Graves’ disease, also known as toxic diffuse goiter, is the most common cause of hyperthyroidism in the United States. It is named after Robert Graves, an Irish physician, who described this form of hyperthyroidism about 150 years ago. Hyperthyroidism is a disorder that occurs when the thyroid gland makes more thyroid hormone than the body needs.
The thyroid is a 2-inch-long, butterfly-shaped gland in the front of the neck below the larynx, or voice box. The thyroid makes two thyroid hormones, triiodothyronine (T3) and thyroxine (T4). T3 is made from T4 and is the more active hormone, directly affecting the tissues. Thyroid hormones circulate throughout the body in the bloodstream and act on virtually every tissue and cell in the body.
Thyroid hormones affect metabolism, brain development, breathing, heart and nervous system functions, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels. Hyperthyroidism causes many of the body’s functions to speed up.
Thyroid hormone production is regulated by another hormone called thyroid-stimulating hormone (TSH), which is made by the pituitary gland in the brain. When thyroid hormone levels in the blood are low, the pituitary releases more TSH. When thyroid hormone levels are high, the pituitary responds by decreasing TSH production.
Graves’ disease is an autoimmune disorder. Normally, the immune system protects the body from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances. But in autoimmune diseases, the immune system attacks the body’s own cells and organs.
With Graves’ disease, the immune system makes an antibody called thyroid-stimulating immunoglobulin (TSI)—sometimes called TSH receptor antibody—that attaches to thyroid cells. TSI mimics TSH and stimulates the thyroid to make too much thyroid hormone. Sometimes the TSI antibody instead blocks thyroid hormone production, leading to conflicting symptoms that may make correct diagnosis more difficult.
What cause Graves’ disease?
Graves’ disease is triggered by a process in the body’s immune system, which normally protects us from foreign invaders such as bacteria and viruses. The immune system destroys foreign invaders with substances called antibodies produced by blood cells known as lymphocytes. Sometimes the immune system can be tricked into making antibodies that cross-react with proteins on our own cells. In many cases these antibodies can cause destruction of those cells. In Graves’ disease these antibodies (called the thyrotropin receptor antibodies (TRAb) or thyroid stimulating immunoglobulins (TSI) do the opposite – they cause the cells to work overtime. The antibodies in Graves’ disease bind to receptors on the surface of thyroid cells and stimulate those cells to overproduce and release thyroid hormones. This results in an overactive thyroid (hyperthyroidism).
What are the symptoms of Graves’ disease?
People with Graves’ disease may have common symptoms of hyperthyroidism such as
• Nervousness or irritability
• Fatigue or muscle weakness
• Heat intolerance
• Trouble sleeping
• hand tremors
• Rapid and irregular heartbeat
• Frequent bowel movements or diarrhea
• Weight loss
• Goiter, which is an enlarged thyroid that may cause the neck to look swollen and can interfere with normal breathing and swallowing
A small number of people with Graves’ disease also experience thickening and reddening of the skin on their shins. This usually painless problem is called pretibial myxedema or Graves’ dermopathy.
In addition, the eyes of people with Graves’ disease may appear enlarged because their eyelids are retracted seem pulled back into the eye sockets and their eyes bulge out from the eye sockets. This condition is called Graves’ ophthalmopathy (GO).
What is Graves’ ophthalmopathy?
Graves’ ophthalmopathy is a condition associated with Graves’ disease that occurs when cells from the immune system attack the muscles and other tissues around the eyes.
Graves’ disease is the only kind of hyperthyroidism that can be associated with inflammation of the eyes, swelling of the tissues around the eyes and bulging of the eyes (called Graves’ ophthalmopathy or orbitopathy). Overall, a third of patients with Graves’ disease develop some signs and symptoms of Graves’ eye disease but only 5% have moderate-to-severe inflammation of the eye tissues to cause serious or permanent vision trouble. Patients who have any suggestion of eye symptoms should seek an evaluation with an eye doctor (an ophthalmologist) as well as their endocrinologist.
Eye symptoms most often begin about six months before or after the diagnosis of Graves’ disease has been made. Seldom do eye problems occur long after the disease has been treated. In some patients with eye symptoms, hyperthyroidism never develops and, rarely, patients may be hypothyroid. The severity of the eye symptoms is not related to the severity of the hyperthyroidism.
Early signs of trouble might be red or inflamed eyes, a bulging of the eyes due to inflammation of the tissues behind the eyeball or double vision. Diminished vision or double vision are rare problems that usually occur later, if at all. We do not know why, but problems with the eyes occur much more often and are more severe in people with Graves’ disease who smoke cigarettes.
How is Graves’ disease diagnosed?
Health care providers can sometimes diagnose Graves’ disease based only on a physical examination and a medical history. Blood tests and other diagnostic tests, such as the following, then confirm the diagnosis.
TSH test. The ultrasensitive TSH test is usually the first test performed. This test detects even tiny amounts of TSH in the blood and is the most accurate measure of thyroid activity available.
T3 and T4 test. Another blood test used to diagnose Graves’ disease measures T3 and T4 levels. In making a diagnosis, health care providers look for below-normal levels of TSH, normal to elevated levels of T4, and elevated levels of T3.
Because the combination of low TSH and high T3 and T4 can occur with other thyroid problems, health care providers may order other tests to finalize the diagnosis. The following two tests use small, safe doses of radioactive iodine because the thyroid uses iodine to make thyroid hormone.
Radioactive iodine uptake test. This test measures the amount of iodine the thyroid collects from the bloodstream. High levels of iodine uptake can indicate Graves’ disease.
Thyroid scan. This scan shows how and where iodine is distributed in the thyroid. With Graves’ disease the entire thyroid is involved, so the iodine shows up throughout the gland. Other causes of hyperthyroidism such as nodules—small lumps in the gland—show a different pattern of iodine distribution
TSI test. Health care providers may also recommend the TSI test, although this test usually isn’t necessary to diagnose Graves’ disease. This test, also called a TSH antibody test, measures the level of TSI in the blood. Most people with Graves’ disease have this antibody, but people whose hyperthyroidism is caused by other conditions do not.
How is Graves’ disease treated?
All hyperthyroid patients should be initially treated with beta-blockers. Treatment options to control Graves’ disease hyperthyroidism include antithyroid drugs (generally methimazole [Tapazole®], although propylthiouracil [PTU] may be used in rare instances such as the first trimester of pregnancy), radioactive iodine and surgery.
Antithyroid medications are typically preferred in patients who have a high likelihood of remission (women, mild disease, and small goiters, negative or low titer of antibodies). These medications do not cure Graves’ hyperthyroidism, but when given in adequate doses are effective in controlling the hyperthyroidism.
If methimazole is chosen, it can be continued for 12-18 months and then discontinued if TSH and TRAb levels are normal at that time. If TRAb levels remain elevated, the chances of remission are much lower and prolonging treatment with antithyroid drugs is safe and may increase chances of remission. Long term treatment of hyperthyroidism with antithyroid drugs may be considered in selected cases.
If your hyperthyroidism due to Graves’ disease persists after 6 months, then your doctor may recommend definitive treatment with either radioactive iodine or surgery.
If surgery (thyroidectomy) is selected as the treatment modality, the surgery should be performed by a skilled surgeon with expertise in thyroid surgery to reduce the risk of complications.
Your doctor should discuss each of the treatment options with you including the logistics, benefits and potential side effects, expected speed of recovery and costs. Although each treatment has its advantages and disadvantages, most patients will find one treatment plan that is right for them. Hyperthyroidism due to Graves’ disease is, in general, controllable and safely treated and treatment is almost always successful.