Graves' Disease

Medically reviewed by Carina Fung, PharmD, BCPPS

What is Graves' disease?

Graves’ disease1 is an autoimmune disorder that causes the overproduction of thyroid hormones, resulting in hyperthyroidism (an overactive thyroid). Although the condition can affect anyone, Graves’ disease is the most common2 in women and those between the ages of 30 and 50.

The thyroid is a small, butterfly-shaped gland found in the front of the neck. This gland produces hormones that control how the body uses energy. These hormones affect nearly every organ in the body—they even control the way the heart beats.

Graves’ disease is considered to be an autoimmune disorder—it is characterized by the immune system attacking the thyroid. This causes the gland to produce more thyroid hormones than are needed (two types in particular: triiodothyronine [T3] and thyroxine [T4]).

The primary goals of treatment for Graves’ disease are inhibiting the excess production of thyroid hormones and improving patients’ signs and symptoms.

Thyroid eye disease (Graves’ ophthalmopathy)

Graves’ eye disease3, more colloquially known as thyroid eye disease4 (TED), is a condition that most commonly develops in people with overactive thyroid glands caused by Graves’ disease.

Roughly 30% of people5 with Graves’ disease exhibit signs and symptoms of a condition known as Graves’ ophthalmopathy. In this condition, more colloquially known as thyroid eye disease (TED), inflammation and other events concerning the immune system affect the muscles and tissues around the eyes.

There are two forms of TED: active and inactive6. For most people, TED changes over time, fluctuating between the two.

Signs and symptoms of thyroid eye disease first appear during active TED. Scarring may also begin to form behind the eyes at this time.

After a while, TED will change from active to inactive. During inactive periods, some signs and symptoms of TED may go away, while others may become permanent.

Because TED may only be active for a limited period of time, early diagnosis and treatment are important. Medication is only effective in treating TED when the condition is active.

How common is Graves’ disease?

Although a number of disorders may result in hyperthyroidism, Graves’ disease is the most common form7 of hyperthyroidism in the United States.

Graves’ disease affects roughly 1 in 200 people8. This condition is the most common cause of hyperthyroidism in the United States.

Up to 5 out of every 10 people9 with Graves’ disease will develop thyroid eye disease: 8 out of 10 people with TED are diagnosed within 18 months of being diagnosed with Graves’ disease. About 1 in 3 people with Graves’ disease develop mild TED, while roughly 5% develop severe TED.

Graves' disease causes

As with any autoimmune disorder, Graves’ disease is caused by a malfunction in the body’s disease-fighting (immune) system. While it is uncertain10 exactly why some people develop autoimmune disorders like Graves’ disease, researchers suppose that it may be due to a combination of genes and an outside trigger (like a virus).

One of the normal responses of the immune system is the production of antibodies, which are designed to target specific pathogens (invaders like viruses, bacteria, or other foreign substances). For reasons that aren’t yet well understood, the immune systems of people with Graves’ disease produce an antibody to the thyroid cell receptor for thyroid-stimulating hormone (TSH).

This antibody, called thyrotropin receptor antibody (TRAb), is the cause of hyperthyroidism in Graves’ disease. It is present in 90% of patients11 with the condition.

TRAb attaches to thyroid cells and acts like TSH, a hormone produced in the pituitary gland that tells the thyroid how much hormone to make. Normally, thyroid-stimulating hormone regulates the gland’s functioning. TRAb, however, acts like TSH—it overrides normal thyroid regulation, causing an overproduction of thyroid hormones (hyperthyroidism).

Graves’ disease risk factors

Anyone can develop Graves’ disease; however, several risk factors12 can increase your likelihood of developing the condition, including:

  • Family history: Having a family history of Graves’ disease is a known risk factor for an individual developing the condition. This is likely due to a gene or genes that increase susceptibility to Graves’ disease.
  • Female sex: Women are about 7 or 8 times more likely to develop Graves’ disease than men.
  • Age: Graves’ disease usually develops in people between the ages of 30 and 50.
  • Other autoimmune disorders: People with other autoimmune disorders like type 1 diabetes or rheumatoid arthritis are at an increased risk of developing Graves’ disease. Other conditions linked13 with Graves’ disease include pernicious anemia, lupus, Addison’s disease, celiac disease, and vitiligo.
  • Smoking: Cigarette smoking can affect the immune system, increasing the risk of Graves’ disease. Smokers with Graves’ disease also have an increased risk of developing Graves’ ophthalmopathy (thyroid eye disease).
  • Pregnancy: Being pregnant or having recently given birth can increase the risk for Graves’ disease—especially among women who are genetically susceptible to the condition.
  • Emotional or physical stress: Extreme stress or illness can trigger the onset of Graves’ disease in people with genetic predispositions for the condition.

Thyroid eye disease causes

Thyroid eye disease, or Graves’ ophthalmopathy, develops14 as a result of certain carbohydrates building up in the muscles and tissues behind the eyes. While the cause of this condition is not entirely known either, it appears that TRAb—the antibody that causes thyroid dysfunction—may also have an “attraction” to the tissues surrounding the eyes.

