Components of the total serum thyroid hormone concentrations during pregnancy: high free thyroxine and blunted thyrotropin (TSH) response to TSH-releasing hormone in the first trimester.

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. During the 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 throughout the first trimester, but because of wide variance, free T3 was significantly 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 testing of women scheduled for abortion in the first and second trimesters revealed marked inhibition of TSH response to 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 bound to prealbumin (T4-PA) and to albumin (T4-Alb) decreased significantly in the third trimester compared with either control or first trimester concentrations. The concentration of free T3 was positively 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 thyrotropic 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 free T4 or T4-TBG, are possible precursors for the extrathyroidal generation of T3.