be controlled with medication (surgery is done in the second trimester)
• Need for rapid control, poor adherence to medication, or a strong preference to avoid radioactive iodine

Preparing for surgery

• Normal thyroid levels first. The ATA strongly recommends restoring normal thyroid function with methimazole (often 1 to 3 months) before the operation, with or without a beta-blocker, to prevent thyroid storm.
• Potassium iodide (SSKI or Lugol solution) in the days just before surgery, which makes the gland less vascular and reduces blood loss.
• Calcium and vitamin D are checked and corrected before surgery, because Graves' patients are at higher risk of low calcium afterward. Calcitriol may be given for patients at higher risk.
• When surgery is urgent or antithyroid drugs cannot be used, a rapid preparation regimen (beta-blocker, iodine, steroids) is used.

Benefits and risks

Surgery gives a quick, definitive cure with no radiation and no long-term drug toxicity. The risks of total thyroidectomy are low calcium from parathyroid injury (temporary or, rarely, permanent), injury to the voice box nerve causing hoarseness, bleeding, and anesthesia risks. These risks depend heavily on surgeon volume. The ATA found that surgeons performing more than 25 thyroid operations a year have better outcomes, with lower complication rates, shorter stays and lower cost. Dr. Shifrin performs more than 400 thyroid and parathyroid operations a year. Learn about thyroid surgery or request a consultation.

Graves' eye disease (thyroid eye disease)

Thyroid eye disease affects about 1 in 5,000 people a year. It usually goes along with Graves' hyperthyroidism, but about 10% of patients have normal or low thyroid function. Signs include eyelid retraction, a stare, eyelid swelling, redness, a gritty or watery feeling, bulging eyes (proptosis), pain on eye movement, and double vision.

• See an ophthalmologist if you have any eye symptoms. Loss of vision, faded colors, or sudden double vision is an emergency.
• Stop smoking and avoid secondhand smoke. Keep your thyroid levels normal and avoid both over- and underactive thyroid.
• Mild disease: artificial tears and eye ointment, sleeping with the head raised, and sunglasses. Selenium for 6 months is recommended in Europe for mild disease of short duration; the benefit in selenium-sufficient regions such as the U.S. is uncertain.
• Active moderate-to-severe disease: intravenous steroids are first-line, sometimes combined with mycophenolate. Teprotumumab, approved by the FDA in 2020, reduces bulging in most patients in trials, but has side effects (such as hearing changes and high blood sugar). Other options include tocilizumab, radiation, and orbital surgery for the stable phase.
• Thyroid eye disease tends to burn out within 1 to 3 years, and there is a 5 to 10% chance of recurrence.
• Because RAI can worsen the eyes, patients with moderate or severe eye disease are treated with antithyroid drugs or surgery.

History and discovery of Graves' disease

• The 12th-century Persian physician Sayyid Ismail al-Jurjani (Zayn al-Din Gorgani, 1040 to 1136) is credited with the first description, noting goiter together with bulging eyes in his medical encyclopedia, the Thesaurus of the Shah of Khwarazm.
• Caleb Hillier Parry, an English physician, noted the condition in 1786, though his case was not published until 1825.
• Robert James Graves, an Irish physician, described goiter with exophthalmos in 1835.
• Karl Adolph von Basedow, a German physician, independently reported the same findings in 1840.

Related pages

References and guidelines

1. Hoang TD, Stocker DJ, Chou EL, Burch HB. 2022 Update on Clinical Management of Graves' Disease and Thyroid Eye Disease. Endocrinol Metab Clin North Am. 2022;51(2):287-304. doi:10.1016/j.ecl.2021.12.004
2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343-1421. doi:10.1089/thy.2016.0229
3. Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17(3):456-520. (superseded by reference 2)
4. Stalberg P, et al. Surgical treatment of Graves' disease: evidence-based approach. World J Surg. 2008.
5. Erbil Y, et al. The effect of antithyroid drug treatment duration on thyroid gland microvessel density and intraoperative blood loss in patients with Graves' disease. Surgery. 2008;143(2):216-225.
6. Erbil Y, et al. Effect of Lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease. J Clin Endocrinol Metab. 2007;92(6):2182-2189.
7. Boostrom S, et al. Total thyroidectomy is the preferred treatment for patients with Graves' disease and a thyroid nodule. Otolaryngol Head Neck Surg. 2007;136.
8. Sosa JA, Udelsman R, et al. The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann Surg. 1998;228(3).
9. Stavrakis AI, et al. Surgeon volume as a predictor of outcomes in inpatient and outpatient endocrine surgery. Surgery. 2007;142(6).
10. Pieracci FM, Fahey TJ. Effect of hospital volume of thyroidectomies on outcomes following substernal thyroidectomy. World J Surg. 2008;32(5).
11. Clark OH. Textbook of Endocrine Surgery. 2006.

This page is for general education and does not replace a medical evaluation.