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Graves’ Disease

National Endocrine and Metabolic Diseases Information Service

What is Graves’ disease?


Graves’ disease, also known as toxic Pituitary
gland
diffuse goiter, is the most common cause
of hyperthyroidism in the United States.
U.S. Department
of Health and Hyperthyroidism is a disorder that occurs
Human Services when the thyroid gland makes more thyroid
hormone than the body needs.
NATIONAL
INSTITUTES
OF HEALTH
The Thyroid
The thyroid is a 2-inch-long, butterfly-shaped
gland in the front of the neck below the TSH
larynx, or voice box. The thyroid makes two
thyroid hormones, triiodothyronine (T3) and
thyroxine (T4). T3 is made from T4 and is
the more active hormone, directly affecting
Thyroid
the tissues. Thyroid hormones circulate
throughout the body in the bloodstream and
act on virtually every tissue and cell in the
body.
T3-T4
Thyroid hormones affect metabolism,
brain development, breathing, heart and
nervous system functions, body temperature, The thyroid’s production of thyroid hormones—T3
muscle strength, skin dryness, menstrual and T4—is regulated by thyroid-stimulating hormone
(TSH), which is made by the pituitary gland.
cycles, weight, and cholesterol levels.
Hyperthyroidism causes many of the body’s
functions to speed up.
Thyroid hormone production is regulated by What are the symptoms of
another hormone called thyroid-stimulating
hormone (TSH), which is made by the Graves’ disease?
pituitary gland in the brain. When thyroid People with Graves’ disease may have
hormone levels in the blood are low, the common symptoms of hyperthyroidism
pituitary releases more TSH. When thyroid such as
hormone levels are high, the pituitary
• nervousness or irritability
responds by decreasing TSH production.
• fatigue or muscle weakness
Autoimmune Disorder • heat intolerance
Graves’ disease is an autoimmune disorder.
Normally, the immune system protects • trouble sleeping
the body from infection by identifying and • hand tremors
destroying bacteria, viruses, and other
• rapid and irregular heartbeat
potentially harmful foreign substances. But
in autoimmune diseases, the immune system • frequent bowel movements or diarrhea
attacks the body’s own cells and organs.
• weight loss
With Graves’ disease, the immune system • goiter, which is an enlarged thyroid that
makes an antibody called thyroid-stimulating may cause the neck to look swollen and
immunoglobulin (TSI)—sometimes called can interfere with normal breathing and
TSH receptor antibody—that attaches swallowing
to thyroid cells. TSI mimics TSH and
stimulates the thyroid to make too much A small number of people with Graves’
thyroid hormone. Sometimes the TSI disease also experience thickening and
antibody instead blocks thyroid hormone reddening of the skin on their shins. This
production, leading to conflicting symptoms usually painless problem is called pretibial
that may make correct diagnosis more myxedema or Graves’ dermopathy.
difficult. In addition, the eyes of people with Graves’
disease may appear enlarged because their
eyelids are retracted—seem pulled back into
the eye sockets—and their eyes bulge out
from the eye sockets. This condition is called
Graves’ ophthalmopathy (GO).

2 Graves’ Disease
Who is likely to develop
What is Graves’ Graves’ disease?
ophthalmopathy? Scientists cannot predict who will develop
Graves’ ophthalmopathy is a condition Graves’ disease. However, factors such
associated with Graves’ disease that as age, sex, heredity, and emotional and
occurs when cells from the immune environmental stress are likely involved.
system attack the muscles and other Graves’ disease usually occurs in people
tissues around the eyes. younger than age 40 and is seven to eight
The result is inflammation and a times more common in women than men.1
buildup of tissue and fat behind the eye Women are most often affected between
socket, causing the eyeballs to bulge out. ages 30 and 60. And a person’s chance of
Rarely, inflammation is severe enough developing Graves’ disease increases if other
to compress the optic nerve that leads to family members have the disease.
the eye, causing vision loss. Researchers have not been able to find a
Other GO symptoms are specific gene that causes the disease to be
passed from parent to child. While scientists
• dry, gritty, and irritated eyes know some people inherit an immune system
• puffy eyelids that can make antibodies against healthy
cells, predicting who will be affected is
• double vision difficult.
• light sensitivity People with other autoimmune diseases have
• pressure or pain in the eyes an increased chance of developing Graves’
disease. Conditions associated with Graves’
• trouble moving the eyes disease include type 1 diabetes, rheumatoid
About 25 to 30 percent of people with arthritis, and vitiligo—a disorder in which
Graves’ disease develop mild GO, and some parts of the skin are not pigmented.
2 to 5 percent develop severe GO.1 This
eye condition usually lasts 1 to 2 years
and often improves on its own.
GO can occur before, at the same
time as, or after other symptoms of
hyperthyroidism develop and may even
occur in people whose thyroid function
is normal. Smoking makes GO worse.

