Endocrine Abstracts

Context: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide, affecting 2–8% of all pregnancies. We have previously shown that women with high-normal levels of FT4 during early pregnancy have a 2.1-fold increased risk of preeclampsia – but there was no apparent association with low TSH. However, the thyroid is stimulated by human chorionic gonadotropin (hCG) during early pregnancy and therefore we hypothesized that women with high-normal thyroid function due to high hCG levels would have a different risk of preeclampsia as compared to women with high-normal thyroid function and low hCG.

Design, Setting, and Participants: In 5153 women TSH, FT4, hCG and TPO-antibody levels were measured during early pregnancy (<18^th week). The association of high-normal FT4 (5^th quintile) or low TSH with preeclampsia was analysed using multivariable logistic regression stratified per 20.000 IU/l hCG (up to >60.000). All analyses were adjusted for gestational and maternal age, smoking, education, ethnicity, parity, BMI and fetal gender.

Results: The combination of high-normal FT4 levels with low hCG (<20.000 IU/l) was associated with an 11.1-fold increased risk of preeclampsia (P<0.05).

The combination of low TSH with low hCG (<20.000 IU/l) was associated with an increased risk of preeclampsia ranging between a 9.2-fold increased risk for TSH <0.1 mU/l, to an 8.7-fold increased risk for TSH <5^th percentile and to an 3.8-fold increased risk for TSH <0.4 mU/l (all P<0.05).

The combination of high-normal FT4 and hCG > 20.000 or low TSH and hCG>20.000 was not associated with an increased risk of preeclampsia. All analyses remained similar after exclusion of TPOAb positive women.

Conclusion: The additional measurement of hCG in women with high normal thyroid function tests markedly improves the identification of women at high-risk of developing preeclampsia. This is likely to be due to the fact that hCG measurements allow for distinguishing physiologically high thyroid function caused by high hCG levels from pathophysiological high thyroid function due to autonomous production and/or TSH receptor stimulation antibodies.