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Function Tests

National Endocrine and Metabolic Diseases Information Service

What is the thyroid gland? The thyroid is a small, butterfly-shaped gland Pituitary located in the front of the neck below the lar­ gland ynx, or voice box. The thyroid gland makes U.S. Department of Health and two thyroid , (T3) Human Services and thyroxine (T4), which circulate in the bloodstream and act on virtually every tis­ NATIONAL sue and cell in the body. INSTITUTES OF HEALTH affect , brain development, breathing, and nervous system func­ tions, body temperature, muscle strength, TSH skin dryness, menstrual cycles, weight, cho­ lesterol levels, and more. Thyroid production in the thyroid is regulated by another hormone called Thyroid thyroid-stimulating hormone (TSH). TSH is made by the , which is located in the brain. From the pituitary gland, TSH

travels to the thyroid where it stimulates the T3-T4 production of T3 and T4 and their release into the bloodstream. The thyroid gland’s production of thyroid hormones (T3 and T4) is regulated by thyroid-stimulating Why are thyroid function hormone (TSH), which is made by the pituitary gland. tests performed? Thyroid function tests are used to evaluate metabolic rate, weight loss, sweating, rapid the thyroid’s functioning and to diagnose and heart rate, and high blood pressure, among help determine the cause of thyroid diseases. other symptoms. Too little thyroid hormone causes , which slows down Sometimes the body produces too much bodily functions and leads to fatigue, weight or too little thyroid hormone. Too much gain, cold intolerance, and related symptoms. thyroid hormone in the bloodstream causes , which results in increased Hyperthyroidism and hypothyroidism are thyroid hormone levels in the blood are most often caused by autoimmune diseases. low. The thyroid responds by making more Normally, the immune system produces anti­ hormone. Then, when the body has enough bodies that defend the body against foreign thyroid hormone circulating in the blood, substances such as bacteria. In autoimmune TSH output drops. The cycle repeats con­ diseases, however, the immune system pro­ tinuously to maintain a healthy level of duces “autoantibodies” that attack the body’s thyroid hormone in the body. The TSH test own healthy cells and tissues—in this case, measures the amount of TSH being secreted the thyroid. Graves’ disease is the most com­ by the pituitary. mon cause of autoimmune hyperthyroidism. In people whose thyroid produces too Hashimoto’s disease is the most common much thyroid hormone, the pituitary shuts cause of autoimmune hypothyroidism. Both down TSH production, leading to low or Graves’ disease and Hashimoto’s disease even undetectable TSH levels in the blood. are due to an immune attack on the thyroid. An abnormally low TSH level suggests In Graves’ disease, the attacking antibodies hyperthyroidism. stimulate thyroid hormone production. In people whose thyroid is not functioning Blood tests assess thyroid function by mea­ normally and produces too little thyroid suring TSH and thyroid hormone levels and hormone, the thyroid cannot respond nor­ detecting certain autoantibodies present in mally to TSH by producing thyroid hormone. autoimmune . Radiologic As a result, the pituitary keeps making tests either assess thyroid function or detect TSH, trying to get the thyroid to respond. abnormalities in the thyroid gland. An abnormally high TSH level suggests hypothyroidism. What blood tests are used to Occasionally, however, a low TSH level can assess thyroid function? indicate a type of hypothyroidism called Usually the first performed is the secondary hypothyroidism. Instead of a TSH test. TSH is the key hormone for diag­ problem with the thyroid gland, this type of nosing hyperthyroidism and hypothyroidism. hypothyroidism is caused by an abnormality If results of the TSH test are abnormal, one in the pituitary that prevents it from making or more additional tests are needed to help enough TSH to stimulate thyroid hormone determine the cause of the problem. production. TSH Test Very rarely, hyperthyroidism can result from This blood test is the most sensitive test of a problem with the pituitary rather than the thyroid function available. The TSH test can thyroid. Noncancerous, or benign, pituitary detect TSH blood levels as low as 0.01 milli­ tumors may overproduce TSH and cause international units per liter (mIU/L). The thyroid hormone levels to rise. However, normal range for TSH is between 0.3 and such tumors are extremely rare. The usual 4 mIU/L, although the range varies from one cause of a high TSH level is an underfunc­ laboratory to another. tioning thyroid gland or inadequate dosage of thyroid hormone medication in patients The TSH test is based on the way TSH and taking replacement hormone. thyroid hormones work together. Normally, the pituitary boosts TSH production when

