Thyroid Function Tests | Description | Precautions | Aftercare | Purpose | Risks
Definition
Thyroid function tests are blood tests used to evaluate how effectively the thyroid gland is working. These tests include the thyroid-stimulating hormone test (TSH), free and total thyroxine tests (FT4,T4), the free and total triiodothyronine tests (FT3,T3), the thyroxine-binding globulin test (TBG), and the T-uptake test.
Purpose
Thyroid function tests are used to:
Help diagnose an underactive thyroid (hypothyroidism) and an overactive thyroid (hyperthyroidism).
Evaluate thyroid gland activity.
Monitor response to thyroid therapy.
Thyroid hormones regulate the rate of cellular activity and affect body temperature, appetite, sleep, and mental health. A low level of thyroid hormone results in myxedema. Although the severity of disease may range from very mild to severe, symptoms associated with hypothyroidism are anemia, malaise, intolerance to cold, hyperlipidemia, fluid retention, and depression. A high level of thyroid hormone causes hyperthyroidism. Classical symptoms include insomnia, intolerance to heat, weight loss, and rapid heart rate.
Both hypoand hyperthyroidism can be caused by several mechanisms. Primary hypo- and hyperthyroidism are caused by conditions intrinsic to the thyroid, while secondary hypo- and hyperthyroidism are caused by pituitary-hypothalmic failure. T4 is present in much higher concentrations than T3, but T3 is physiologically more potent. Thyroid hormones are active only when not protein bound (i.e., as free hormone). Circulating free hormone levels are regulated by pituitary release of thyroid stimulating hormone (TSH). The release of TSH is controlled by negative feedback. Increased blood levels of free hormone inhibit pituitary release of TSH.
Precautions
Many drugs affect the results of thyroid function tests without causing thyroid disease. Some common drugs known to depress thyroid hormone levels are dopamine, corticosteroids, lithium, salicylates, anti-convulsants, and androgens. Thyroid hormone levels may be increased by estrogens, clofibrate, and opiates. TSH, TBG, and T-uptake levels are also affected by many of the drugs cited above. In addition, acute and chronic illnesses and pregnancy also affect thyroidfunction tests. Such conditions may be confused with clinical hypo- or hyperthyroidism. When possible, patients may be asked to discontinue medications that are known to interfere with the testsseveral days or more prior to testing.
While most drugs that interfere with thyroid function tests do so by altering thyroxine-binding protein concentrations, peripheral conversion of T4 to T3, and other in vivo mechanisms, a few substances (mainly heterophile and autoantibodies) may interfere directly with the analysis. Such interference should be suspected by a physician who sees a test result that is inconsistent with the patient's symptoms or other thyroid function test results.
Description
Currently, thyroid testing is performed on plasma or serum specimens using immunoassay methods including enzyme-multiplied immunoassay technique (EMIT), cloned enzyme donor immunoassay (CEDIA), radioimmunoassay (RIA), fluorescence polarization immunoassay (FPIA), and chemiluminescence.
The high-sensitivity thyroid-stimulating hormone (TSH) test is the most sensitive and specific screening test for thyroid disease. TSH levels change exponentially with changes in T4 and T3 and are less likely to be elevated or depressed by nonthyroid illnesses or drugs.
This strategy is more cost-effective than a panel approach (e.g., TSH + FT4 or FT4 +FT3) but necessitates the use of a TSH assay with a functional sensitivity below 0.02 mU/L. This level of sensitivity is required to differentiate primary hyperthyroidism, which causes levels to be near undetectable from the low end of the reference range, which is only 0.4 mU/L. A normal TSH level rules out clinical thyroid disease. Low TSH levels may result from primary hyperthyroidism or secondary hypothyroidism caused by pituitary TSH deficiency. High TSH levels are caused by primary hypothyroidism or secondary hyperthyroidism resulting from pituitary adenoma. Abnormal TSH levels are followed by measurements of T3 and T4 (preferably free T4) to confirm the diagnosis. For example, a person with a low TSH who has primary hyperthyroidism will have an elevated T3 and usually an elevated free T4; a person with a low TSH caused by pituitary disease will have low levels of these hormones. Measurement of T4 (and FT4) is considered a more specific indicator of hypothyroidism than T3, while T3 (and FT3) are more sensitive in detecting cases of hyperthyroidism than is T4.
