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Estrogens, endogenous or exogenous, commonly affect tests of thyroid function by increasing total
T4 due to an increase in the concentration of TBG, but serum free T4 remains normal. Rather than
simply increasing the production of TBG, estrogens act to increase the glycosylation of TBG, which
slows its clearance, leading to a higher TBG concentration, or binding capacity, with normal binding
affinity (Ain & Refetoff, 1988). In pregnancy, the mean total serum T4 concentration is increased by
about 30%, with up to 40% of values falling outside the normal reference range in the second and
third trimesters. Transdermal oestrogens do not show this effect to the same extent, because their
effect on hepatic protein synthesis is less marked (Chetkowski et al, 1986). It remains uncertain
which of the other drugs that increase the concentration of TBG (table 1) act by increasing protein
synthesis, and which modify the clearance of TBG.
In response to an increase in binding protein, there will be an initial tendency for the free hormone concentration to decrease, leading to a transient increase in serum TSH; an increase in total hormone concentration then restores the baseline free serum T4 concentration, but the free fraction of T4 is lower. Turnover rate of T4 remains unchanged, but the extracellular pool is increased. Changes in T3 binding are similar. Standard techniques for estimation of free T4 and free T3 generally compensate well for binding alterations due to changes in TBG concentration. The commencement of androgen treatment for breast cancer, which resulted in a 50% lowering of serum TBG, has been reported to result in acute features of thyrotoxicosis in some women maintained on stable replacement dosage of T4 for hypothyroidism (Arafah, 1994). An initial T4 dose reduction by 20-50% was recommended, although the need for permanent dose modification has not been established. |
