Graves' disease (patient information)

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 * Assistant Editor-in-Chief: Meagan E. Doherty

Overview
Graves’ disease, also known as toxic diffuse goiter, is the most common cause of hyperthyroidism in the United States. Hyperthyroidism is a disorder that occurs when the thyroid gland makes more thyroid hormone than the body needs.

The thyroid is a small, butterfly-shaped gland in the front of the neck below the larynx, or voice box. The thyroid gland makes two thyroid hormones, triiodothyronine (T3) and thyroxine (T4). Thyroid hormones affect metabolism, brain development, breathing, heart and nervous system functions, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels.

Thyroid hormone production is regulated by another hormone called thyroid-stimulating hormone (TSH), which is made by the pituitary gland located in the brain.

Graves’ disease is an autoimmune disorder, meaning the body’s immune system acts against its own healthy cells and tissues. In Graves’ disease, the immune system makes antibodies called thyroid-stimulating immunoglobulin (TSI) that attach to thyroid cells. TSI mimics the action of TSH and stimulates the thyroid to make too much thyroid hormone. Sometimes the antibodies can instead block thyroid hormone production, leading to a confusing clinical picture. The diagnosis and treatment of Graves’ disease is often performed by an endocrinologist—a doctor who specializes in the body’s hormone-secreting glands.

What are the symptoms of Graves' disease?

 * Anxiety
 * Breast enlargement in men
 * Difficulty concentrating
 * Double vision
 * Eyeballs that stick out (exophthalmos)
 * Eye irritation and tearing
 * Fatigue
 * Frequent bowel movements
 * Goiter
 * Heat intolerance
 * Increased appetite
 * Increased sweating
 * Insomnia
 * Menstrual irregularities in women
 * Muscle weakness
 * Nervousness
 * Rapid or irregular heartbeat (palpitations or arrhythmia)
 * Restlessness and difficulty sleeping
 * Shortness of breath with exertion
 * Tremor
 * Weight loss (rarely, weight gain)

What causes Graves' disease?
The thyroid gland is an important organ of the endocrine system. It is located in the front of the neck just below the voice box. This gland releases the hormones thyroxine (T4) and triiodothyronine (T3), which control body metabolism. Controlling metabolism is critical for regulating mood, weight, and mental and physical energy levels.

If the body makes too much thyroid hormone, the condition is called hyperthyroidism.

Who is at highest risk?
Scientists don’t know exactly why some people develop Graves’ disease, but they believe factors such as age, sex, heredity, and emotional and environmental stress are involved.

Graves’ disease usually occurs in people younger than age 40 and is five to 10 times more common in women than men. An individual’s chance of developing Graves’ disease increases if other family members have it.

Researchers have not been able to find a specific gene that causes the disease to be passed from one generation to the next. Scientists know that some people inherit an immune system that can make antibodies against healthy cells, but predicting who will be affected is difficult.

People with other autoimmune diseases have an increased chance of developing Graves’ disease. Type 1 diabetes, rheumatoid arthritis, and vitiligo—a disorder in which some parts of the skin are not pigmented—are among the conditions associated with Graves’ disease.

Diagnosis
Doctors can sometimes diagnose Graves’ disease based only on a physical examination and a medical history. Laboratory tests confirm the diagnosis.

The ultrasensitive TSH test is usually the first test a doctor performs. This test detects even tiny amounts of TSH in the blood and is the most accurate measure of thyroid activity available. Another blood test used to diagnose Graves’ disease measures T3 and T4. In making a diagnosis, doctors 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, doctors may order other tests to finalize the diagnosis. Two of these tests are based on the fact that the thyroid gland uses iodine to make thyroid hormone. Both tests use small, safe doses of radioactive iodine.
 * The radioactive iodine uptake test measures the amount of iodine the thyroid collects from the bloodstream. High levels of iodine uptake can indicate Graves’ disease.
 * A thyroid scan shows how and where iodine is distributed in the thyroid. In Graves’ disease, the entire thyroid gland is involved so the iodine shows up throughout the gland. Other causes of hyperthyroidism such as nodules—small lumps in the gland—will show a different pattern of iodine distribution.

Doctors may also consider the thyroid-stimulating immunoglobulin 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.

When to seek urgent medical care?
Call your health care provider if you have symptoms of Graves disease. Also call if your eye problems or general symptoms get worse (or do not improve) with treatment.

Go to the emergency room or call the local emergency number (such as 911) if you have symptoms of hyperthyroidism with:
 * Decrease in consciousness
 * Fever
 * Rapid, irregular heartbeat

Treatment options
Doctors may prescribe one or more of the three treatment options: radioiodine therapy, antithyroid drugs, or thyroid surgery. Radioiodine therapy is the most commonly used treatment for Graves’ disease in the United States.

Radioiodine Therapy
In radioiodine therapy, the patient takes radioactive iodine-131 by mouth. Because the thyroid gland collects iodine to make thyroid hormone, it will collect the radioactive iodine from the bloodstream in the same way. Iodine-131—stronger than the radioactive iodine used in diagnostic tests—will gradually destroy the cells that make up the thyroid gland but will not affect other tissues in the body.