TSH levels are sometimes abnormal in persons with subclinical thyroid disease and in patients with severe acute or chronic illness (called euthyroid sick syndrome). These cases may require the thyrotropin-releasing hormone stimulation test (TRH stimulation test) and reverse T3 test to determine if underlying thyroid disease is present. TRH stimulation is performed by measurement of the TSH level followed by IV administration of thyrotropin releasing factor. The TSH is measured 30 and 60 minutes after the injection. Persons with primary hypothyroidism show an excessive TSH response. The TRH stimulation test is usually normal in persons with euthyroid sick syndrome. Reverse T3forms from peripheral conversion of T4 to T3. Levels of rT3 are low in persons with hypothyroidism and usually increased in persons with euthyroid sick syndrome.
Pregnancy, certain diseases (e.g., viral hepatitis), and several drugs (e.g., steroids) affect the level of thyroxine-binding proteins. In such cases, the level of total hormone will be abnormal, but the level of free hormone will be unaffected. FT4 and FT3 improve diagnostic accuracy for detecting hypo- and hyperthyroidism in patients with thyroid hormonebinding abnormalities that compromise the diagnostic utility of total hormone tests.
In cases where abnormal levels of thyroxinebinding proteins is suspected, two tests are helpful, the T-uptake test and measurement of thyroxine binding globulin (TBG). The T-uptake test [historically called the triiodothyronine resin uptake (T3RU) test] measures the available binding sites on TBG. The test is reported as the thyroid hormone-binding ratio (THBR). The THBR is determined by dividing the percent T-uptake of the patient by that for a normal sample. The ratio is high in hyperthyroidism and low in hypothyroidism. When thyroxine-binding proteins are reduced, the THBR is high; and when binding proteins are elevated, the THBR is low.
The thyroxine-binding globulin (TBG) test measures blood levels of this substance, which is manufactured in the liver. TBG bindsto T3 and T4, and prevents the kidneys from filtering the hormones from the blood. Bound hormone is not physiologically active. The hormone-protein complex is reversible, and in equilibrium with free hormone levels. Therefore, when binding proteins such as TBG are increased, there will be an increase in the amount of total hormone.
Additional tests:
Ultrasound exams of the thyroid gland are used to detect signs of growth and other irregularities.
Thyroid scans using radioactive iodine or technetium (a radioactive metallic element) reveal the size and activity of the gland. Growths or nodules are seen and can be classified as inactive (cold) or active (hot) depending upon the amount of radioactivity present.
Thyroid-specific autoantibodies. Autoimmune disease is the most frequent cause of both hypo- and hyperthyroidism. Commonly performed tests for thyroid autoantibodies are thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and TSH receptor antibodies (TRAb). Although low levels of these antibodies may be found in healthy persons, elevated levels point to the presence of autoimmune disease that involves the thyroid.
Thyroglobulin (Tg) methods are critical for the post-operative management of patients with differentiated thyroid carcinoma (DTC).
Preparation
There is no need to make changes in diet or activities. The patient may be asked to stop taking certain medications until after the test is performed. Venipuncture is performed in the usual manner following standard precautions for prevention of exposure to bloodborne pathogens.
Aftercare
Aftercare consists of routine care of the area around the puncture mark. Pressure is applied for a few seconds, and the wound is covered with a bandage.
Complications
Generally, thyroid function tests are easily interpreted by a physician. However, under certain circumstances interpretation of results is less straightforward. According to an article published in the February 2001 issue of Lancet, one or more of the following features should prompt further investigation:
abnormal thyroid function in childhood
familial disease
thyroid function results inconsistent with the clinical picture
an unusual pattern of thyroid function tests results
transient changes in thyroid function
Results
Not all laboratories measure all of the thyroid function tests that are available. Different methods may result in different normal ranges. Each laboratory will provide a range of values that are considered normal for each test. Some acceptable ranges are listed below.
KEY TERMS
Cirrhosis— Progressive disease of the liver, associated with failure in liver cell functioning and blood flow in the liver. Tissue and cells are damaged, the liver becomes fibrous, and jaundice can result.
Clofibrate (Altromed-S)— Medication used to lower levels of blood cholesterol and triglycerides.
Graves' disease— The most common form of hyperthyroidism, characterized by bulging eyes, rapid heart rate, and other symptoms.
Hepatitis— Inflammation of the liver.
Hyperthyroidism— Overactive thyroid gland; symptoms include irritability/nervousness, muscle weakness, tremors, irregular menstrual periods, weight loss, sleep problems, thyroid enlargement, heat sensitivity, and vision/eye problems. The most common type of this disorder is called Graves' disease.
Hypothyroidism— Underactive thyroid gland; symptoms include fatigue, difficulty swallowing, mood swings, hoarse voice, sensitivity to cold, forgetfulness, and dry/coarse skin and hair.
Myxedema— Hypothyroidism, characterized by thick, puffy features, an enlarged tongue, and lack of emotion.
Nephrosis— Any degenerative disease of the kidney (not to be confused with nephritis, an inflammation of the kidney due to bacteria).
