FT4

Free thyroxine (FT4) is the portion of the thyroid hormone thyroxine that circulates in the blood without being bound to transport proteins. It represents the biologically active fraction that can enter body cells and influence metabolism. Most circulating T4 is bound to proteins, primarily thyroxine-binding globulin, with only a small, free fraction available to tissues. FT4 levels tend to reflect thyroid gland function and peripheral conversion of T4 to the more active triiodothyronine (T3).

FT4 is measured in serum using immunoassays, with more accurate methods such as equilibrium dialysis or ultrafiltration sometimes used in specialized laboratories. Reference ranges vary by assay and population, but adult values are typically about 0.8–1.8 ng/dL (10–23 pmol/L). FT4 is often interpreted together with the thyroid-stimulating hormone (TSH) to assess thyroid status.

Clinical interpretation: In primary hyperthyroidism, FT4 is elevated with suppressed TSH. In hypothyroidism, FT4 is low with elevated TSH. A low FT4 with a normal or inappropriately low TSH can indicate central (secondary) hypothyroidism or pituitary disease. FT4 is also used to monitor thyroid hormone replacement therapy, with goals adjusted to achieve a target FT4 level corresponding to clinical response and TSH status.

Limitations and considerations: FT4 measurements can be affected by non-thyroidal illness, pregnancy, and certain medications, and some immunoassays may yield inaccurate results due to interference (e.g., biotin supplements or heterophile antibodies). Because TSH remains the most sensitive initial test for thyroid dysfunction, FT4 is typically used to interpret ambiguous TSH results or to assess pituitary function and treatment adequacy.