1Yeung SJ, Habra MA, Chiu AC. Graves’


disease. emedicine website. www.emedicine.
medscape.com/article/120619-overview. Updated
2010. Accessed December 10, 2011.

3 Graves’ Disease
How is Graves’ disease TSI test. Health care providers may also
recommend the TSI test, although this test
diagnosed? usually isn’t necessary to diagnose Graves’
Health care providers can sometimes disease. This test, also called a TSH antibody
diagnose Graves’ disease based only on a test, measures the level of TSI in the blood.
physical examination and a medical history. Most people with Graves’ disease have this
Blood tests and other diagnostic tests, such antibody, but people whose hyperthyroidism
as the following, then confirm the diagnosis. is caused by other conditions do not.
TSH test. The ultrasensitive TSH test is More information about testing for thyroid
usually the first test performed. This test problems is provided by the National
detects even tiny amounts of TSH in the Endocrine and Metabolic Diseases
blood and is the most accurate measure of Information Service (NEMDIS) in the fact
thyroid activity available. sheet, Thyroid Function Tests, available at
T3 and T4 test. Another blood test used to www.endocrine.niddk.nih.gov.
diagnose Graves’ disease measures T3 and
T4 levels. In making a diagnosis, health care How is Graves’ disease
providers look for below-normal levels of treated?
TSH, normal to elevated levels of T4, and
elevated levels of T3. People with Graves’ disease have three
treatment options: radioiodine therapy,
Because the combination of low TSH and medications, and thyroid surgery.
high T3 and T4 can occur with other thyroid Radioiodine therapy is the most common
problems, health care providers may order treatment for Graves’ disease in the United
other tests to finalize the diagnosis. The States. Graves’ disease is often diagnosed
following two tests use small, safe doses of and treated by an endocrinologist—a doctor
radioactive iodine because the thyroid uses who specializes in the body’s hormone-
iodine to make thyroid hormone. secreting glands.
Radioactive iodine uptake test. This test Radioiodine Therapy
measures the amount of iodine the thyroid
collects from the bloodstream. High levels of In radioiodine therapy, patients take
iodine uptake can indicate Graves’ disease. radioactive iodine-131 by mouth. Because
the thyroid gland collects iodine to
Thyroid scan. This scan shows how and make thyroid hormone, it will collect the
where iodine is distributed in the thyroid. radioactive iodine from the bloodstream in
With Graves’ disease the entire thyroid is the same way. Iodine-131—stronger than
involved, so the iodine shows up throughout the radioactive iodine used in diagnostic
the gland. Other causes of hyperthyroidism tests—gradually destroys the cells that make
such as nodules—small lumps in the up the thyroid gland but does not affect
gland—show a different pattern of iodine other body tissues.
distribution.

