thyroid-binding globulin
Summary
Thyroxine-binding globulin (TBG) is the major plasma transport protein for thyroid hormones (T4 and T3), synthesized in the liver. It binds ~70-75% of circulating T4 and T3, keeping free hormone levels low and buffering hormone availability. Changes in TBG levels alter total thyroid hormone levels but not free (active) hormone levels, which are regulated by the hypothalamic-pituitary-thyroid axis.
Detail
TBG is a glycoprotein produced by hepatocytes that binds thyroxine (T4) and triiodothyronine (T3) with high affinity, serving as the primary carrier protein in serum (other carriers include transthyretin and albumin). Only a small fraction (~0.02% of T4, ~0.2% of T3) circulates as free, biologically active hormone; the rest is protein-bound and inactive, forming a large reservoir that buffers against rapid fluctuations.
Clinical significance: Since standard lab assays often measure total T4/T3, conditions altering TBG concentration can affect total hormone levels while free hormone (and thus clinical thyroid status) remains normal—patients stay clinically euthyroid because feedback mechanisms adjust production to maintain normal free hormone levels.
- Increased TBG: pregnancy, estrogen therapy/OCPs (estrogen increases hepatic synthesis and sialylation, reducing clearance), tamoxifen, acute hepatitis, and genetic TBG excess → increased total T4/T3, normal free T4, normal TSH. - Decreased TBG: nephrotic syndrome (urinary loss), cirrhosis, androgens/glucocorticoids, severe illness, malnutrition, genetic TBG deficiency → decreased total T4/T3, normal free T4, normal TSH.
This distinction is a classic board-testable concept: differentiate true thyroid dysfunction (abnormal free T4/TSH) from TBG-related changes (abnormal total T4/T3 but normal free T4/TSH). Measuring free T4 or using the free T4 index (accounting for TBG) helps clarify true thyroid status. Certain drugs (e.g., salicylates, NSAIDs, furosemide) can displace T4 from TBG, transiently altering free hormone levels without true thyroid dysfunction.
Sources
- First Aid for the USMLE Step 1
- Guyton and Hall Textbook of Medical Physiology
- Harrison's Principles of Internal Medicine
- Kaplan USMLE Step 1 Endocrine Lecture Notes
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