Reverse T3 (rT3)— An isomer of T3 that is formed from deiodination of T4 in the blood. It is not physiologically active.
Salicylates— Aspirin and certain other nonsteroidal anti-inflammatory drugs (NSAIDs).
T3— Also called triiodothyronine. The more active of the two thyroid hormones.
T4— The principal thyroid hormone, called tetraiodothyronine.
T-uptake test— Also known as the T3 resin uptake test, this test measures the number of available binding sites on TBG.
Thyroid gland— A butterfly-shaped gland in front and to the sides of the upper part of the windpipe; influences body processes like growth, development, reproduction, and metabolism.
Thyroid-stimulating hormone (TSH)— A pituitary polypeptide that regulates the activity of thethyroid gland.
Thyrotropin-releasing hormone (TRH)— A neuropeptide produced by the hypothalamus that stimulates pituitary synthesis of TSH.
Thyroxine-binding globulin (TBG)— The primary thyroxine binding protein in blood.
TSH
Normal TSH levels for adults are 0.4-5.0 mU/L.
T4
Normal T4 levels are:
10.1-2.0 microg/dl at birth
7.5-16.5 microg/dl at 1-4 months
5.5-14.5 microg/dl at 4-12 months
5.6-12.6 microg/dl at 1-6 years
4.9-11.7 microg/dl at 6-10 years
4-11 ug/dl at 10 years and older
Levels of free T4 (thyroxine not attached to TBG) are higher in teenagers than in adults.
Normal T4 levels do not necessarily indicate normal thyroid function. T4 levels can register within normal ranges in a patient who:
is pregnant
has recently had contrast x rays
has nephrosis or cirrhosis
T3
Normal T3 levels are:
90-170 ng/dl at birth
115-190 ng/dl at 6-12 years
110-230 ng/dl in adulthood
TBG
Normal TBG levels are:
1.5-3.4 mg/dl or 15-34 mg/L in adults
2.9-5.4 mg/dl or 29-54 mg/L in children
T-Uptake (THBR)
Normal THBR levels are:
0.75-1.05 at birth
0.83-1.15 at 1-15 years
0.85-1.11 for adult males
0.80-1.04 for adult females
0.68-0.87 for second half of pregnancy
LATS
Long-acting thyroid stimulator is found in the blood of only 5% of healthy people.
Health care team roles
Thyroid function tests are ordered and interpreted by a physician. In difficult cases, an endocrine specialist may be needed. A phlebotomist, or sometimes a nurse, collects the blood, and a clinical laboratory scientist CLS(NCA)/medical technologist MT(ASCP) or clinical laboratory technician CLT(NCA)/medical laboratory technician MLT(ASCP) performs the testing.
Resources
BOOKS
Burtis, C.A., and E.R. Ashwood, eds. Tietz Textbook of Clinical Chemistry, 3rd ed. Philadelphia, PA: Saunders, 1999.
Fischbach, Frances Talaska. A Manual of Laboratory and Diagnostic Tests, 5th ed. Philadelphia, PA: J.B. Lippincott Co., 1996.
Pagana, Kathleen Deska, and Timothy James Pagana. Mosby's Diagnostic and Laboratory Test Reference, 3rd ed. St. Louis, MO: Mosby-Year Book, Inc., 1997.
Shaw, Michael, ed. Everything You Need to Know About Medical Tests. Springhouse, PA: Springhouse Corp., 1996.
PERIODICALS
Boschert, S. "Drugs can alter thyroid function test results." Family Practice News 29, no. 11 (June 1, 1999): 34.
Dayan, C.M. "Interpretation of thyroid function tests." The Lancet 357, no. 9256 (Feb 24, 2001): 619.
Kendall-Taylor, P., et. al. "Thyroid function tests. (Letter to the Editor)." British Medical Journal321, no. 7268 (Oct 28, 2000): 1080.
O'Reilly, D. "Thyroid function tests time for a reassessment." BMJ 320 (May 13, 2000):1332-1334.
Tate, J., and F. Tasota. "Assessing thyroid function with serum tests." Nursing 31, no. 1 (Jan 2001): 22.
ORGANIZATIONS
The American Thyroid Association, Inc. Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467. 〈http://www.thyroid.org〉.
The Thyroid Foundation of America, Inc. Ruth Sleeper Hall, RSL350, 40 Parkman St., Boston, MA 02114-2698. (800) 832-8321. 〈http://www.tfaeweb.org/pub/tfa〉.
OTHER
Spencer, C. "Assay of Thyroid Hormones and Related Substances."〈http://www.thyroidmanager.org/FunctionTests/assay-frame.htm〉. Revised Aug. 1, 1999.
