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Graves' Disease Information

Graves-Basedow disease is a medical disorder that may manifest several different conditions including hyperthyroidism (over activity of thyroid hormone production), infiltrative exophthalmos (protruberance of one or both eyes and associated problems) and infiltrative dermopathy (a skin condition usually of the lower extremities). This disorder is the most common cause of hyperthyroidism.

Also known in the English-speaking world simply as Graves' disease, the disease occurs most frequently in women (8:1 compared to men). It occurs most often in middle age but is not uncommon in adolescents, during pregnancy, at the time of menopause and in people over age 50.

Symptoms may include fatigue, weight loss (despite a good appetite), rapid heart beat, heat intolerance, muscle weakness, palpitation, increased bowel activity, emotional lability, and restlessness. In pre-menstrual women, there may be a reduction in the amount of menses (oligomenorrhea). Because similar antibodies to those stimulating the thyroid may also react with the eye muscles, patients may develop an enlargement of the ocular muscles with resultant forward movement of the eyeball and inflammation of the tissues around the eye. Enlargement of the eye muscles may result in difficulty with proper movement and coordination of the eyes and cause double vision and an obvious disparity in the relative position of both eyes. These ocular manifestations of Graves-Basedow disease are more common in smokers and tend to worsen (or develop for the first time) following radio-iodine treatment of the thyroid condition.

The ocular manifestations of Graves-Basedow disease are more common in smokers and tend to worsen (or develop for the first time) following radioiodine treatment of the thyroid condition. Thus, they are not caused by hyperthyroidism per se; this common misperception may result from the fact that hyperthyroidism from other causes may cause eyelid retraction or eyelid lag (so-called hyperthyroid stare) which can be confused with the general appearance of proptosis/exopthalmos, despite the fact that the globes do not actually protrude in other causes of hyperthyroidism. Also, both conditions may exist at the same time in the hyperthyroid patient with Graves-Basedow disease.

Treatment of the hyperthyroidism of Graves-Basedow disease may be with medications such as methimazole or propylthiouracil (PTU), which reduce the production of thyroid hormone, or with radioactive iodine. Surgical removal of the thyroid is another option, but still requires preoperative treatment with methimazole or PTU. This is done to render the patient "euthyroid" (i.e. normothyroid) before the surgery since operating on a frankly hyperthyroid patient is dangerous. Therapy with radioactive iodine (I-131) is the most common treatment in the United States and in many other parts of the world. Thyroid blocking drugs and/or surgical thyroid removal is used more often than radioactive iodine as definitive treatment in Japan, perhaps because of general fear of radioactivity among many Japanese.

The development of radioactive iodine (I-131) in the early 1940s and its widespread adoption as treatment for Graves' Disease has led to a progressive reduction in the use of surgical thyroidectomy for this problem. In general, RAI therapy is effective, less expensive, and avoids the small but definite risks of surgery. Treatment with antithyroid medications must be given for six months to two years, in order to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells.

Excessive production of thyroid hormone may cause the patient to develop many complaints, including hyperstimulation, restlessness, heat intolerance, tremor, palpitation and heart dysrhythmia, increased bowel activity, and emotionally lability. President George H.W. Bush developed new atrial fibrillation and was diagnosed in 1991 with hyperthyroidism due to the disease and was treated at Walter Reed Medical Center with radioactive iodine. By coincidence (or so it is presumed, since the ultimate cause of this disease remains unknown), the president's wife Barbara Bush also developed the disease about the same time, which in her case produced severe infiltrative exopthalmos and a cosmetic change in the appearance of her eyes.

Medical treatment of Graves' disease includes antithyroid drugs, radioactive iodine and thyroidectomy (surgical excision of the gland).

The main antithyroid drugs are methimazole (US), carbimazole (UK) and propylthiouracil (PTU). These drugs block the binding of iodine and coupling of iodotyrosines. The most dangerous side-effect is agranulocytosis (1/250, more in PTU); this is an idiosyncratic reaction which does not stop on cessation of drug). Others include granulocytopenia (dose dependent, which improves on cessation of the drug) and aplastic anemia. Patients on these medications should stop the medication and see a doctor if they develop sore throat or fever. The most common side effects are rash and peripheral neuritis. These drugs also cross the placenta and are secreted in breast milk.

This modality is suitable for most patients, although some prefer to use it mainly for older patients. Indications for radioiodine are: failed medical therapy or surgery and where medical or surgical therapy are contraindicated.

Contraindications to RAI are pregnancy (absolute), ophthalmopathy (relative- it can aggravate thyroid eye disease), solitary nodules. Disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring hormone suppletion. It acts slowly and has a relapse rate that depends on the dose administered.

Surgery is suitable for young patients and pregnant patients. Indications are: a large goitre (especially when compressing the trachea), suspicious nodules or suspected cancer (to pathologically examine the thyroid) and patients with opthalmopathy.

Both bilateral subtotal thyroidectomy and the Hartley-Dunhill procedure (hemithyroidectomy on 1 side and partial lobectomy on other side) are possible.

Advantages are: immediate cure and potential removal of carcinoma. Its risks are injury of the recurrent laryngeal nerve, hypoparathyroidism (due to removal of the parathyroid glands), hematoma (which can be life-threatening if it compresses the trachea) and scarring.

For mild eye disease - artificial tears, steroid eyedrops, oral steroids (to reduce chemosis). For moderate eye disease - lateral tarsorrhaphy. For severe eye disease - orbital decompression or retro-orbital radiation.

If left untreated, more serious complications could result, including birth defects in pregnancy, increased risk of a miscarriage, and in extreme cases, death. Graves-Basedow disease is often accompanied by an increase in heart rate, which may lead to further heart complications. If the eyes are proptotic (bulging) severely enough that the lids do not close completely at night, severe dryness will occur with a very high risk of a secondary corneal infection which could lead to blindness. Pressure on the optic nerve behind the globe can lead to visual field defects and vision loss as well.

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