Transport, Metabolism and Excretion of Thyroid Hormone

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Chapter: Essential pharmacology : Thyroid Hormones And Thyroid Inhibitors

Thyroid hormones are avidly bound to plasma proteins—only 0.03–0.08% of T4 and 0.2–0.5% of T3 are in the free form. Almost all protein bound iodine (PBI) in plasma is thyroid hormone, of which 90–95% is T4 and the rest T3.


TRANSPORT, METABOLISM AND EXCRETION

 

Thyroid hormones are avidly bound to plasma proteins—only 0.03–0.08% of T4 and 0.2–0.5% of T3 are in the free form. Almost all protein bound iodine (PBI) in plasma is thyroid hormone, of which 90–95% is T4 and the rest T3. Binding occurs to 3 plasma proteins. In the order of affinity for T4, these are:

 

·        Thyroxine binding globulin (TBG)

·        Thyroxine binding prealbumin (transthyretin)

·        Albumin

 

The normal concentration of PBI is 4–10 μg/ dl; only 0.1–0.2 μg/dl of this is T3, rest is T4. During pregnancy thyroxine binding globulin is increased—PBI levels are elevated, but there is no effect on thyroid status as the concentration of free hormone remains unaltered.

 

Only the free hormone is available for action as well as for metabolism and excretion. Metabolic inactivation of T4 and T3 occurs by deiodination and glucuronide/sulfate conjugation of the hormones as well as of their de-iodinated products. Liver is the primary site (also salivary glands and kidneys). The conjugates are excreted in bile. A significant fraction is deconjugated in intestines and reabsorbed (enterohepatic circulation) to be finally excreted in urine.

 

Plasma t½ of T4 is 6–7 days, while that of T3 is 1–2 days. The halflives are shortened in hyperthyroidism and prolonged in hypothyroidism due respectively to faster and slower metabolism.

 

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