T4 Total

Thyrotropin releasing hormone (TRH), a hypothalamic peptide, stimulates the anterior pituitary to synthesize and secrete thyroid stimulating hormone (TSH). TSH stimulates the release of triiodothyronine (T3) and thyroxine (T4)  from thyroglobulin and their secretion by the thyroid. T4 and T3 are secreted in a ratio of 10:1. Most circulating T4 and T3 are protein bound. Only the free fraction is metabolically active. In peripheral tissues, T4 is converted to T3, which is the active hormone that migrates into the target cell nuclei and binds to DNA.

Primary hypothyroidism is the most common thyroid disorder. In this condition, the thyroid fails to respond to TSH.  The pituitary secretes more TSH in response to decreasing circulating T4 concentrations.  The failing thyroid gland partially compensates by increasing the ratio of secreted T3 to T4. If this last attempt to restore homeostasis fails, the patient’s metabolic rate falls. At this stage of hypothyroidism, TSH is elevated and T4 and free T4 are decreased.  

The opposite condition, hyperthyroidism or thyrotoxicosis, is caused by too much circulating T4. Graves’s disease, an autoimmune disorder caused by antibody to TSH receptors, leads to uncontrolled release of T4 and T3, which suppress circulating TSH.  Serum T4, FT4, T3, and FT3 concentrations are elevated two to three times above the upper limit of normal and TSH is undetectable.  

Traditionally, at least two thyroid function tests, thyroxine (T4) and T3 uptake T3U, were ordered on each patient. The product of these tests was reported as the free thyroxine index (FTI) or T7.  New methods for direct measurement of free T4 has eliminated the need to estimate free hormone levels with T3U and FTI.

Thyroxine is a good index of thyroid function when thyroid binding proteins are normal. However, changes in binding proteins can occur that affect the level of total T4 but leave the level of unbound hormone unchanged.

Elevated thyroxine levels are associated with hyperthyroidism and acute thyroiditis. Decreased levels are found in hypothyroidism and chronic thyroiditis. Nonthyroid illness may cause significant confusion in the interpretation of thyroxine.  

Thyroxine may be increased by the following medications; estrogen, oral contraceptives, clofibrate, fluorouracil, and exogenous thyroxine. Thyroxine may be decreased by androgens, glucocorticoids, L-asparaginase, phenytoin, carbamazepine,  rifampin, and dopamine.

Thyroxine is measured by a competitive immunoassay. The adult reference range is 4.5–11.7 ug/dL.

Specimen requirement is one red-top gel barrier tube of blood.

Thyroxine is no longer recommended for routine thyroid screening. Thyroid stimulating hormone (TSH) and Free T4 are preferred.

Reference

Bethune JE. Interpretation of thyroid function tests. Dis Mon. 1989 Aug; 35(8):541-595.