Components of the Total Serum Thyroid Hormone Concentrations during Pregnancy: HighFree Thyroxine and Blunted Thyrotropin (TSH) Response to TSHReleasing Hormone in the First Trimester*

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Abstract
The distribution of thyroid hormones between free solution and their several protein-binding sites during pregnancy was studied under physiological conditions of temperature and pH. Single serum specimens were obtained from individual women at different stages of pregnancy. Duringthe first 5 weeks of pregnancy, mean serum free T4 and free T3 concentrations were 50% higher than in nonpregnant women or women during (the third trimester. Free T4 was increased significantly through- (out the first trimester, but because of wide variance, free T3 wassignificantly above control values only during the first 5 weeks. Free T4 and free T3 concentrations decreased to control levels in the third trimester. These changes in free T4 concentrations are consistent with a weak thyrotropic action of hCG, which attained maximal concentrations early in the first trimester and then decreased markedly in the second and third trimesters. TRH testingof women scheduled for abortion in the first and second trimesters revealed marked inhibition of TSH response o t TRH in those first trimester women who had elevated free T4 concentrations. (The percent free T4 did not decrease during the first 5 weeks, but then declined progressively to term as T4-binding globulin)(TBG) affinity, defined as the product of the capacity and affinity constant, progressively increased. T4 bound to TBG T4 TBG increased from early in the first trimester to term, and (then decreased in postterm pregnancy and postpartum. T4 bounot prealbumin T4-PA) and to albumin T4-Alb) decreased significantly in the third trimestercompared with either control or first trimesterconcentrations. The concentration of free T3 waspositively correlated with T4-PA (r = 0.25) and T4-Alb (r = 0.31), but not with free T4 (r= 0.18) or T4-TBG (r = -0.30)concentrations. These results suggest that 1) only the high concentrations of hCG present in the first trimester of pregnancy have a thyro-tropic effect in excess of normal levels of TSH, and this can be sufficient to suppress the TSH response to TRH; 2) hepatic TBG secretion continues to respond to the continuously rising (estrogen levels throughout pregnancy; and 3) T4-PA and T4-Alb,)but not freeT4 of T4-TBG, are possible precursors for the) extrathyroidal generation of T3. {J Clin Endocrinol Metab60: 678,1985)

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