Free T4

Overview

Free T4 measures the unbound, biologically active fraction of thyroxine (T4), the major hormone secreted by the thyroid gland that regulates metabolism, growth, and development through nuclear receptor binding. It represents the physiologically available thyroid hormone not bound to carrier proteins (thyroid-binding globulin, albumin, transthyretin). Elevated levels indicate hyperthyroidism (Graves disease, toxic nodule), while low levels suggest hypothyroidism (Hashimoto thyroiditis, iodine deficiency). Free T4 is clinically useful for confirming thyroid dysfunction when TSH is abnormal and assessing thyroid hormone status independent of binding protein variations.

Clinical Use Cases

  • Confirming primary hyperthyroidism or hypothyroidism with abnormal TSH.
  • Evaluating central hypothyroidism (normal/low TSH, low free T4).
  • Monitoring levothyroxine replacement therapy.
  • Assessing thyroid function in pregnancy, critical illness, or binding protein abnormalities.

Specimen Types

  • Serum.
  • Plasma (lithium heparin).

Measurement Methods

  • Equilibrium dialysis followed by immunoassay (gold standard).
  • Two-step or one-step analog immunoassays (chemiluminescent).
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Test Preparation and Influencing Factors

  • No fasting required.
  • Estrogens, pregnancy, liver disease increase binding proteins (may affect analog methods).
  • Non-thyroidal illness syndrome, drugs (amiodarone, glucocorticoids) alter levels.
  • Biotin supplementation interferes with sandwich immunoassays.

Synonyms

  • Free thyroxine.
  • FT4.
  • Unbound T4.

Further Reading