Endocrinology fT4

Free Thyroxine (fT4).

Quantitative determination of free thyroxine from a dried blood spot using chemiluminescence immunoassay (CLIA) on the LIAISON platform.

Quick Reference
Method
CLIA (LIAISON)
Sample Types
DBS
Analytes

1 analyte

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What does this test assess?

Free T4 measurement complements TSH in the assessment of thyroid function, enabling differentiation between overt and subclinical thyroid disease and classification of the cause of thyroid dysfunction.

Clinical indications include:

  • Confirmation and classification of thyroid dysfunction detected by abnormal TSH
  • Differentiation of overt from subclinical hypothyroidism and hyperthyroidism
  • Monitoring of thyroid hormone replacement therapy dosing
  • Assessment of central (secondary) hypothyroidism where TSH may be unreliable
  • Evaluation of thyroid function during pregnancy (trimester-specific ranges)
  • Monitoring of antithyroid drug therapy in hyperthyroidism

Measured analytes

Analyte / GroupComponentsClinical Significance
fT4 Free thyroxine (unbound T4) The biologically active, unbound fraction of thyroxine; directly reflects thyroid hormone availability to tissues
Note

Free T4 represents approximately 0.03% of total T4 and is unaffected by changes in binding protein concentrations, making it a more reliable marker than total T4.

About free thyroxine

Thyroxine (T4) is the predominant thyroid hormone produced by the thyroid gland. In circulation, more than 99.9% is bound to transport proteins (TBG, albumin, transthyretin), with only a tiny free fraction available to enter cells and exert biological effects. It is this free fraction that is measured as fT4.

~12–22 pmol/L

Typical adult reference range

T4 → T3

T4 is converted to the more active T3 in peripheral tissues

Free fraction

Only 0.03% of total T4 is biologically active

fT4 is particularly valuable when TSH alone is insufficient for clinical decision-making. In overt hypothyroidism, both TSH is elevated and fT4 is low. In subclinical hypothyroidism, TSH is elevated but fT4 remains normal. This distinction guides treatment decisions, as overt disease typically requires immediate treatment while subclinical disease may warrant monitoring.

In pregnancy, thyroid hormone requirements increase by 25–50%, and trimester-specific reference ranges are required for accurate interpretation. Inadequate maternal thyroid hormone supply can adversely affect foetal neurodevelopment.

Analytical technique

fT4 is measured using the LIAISON chemiluminescence immunoassay (CLIA) platform, adapted for the DBS matrix. The assay employs a competitive immunoassay format optimised for the free hormone fraction.

Sample information

Typically ordered alongside TSH for a complete thyroid function assessment. DBS collection enables paired TSH/fT4 testing from a single sample card.

Literature

  1. Baloch Z, et al. “Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease.” Thyroid, 2003, 13(1):3-126. 10.1089/105072503321086962
  2. Alexander EK, et al. “2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum.” Thyroid, 2017, 27(3):315-389. 10.1089/thy.2016.0457

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