Graves’ Disease

The thyroid gland is a butterfly-shaped endocrine gland that is located in the lower front of the neck. The thyroid makes thyroid hormones, which are secreted into the blood and then carried to every tissue in the body. Thyroid hormones help the body use energy, stay warm and keep the brain, heart, muscles, and other organs working appropriately.

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).

• Hyperthyroidism
  The majority of symptoms of Graves’ disease are caused by the excessive production of thyroid hormones by the thyroid gland (see Hyperthyroidism brochure). These may include, but are not limited to, racing heartbeat, hand tremors, trouble sleeping, weight loss, muscle weakness, neuropsychiatric symptoms and heat intolerance.
• Eye disease
  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.
• Skin disease
  Rarely, patients with Graves’ disease develop a lumpy reddish thickening of the skin in front of the shins known as pretibial myxedema (called Graves’ dermopathy). This skin condition is usually painless and relatively mild, but it can be painful for some. Like the eye trouble of Graves’ disease, the skin problem does not necessarily begin precisely when the hyperthyroidism starts. Its severity is not related to the level of thyroid hormone.

The diagnosis of hyperthyroidism is made on the basis of your symptoms and findings during a physical exam and it is confirmed by laboratory tests that measure the amount of thyroid hormones (thyroxine, or T4, and triiodothyronine, or T3) and thyroid-stimulating hormone (TSH) in your blood (see the Hyperthyroidism brochure). Clues that your hyperthyroidism is caused by Graves’ disease are the presence of Graves’ eye disease and/or dermopathy (see above), a symmetrically enlarged thyroid gland and a history of other family members with thyroid or other autoimmune problems, including type 1 diabetes, rheumatoid arthritis, pernicious anemia (due to lack of vitamin B12) or painless white patches on the skin known as vitiligo.

The choice of initial diagnostic testing depends on cost, availability and local expertise. Measurement of antibodies, such as TRAb or TSI, is cost effective and if positive, confirms the diagnosis of Graves’ disease without further testing needed. If this test is negative (which can also occur in some patients with Graves’ disease), or if this test is not available, then your doctor should refer you to have a radioactive iodine uptake test (RAIU) to confirm the diagnosis.

Also, in some patients, measurement of thyroidal blood flow with ultrasonography may be useful to establish the diagnosis if the above tests are not readily available.

The treatment of hyperthyroidism is described in detail in the Hyperthyroidism brochure. 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, 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.

If you receive definitive treatment for your Graves’ hyperthyroidism (such as radioactive iodine or surgery), you will eventually develop hypothyroidism (underactive thyroid). Even if you are treated with antithyroid drugs alone, hypothyroidism can still occur. Your doctor will check your thyroid function tests frequently to assess thyroid function following treatment. When hypothyroidism occurs, you will need to take a thyroid hormone tablet once a day at the right dose (see Hypothyroidism brochure).

Graves’ disease is an autoimmune disease and has a genetic predisposition. However, no specific gene has been identified for screening to date.