Part of “CHAPTER 30 – THYROID PHYSIOLOGY: SYNTHESIS AND RELEASE, IODINE METABOLISM, BINDING AND TRANSPORT“

Approximately 120 nmol of T₄, 47 nmol of T₃, and 50 nmol of reverse T₃ (rT₃) appear in the serum each day in a typical 70-kg person11,12 and 13 (Table 30-2). The balance between production and degradation is mediated by, among other things, nutrition, non-thyroidal illness, exercise, pregnancy, and medications. At steady-state conditions, this balance is reflected by serum values that represent only ˜29% of T₄, 14% of T₃, and 14% of rT₃ total body hormone stores or pool (Q_tot). Less than 1% of the total circulating amount of each hormone is free in the plasma (see Table 30-2). This extraordinary degree of binding to transport proteins has several important consequences: (a) The plasma contains a large capacity to store hormone, serving as a reservoir or a buffer against fluctuations in blood levels; (b) Little hormone is lost through the kidneys by glomerular filtration of free hormone; and (c) Changes in binding proteins affect the serum reservoir but do not affect the amount of free hormone, presumably not altering the physiologic actions of the hormone (see Table 30-1). Either the binding protein capacity, the free hormone concentration, or the binding protein concentration may be measured to clarify the changes in circulating T₄ or T₃ concentrations that accompany genetic or acquired aberrations in the binding proteins (also see Chap. 33 and ref. 13a).

Table 30-2 shows some of the similarities and differences between the major iodothyronines. T₃ has 10% and rT₃ has only 2% of Q_tot compared with T₄. Although ˜50% of T₄ and rT₃ circulates in the blood and other rapidly equilibrating tissues, such as liver and kidney, only ˜25% of T₃ is found in these same kinetic compartments. Hormone stores are turned over at a rate of ˜10% per day for T₄, 70% per day for T₃, and 350% per day for rT₃. Thus, with inhibited production of endogenous hormone (see Table 30-2) or increased appearance of exogenous hormone (e.g., increased dosage), the new steady-state conditions are reached within weeks for T₄, within days for T₃, and within hours for rT₃.11,12 Compared with T₃, T₄ has a higher binding affinity (see Table 30-1) and slower plasma clearance rate (relative to the distribution volume [V_D]), making T₄ a stable circulating hormone reservoir and substrate for T₃ formation. The rapid plasma clearance rate of T₃, relative to its V_D, is associated with more labile equilibration or disequilibration, reflecting shorter response times of circulating T₃ to environmental and nutritional influences.