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This version published online on June 10, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0568
A more recent version of this article appeared on September 1, 2008
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Submitted on March 11, 2008
Accepted on May 29, 2008

Variability in Thyroid Stimulating Hormone Suppression by human Chronic Gonadotropin during Early Pregnancy

James E. Haddow MD*, Monica McClain PhD, Geralyn Lambert-Messerlian PhD, Glenn E. Palomaki BS, Jacob A. Canick PhD, Jane Cleary-Goldman M.D., Fergal D. Malone MD, T. Flint Porter MD, David A. Nyberg MD, Peter Bernstein MD, Mary E. D'Alton MD, and for the FaSTER Research Consortium

The Warren Alpert Medical School of Brown University, Providence, RI; Columbia University College of Physicians and Surgeons, New York, NY; Royal College of Surgeons in Ireland, Dublin, Ireland; University of Utah and Intermountain HealthCare, Salt Lake City, UT; Swedish Medical Center, Seattle, WA; Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY

* To whom correspondence should be addressed. E-mail: jhaddow{at}ipmms.org.

Objective: Further explore relationships between hCG, TSH, and free T4 in pregnant women at 11 through 18 weeks' gestation.

Study Design: Analyze hCG in comparison to TSH and free T4, in paired first and second trimester sera from 9,562 women in the FaSTER (First and Second Trimester Evaluation of Risk for Fetal Aneuploidy) Trial Study.

Results: hCG is strongly correlated with BMI, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index (BMI) and percent of women who smoke both decrease, while the percent of primigravid women increases (P < 0.0001). hCG/ TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and 5th centiles become sharply lower at higher hCG levels, while 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11 through 13 weeks' gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15 through 18 weeks' gestation. Multivariate analyses with TSH and free T4 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.


Key words: hCG • TSH • Free T4 • Correlations • Early Pregnancy







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