Graves Disease Hyperthyoidism – Pathophysiology
Graves’ disease is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism). Although a number of disorders may result in hyperthyroidism, Graves’ disease is a common cause.
Because thyroid hormones affect a number of different body systems, signs and symptoms associated with Graves’ disease can be wide ranging and significantly influence your overall well-being. Although Graves’ disease may affect anyone, it’s more common among women and before the age of 40.
The primary treatment goals are to inhibit the overproduction of thyroid hormones and lessen the severity of symptoms.
Common signs and symptoms of Graves’ disease include:
- Anxiety and irritability
- A fine tremor of your hands or fingers
- Heat sensitivity and an increase in perspiration or warm, moist skin
- Weight loss, despite normal eating habits
- Enlargement of your thyroid gland (goiter)
- Change in menstrual cycles
- Erectile dysfunction or reduced libido
- Frequent bowel movements
- Bulging eyes (Graves’ ophthalmopathy)
- Thick, red skin usually on the shins or tops of the feet (Graves’ dermopathy)
- Rapid or irregular heartbeat (palpitations)
About 30 percent of people with Graves’ disease show some signs and symptoms of a condition known as Graves’ ophthalmopathy. In Graves’ ophthalmopathy, inflammation and other immune system events affect muscles and other tissues around your eyes. The resulting signs and symptoms may include:
- Bulging eyes (exophthalmos)
- Gritty sensation in the eyes
- Pressure or pain in the eyes
- Puffy or retracted eyelids
- Reddened or inflamed eyes
- Light sensitivity
- Double vision
- Vision loss
An uncommon manifestation of Graves’ disease, called Graves’ dermopathy, is the reddening and thickening of the skin, most often on your shins or the tops of your feet.
When to see a doctor
A number of medical conditions can cause the signs and symptoms associated with Graves’ disease. See your doctor if you experience any potential Graves-related problems to get a prompt and accurate diagnosis.
Seek emergency care if you’re experiencing heart-related signs and symptoms, such as a rapid or irregular heartbeat, or if you develop vision loss.
Graves’ disease is caused by a malfunction in the body’s disease-fighting immune system, although the exact reason why this happens is still unknown.
One normal immune system response is the production of antibodies designed to target a specific virus, bacterium or other foreign substance. In Graves’ disease — for reasons that aren’t well understood — the body produces an antibody to one part of the cells in the thyroid gland, a hormone-producing gland in the neck.
Normally, thyroid function is regulated by a hormone released by a tiny gland at the base of the brain (pituitary gland). The antibody associated with Graves’ disease — thyrotropin receptor antibody (TRAb) — acts like the regulatory pituitary hormone. That means that TRAb overrides the normal regulation of the thyroid, causing an overproduction of thyroid hormones (hyperthyroidism).
Cause of Graves’ ophthalmopathy
This condition results from a buildup of certain carbohydrates in the skin — the cause of which also isn’t known. It appears that the same antibody that can cause thyroid dysfunction may also have an “attraction” to tissues surrounding the eyes.
Graves’ ophthalmopathy often appears at the same time as hyperthyroidism or several months later. But signs and symptoms of ophthalmopathy may appear years before or after the onset of hyperthyroidism. Graves’ ophthalmopathy can also occur even if there’s no hyperthyroidism.
Although anyone can develop Graves’ disease, a number of factors can increase the risk of disease. These risk factors include the following:
- Family history. Because a family history of Graves’ disease is a known risk factor, there is likely a gene or genes that can make a person more susceptible to the disorder.
- Gender. Women are much more likely to develop Graves’ disease than are men.
- Age. Graves’ disease usually develops in people younger than 40.
- Other autoimmune disorders. People with other disorders of the immune system, such as type 1 diabetes or rheumatoid arthritis, have an increased risk.
- Emotional or physical stress. Stressful life events or illness may act as a trigger for the onset of Graves’ disease among people who are genetically susceptible.
