Graves Disease

Graves' disease is the type of hyperthyroidism caused by a generalized overactivity of the entire thyroid gland. It is also called "diffuse toxic goiter": "diffuse" because the entire thyroid gland is involved in the disease process; "toxic" because the patient appears hot and flushed, as if feverish due to an infection; and "goiter" because the thyroid gland enlarges in this condition. It is often referred to as Graves' disease in honor of the Irish physician Robert Graves who was the first to describe this form of hyperthyroidism.
 

An Autoimmune Disorder

Current research shows that the process which triggers Graves' disease involves the immune system of the body, which normally protects us from foreign invaders such as bacteria and viruses, as well as from abnormal body cells such as cancer cells. The immune system recognizes foreign invaders or abnormal cells and destroys them by means of antibodies produced by blood cells known as lymphocytes.
 

It is likely that 10 to 15 percent of people inherit an immune system with a problem. Their lymphocytes have the capacity to make antibodies against their own tissues which stimulate or damage those cells. In Graves' disease, antibodies are produced against certain proteins on the surface of thyroid cells, stimulating those cells to overproduce thyroid hormones. This results in an overactive thyroid.
 

Although up to 10 percent of the population has the type of immune system that can lead to Graves' disease, only about one in ten of these individuals ever actually develop hyperthyroidism. This may be due to the fact that they are never exposed to the environmental factors that can trigger the problem.
 

What are the Environmental Triggers?

Physicians have long suspected that a severe emotional stress, such as the death of a loved one, can trigger Graves' disease in some patients. Dr. Graves himself commented on stressful events in his patients' lives which preceded other evidence of hyperthyroidism by several months. Indeed, recent evidence suggests that increased blood levels of cortisone and adrenaline, which may be caused by stress, can, in turn, affect antibody production by the immune system. However, many patients who develop Graves' disease have no identifiable stress in their lives.
 

What are the Symptoms of Graves' Disease?

If you develop Graves' disease, several weeks or months may pass before you realize that you are sick. The onset is gradual, and the symptoms may be mistaken for simple nervousness due to a stressful life situation. If you have been trying to lose weight by dieting, success with your diet may be pleasing, until the hyperthyroidism which has accelerated the weight loss leads to other problems such as trembling, muscle weakness of the upper arms and thighs, and insomnia.
 

As your thyroid becomes increasingly overactive, you may notice an increase in pulse rate, often with sudden episodes of palpitations, increased sweating, and heat intolerance. Your skin may become fine, and hair loss may be noticed as your hair becomes more delicate. Bowel movements may happen more frequently, though diarrhea is uncommon. If you are a woman (and Graves' disease is four to eight times more common in women than in men), your menstrual flow may lighten and the interval between menstrual periods may lengthen.
 

What about the Eyes and Skin?

Graves' disease is the only kind of hyperthyroidism that is associated with inflammation of the eyes, swelling of the tissues around the eyes, and protrusion of the eyes. We do not know the cause of these problems.
 

Although many patients with Graves' disease experience redness and irritation of the eyes in the course of their disease, less than 1 percent ever develop enough inflammation of the eye tissues to cause serious or permanent trouble. The severity is not related to the degree of thyroid hormone abnormality. Early signs of trouble might include bulging of the eyes due to inflammation of the tissues behind the eyeball, double vision, red or inflamed eyes, or diminished vision. Eye symptoms generally begin within a six-month period before or after the diagnosis of Graves' disease has been made.

Very occasionally, patients with Graves' disease develop a lumpy reddish thickening of the skin in front of the shins known as pretibial myxedema. This skin condition is usually painless and not serious and, like the eye trouble of Graves' disease, does not necessarily begin precisely when the hyperthyroidism starts. Its severity is not related to the level of thyroid hormone. We do not know why this problem is usually limited to the lower leg nor why so few people have it.

How is the Diagnosis of Graves' Disease Made?

If your physician suspects that you have hyperthyroidism, confirmation of the diagnosis is usually a simple matter. Physical examination usually reveals an enlarged thyroid gland and a rapid pulse, in addition to delicate skin and the tremor of your fingertips. Your reflexes are likely to be rapid, and you may have some of the eye or skin abnormalities described above.
 

Additional clues that you may have hyperthyroidism often come from a review of the medical history of your family. Some relatives may have had hyperthyroidism or an underactive thyroid; others may have acquired gray hair prematurely (beginning in their 20's). Similarly, there may be a history of related immune problems in the family, including juvenile diabetes, pernicious anemia (due to lack of vitamin B-12), or painless white spots on the skin known as vitiligo.

Confirmation of your physician's suspicion that you have hyperthyroidism is usually obtained in a simple blood test which reveals high levels of thyroid hormones. Also, the level of TSH (thyroid-stimulating hormone) made by your pituitary gland is low. Occasionally, the doctor may wish to measure the thyroid-stimulating antibodies (TSAb) in your blood. Sometimes a radioactive image, or scan, of the thyroid is obtained which demonstrates overactivity of the entire thyroid gland. This is characteristic of Graves' disease and eliminates the possibility that your hyperthyroidism is due to overactive nodules or lumps within the gland. In those rare instances in which a patient is hyperthyroid due to thyroiditis (inflammation of the gland), there is usually very low uptake of radioiodine by the thyroid.

How is Graves' Disease Treated?

Reports from the 1800s describe a mortality rate as high as 50 percent in patients with Graves' disease when rest and sedation were the only treatment available for the condition. Fortunately, there are three good ways to treat the problem now.

