T4 (Thyroxine), Total Only, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Thyroxine (T4) is synthesized in the thyroid gland. T4 is metabolized to triiodothyronine (T3) peripherally by deiodination. T4 is considered a reservoir or prohormone for T3, the biologically most active thyroid hormone. About 0.05% of circulating T4 is in the free or unbound portion. The remainder is bound to thyroxine-binding globulin (TBG), prealbumin and albumin.
The hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the pituitary to release thyroid-stimulating hormone (TSH). TSH stimulates the thyroid to secrete T4. T4 is partially converted peripherally to T3. High amounts of T4 and T3 (mostly from peripheral conversion of T4) cause hyperthyroidism.
T4 and T3 cause positive feedback to the pituitary and hypothalamus with resultant suppression or stimulation of the thyroid gland as follows: decrease of TSH if T3 or T4 is high (hyperthyroidism), and increase of TSH if T3 or T4 is low (hypothyroidism).
Measurement of total T4 gives a reliable reflection of clinical thyroid status in the absence of protein binding abnormalities. However, changes in binding proteins can occur which affect the level of total T4 but leave the level of unbound hormone unchanged.
See Thyroid Function Ordering Algorithm in Special Instructions.
Monitoring treatment with synthetic hormones (synthetic triiodothyronine will cause a low total thyroxine [T4])
Monitoring treatment of hyperthyroidism with thiouracil and other antithyroid drugs
Total T4 levels offer a good index of thyroid function when the thyroid-binding globulin is normal and nonthyroidal illness is not present
Values >11.7 mcg/dL in adults or > age-related cutoffs in children are seen in hyperthyroidism and patients with acute thyroiditis.
Values <4.5 mcg/dL in adults or < age-related cutoffs in children are seen in hypothyroidism, myxedema, cretinism, chronic thyroiditis, and occasionally, subacute thyroiditis.
Increased total thyroxine (T4) is seen in pregnancy and patients who are on estrogen medication. These patients have increased total T4 levels (increased thyroxine-binding globulin [TBG] levels).
Decreased total T4 is seen in patients on treatment with anabolic steroids, or nephrosis (decreased TBG levels).
A thyrotropin-releasing hormone stimulation test may be required for certain cases of hyperthyroidism.
Clinical findings are necessary to determine if thyroid-stimulating hormone, TBG, or free T4 testing is needed.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
In pregnancy, incomplete release of thyroxine (T4) from its binding proteins might result in falsely low total T4 levels. Therefore, total T4 should not be used as the only marker for thyroid function evaluation.
Thyroid-stimulating hormone (TSH) may be better than thyroxine (T4) as the initial test of thyroid status. TSH is elevated in primary hypothyroidism. TSH is low in primary hyperthyroidism.
Free T4 may more accurately measure the physiologic amount of T4.
Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedure, may have circulating antianimal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.
This test cannot be used in patients receiving treatment with lipid-lowering agents containing dextrothyroxine unless therapy is discontinued for 4 to 6 weeks to allow the physiological state to become re-established prior to testing.
Autoantibodies to thyroid hormones can interfere with testing.
Binding protein anomalies may cause values which deviate from the expected results. Pathological concentrations of binding proteins can lead to results outside the reference range, although the patient may be in a euthyroid state.
In rare cases, interference due to extremely high titers of antibodies to analyte specific antibodies, ruthenium or streptavidin can occur.
In patients receiving therapy with high biotin doses (ie, >5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Adult (> or =20 years): 4.5-11.7 mcg/dL
0-5 days: 5.0-18.5 mcg/dL
6 days-2 months: 5.4-17.0 mcg/dL
3-11 months: 5.7-16.0 mcg/dL
1-5 years: 6.0-14.7 mcg/dL
6-10 years: 6.0-13.8 mcg/dL
11-19 years: 5.9-13.2 mcg/dL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Wilson JD, Foster DW, Kronenburg MD, et al: Williams textbook of Endocrinology. Ninth edition. WB Saunders Company, 1998