- Pregnancy. Pregnancy or recent childbirth may increase the risk of the disorder, particularly among women who are genetically susceptible.
- Smoking. Cigarette smoking, which can affect the immune system, increases the risk of Graves’ disease. Smokers who have Graves’ disease are also at increased risk of developing Graves’ ophthalmopathy.
Complications of Graves’ disease can include:
- Pregnancy issues. Possible complications of Graves’ disease during pregnancy include miscarriage, preterm birth, fetal thyroid dysfunction, poor fetal growth, maternal heart failure and preeclampsia. Preeclampsia is a maternal condition that results in high blood pressure and other serious signs and symptoms.
- Heart disorders. If left untreated, Graves’ disease can lead to heart rhythm disorders, changes in the structure and function of the heart muscles, and the inability of the heart to pump enough blood to the body (congestive heart failure).
- Thyroid storm. A rare, but life-threatening complication of Graves’ disease is thyroid storm, also known as accelerated hyperthyroidism or thyrotoxic crisis. It’s more likely when severe hyperthyroidism is untreated or treated inadequately.The sudden and drastic increase in thyroid hormones can produce a number of effects, including fever, profuse sweating, vomiting, diarrhea, delirium, severe weakness, seizures, markedly irregular heartbeat, yellow skin and eyes (jaundice), severe low blood pressure, and coma. Thyroid storm requires immediate emergency care.
- Brittle bones. Untreated hyperthyroidism also can lead to weak, brittle bones (osteoporosis). The strength of your bones depends, in part, on the amount of calcium and other minerals they contain. Too much thyroid hormone interferes with your body’s ability to incorporate calcium into your bones.
Tests and diagnosis
The diagnosis of Graves’ disease may include:
- Physical exam. Your doctor examines your eyes to see if they’re irritated or protruding and looks to see if your thyroid gland is enlarged. Because Graves’ disease increases your metabolism, your doctor will check your pulse and blood pressure and look for signs of tremor.
- Blood sample. Your doctor will order blood tests to determine your levels of thyroid-stimulating hormone (TSH), the pituitary hormone that normally stimulates the thyroid gland, as well as levels of thyroid hormones. People with Graves’ disease usually have lower than normal levels of TSH and higher levels of thyroid hormones.Another laboratory test measures the levels of the antibody known to cause Graves’ disease. This test usually isn’t necessary to make a diagnosis, but a negative result might indicate another cause for hyperthyroidism.
- Radioactive iodine uptake. Your body needs iodine to make thyroid hormones. By giving you a small amount of radioactive iodine and later measuring the amount of it in your thyroid gland with a specialized scanning camera, your doctor can determine the rate at which your thyroid gland takes up iodine. The amount of radioactive iodine taken up by the thyroid gland helps determine if Graves’ disease or another condition is the cause of the hyperthyroidism. This test may be combined with a radioactive iodine scan to show a visual image of the uptake pattern.
- Ultrasound. Ultrasound uses high-frequency sound waves to produce images of structures inside the body. Ultrasound can show if the thyroid gland is enlarged, and is most useful in people who can’t undergo radioactive iodine uptake, such as pregnant women.
- Imaging tests. If the diagnosis of Graves’ ophthalmopathy isn’t clear from a clinical assessment, your doctor may order an imaging test, such as CT scan, a specialized X-ray technology that produces thin cross-sectional images. Magnetic resonance imaging (MRI), which uses magnetic fields and radio waves to create either cross-sectional or 3-D images, may also be used.
Treatments and drugs
The treatment goals for Graves’ disease are to inhibit the production of thyroid hormones and to block the effect of the hormones on the body. Some treatments include:
Radioactive iodine therapy
With this therapy, you take radioactive iodine, or radioiodine, by mouth. Because the thyroid needs iodine to produce hormones, the radioiodine goes into the thyroid cells and the radioactivity destroys the overactive thyroid cells over time. This causes your thyroid gland to shrink, and symptoms lessen gradually, usually over several weeks to several months.
