Thyroxine-binding globulin (TBG) is the main transport protein for thyroid hormones in the bloodstream, carrying approximately 70–75% of circulating T4 and T3. Only the unbound (free) fraction of thyroid hormones is biologically active — so TBG levels significantly influence the interpretation of total thyroid hormone measurements.
TBG levels are increased by oestrogen (including oral contraceptives and pregnancy) and decreased by androgens, corticosteroids, nephrotic syndrome, and liver disease. Abnormal TBG levels can make total T4 appear falsely elevated or low, even when free T4 is normal. TBG testing is most useful when total thyroid hormone levels don't match the clinical picture or when free hormone measurements give unexpected results.
FAQs
Why does pregnancy raise thyroid hormone levels on blood tests?
Oestrogen in pregnancy raises TBG, increasing the binding capacity for thyroid hormones. Total T4 and T3 rise by 30-50%, but free T4 and free T3 remain relatively normal. This is why free hormone measurements are preferred during pregnancy.
Is TBG deficiency dangerous?
Inherited TBG deficiency (X-linked, more common in males) causes low total T4 but normal free T4 and TSH. It is a benign condition requiring no treatment. It is important to recognise to avoid unnecessary thyroid hormone supplementation.
Why do free rather than total thyroid hormone levels matter clinically?
Only free (unbound) thyroid hormones are biologically active and can enter cells. Total levels can be altered by changes in TBG without affecting actual thyroid function. Free T4 and free T3 reflect the hormone available to tissues.
When is it important to measure TBG?
TBG measurement is most useful when total and free thyroid hormone results are discordant, when oestrogen use or liver disease may be altering TBG levels, and when a TBG abnormality is suspected to explain confusing thyroid test results.