4 Graves’ Disease
Many health care providers use a large Medications
enough dose of iodine-131 to shut down the Beta blockers. Health care providers
thyroid completely, but some prefer smaller may prescribe a medication called a beta
doses to try to bring hormone production blocker to reduce many of the symptoms
into the normal range. More than one round of hyperthyroidism, such as tremors, rapid
of radioiodine therapy may be needed. heartbeat, and nervousness. But beta
Results take time and people undergoing this blockers do not stop thyroid hormone
treatment may not notice improvement in production.
symptoms for several weeks or months.
Antithyroid medications. Health care
People with GO should talk with a health providers sometimes prescribe antithyroid
care provider about any risks associated medications as the only treatment for
with radioactive iodine treatments. Several Graves’ disease. Antithyroid medications
studies suggest radioiodine therapy interfere with thyroid hormone production
can worsen GO in some people. Other but don’t usually have permanent results.
treatments, such as prescription steroids, Use of these medications requires frequent
may prevent this complication. monitoring by a health care provider.
Although iodine-131 is not known to cause More often, antithyroid medications are
birth defects or infertility, radioiodine used to pretreat patients before surgery or
therapy is not used in pregnant women or radioiodine therapy, or they are used as
women who are breastfeeding. Radioactive supplemental treatment after radioiodine
iodine can be harmful to the fetus’ thyroid therapy.
and can be passed from mother to child Antithyroid medications can cause side
in breast milk. Experts recommend that effects in some people, including
women wait a year after treatment before
becoming pregnant. • allergic reactions such as rashes and

itching

Almost everyone who receives radioactive


iodine treatment eventually develops • a decrease in the number of white blood
hypothyroidism, which occurs when the cells in the body, which can lower a
thyroid does not make enough thyroid person’s resistance to infection
hormone. People with hypothyroidism must • liver failure, in rare cases
take synthetic thyroid hormone, a medication
that replaces their natural thyroid hormone.

5 Graves’ Disease
Another antithyroid medication,
Stop your antithyroid medication and propylthiouracil (PTU), is available for
call your health care provider right away women in this stage of pregnancy or for
if you develop any of the following while women who are allergic to or intolerant of
taking antithyroid medications: methimazole and have no other treatment
options. Health care providers may prescribe
• fatigue PTU for the first trimester of pregnancy and
• weakness switch to methimazole for the second and
third trimesters.
• vague abdominal pain
Some women are able to stop taking
• loss of appetite antithyroid medications in the last 4 to
• skin rash or itching 8 weeks of pregnancy due to the remission
of hyperthyroidism that occurs during
• easy bruising
pregnancy. However, these women should
• yellowing of the skin or whites of continue to be monitored for recurrence of
the eyes, called jaundice thyroid problems following delivery.
• persistent sore throat Studies have shown that mothers taking
• fever antithyroid medications may safely
breastfeed. However, they should take only
moderate doses, less than 10−20 milligrams
daily, of the antithyroid medication
In the United States, health care providers methimazole. Doses should be divided and
prescribe the antithyroid medication taken after feedings, and the infants should
methimazole (Tapazole, Northyx) for most be monitored for side effects.2
types of hyperthyroidism. Women requiring higher doses of
Antithyroid medications and pregnancy. the antithyroid medication to control
Because pregnant and breastfeeding women hyperthyroidism should not breastfeed.
cannot receive radioiodine therapy, they
are usually treated with an antithyroid
medication instead. However, experts
agree that women in their first trimester
of pregnancy should probably not take
methimazole due to the rare occurrence of
damage to the fetus.

2Ogunyemi DA. Autoimmune thyroid disease and

pregnancy. emedicine website. http://emedicine.


medscape.com/article/261913-overview. Updated
March 12, 2012. Accessed April 10, 2012.