Many doctors use a large enough dose of iodine-131 to shut down the thyroid completely, but some prefer smaller doses to try to bring hormone production into the normal range. More than one round of radioiodine therapy may be needed. Results take time and a person undergoing this treatment may not notice improvement in symptoms for several weeks or months.

Although iodine-131 is not known to cause birth defects or infertility, radioiodine therapy is not used in pregnant women or women who are breastfeeding. Radioactive iodine can be harmful to the fetus’ thyroid, and it can be passed from mother to child in breast milk.

Almost everyone who receives radioactive iodine treatment eventually develops hypothyroidism, which occurs when the thyroid does not make enough thyroid hormone. People with hypothyroidism must take synthetic thyroid hormone.

Medications
Doctors may prescribe a drug called a beta blocker to reduce symptoms until other treatments take effect. Beta blockers act quickly to relieve symptoms such as hand tremors, rapid heart beat, and nervousness. These drugs act by blocking the effects of thyroid hormone on the body, but they do not stop thyroid hormone production.

Two antithyroid drugs, methimazole and propylthiouracil (PTU), interfere with the way the thyroid gland uses iodine to make thyroid hormones. Doctors sometimes use antithyroid drugs as the only treatment for Graves’ disease, but these drugs usually do not produce permanent results and their use requires frequent monitoring by a health care provider. More often, antithyroid drugs are used to pretreat patients older than 60 or those who have other health problems before beginning radioiodine therapy, or as a supplemental treatment after radioiodine therapy.

Because pregnant and breastfeeding women cannot receive radioiodine therapy, they are usually treated with an antithyroid drug instead. Pregnant women should not take methimazole and should be monitored if they take PTU. Women who are breastfeeding should take the smallest dose necessary of either drug.

Antithyroid drugs can cause side effects in some people. Allergic reactions such as rashes and itching are the most common side effects. Rarely, antithyroid drugs cause liver failure or a decrease in the number of white blood cells, which can lower resistance to infection.

Thyroid Surgery
Surgery is the least-used option in treating Graves’ disease. However, doctors sometimes choose surgery to treat pregnant women who cannot tolerate antithyroid drugs, people in whom thyroid cancer is suspected, or those who fail other forms of treatment. Graves’ disease itself does not cause cancer.

When surgery is used, many doctors recommend the entire thyroid be removed, thus eliminating the chance that hyperthyroidism will return. If the entire thyroid is removed, lifelong thyroid hormone replacement is necessary.

Although uncommon, certain problems can occur in thyroid surgery. The parathyroid glands could be damaged because they are located very close to the thyroid gland. These glands help control calcium levels in the body. Damage to the laryngeal nerve, also located close to the thyroid gland, could lead to voice changes or breathing problems. When surgery is performed by an experienced surgeon, less than 1 percent of patients have permanent complications.

Eye Care
The eye problems associated with Graves’ disease may not improve following thyroid treatment, so the two problems are often treated separately.

Eye drops can relieve dry, gritty, irritated eyes—the most common of the milder symptoms. If pain and swelling occur, doctors may prescribe a steroid drug such as prednisone. Other drugs that suppress the immune response may also provide relief. Special lenses for glasses can help with light sensitivity and double vision. Patients may be advised to sleep with the head elevated to reduce eyelid swelling. For people who are unable to fully close their eyelids, taping the eyelids shut at night can help prevent dry eyes.

In more severe cases, external radiation applied to the eyes may be used to reduce inflammation. Like other types of radiation treatment, the beneficial effects are not immediate, but most people feel relief from symptoms as soon as 1 to 2 months after treatment.

Surgery may be used to improve the protrusion of the eyes and correct the vision changes caused by pressure on the optic nerve. A procedure called orbital decompression makes the eye socket bigger, giving the eye room to sink back to a more normal position. Eyelid surgery can return retracted eyelids to their normal position.

Diseases with similar symptoms

 * Crohn's disease
 * Hyperthyroidism
 * Inflammatory bowel disease
 * Pheochromocytoma
 * Short QT syndrome
 * Thyroiditis

Where to find medical care for Graves' disease
Directions to Hospitals Treating Graves' disease

What to expect (Outlook/Prognosis)
Graves disease often responds well to treatment. However, thyroid surgery or radioactive iodine usually will cause hypothyroidism. Without getting the correct dose of thyroid hormone replacement, hypothyroidism can lead to:
 * Depression
 * Mental and physical sluggishness
 * Weight gain

Antithyroid medications can also have serious side effects.

Possible complications

 * Complications from surgery, including:
 * Hoarseness from damage to the nerve leading to the voice box
 * Low calcium levels from damage to the parathyroid glands (located near the thyroid gland)
 * Scarring of the neck
 * Eye problems (called Graves ophthalmopathy or exophthalmos
 * Heart-related complications, including:
 * Rapid heart rate
 * Congestive heart failure (especially in the elderly)
 * Atrial fibrillation
 * Thyroid crisis (thyrotoxic storm), a severe worsening of overactive thyroid gland symptoms
 * Increased risk for osteoporosis, if hyperthyroidism is present for a long time
 * Complications related to thyroid hormone replacement
 * If too little hormone is given, fatigue, weight gain, high cholesterol, depression, physical sluggishness, and other symptoms of hypothyroidism can occur
 * If too much hormone is given, symptoms of hyperthyroidism will return