Gestational trimester-specific reference ranges for serum thyrotropin and free thyroxine in Japanese

Abstract

Thyroid diseases in pregnant and lactating women may result in adverse outcomes for both mothers and infants. A reference range for thyroid function is required in different areas; however, few studies on the gestational change or reference ranges of thyrotropin (TSH) and free thyroxine (FT4) concentrations for Japanese pregnant women have been reported. To establish the gestational trimester-specific reference ranges of serum TSH and FT4 concentrations, our previously published data on 481 pregnant women with the mean age of 30.8 years who provided serum samples as early as gestational week (GW) 6 was compiled by using their percentile values. The overall median urinary iodine concentration (UIC) during pregnancy was 201 μg/L suggesting adequate iodine intake. The prevalence of positive serum thyroid autoantibody (ThAb), i.e., antithyroid peroxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb), was 11.4%. The reference ranges (2.5-97.5th percentile) of serum TSH and FT4 concentration calculated for samples with negative TgAb and TPOAb were 0.04-6.06 mIU/L in the first trimester (T1), 0.31-3.11 mIU/L in the second trimester (T2) and 0.48-3.93 mIU/L in the third trimester (T3) for TSH, and 1.10-1.87 ng/dL (T1), 0.76-1.56 ng/dL (T2) and 0.76-1.14 ng/dL (T3) for FT4. Compared to published data around the world in the 2017 American Thyroid Association (ATA) guideline, both the upper and lower limits of our TSH and FT4 reference ranges in the first trimester were higher than those in other countries. Further research is necessary in larger samples.

Defining Trimester-Specific Reference Intervals for Thyroid Hormones: Insights from a Bulgarian Monocenter Study

“…The established trimester-specific reference intervals differ from the fixed and established ones, which would significantly change the strategy for initiating pharmacotherapy in pregnant women. Comparable deviations from established TSH reference limits in pregnancy have been documented in studies from various countries, including Japan, Turkey, UAE, India, Korea, Brazil, Poland, Pakistan, and Chile [2,11,19,22,23,[31][32][33][34]. For instance, a study by Morais et al identified an upper limit for TSH in postnatal pregnant women corresponding to fixed reference ranges recommended by the ATA [24].…”

“…According to guidelines published by ETA, ATA, and the Endocrine Society, the upper reference interval for TSH during the first trimester remained at 2.5 mIU/L for an extended period [3][4][5]. However, many studies published after 2011 indicate that this limit increases the diagnosis of subclinical hypothyroidism, leading to overdiagnosis and unnecessary treatment [11,12,[15][16][17][18][19]. Furthermore, TSH levels associated with FT4 reduction typically fall between 4 and 5 mIU/L.…”