What does the Free T4 test measure?

## Editorial Commentary

Free T4 measurement has been the subject of extensive methodological debate over four decades. The challenge is fundamental: free T4 represents a tiny fraction of total T4, with the equilibrium between bound and free fractions easily disturbed by sample handling and assay conditions. Modern direct equilibrium dialysis methods are considered the reference standard but are not widely available in routine laboratories. Most commercial labs use one-step or two-step analog immunoassays which approximate free T4 reasonably well in most clinical contexts but can show artifactual results in extremes of thyroid binding globulin alteration.

This means the practitioner ordering Free T4 should know which assay platform their laboratory partner uses and understand its limitations. Pregnancy is the clinical context most likely to surface assay variability — trimester-specific reference ranges should be applied where the laboratory provides them, and discordance between Free T4 and TSH in pregnancy warrants confirmation by an alternative assay principle before treatment changes are made.

For the practitioner, the practical implication is that Free T4 results are interpreted in the context of TSH, the patient's clinical picture, and any pregnancy or binding-protein-altering medication exposure — never as an isolated number.