New Studies Needed for Pregnancy-Specific Cut-off Values for TPOAb Positivity

Factors Affecting Follow-Up in Women With Gestational Diabetes
Factors Affecting Follow-Up in Women With Gestational Diabetes
Current cut-offs for pregnancy-specific thyroid autoantibody positivity vary from by assay.

Pregnancy-specific cut-off values for thyroid autoantibody (TPOAb) positivity for many of the commonly used assays require further examination to better inform clinicians, researchers reported at the 86th Annual Meeting of the American Thyroid Association (ATA).

“We investigated the association of TPOAb concentrations with TSH (thyroid-stimulating hormone) and FT4 (free thyroxine) concentrations during pregnancy in 3 population-based cohorts encompassing more than 11 000 pregnant women. We found that women with TPOAb concentrations already well below currently advocated cut-offs for TPOAb positivity, have higher TSH and lower FT4 concentrations in all 3 cohorts,” said study investigator Tim Korevaar, MD, MSc, a PhD student at Erasmus University Medical Center, Rotterdam, Netherlands.

He and his colleagues investigated the threshold at which TPOAb levels begin to affect thyroid function and the thyroidal response to human chorionic gonadotropin (hCG). Dr Korevaar said that TPOAb positivity during pregnancy is present in 5% to 22% of the general population. He noted the various cut-offs for TPOAb positivity are reported to range from 15 IU/L to 143 IU/L and that the cut-offs are determined by assay manufacturers in a very heterogeneous manner.

The researchers analyzed data from 3 Dutch prospective cohorts. These patients had TSH, FT4, TPOAbs, and hCG (2 of 3 cohorts) measured once in 5435 pregnant women before 18 weeks gestation from the Generation-R study and 4078 women from the ABCD study. Similar measurements were taken twice in 1663 pregnant women from HAPPY (before 18 weeks and at a median 32 weeks). The researchers used multivariable linear regression models adjusting for age, smoking, BMI, parity, ethnicity, education, and fetal sex.   

Results demonstrated a positive association between TPOAbs and TSH and a negative association between TPOAbs and FT4 during early pregnancy.

The researchers subsequently investigated from what population-based percentile cut-off this started to occur in the data. They found that in all 3 cohorts, the TSH was higher from the 93rd percentile onwards.

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The study findings suggest that there needs to be a much closer study of what are appropriate cut-off rates in this patient population and also that population-based reference ranges for TPOAbs are feasible.

“This is clinically relevant because the new draft 2016 ATA guidelines advocate that treatment can be considered in TPOAb-positive women from a TSH greater than 2.5 mU/L while this cut-off is a population-based cut-off or 4.0 mU/L in TPOAb-negative women. As such, the definition of TPOAb positivity has a direct influence on treatment considerations during pregnancy,” said Dr Korevaar. “The most important take-home message is that current manufacturer cut-offs for TPOAb positivity may be too high, although this differs per TPOAb assay. Therefore, future studies have to identify pregnancy-specific cut-off values for TPOAb positivity for different commonly used assays.”

Disclosures: Dr Korevaar reports no financial relationships or commercial interests.

For more coverage of ATA 2016, click here.


  1. Korevaar T, Pop V, Chaker L, Medici M, Visser T, Peeters R. Oral Abstract 20. TPOAb levels well below commonly used cut-offs already affect gestational thyroid function and the thyroidal response to hCG. Presented at: American Thyroid Association Annual Meeting; September 21-25, 2016; Denver, Colorado.