Drugs

Antithyroid drugs, such as propylthiouracil (PTU) and methimazole (Tapazole®), act by making it more difficult for your thyroid to use iodine. Since your thyroid uses iodine to make thyroid hormone, the net effect is a decrease in thyroid hormone production. These drugs are used when prompt control of hyperthyroidism is desired, when the hyperthyroidism is mild, or when it occurs in children or young adults. They are especially helpful as temporary treatment in elderly patients with heart disease, including angina or rhythm disorders, who risk heart damage when severely hyperthyroid.
 

Treatment with antithyroid drugs for a period of 12 to 18 months will result in prolonged remission of the disease in about 20 to 30 percent of patients, and is most likely in patients with milder disease at the beginning of treatment.

Antithyroid drugs cause allergic reactions in about 5 percent of patients who take them. The common minor reactions include red skin rashes, hives, and occasionally fever and joint pains. Far more serious is a decrease in the number of neutrophils (white blood cells) which may lower your resistance to infection. Very rarely these white cells may disappear completely, producing a condition known as agranulocytosis, an extremely serious and potentially fatal problem if a serious infection occurs. Fortunately, this side effect is very rare.

If you take one of these drugs and experience an infection such as a sore throat, you should stop the drug immediately and have a white blood cell count that day. Even if your white blood cell count has been lowered by the drug, it will return to normal if the drug is stopped immediately. But if you continue to take one of these drugs in spite of a low white blood cell count, there is a risk of a more serious, even life-threatening infection.

Radioiodine

Because of the failure of antithyroid drugs to cure most patients, the majority of patients today are treated with radioactive iodine. The radioactive iodine used in this treatment is administered by mouth, usually in a small capsule or a drink of water. Over the ensuing hours the radioactive iodine goes from the stomach into the bloodstream and ultimately passes into the thyroid gland where it remains for a long enough time to damage some of the thyroid cells. Then, within days, it disappears from the body, either eliminated in the urine or transformed by radioactive decay into a nonradioactive state.
 

Most patients get well in three to six months, although some may remain hyperthyroid if the dose was too small. Patients who remain hyperthyroid can be given a second or even a third dose of radioactive iodine. A large majority of patients develop an underactive thyroid (hypothyroidism) after radioiodine. This can easily be treated with a thyroid hormone supplement once a day.

Radioactive iodine has been used to treat patients for hyperthyroidism since about 1940. Because of concern that the radioactive iodine might somehow damage other cells in the body, produce cancer, or have other long-term unwanted effects, the physicians who first used radioiodine treatments were careful to treat only adults and to follow them carefully for the rest of their lives. Fortunately, no serious complications from radioiodine treatment have become apparent over nearly 50 years of careful patient follow-up. As a result, in America more than 70 percent of adults who develop hyperthyroidism are treated in this manner. Children are now being treated increasingly with radioiodine and even in these patients there have been almost no complications.

Surgery

Your hyperthyroidism can be permanently cured by means of an operation in which most of your thyroid gland is removed. An operation could be risky unless your hyperthyroidism is first controlled by an antithyroid or a beta blocking drug, described below. Treatment with either propylthiouracil or Tapazole® should lower your thyroid hormone levels to normal in about six weeks, and restores your body to almost normal before surgery.

Usually for some days prior to surgery, your physician will want you to take some drops of nonradioactive iodine (either Lugol's iodine or supersaturated potassium iodide, SSKI). This extra iodine helps the surgeon by reducing the blood supply to the thyroid gland, thereby making surgery easier and safer.
 

Once the thyroid gland is removed, the source of the hyperthyroidism is gone and you will either remain well or become hypothyroid, depending upon the amount of thyroid tissue removed in the operation. As with hypothyroidism after radioiodine treatment, if you are hypothyroid after surgery, your health can be restored to normal by treatment once a day with a thyroid hormone supplement.

Beta-Blockers

No matter which of these three methods of treatment you have for your hyperthyroidism, your physician may, in addition, prescribe a beta-adrenergic blocking drug such as atenolol (Tenormin®), nadolol (Corgard®), metoprolol (Lopressor®), or propranolol (Inderal®) to block the action of circulating thyroid hormone on your body tissues, slowing your heart rate and lessening your nervousness. These drugs may be extremely helpful in reducing symptoms until one of the other forms of treatment has had a chance to take effect. They are not used, however, in patients who have asthma or heart failure which may be worsened with these drugs. Also, diabetic patients taking insulin need to be careful, since the warning symptoms of low blood sugar may be lost while taking one of these beta-blocking drugs.

What will be the Outcome of Treatment?

No matter how your hyperthyroidism is controlled, it is probable that you will experience hypothyroidism someday. This is because the natural history of the condition tends to lead towards hypothyroidism, probably due to low-grade inflammation (chronic thyroiditis) of your thyroid gland. Hypothyroidism will occur sooner if your thyroid has been damaged by radioactive iodine or partly removed in an operation. But, even if you are treated with antithyroid drugs alone, hypothyroidism can still occur.
 

Since the natural tendency is to progress toward hypothyroidism sometime after you have been hyperthyroid, every patient who has ever had hyperthyroidism due to Graves' disease should have blood tests once a year to measure thyroid function. Low thyroid hormone levels cause your pituitary gland to produce increased amounts of thyroid-stimulating hormone (TSH). Since a high TSH blood level is the most sensitive indicator of hypothyroidism, your annual thyroid evaluation should always include a TSH test.

When hypothyroidism occurs, it can be simply and safely controlled by a thyroid hormone tablet taken once a day. Since the potency of generic thyroid tablets has in the past varied considerably, your physician will likely specify a brand name of thyroxine (T4) to treat your hypothyroidism.

Other Considerations

Hyperthyroidism due to Graves' disease is, in general, easily controlled and safely treated. Where complications occur, such as the associated eye disorders, an eye doctor's opinion may be extremely helpful. For the most part, however, the condition is neither difficult to diagnose or treat, and the results of therapy are gratifying.