6 Graves’ Disease
Thyroid Surgery Eye Care
Surgery is the least-used option for treating The eye problems associated with Graves’
Graves’ disease. Sometimes surgery may be disease may not improve following thyroid
used to treat treatment, so the two problems are often
treated separately.
• pregnant women who cannot tolerate
antithyroid medications Eye drops can relieve dry, gritty, irritated
eyes—the most common of the milder
• people suspected of having thyroid
symptoms. If pain and swelling occur, health
cancer, though Graves’ disease does not
care providers may prescribe a steroid such
cause cancer
as prednisone. Other medications that
• people for whom other forms of
suppress the immune response may also
treatment are not successful
provide relief.
Before surgery, the health care provider Special lenses for glasses can help with light
may prescribe antithyroid medications sensitivity and double vision. People with
to temporarily bring a patient’s thyroid eye symptoms may be advised to sleep with
hormone levels into the normal range. This their head elevated to reduce eyelid swelling.
presurgical treatment prevents a condition If the eyelids do not fully close, taping them
called thyroid storm—a sudden, severe shut at night can help prevent dry eyes.
worsening of symptoms—that can occur
when hyperthyroid patients have general In more severe cases, external radiation
anesthesia. may be applied to the eyes to reduce
inflammation. Like other types of radiation
When surgery is used, many health care treatment, the benefits are not immediate;
providers recommend the entire thyroid most people feel relief from symptoms 1 to
be removed to eliminate the chance that 2 months after treatment.
hyperthyroidism will return. If the entire
thyroid is removed, lifelong thyroid hormone Surgery may be used to improve bulging
medication is necessary. of the eyes and correct the vision changes
caused by pressure on the optic nerve. A
Although uncommon, certain problems can procedure called orbital decompression
occur in thyroid surgery. The parathyroid makes the eye socket bigger and gives the
glands can be damaged because they are eye room to sink back to a more normal
located very close to the thyroid. These position. Eyelid surgery can return retracted
glands help control calcium and phosphorous eyelids to their normal position.
levels in the body. Damage to the laryngeal
nerve, also located close to the thyroid, can
lead to voice changes or breathing problems.
But when surgery is performed by an
experienced surgeon, less than 1 percent of
patients have permanent complications.1
People who need help finding a surgeon can
contact one of the organizations listed under
“For More Information.”

7 Graves’ Disease
Can treatment for Graves’ Dietary Supplements
disease affect pregnancy? Iodine is an essential mineral for the thyroid.
Treatment for Graves’ disease can sometimes However, people with autoimmune thyroid
affect pregnancy. After treatment with disease may be sensitive to harmful side
surgery or radioactive iodine, TSI antibodies effects from iodine. Taking iodine drops or
can still be present in the blood, even when eating foods containing large amounts of
thyroid levels are normal. If a pregnant iodine—such as seaweed, dulse, or kelp—
woman has received either of these may cause or worsen hyperthyroidism. More
treatments prior to becoming pregnant, the information about iodine is provided by the
antibodies she produces may travel across National Library of Medicine in the fact
the placenta to the baby’s bloodstream and sheet, Iodine in diet, available at www.nlm.
stimulate the fetal thyroid. nih.gov/medlineplus.

A pregnant woman who has been treated Women need more iodine when they are
with surgery or radioactive iodine should pregnant—about 250 micrograms a day—
inform her health care provider so her because the baby gets iodine from the
baby can be monitored for thyroid-related mother’s diet. In the United States, about
problems later in the pregnancy. Pregnant 7 percent of pregnant women may not
women may safely be treated with antithyroid get enough iodine in their diet or through
medications. prenatal vitamins.3 Choosing iodized salt—
salt supplemented with iodine—over plain
For more information about pregnancy and salt and prenatal vitamins containing iodine
antithyroid medications, see “Medications” will ensure this need is met.
under the section titled “How is Graves’
To help ensure coordinated and safe care,
disease treated?” More information about
people should discuss their use of dietary
pregnancy and thyroid disease is provided by
supplements, such as iodine, with their health
the NEMDIS in the fact sheet, Pregnancy and
care provider. Tips for talking with health
Thyroid Disease, available at www.endocrine.
care providers are available at the National
niddk.nih.gov.
Center for Complementary and Alternative
Medicine’s Time to Talk campaign at www.
Eating, Diet, and Nutrition nccam.nih.gov.
Experts recommend that people eat a
balanced diet to obtain most nutrients.
More information about diet and nutrition
is provided by the National Agricultural
Library available at www.nutrition.gov.

3Zimmerman MB. Iodine deficiency in pregnancy


and the effects of maternal iodine supplementation on
the offspring: a review. American Journal of Clinical
Nutrition. 2009;89(2):668S–672S.