The immune system is also affected by Graves’ eye disease. The malfunctioning immune system causes the muscle and fat tissues behind the eye(s) to become inflamed and swollen. Over time, this swelling can cause permanent changes and/or damage to the eyes.

Thyroid eye disease risk factors

Many of the same risk factors are shared by Graves’ disease and TED. Some risk factors15 that can increase your risk for thyroid eye disease include:

  • Female sex: Women are 5 times more likely than men to develop thyroid eye disease.
  • Age: TED occurs most commonly in people ages 40–49 and 60–69.
  • Family history: Because thyroid problems often run in families, you may be at greater risk of developing a condition that affects your thyroid if someone in your family already has one.
  • Radioactive iodine: Taking radioactive iodine, a medicine used to treat Graves’ disease, can increase your chances of getting TED (and can make TED worse).
  • Smoking: Smokers are up to 8 times more likely to develop thyroid eye disease than nonsmokers. Smoking can also make TED more severe and make treatment less effective.

Graves' disease symptoms

Because thyroid hormones affect several different body symptoms, the signs and symptoms of Graves’ disease can significantly influence your overall well-being.

The common signs and symptoms16 of Graves’ disease can overlap with those of hyperthyroidism. They can include:

  • Anxiety and irritability
  • Tremor (shaking) in the hands or fingers
  • Heat sensitivity and increased perspiration or warm, moist skin
  • Weight loss, despite normal eating habits
  • Enlargement of the thyroid gland (called a goiter)
  • Changes in menstrual cycles
  • Erectile dysfunction or decreased libido
  • Frequent bowel movements
  • Bulging eyes (Graves’ ophthalmopathy, or thyroid eye disease)
  • Fatigue, tiredness, or muscle weakness
  • Red, thickened skin on the shins or tops of the feet (Graves’ dermopathy or pretibial myxedema)—usually painless and mild, but can be painful in some people
  • Rapid or irregular heartbeat (palpitations)
  • Trouble sleeping

Thyroid eye disease symptoms

Active thyroid eye disease affects everyone differently. The condition frequently appears at the same time at hyperthyroidism, but can also occur even in patients without hyperthyroidism.

Some of the signs and symptoms17 of thyroid eye disease may come on quickly, while others may develop slowly—they may appear years before or after the onset of hyperthyroidism.

Common symptoms of TED include:

  • Retracted eyelids: Eyelids may pull back so that more of the eye is exposed than normal. You may also experience difficulty fully closing your eyes.
  • Swollen, puffy eyelids: May also be accompanied by redness. This symptom, which may be called eyelid edema, is sometimes mistaken for allergies or an infection.
  • Bulging eyes: One or both of your eyes may bulge forward. This is referred to as proptosis or exophthalmos.
  • Dry, gritty eyes: Eyes may feel dry or sandy, or you may feel like there is a foreign body in your eye.
  • Red, swollen eyes: Your eyes may look red or bloodshot. This is referred to as erythema or chemosis.
  • Watery, teary eyes
  • Eye pain or pressure: You may feel pain in, around, or behind your eye(s), in some cases accompanied by a headache.
  • Sensitivity to light: Your eyes may become abnormally sensitive to light (photophobia).
  • Blurry vision: Vision may appear blurry or out of focus.
  • Double vision: You may see two images of the same object (diplopia).
  • Vision loss, in severe cases

Graves’ disease complications

Graves’ disease can lead to complications18 or increase your risk of developing other conditions. Some complications of Graves’ disease include:

  • Pregnancy issues: Graves’ disease can lead to numerous pregnancy-related complications, including miscarriage, preterm birth, fetal thyroid dysfunction, poor fetal growth, maternal heart failure, and preeclampsia (a condition in the mother that results in high blood pressure and other serious signs and symptoms)
  • Heart disorders: When left untreated, Graves’ disease can lead to heart rhythm disorders (arrhythmias), 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: This condition, also known as accelerated hyperthyroidism or thyrotoxic crisis, is a rare but life-threatening complication of Graves’ disease. It requires immediate emergency medical care. Thyroid storm is more likely to occur when hyperthyroidism is left untreated or isn’t sufficiently treated. This sudden increase in thyroid hormones characteristic of thyroid storm can lead to fever, profuse sweating, vomiting, diarrhea, delirium, severe weakness, seizures, significantly abnormal heartbeat, yellow skin and eyes (jaundice), severe low blood pressure (hypotension), and coma.
  • Osteoporosis: If left untreated, hyperthyroidism can lead to weak, brittle bones (osteoporosis). This is due to the fact that an excess of thyroid hormones can interfere with the body’s ability to incorporate calcium into the bones, causing them to weaken.
  • Thyroid eye disease: About 30% of people19 with Graves’ disease experience at least some signs and symptoms of Graves' ophthalmopathy (thyroid eye disease). As with any condition, talk to your healthcare provider if you experience any of the signs or symptoms of Graves’ disease or thyroid eye disease. He or she will be able to provide you with the proper diagnosis and treatment.

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