Radioiodine therapy may increase your risk of new or worsened symptoms of Graves’ ophthalmopathy. This side effect is usually mild and temporary, but the therapy may not be recommended if you already have moderate to severe eye problems.
Other side effects may include tenderness in the neck and a temporary increase in thyroid hormones. Radioiodine therapy isn’t used for treating pregnant or nursing women.
Because this treatment causes thyroid activity to decline, you’ll likely need treatment later to supply your body with normal amounts of thyroid hormones.
Anti-thyroid medications interfere with the thyroid’s use of iodine to produce hormones. These prescription medications include propylthiouracil and methimazole (Tapazole).
When these two drugs are used alone, a relapse of hyperthyroidism may occur at a later time. Taking the drug for longer than a year, however, may result in better long-term results. Anti-thyroid drugs may also be used before or after radioiodine therapy as a supplemental treatment.
Side effects of both drugs include rash, joint pain, liver failure or a decrease in disease-fighting white blood cells. Methimazole isn’t used to treat pregnant women in the first trimester because of the slight risk of birth defects. Therefore, propylthiouracil is the preferred anti-thyroid drug during the first trimester for pregnant women.
These medications don’t inhibit the production of thyroid hormones, but they do block the effect of hormones on the body. They may provide fairly rapid relief of irregular heartbeats, tremors, anxiety or irritability, heat intolerance, sweating, diarrhea, and muscle weakness.
Beta blockers include:
- Propranolol (Inderal)
- Atenolol (Tenormin)
- Metoprolol (Lopressor, Toprol-XL)
- Nadolol (Corgard)
Beta blockers aren’t often prescribed for people with asthma, because the drugs may trigger an asthma attack. These drugs may also complicate management of diabetes.
Surgery to remove all or part of your thyroid (thyroidectomy or subtotal thyroidectomy) is also an option for the treatment of Graves’ disease. After the surgery, you’ll likely need treatment to supply your body with normal amounts of thyroid hormones.
Risks of this surgery include potential damage to your vocal cords and the tiny glands located adjacent to your thyroid gland (parathyroid glands). Your parathyroid glands produce a hormone that controls the level of calcium in your blood. Complications are rare under the care of a surgeon experienced in thyroid surgery.
Treating Graves’ ophthalmopathy
Mild symptoms of Graves’ ophthalmopathy may be managed by using over-the-counter artificial tears during the day and lubricating gels at night. If your symptoms are more severe, your doctor may recommend:
- Corticosteroids. Treatment with prescription corticosteroids, such as prednisone, may diminish swelling behind your eyeballs. Side effects may include fluid retention, weight gain, elevated blood sugar levels, increased blood pressure and mood swings.
- Prisms. You may have double vision either because of Graves’ disease or as a side effect of surgery for Graves’ disease. Though they don’t work for everyone, prisms in your glasses may correct your double vision.
- Orbital decompression surgery. In this surgery, your doctor removes the bone between your eye socket (orbit) and your sinuses — the air spaces next to the orbit. This gives your eyes room to move back to their original position.This treatment is usually used if pressure on the optic nerve threatens the loss of vision. Possible complications include double vision.
- Orbital radiotherapy. Orbital radiotherapy was once a common treatment for Graves’ ophthalmopathy, but the benefits of the procedure aren’t clear. Orbital radiotherapy uses targeted X-rays over the course of several days to destroy some of the tissue behind your eyes. Your doctor may recommend orbital radiotherapy if your eye problems are worsening and prescription corticosteroids alone aren’t effective or well-tolerated.
Graves’ ophthalmopathy doesn’t always improve with treatment for Graves’ disease. Symptoms of Graves’ ophthalmopathy may even get worse for three to six months. After that, the signs and symptoms of Graves’ ophthalmopathy usually stabilize for a year or so and then begin to get better, often on their own.
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