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The Overactive Thyroid:

Hyperthyroidism Caused by Graves' Disease (Diffuse Toxic Goiter)

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The most common type of hyperthyroidism is produced by a generalized overactivity of the entire thyroid gland. This is called diffuse toxic goiter: diffuse because the entire gland is involved in the disease process, toxic because the patient appears hot and flushed, as if he or she were "toxic" due to an infection, and goiter because the overactivity enlarges the gland. Goiter is also known as Graves' disease, in honor of the Irish physician, Robert J. Graves, who was one of the first to describe this condition and who first noted the protrusion of the eyes that is sometimes associated with it. Between 1 and 2% of all people in the United States will develop Graves' disease. It is 3 to 4 times more common in women than in men, and typically begins between the ages of 20 and 40.

If you develop Graves' disease, your thyroid will begin to produce more and more thyroid hormone. As it does so, the gland will usually grow larger and will, in most cases, grow big enough to protrude noticeably in the front of your neck. You may notice the enlargement in your neck yourself, or you may not notice anything until a friend or your physician points it out. If the goiter is small, you may only sense the presence of a lump while swallowing. Typically, in this form of hyperthyroidism your thyroid gland is not tender, and it is not uncomfortable when you swallow.

As you develop hyperthyroidism, you may lose weight even though you seem to eat plenty of food. You may feel nervous and jumpy and may become quite irritable and quarrelsome. You are likely to perspire more than usual and dislike hot weather. Your skin may gradually become thin and delicate, and you may notice that you are losing some of the hair on your head. As your fingernails grow more rapidly, you may notice an irregularity of the nail margin, making it difficult for you to keep your fingernails clean. It is also possible that you could develop itchy hives on your skin.

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Signs & Symptoms of Graves' disease

Muscle weakness, especially involving your upper arms and thighs, may make it difficult for you to carry heavy packages or to climb stairs. You may, in fact, experience such marked leg weakness that you cannot stand up from a squatting position without help. You may notice that your hands shake, and at times this tremor may become so severe that you can't even carry a cup of coffee without its rattling or spilling in its saucer. Your heartbeat may speed up from a normal rate of 70 or 80 to well over 100 beats per minute. Occasionally, without warning, your pulse may quicken abruptly, causing very rapid palpitations that last several minutes and then end as mysteriously and abruptly as they began. You are unlikely to have real diarrhea, but your bowel movements may become loose and more frequent.

If you are a woman, your menstrual cycle may change. Your flow may become much lighter and the interval between menstrual periods may lengthen. More rarely, your periods may become irregular, or may cease entirely, making it more difficult for you to become pregnant. If pregnancy does occur, there appears to be an increased likelihood that you will have a miscarriage. Women usually notice little change in their breasts, but if you are a man, your breasts may become slightly larger and may be tender.

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Eye Involvement

One of the most puzzling and least understood aspects of Graves' disease is the way it may affect your eyes. Usually the change is simply an elevation of your upper eyelids that makes your eyes appear more prominent. Occasionally, however, swelling of the tissue behind your eyeballs may cause actual protrusion of the eyes known as exophthalmos or proptosis. Sometimes your eyes will feel dry or become red and irritated. A few patients have involvement of their eye muscles that may make them see double. In its most extreme (and very rare) form, the nerve to one or both of your eyes becomes inflamed and you may have trouble with your vision. This condition is known as optic neuropathy.

Elevation of the upper eyelids may be seen in anyone who has a high level of thyroid hormone, even someone who is taking thyroid hormone tablets in excess. The other things that can happen to your eyes in Graves' disease are unrelated to your blood level of thyroid hormone. If you are one of the people with Graves' disease who develops eye inflammation and protrusion, the eye problems probably will begin when you first become hyperthyroid. Quite often, however, eye problems and thyroid overactivity occur at different times, occasionally separated from one another by many years. Very rarely, a person may develop eye trouble as the only manifestation of Graves' disease.

Eye disease is therefore one problem that occurs only in the type of hyperthyroidism that is caused by Graves' disease. Another condition unique to Graves' disease is a very rare skin disorder that appears on the front of your legs and rarely on top of your feet. This is called pretibial myxedema, and takes the form of a lumpy, reddish colored thickening of your skin. It is usually painless and not serious. As with the eye trouble in Graves' disease, pretibial myxedema may occur anytime. Its appearance does not necessarily coincide with the beginning of your thyroid problem, nor is its severity related to your blood level of thyroid hormone. One of the rarest manifestations of Graves' disease is thyroid acropachy, which causes the tissues around the base of the nails to become swollen, but not painful. Periodic paralysis is yet another condition seen in occasional patients with Graves' disease. This disorder causes sudden attacks of profound weakness of all of the muscles of the body. In susceptible patients, sugar or starchy foods appear to cause a lowering of the blood potassium level, which prevents normal muscle function. For unknown reasons, periodic paralysis is most often seen in Asian men with Graves' disease.

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Causes of Graves' disease

Graves' disease seems to be caused by the interaction of a variety of different factors, including heredity, your body's immune system, your age, sex hormones, and stress. Some sort of genetic predisposition seems to be needed first, and can be thought of as an inherited tendency to develop hyperthyroidism. If you have this factor, you may develop Graves' disease at some time during your life, or you may not, but if you lack this genetic factor, you probably cannot develop this disorder.

This type of hyperthyroidism clearly runs in families. If you have Graves' disease, and if sensitive thyroid tests could be carried out on your relatives, they might show mild thyroid abnormalities in one of your parents and one of your grandparents, in some of your aunts, uncles, brothers, and sisters, and possibly in some of your children as well. Fortunately, few of these relatives will ever become sick enough from their thyroid problems to require treatment; but some of them should be checked occasionally in this regard by their family physician.

Studies in identical twins confirm the importance of genetics in Graves' disease and also show the ability of other factors to modify the disease. Usually, identical twins either both have Graves' disease or neither develops the problem. But since other factors influence the disease process, twins rarely experience the onset of hyperthyroidism at the same time, and the course of the disease in the twins may be quite different.

There appear to be many different factors that can "trigger off" Graves' disease in a person who has inherited a tendency to it. Many thyroid specialists believe that stress can play a role in starting the hyperthyroidism, for we have all seen patients in whom a stressful situation, such as a death in the family, has preceded the onset of this condition. Sex hormones are also important, for the disease is seven to nine times more common in women than in men, and not infrequently begins after a hormonal change such as pregnancy. Age also seems to have something to do with the onset of Graves' disease, since it is most likely to appear when you are between the ages of twenty and forty. Finally, your body's immune system appears to play a role in the production of this disorder.

By an unknown mechanism, substances called autoantibodies appear in your blood. These autoantibodies bind to the cells in your thyroid gland and stimulate the thyroid to overactivity by mimicking the effects of pituitary thyroid stimulating hormone (TSH). This causes the thyroid to enlarge and to make more thyroid hormone. Thus, instead of being under the control of your pituitary gland , which is the normal situation, your thyroid becomes controlled by these abnormal antibodies in your blood.

The immune disorder that characterizes Graves' disease usually develops spontaneously, but recent studies have shown that you could be at increased risk for the disease if your thyroid gland was inadvertently damaged by x-rays for cancer therapy in the past or if you are taking one of the new immune-altering drugs like interferon and interleukin.


In summary, a susceptible person develops Graves' disease because of one or more factors that trigger off thyroid overactivity. As thyroid function increases, more thyroid hormones are released into the blood stream, producing the symptoms of hyperthyroidism.