Thyroid related
Thyroxine (total T4)

Topic Completed: 1 March 2011

Revised: 31 December 2018, last major update March 2011

Copyright: (c) 2002-2016,, Inc.

PubMed Search: Thyroxine [title]

Nat Pernick, M.D.
Page views in 2018: 122
Page views in 2019 to date: 210
Cite this page: Pernick N. Thyroxine (total T4). website. Accessed December 14th, 2019.
Definition / general
  • Note: in this topic, "T4" means total T4, unless stated otherwise
  • Usual daily production is 110 nmol/day; half life is 7 days
  • 100% produced in thyroid
  • 50% of T4 is 5' deiodinated to form T3, 40% is 5 deiodinated to form reverse T3 via 5-deiodinase
  • Higher T4/T3 ratio when abundant iodide
  • 70% of T4 is bound to thyroxine binding globulin, 20% to transthyretin (thyretin), 10% to albumin
    • Up to 5% to IgM, IgG and lipoproteins
  • < 1% of T4 is free, but this form is active
    • Protein bound T4 is inactive and does not enter cells

  • Altered protein-binding characteristics:
    • Account for more abnormal T4 values than actual thyroid dysfunction
    • May be due to drugs that increase protein binding and cause increased T4
      • Patient may be clinically euthyroid
      • Recommend measuring free T4
    • May be due to familial dysalbuminemic hyperthyroxinemia (increased albumin binding of T4), clinically euthyroid (J Pediatr Endocrinol Metab 2002;15:801)
    • Patient may be euthyroid with high T4 but peripheral resistance (Best Pract Res Clin Endocrinol Metab 2006;20:529)
  • TSH is a more sensitive and specific screening test for thyroid dysfunction than total T4, but total T4 may be helpful in interpreting TSH results


Thyroxine administration
  • T4 levels usually constant

T3 administration
  • Does not affect T4 levels

  • Immunoassay

Reference range

Conversion factor
  • Primary hypothyroidism: low T4 and high TSH
  • Primary hyperthyroidism: high T4 and T3 and low TSH
  • T4 thyrotoxicosis: high T4, low / normal T3; due to iodine, beta blockers, amiodarone, steroids or nonthyroidal illness
  • T3 thyrotoxicosis: low / normal T4, high T3, low TSH
  • Severe nonthyroidal illness: low T3, low T4, associated with poor prognosis
  • Euthyroid hyperthyroxinemia:
    • High T4, normal TSH, otherwise euthyroid
    • Due to increased binding proteins associated with estrogens (pregnancy) or liver disease, psychiatric illness (Acta Psychiatr Scand 2006;114:132), familial dysalbuminemia
    • Recommended to measure free T4, which correlates better with thyroid functional status
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