Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Thyroid Hormones
Transport and Metabolism of Thyroid Hormones

From half to two-thirds of T4 and T3 are present extrathyroidally in the body, with the majority circulating in bound form complexed with two carrier Proteins: thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA). Quantitatively, TBG is of greater importance; it is a glycoprotein with a Molecular Weight of 50,000. It binds T4 and T3 with an affinity 100 times greater than that of TBPA and a binding capacity of 20 µg/100 ml of plasma. Under normal physiological conditions, TBG non-covalently binds nearly all plasma T4 and T3 (Table 46.1). The biological activity of these Hormones is determined by the small unbound (free) fraction. Despite significant differences in total hormone concentrations, the free fraction of T3 is comparable to that of T4, whereas the plasma half-life of T4 is 4 to 5 times longer than that of T3.

TBG also acts as a regulated variable, an important factor that must be taken into account when evaluating thyroid function diagnostically, since most assays for T4 or T3 measure total hormone concentration in plasma rather than the free fraction. TBG is synthesized in the Liver, and its production is stimulated by estrogens (during Pregnancy and with oral contraceptives). Conversely, TBG synthesis is reduced by the administration of therapeutic androgens or glucocorticoids, as well as in certain hepatic disorders. Hereditary elevations or deficiencies in TBG levels are also known. In all such cases, total T4 and T3 levels shift accordingly, while the free hormone fraction remains unchanged. Phenytoin and salicylates compete with T3 and T4 for binding sites on TBG, resulting in a decrease in total hormone levels without altering the concentration of their free forms—a critical consideration when interpreting diagnostic test results. Extrathyroidal deiodination converts T4 into T3. T3 appears to be the predominantly active metabolic molecular form of the hormone, as it binds to target Cell receptors with an affinity 10 times greater than that of T4. Approximately 80% of circulating T4 undergoes peripheral conversion to T3 or reverse T3 (rT3), which serves as the primary source of T3. Reverse T3 is a very weak hormone agonist that is produced in relatively large quantities during chronic illness, carbohydrate starvation, and in fetal development. Propylthiouracil and propranolol inhibit The conversion of T4 to T3.

Class="center">Table 46.1. Comparison of Plasma T4 and T3 Levels

Total hormone content (µg%)

Free hormone

Blood half-life

% of total content

- in ng%

in moles

t1/2 (days)

Т4 8 0,03

~ 2,24

3,0∙10-11

6,5

Т3 0,15 0,3

~ 0,4

~ 0,6∙10-11

1,5

Other pathways of thyroid hormone METABOLISM include complete deiodination or inactivation via deamination or decarboxylation. Hepatic conjugation (glucuronidation and sulfation) yields more hydrophilic molecules that are excreted into the Bile, reabsorbed in the intestine, deiodinated in the Kidneys, and eliminated in the urine.



Last update: 06/08/2026

Editorial and Educational Adaptation: This material has been compiled based on the primary/original source text. The project team performed an editorial review, corrected technical inaccuracies, structured sections, and adapted the content for an educational format.

What was processed:

  • elimination of formatting defects (OCR errors, structural breaks, corrupted characters);
  • editorial organization of content;
  • standardization of terminology in accordance with academic sources;
  • verification of factual statements against the original source text.

All mentions of the author, publication year, and origin of the primary text have been preserved in accordance with the source.