Variability in thyroid-stimulating hormone suppression by human chronic gonadotropin during early pregnancy

Objective: The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T-4 in pregnant women at 11 through 18 wk gestation. Study Design: The design of the study was to analyze hCG in comparison with TSH and free T-4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study. Results: hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T-4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases ( P < 0.0001). hCG/TSH correlations are weak in both trimesters ( r(2) = 0.03 and r(2) = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T-4 correlations are weak in both trimesters (r(2) = 0.06 and r(2) = 0.003). At 11-13 wk gestation, free T-4 concentrations rise uniformly at all centiles, as hCG increases ( test for trend, P < 0.0001), but not at 15-18 wk gestation. Multivariate analyses with TSH and free T-4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations. Conclusions: In early pregnancy, a woman's centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately.