The laboratory tests most helpful for the diagnosis and monitoring of patients with Graves’ disease include the Free T4 (FT4), Free T3 (FT3), TSH test, and TSI test. As with other wiki pages, feel free to edit this page and add other insights you may have regarding these tests.
The Free T4 Test
The free T4 test measures thyroxine (T4) that is available to react with the body’s cells. In its free form, FT4 is cleaved from carrier protein molecules and has the ability to react with cells, causing the actions associated with thyroxine. FT4 is increased in hyperthyroidism and thyroid hormone resistance. It is decreased in both primary and secondary hypothyroidism. About 80% of T4 is converted within the body, to the more potent hormone T3. The usual reference range for FT4 is 0.80-1.80 ng/dl
The Free T3 Test
The free T3 test measures triiodothyronine (T3) that is available to react with the body’s cells. In its free form, FT3 is cleaved from carrier protein molecules and has the ability to react with cells, causing the actions associated with triiodothyronine. While the body produces very little T3, the majority of T3 is formed from the conversion (de-iodination) of T4. In its available form, FT3 is about 7-10 times more potent than FT4. In Graves’ disease, many patients have T3 thyrotoxicosis, a condition of increased T3 production and conversion from T4. Patients who are monitored with FT4 alone can present an incomplete clinical picture. FT3 is increased in Graves’ disease, T3 thyrotoxicosis, TSH dependent hyperthyroidism, and from medications increasing T4 to T3 conversion, such as acetaminophen. FT3 is decreased in nonthyroidal illness (low T3 syndrome), hypothyroidism, and by poor T4 conversion syndromes caused by metabolic changes or certain medications. The usual reference range for FT3 is 230-420 pg/dl.
NOTE: Methods for free thyroid hormone can rarely be falsely elevated in patients who have abnormally high or low levels of thyroxine-binding-globulin (TBG) caused by conditions of dysalbuminemia, or very high levels of estrogen or non-steroidal anti-inflammatory medications. High or low TBG levels can both falsely raise or lower FT3 levels. Although these interferences are rarely seen in free thyroid hormone tests, methods for measuring free thyroid hormone using dialysis methods, which eliminate all protein related interferences, are now available. Their use is generally not recommended because they are time-consuming and more expensive . Total T4 and T3 levels are always affected by these substances and are no longer recommended by monitoring thyroid function.
The TSH Test
TSH refers to the pituitary hormone, thyroid stimulating hormone, which is also known as thyrotropin. TSH is normally secreted at a constant pulsating rate, which peaks at night. TSH stimulates thyroid cells, ordering them to produce and release thyroid hormone. When the pituitary, via a signal from the hypothalamus, recognizes that the body has too much thyroid hormone for its needs, it slows down or stops producing TSH. Before thyroid hormone levels become abnormally high, TSH is low and is often suppressed to levels <.01 mu/ml. A low TSH does not signify that thyroid hormone levels are excessively high. In subclinical hyperthyroidism, TSH remains low, but thyroid hormone levels are normal. TSH may also be decreased in conditions of fasting, from many medications including corticosteroids, and in endogenous depression. Recent studies show that receptors in the pituitary gland recognize both blocking and stimulating TSH receptor antibodies as if they were TSH molecules. Thinking that there are adequate supplies of TSH in the blood circulation, the pituitary slows down or stops its production of TSH. Therefore, when the TSH test is used as a diagnostic tool in autoimmune thyroid disease, it can be misleading. For this reason and also because TSH has a minimum lag time of 6 weeks before reflecting changes in thyroid hormone levels, its use is not recommended as an exclusive tool for monitoring patients on TSH therapy. In the absence of abundant TSH receptor antibodies, TSH can be a valuable tool because it often rises before thyroid hormone levels become abnormally low. In this feedback mechanism, the pituitary secretes TSH in an effort to prevent hypothyroidism. Low levels are seen in hyperthyroidism, subclinical hyperthyroidism, autonomous thyroid hormone secretion, TSH deficiency syndromes, and in persons on suppressive therapy for thyroid cancer. TSH is elevated in primary hypothyroidism, subclinical hypothyroidism, and in certain TSH secreting tumors. The usual reference range for TSH was changed in October, 2002 to 0.3-3.04 mu/L