2 Thyroid Function Tests T4 Tests T3 Test T4 is the principal thyroid hormone and Only about 20 percent of the T3 circulating exists in two forms—T4 that is bound to in the blood comes from the thyroid gland, proteins in the blood and kept in reserve while all of the circulating T4 comes from the until the body needs it, and a small amount thyroid. The remaining 80 percent of circu­ of unbound or “free” T4 (FT4), which is the lating T3 comes from various cells all over active form of the hormone and is available the body where T4 is converted to T3. T3 is to body tissues. The normal range for total far more active than T4 and, like T4, exists in T4—bound and free together—is usually both bound and free states. In some cases of about 4.5 to 12.6 micrograms per deciliter hyperthyroidism, FT4 is normal but free T3 (µg/dL), although the range varies from (FT3) is elevated, so measuring both forms is one laboratory to another. The normal FT4 useful if hyperthyroidism is suspected. The range is about 0.7 to 1.8 nanograms per normal FT3 range is about 0.2 to 0.5 ng/dL. deciliter (ng/dL). The T3 test is not useful in diagnosing hypo­ thyroidism because levels are not reduced Elevated total T or FT suggests hyperthy­ 4 4 until the hypothyroidism is severe. roidism, and low total T4 or FT4 suggests hypothyroidism. Sometimes total T4 levels Thyroid-stimulating are abnormal because the protein-bound T4 Immunoglobulin (TSI) Test is abnormally high or low due to elevated or low concentrations of the protein that TSI is an autoantibody present in Graves’ disease, the most common cause of hyper­ binds T4. Therefore, FT4 must be calculated separately. thyroidism. TSI mimics TSH by stimulating the thyroid cells, causing the thyroid gland Measuring FT4 directly requires complicated to secrete excess hormone. The TSI test laboratory procedures, so FT4 is usually detects TSI circulating in the blood and is estimated based on the ratio of binding usually measured in specific instances in protein to total T4. Normal FT4 levels, when people with Graves’ disease—when the diag­ the total T4 is high or low, indicate the issue nosis is obscure, during pregnancy, and to is the binding protein, not the thyroid. For determine if remission has occurred. example, pregnancy or the use of oral contra­ ceptives increases levels of binding protein Antithyroid Antibody Test in the blood. In this case, the total T4 will be Antithyroid antibodies are present in high due to the binding protein but the per­ Hashimoto’s disease, the most common son does not have hyperthyroidism. Severe cause of hypothyroidism. Antithyroid anti­ illness or the use of corticosteroids—a class bodies are markers in the blood, and their of medications that treat asthma, arthritis, presence is extremely helpful in diagnosing and skin conditions, among other health Hashimoto’s disease. Two principal types of problems—can decrease binding protein antithyroid antibodies are levels. The total T4 measurement will be low as a consequence, but the person does not • anti-TG antibodies, which attack a pro­ have hypothyroidism. In either case—having tein in the thyroid called thyroglobulin high binding protein or having low binding • anti-thyroperoxidase, or anti-TPO, protein—the FT4 will be normal and the per­ antibodies, which attack an enzyme in son has normal thyroid function—also called thyroid cells called thyroperoxidase euthyroid.

3 Thyroid Function Tests What radiologic tests are T4 levels. Because the thyroid is inflamed, it does not take up the radioactive given used to assess thyroid as part of the RAIU test. Hyperthyroidism function? seen in Graves’ disease would be marked by Two radiologic tests—the radioactive iodine high blood T4 and a high RAIU. In thyroid­ uptake (RAIU) test and a thyroid scan—may itis, temporary hyperthyroidism may exist be used to aid diagnosis and treatment. because of the release of T4 into the blood, but the RAIU is low because of the inflam­ RAIU Test mation. Temporary hyperthyroidism in The thyroid uses iodine from food to make thyroiditis is often followed by a period of thyroid hormone. The RAIU test measures hypothyroidism before the thyroid heals. the amount of iodine the thyroid collects The radioactive compound used in the RAIU from the bloodstream. The test helps test is safe to ingest in the small amount doctors evaluate how the thyroid is func­ given. Pregnant and nursing women should tioning and determine the cause of hyper­ not undergo this test, however, because the thyroidism. The RAIU is not used to assess radioactive material can travel across the hypothyroidism. to the baby’s bloodstream or be For this test, the patient swallows a small transmitted to the baby via breast milk. amount of radioactive iodine in liquid or capsule form. After 4 to 6 hours and again Thyroid Scan at 24 hours, the patient returns to the test­ A thyroid scan does not test thyroid function ing center, where the doctor measures the per se, but instead uses radioactive material amount of radioactive iodine taken up by to create a picture of the thyroid. The scan the thyroid. The measurement is taken with shows the size and shape of the thyroid and a small device called a gamma probe, which provides images of irregularities such as resembles a microphone. The gamma probe nodules. Nodules are tumors in the thyroid is positioned near the patient’s neck over the that can either be benign or cancerous and thyroid gland. Measurement takes only a can sometimes produce excess thyroid hor­ few minutes and is painless. mone. The scan does not identify whether the nodules are benign or cancerous. In the diagnosis of hyperthyroidism, a high RAIU reading usually indicates an overac­ For the scan, radioactive iodine or radioac­ tive thyroid that produces too much thyroid tive technetium is either injected into the hormone, as seen in Graves’ disease or toxic patient’s vein or swallowed in liquid or nodular goiter, an enlargement of the thyroid capsule form. The scan takes place 30 min­ gland. A low RAIU reading suggests the utes after an injection or 6 to 24 hours after thyroid is not overactive. the radioactive substance is swallowed. The patient lies on an examining table for Thyroiditis may cause leakage of thyroid the scan, which takes about 30 minutes. A hormone and iodine out of the thyroid gland into the bloodstream, which can lead to high

