TSH Reference Limits Vary During First Trimester of Pregnancy

Pregnant woman
Pregnant woman
A uniform standard for thyroid-stimulating hormone reference limits could lead to frequent misclassification and incorrect choices for therapy.

Recent data revealed that serum thyroid-stimulating hormone (TSH) reference limits differ widely during the first trimester of pregnancy, which suggests that a uniform set of reference limits will lead to misclassification and incorrect choices for therapy.

The findings were published in the Journal of Clinical Endocrinology & Metabolism.

Thyroid hormones are crucial for fetal development, and abnormal thyroid function in pregnancy may severely increase the risk for fetal loss and other pregnancy complications. However, there is currently no consensus regarding maternal thyroid testing reference limits during early pregnancy. Therefore, researchers sought to estimate the weekly changes and predictors of TSH and free T4 (fT4) reference limits during the first trimester of pregnancy.

The study cohort included a random sample from the Danish National Birth Cohort, which included 101 032 pregnant women between 1996 and 2002.

The researchers identified 6671 healthy participants from Danish national health registries and obtained individual characteristics using interview data. They collected biobank sera and measured the reference limits for TSH and fT4 during each pregnancy week of the first trimester, and examined predictors of these reference limits.

During weeks 9 through 12, the TSH upper limit for pregnant women was approximately 0.4 mU/L lower than the limit for nonpregnant women. The lower TSH limit during this time was approximately 0.1 mU/L. At the same time point, the fT4 variations were the reverse of those for TSH with 4% higher reference limits during weeks 9 through 12.

The TSH upper reference limit was lower in multiparous women and women with lower iodine intake, but higher among obese women. Researchers also observed that fT4 was lower among smokers.

According to the study researchers, the results suggest that TSH nonpregnancy reference limits are most effective throughout the first 6 weeks of pregnancy. The results also suggest using the 0.4 mU/L upper TSH limit during weeks 9 through 12, and using the lower TSH reference limit of 0.1 mU/L during weeks 9 through 12. They also noted that TSH may still be below 0.1 mU/L during weeks 10 and 11 of the pregnancy.

“Various individual characteristics influenced the TSH reference limits, as also observed in other studies,” the researchers wrote. “The clinical relevance of adjusting limits according to such characteristics is unknown. For the time being, we suggest using overall limits according to pregnancy week, and to consider individual characteristics only in patients with borderline test results.”

They added, “More studies are needed to expand knowledge on the clinical relevance of the reference range limits derived from testing of healthy pregnant women.”


  1. Laurberg P, Andersenet SL, Hindersson P, et al. Dynamics and predictors of serum TSH and fT4 reference limits in early pregnancy. A study within the Danish National Birth Cohort. J Clin Endocrin Metab. 2016. doi:10.1210/jc.2016-1387.