Recommendations needed for TPOAb cut-off levels during pregnancy

DENVER — The presence of thyroid peroxidase antibodies during pregnancy may affect thyroid function, but no recommended cut-off ranges to identify thyroid peroxidase antibody–positive women are currently available.

However, the draft 2016 American Thyroid Association guidelines on thyroid and pregnancy states that treatment can be considered for lower thyroid-stimulating hormone concentrations in thyroid peroxidase antibody (TPOAb)–positive women as compared with TPOAb–negative women.

“Population-based cut-offs for TPOAb positivity seem feasible — similar to thyroid function reference ranges — and our data indicate that the use of currently provided assays may lead to underdiagnosing of women with thyroid autoimmunity that is associated with higher TSH concentrations,” Tim Korevaar, MD, MSc, of Erasmus University Medical Center in Rotterdam, Netherlands, told Endocrine Today.

Tim Korevaar

Korevaar and colleagues used data from three Dutch prospective cohort studies on pregnant women to determine the threshold at which TPOAb levels begin to affect thyroid function and thyroidal response to human chorionic gonadotropin (hCG).

Overall, 5,435 women from the Generation-R study and 4,078 women from the ABCD study were measured before 18 weeks’ gestation for thyroid-stimulating hormone, free thyroxine, TPOAb and hCG (not in ABCD), and 1,663 women from the HAPPY study were measured at less than 18 weeks’ gestation and again at a median 32 weeks. Manufacturer cut-off for TPOAb was more than 60 IU/L for the Generation-R study and more than 35 IU/L for the HAPPY study.

The relationships of TPOAb to TSH, free T₄ and the thyroidal response to hCG were investigated using multivariable linear regression models adjusted for are, smoking, BMI, parity, ethnicity, education and fetal sex.

A positive relationship was found between TPOAb and TSH, and a negative association between TPOAb and free T₄, during early pregnancy (P < .001 for both). Elevated TSH levels were found with TPOAb levels above 10 IU/L; decreased free T₄ levels were found with TPOAb levels below 30 IU/L. There was a 60% attenuation for the relationship between TSH and TPOAb, and TSH rose from TPOAb cut-offs of 35 IU/L during late pregnancy (P < .001).

During late pregnancy, there was no relationship between TPOAb and free T₄. There was no relationship between hCG and TSH or free T₄ in participants positive for TPOAb compared with those who were TPOAb negative. The lack of relationship between hCG and TSH became recognizable at TPOAb cut-offs of 10 IU/L and between hCG and free T₄ from 30 IU/L.

When all studies were combined using a population-based approach, the results showed that in all three cohorts, from the 92nd percentile onwards, higher TSH concentrations were present.

“Cut-offs for TPOAb positivity are determined very differently, and mostly using data from nonpregnant individuals,” Korevaar told Endocrine Today. “Although all international guidelines advocate the use of population-based reference ranges for TSH and [free] T₄ during pregnancy, there is no such recommendation for TPOAb positivity. However, over the last few years, data suggest that the presence of TPOAb positivity may change the likelihood of whether a woman could benefit from treatment. In this study, we show that thyroid function already becomes lower in women with TPOAb concentrations that are well below the cut-offs provided by manufacturers.”

Korevaar added that the findings need to be replicated with larger numbers of cohorts. A collaboration, the Consortium on Thyroid and Pregnancy, has been formed to investigate cut-off ranges and similar gaps in data within the field.

“Subsequently, we need to investigate from what cut-off the risk of disease starts to increase and then investigate if we can overcome this increased risk through levothyroxine treatment,” Korevaar said. – by Amber Cox

Reference:

Korevaar T, et al. Oral 20. Presented at: 86th Annual Meeting of the American Thyroid Association; Sept. 21-25, Denver.

Disclosure: Korevaar reports no relevant financial disclosures.