4 Thyroid Function Tests device called a gamma camera is suspended What do thyroid function over the table or may be located within a large, doughnut-shaped machine that test results tell doctors? resembles a computerized tomography (CT) The pattern of test results in people with scanner. hyperthyroidism or hypothyroidism can help doctors determine the underlying cause of The gamma camera detects the radioactive the condition. The following tables give the material and sends images to a computer usual pattern of thyroid function test results. that show how and where the radioactive substance has been distributed in the thyroid. Because many complex factors affect thyroid Nodules that produce excess thyroid function and hormone levels, doctors must hormone—so-called “hot,” or toxic, take the patient’s full medical history into nodules—show up clearly because they account when interpreting thyroid function absorb more radioactive material than nor­ tests. mal thyroid tissue. Graves’ disease shows up as a diffuse, overall increase in radioactivity rather than a localized spot.

Table 1. Typical thyroid function test results: Hyperthyroidism

Test Cause TSH T3/T4 TSI RAIU Graves’ disease   +  Thyroiditis (early stage)   –  Thyroid nodules (hot, or toxic)   –  or N

Table 2. Typical thyroid function test results: Hypothyroidism

Test Cause TSH T3/T4 Antithyroid Antibody Hashimoto’s (thyroiditis)   or N + disease Hashimoto’s (thyroiditis)   + disease (later stage) Pituitary abnormality   –

Key: N = Normal  = Above normal  = Below normal + = Positive – = Negative

5 Thyroid Function Tests Points to Remember For More Information • Hyperthyroidism occurs when the thy- American Association of Clinical roid gland produces too much thyroid Endocrinologists hormone or hormone leaks out of the 245 Riverside Avenue, Suite 200 inflamed gland. Hypothyroidism occurs Jacksonville, FL 32202 when the thyroid gland does not pro- Phone: 904–353–7878 duce enough thyroid hormone. Fax: 904–353–8185 Email: [email protected] • Blood tests are used to diagnose hyper- Internet: www.aace.com thyroidism and hypothyroidism and help determine the cause of these disorders. American Thyroid Association • Thyroid-stimulating hormone (TSH) is 6066 Leesburg Pike, Suite 550 the key hormone for diagnosing hyper- Falls Church, VA 22041 thyroidism and hypothyroidism. Phone: 1–800–THYROID (1–800–849–7643) or 703–998–8890 • Radiologic tests that use radioactive Fax: 703–998–8893 materials evaluate how the thyroid is Email: [email protected] functioning and create pictures of the Internet: www.thyroid.org gland to further pinpoint the cause of thyroid disorders. The Endocrine Society 8401 Connecticut Avenue, Suite 900 Chevy Chase, MD 20815 Hope through Research Phone: 1–888–363–6274 or 301 –941–0200 Researchers are investigating the develop- Fax: 301–941–0259 ment, signs and symptoms, and genetics of Email: [email protected] thyroid function disorders to better under- Internet: www.endo-society.org stand thyroid diseases. Scientists continue to study treatment options for hyperthyroidism, Graves’ Disease Foundation hypothyroidism, and other thyroid disorders. 400 International Drive Williamsville, NY 14221 Participants in clinical trials can play a more Phone: 1–877–NGDF123 (1–877–643–3123) active role in their own health care, gain or 716–631–2310 access to new research treatments before Fax: 716–631–2822 they are widely available, and help others by Email: [email protected] contributing to medical research. For infor- Internet: www.ngdf.org mation about current studies, visit www.ClinicalTrials.gov. The Hormone Foundation 8401 Connecticut Avenue, Suite 900 Chevy Chase, MD 20815–5817 Phone: 1–800–HORMONE (1–800–467–6663) Fax: 301–941–0259 Email: [email protected] Internet: www.hormone.org

6 Thyroid Function Tests Acknowledgments You may also find additional information about this www.medlineplus.gov Publications produced by the Clearinghouse topic by visiting MedlinePlus at This publication may contain information about are carefully reviewed by both NIDDK medications. When prepared, this publication scientists and outside experts. This publi­ included the most current information available. cation was reviewed by Lewis Braverman, For updates or for questions about any medications, contact the U.S. Food and Drug Administration M.D., Boston Medical Center, and Leonard toll-free at 1–888–INFO–FDA (1–888–463–6332) Wartofsky, M.D., M.A.C.P., Washington or visit www.fda.gov. Consult your doctor for more Hospital Center. information.

7 Thyroid Function Tests National Endocrine and Metabolic Diseases Information Service 6 Information Way Bethesda, MD 20892–3569 Phone: 1–888–828–0904 TTY: 1–866–569–1162 Fax: 703–738–4929 Email: [email protected] Internet: www.endocrine.niddk.nih.gov The National Endocrine and Metabolic Diseases Information Service is an informa­ tion dissemination service of the National Institute of and Digestive and Diseases (NIDDK). The NIDDK is part of the National Institutes of Health, which is part of the U.S. Department of Health and Human Services. The NIDDK conducts and supports bio­ medical research. As a public service, the NIDDK has established information services to increase knowledge and understanding about health and disease among patients, health professionals, and the public.

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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NIH Publication No. 10–6284 January 2010