The TSI Test
TSI, which stands for thyroid stimulating immunoglobulin, is the antibody responsible for hyperthyroidism in Graves’ disease. TSI are also known as stimulating TSH receptor antibodies or stimulating thyrotropin receptor antibodies because of their ability to stimulate the TSH receptor on thyroid cells. Acting in place of TSH, these antibodies stimulate thyroid cells to produce excess thyroid hormone. TSI also contribute to the related eye disease, Graves’ ophthalmopathy. TSI is used to diagnose Graves’ disease, to monitor response to anti-thyroid drugs and to helping predicting remission. While the normal range is <130% activity, individuals who are normal do not produce TSI and have levels <2% activity. Individuals with levels between 2 and 125 %, which indicates thyroid autoimmunity, do not generally develop symptoms of hyperthyroidism until levels rise. Therefore, levels much lower than 125% are necessary to predict complete remission. Levels, which are close to 100% activity generally rise when patients stop taking anti-thyroid drugs. Ideally, levels would fall to at least 20% before anti-thyroid drugs are safely withdrawn. The reference range is <130% activity or an index of <1.3 for tests that measure the increased activity caused by adding patient serum to a test solution of thyroid cells.
The Thyroid Peroxidase (TPO) Antibody Test
Thyroid peroxidase antibodies are antibodies directed against thyroid peroxidase, an enzyme that catalyzes the iodination and coupling steps in thyroid hormone production. Thyroid peroxidase antibodies are present in autoimmune thyroid inflammatory diseases. They are produced in response to thryoid inflammation. The main use of this test is to confirm that a patient’s diffuse goiter and/or hypothyroidism are due to autoimmune thyroiditis. The test may also help distinguish Graves’ disease from hyperthyroidism caused by toxic nodular goiter. The normal reference range is less than 2 IU/mL
The Thyrotropin (TSH) Receptor Antibody Test (TRAb)
Thyrotropin (TSH) receptor antibodies are a class of thyroid autoantibodies directed against TSH receptor protein, a protein primarily found on thyroid cells. Thyrotropin receptor antibodies include blocking, binding, and stimulating antibodies. Blocking antibodies block the action of TSH on thyroid cells; binding antibodies bind to the TSH receptor and prevent TSH and other TSH receptor antibodies from reacting with the TSH receptor; stimulating TSH receptor antibodies stimulate thyroid cells, acting in place of TSH and ordering the production of excess thyroid hormone.
Thyrotropin receptor antibodies are increased in Graves’ disease, atrophic thyroiditis, postpartum autoimmune thyroid disease, neonatal Graves’ disease, and transient neonatal hypothyroidism. The normal reference range is less than 10% inhibition. In Graves’ disease the range is 10-100% inhibition.
The Thyroglobulin (TG) Antibody Test
Thyroglobulin antibodies are autoantibodies directed against thyroglobulin, the major protein found in thyroid cells. Thyroglobulin antibodies are found in nearly all patients with Hashimoto’s thyroiditis and in about 70 percent of patients with Graves’ disease.
The thyroglobulin antibody test is used to confirm that a patient’s diffuse goiter and/or hypothyroidism is due to autoimmune thyroiditis. The test may also help distinguish Graves’ disease from hyperthyroidism caused by toxic nodular goiter. The normal reference range is less than 2 IU/mL.
Special thanks to Elaine Moore for her explanations of the above tests.
From The Merck Manual of Medical Information – Second Home Edition, p.951, edited by Mark H. Beers. Copyright 2003 by Merck & Co., Inc., Whitehouse Station, NJ. Available at: http://www.merck.com/mmhe/sec13/ch163/ch163b.html. Accessed 3/27/07.