8 Graves’ Disease
Hope through Research
Points to Remember The National Institute of Diabetes and
• Graves’ disease is the most Digestive and Kidney Diseases (NIDDK)
common cause of hyperthyroidism conducts and supports research into many
in the United States. kinds of disorders, including Graves’
disease. Researchers throughout the United
• In Graves’ disease, the immune States and the world are working to better
system stimulates the thyroid understand, prevent, and treat this disease.
gland to make too much thyroid
hormone. National Institutes of Health
(NIH)-supported scientists are investigating
• Common symptoms of the natural history, clinical presentation,
hyperthyroidism include and genetics of thyroid function disorders
nervousness or irritability, to further understand thyroid diseases.
fatigue or muscle weakness, heat Scientists continue to study treatment
intolerance, trouble sleeping, options for Graves’ disease and GO.
hand tremors, rapid and irregular
heartbeat, frequent bowel The following federally funded research
movements or diarrhea, weight studies and clinical trials are currently under
loss, and goiter. way:
• People with Graves’ disease may • Evaluation of Patients With Thyroid
also have bulging eyes, a condition Disorders, funded under NIH clinical
called Graves’ ophthalmopathy trial number NCT00001159
(GO). • Trial of Rituximab for Graves’
• Graves’ disease is most often Ophthalmopathy, funded under NIH
treated with radioiodine therapy, clinical trial number NCT00595335
which gradually destroys the cells • Phase II Randomized Controlled Study
that make up the thyroid gland. of Sequential Orbital Radiotherapy for
Antithyroid medications and Graves’ Ophthalmopathy, funded under
surgery to remove the thyroid are NIH clinical trial number NCT00004660
sometimes used.
Participants in clinical trials can play a more
• The eye problems associated active role in their own health care, gain
with Graves’ disease may require access to new research treatments before
separate treatment. they are widely available, and help others
• A pregnant woman who has been by contributing to medical research. For
treated with surgery or radioactive information about current studies, visit www.
iodine prior to becoming pregnant ClinicalTrials.gov.
should inform her health care
provider so her baby can be
monitored for thyroid-related
problems later in the pregnancy.

9 Graves’ Disease
For More Information The Endocrine Society
8401 Connecticut Avenue, Suite 900
American Academy of Otolaryngology—
Chevy Chase, MD 20815
Head and Neck Surgery
Phone: 1–888–363–6274
1650 Diagonal Road
or 301–941–0200
Alexandria, VA 22314–2857
Fax: 301–941–0259
Phone: 703–836–4444
Email: societyservices@endo-society.org
Internet: www.entnet.org
Internet: www.endo-society.org
American Association of Clinical
Graves’ Disease and Thyroid Foundation
Endocrinologists
P.O. Box 2793
245 Riverside Avenue, Suite 200
Rancho Santa Fe, CA 92067
Jacksonville, FL 32202
Phone: 1–877–643–3123
Phone: 904–353–7878
Fax: 1–877–643–3123
Fax: 904–353–8185
Email: info@ngdf.org
Internet: www.aace.com
Internet: www.gdatf.org
American Thyroid Association
The Hormone Foundation
6066 Leesburg Pike, Suite 550
8401 Connecticut Avenue, Suite 900
Falls Church, VA 22041
Chevy Chase, MD 20815–5817
Phone: 1–800–THYROID (1–800–849–7643)
Phone: 1–800–HORMONE (1–800–467–6663)
or 703–998–8890
Fax: 301–941–0259
Fax: 703–998–8893
Email: hormone@endo-society.org
Internet: www.thyroid.org
Internet: www.hormone.org

10 Graves’ Disease
Acknowledgments
Publications produced by the NIDDK are
carefully reviewed by both NIDDK scientists
and outside experts. This publication was
originally reviewed by Lewis Braverman,
M.D., Boston University School of Medicine
and Boston Medical Center; Leonard
Wartofsky, M.D., M.A.C.P., Washington
Hospital Center; Nicholas J. Sarlis, M.D.,
NIDDK; Nabeel Babar, M.D., NIDDK; and
the National Eye Institute, NIH.

11 Graves’ Disease
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U.S. DEPARTMENT OF HEALTH


AND HUMAN SERVICES
National Institutes of Health

NIH Publication No. 12–6217


July 2012

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