Thyroxine-binding globulin (TBG)

Most thyroid hormone in the blood is bound to carrier proteins, and thyroxine-binding globulin (TBG) is the main one. Only the tiny free (unbound) fraction is active, which is why modern thyroid testing measures free T4 and free T3. But older or total measurements include the bound hormone, so anything that changes the amount of TBG shifts the total up or down even when the thyroid itself is working perfectly normally. TBG is therefore measured mainly to explain a confusing result: when a total T4 or T3 looks high or low but the free hormones and TSH — and the person's clinical state — are normal. A raised TBG (for example in pregnancy, from oestrogen or the contraceptive pill, or from certain inherited variants and liver conditions) lifts the total hormone; a low TBG (from androgens or steroids, significant illness, protein loss, or an inherited deficiency) lowers it. TBG testing is uncommon and used selectively, always interpreted alongside the free thyroid hormones and TSH.

• Pregnancy — a common, normal cause of raised TBG and total thyroid hormone.
• Oestrogen — the contraceptive pill or hormone therapy.
• Inherited high TBG — a benign genetic variant.
• Some liver conditions — such as certain forms of hepatitis.
• The effect is to raise total T4/T3 while free hormones and thyroid function stay normal.

• Androgens or corticosteroids — medications that lower TBG.
• Significant illness or protein loss — e.g. nephrotic syndrome, severe liver disease.
• Inherited TBG deficiency — a benign genetic variant.
• The effect is to lower total T4/T3 while free hormones and thyroid function stay normal.