Thyroid Function Tests Health Article

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 hypo- and 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 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, anticonvulsants, 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 thyroid function tests. Such conditions may be confused with clinical hypo- or hyperthyroidism. When possible, patients may be requested to discontinue medications that are known to interfere with the tests several 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 T₃ forms 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 and 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 hormone binding abnormalities that compromise the diagnostic utility of total hormone tests.

In cases where abnormal levels of thyroxine binding 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 binds to 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:

• Utrasound 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 operative management of patients with differentiated thyroid carcinoma (DTC).