Thyroid Function Reference Values in Healthy Iodine-Sufficient Pregnant Women and Influence of Thyroid Nodules on Thyrotropin and Free Thyroxine Values.

Abstract

Thyroid function assessment in pregnancy requires specific reference intervals stratified by gestational age and according to each laboratory method. Thyroid nodules may influence thyroid function in pregnant women. The aims of this study were to define the reference values of thyrotropin (TSH) and free thyroxine (fT4) in the three pregnancy trimesters in iodine-sufficient pregnant women, and to analyze the influence of thyroid nodules on thyroid function during pregnancy. This was a prospective, longitudinal study comprising 400 pregnant women with no history of thyroid disease and no medication influencing thyroid function. TSH, fT4, antithyroglobulin, and antithyroid peroxidase antibodies were measured each trimester by chemiluminescent immunoassays. Urinary iodine concentration was measured in the first trimester when a thyroid echography was also performed. Women with multiple gestation pregnancies, positive thyroid autoimmunity, TSH values >5 or <0.1 mIU/L with a simultaneous fT4 level above the general population reference value in the first trimester, or clinically significant thyroid nodules (nodules ≥1 cm and/or multiple nodules) were excluded to establish TSH and fT4 reference values. Reference intervals in the first, second, and third trimesters were 0.13-4.16, 0.31-3.73, and 0.58-4.36 mIU/L, respectively, for TSH, and 0.85-1.24, 0.82-1.20, and 0.67-1.06 ng/dL, respectively, for fT4. The total prevalence of thyroid nodules was 28.8% [95% confidence interval (CI) 24.4-33.5%], and 6.0% of the participants showed clinically significant nodules. Pregnant women with thyroid nodules (n = 115) showed consistently lower TSH values during all pregnancy stages (first trimester: median 1.14 mIU/L [interquartile range (IQR) 0.53-1.75 mIU/L] vs. 1.48 mIU/L [IQR 0.94-2.19 mIU/L], p < 0.001; second trimester: 1.22 mIU/L [IQR 0.66-1.77 mIU/L] vs. 1.45 mIU/L [1.04-2.05 mIU/L], p = 0.001; third trimester: 1.74 mIU/L [IQR 1.08-2.36 mIU/L] vs. 1.93 mIU/L [IQR 1.37-2.58 mIU/L], p = 0.041) and higher fT4 values in the first trimester (M ± SD = 1.08 ± 0.14 ng/dL vs. 1.03 ± 0.12, p < 0.001) compared to those without nodules (n = 285). Both pregnant women with clinically significant thyroid nodules and those with nonsignificant ones had lower TSH values than women without nodules. TSH/fT4 reference intervals in pregnant women from the authors' geographical area will thyroid dysfunction in pregnancy to be appropriately diagnosed. The prevalence of thyroid nodules is high in iodine-sufficient pregnant women, and is associated with low TSH values across pregnancy.