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Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

Most of the thyroid hormone circulating in the blood is bound to “transport protein“s. Only a very small fraction of the circulating hormone is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value.

When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

bound to thyroxine-binding globulin (TBG)70%
bound to transthyretin or “thyroxine-binding prealbumin” (TTR or TBPA)10-15%
unbound T4 (fT4)0.03%
unbound T3 (fT3)0.3%

Despite being lipophilic, T3 and T4 cross the cell membrane via carrier-mediated transport, which is ATP-dependent.[

T1a and T0a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor TAAR1 (TAR1, TA1), a G-protein-coupled receptor located in the cell membrane.

Another critical diagnostic tool is measurement of the amount of thyroid-stimulating hormone (TSH) that is present.

Membrane transport