Changes in Central Sensitivity to Thyroid Hormones vs. Urine Iodine during Pregnancy

Central sensitivity to thyroid hormones refers to the responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). Although dose-response relationships between thyroid hormones per se and urinary iodine (UI) levels have been observed, central sensitivity to thyroid hormones in relation to UI remains unexplored. The aim of the present study was to evaluate central sensitivity to thyroid hormones (by means of the Thyroid Feedback Quantile-based Index [TFQI], which is a calculated measure, based on TSH and fT4, that estimates central sensitivity to thyroid hormones) in pregnancy and to assess whether it differs according to gestational age and/or iodine intake.

One thousand, one hundred and two blood and urine samples were collected from pregnant women (with a mean age ± SD of 30.4 ± 4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH and fT4, anti-thyroid peroxidase antibodies and UI were measured in each trimester and at two months postpartum, while the TFQI was calculated for all the study samples. After the elimination of outliers, statistical analysis was conducted with analysis of variance (ANOVA) for the variables versus time period, while Pearson's correlation was used to assess the TFQI versus UI.

The mean TFQI index ranged from -0.060 (second trimester) to -0.053 (two months postpartum), while the corresponding UI was 137 and 165 μg/L, respectively. The TFQI-UI correlation was marginally negative (Pearson r: -0.323, p: 0.04) and significantly positive (r: +0.368, p: 0.050) for UI values over 250 μg/L, in the first and the second trimesters of pregnancy, respectively.

The TFQI is a new index reflecting central sensitivity to thyroid hormones. A lower TFQI indicates higher sensitivity to thyroid hormones. In our sample, the TFQI was mainly positively related to iodine intake in the second trimester of pregnancy (following the critical period of organogenesis). Thus, the observed changes in the TFQI may reflect the different ways of the central action of thyroid hormones, according to the phase of pregnancy. These results have the potential to enhance our comprehension of the changes in the HPT axis' function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.