OR14-03 The Thyroid Hormone Receptor Beta Genotype Of The Fetus Influences The Maternal Thyroid Function During Pregnancy

Abstract

Abstract Disclosure: F. Salas Lucia: None. X. Liao: None. H. Jiang: None. A.M. Dumitrescu: None. S. Refetoff: None. J. Anselmo: None. When women with resistance to thyroid hormone beta (RTHβ) are pregnant, their high serum thyroid hormone (TH) levels are perceived as normal by affected fetuses (AfFe) carrying the same THRB mutation as their mothers. On the contrary, normal fetuses (NlFe) that do not carry the maternal THRB mutation are exposed to supraphysiologic TH levels and have unfavorable outcomes. This shows the impact maternal TH levels have on the fetus. However, whether the fetus might influence the maternal thyroid function remains unknown. To explore this possibility, we studied the maternal thyroid function tests (TFT) TSH, FT3, and FT4 throughout the pregnancies from 8 women harboring the R243Q THRB mutation (AfMo) during a total of 10 pregnancies: 6 carrying AfFe and 4 NlFe fetuses. Cord blood TFT from 3 of the NlFe and 3 AfFe at birth were also obtained. In addition, 8 pregnancies from 7 normal mothers (NlMo) carrying 4 AfFe who inherited the THRB mutation from the father and 4 NlFe were also evaluated for TFT. Cord blood from these pregnancies was not available. Results were compared to those in pregnancies of normal WT women. In all RTHβpregnancies, the maternal TSH values were within the range of pregnancies in WT women (0.35-4.94 mU/L) with an hCG-mediated nadir at the end of the first trimester. Maternal FT4 and FT3 values in RTHβpregnancies were above the upper limit of normal (ULN) of 100, peaking during weeks 5-16 (150±20% and 175±15% ULN, respectively) and progressively decreasing afterward. We found differences in maternal TFTdepending on the THRB genotype of the fetus. From weeks 25-32, the AfMo carrying an AfFe exhibited lower FT4 than when carrying a NlFe (96±2 vs. 108±5.3% ULN; p<0.05). Similarly, from weeks 25-40, the AfMo carrying an AfFe exhibited lower FT3 values than when carrying a NlFe ULN (110±11 vs. 134±13% ULN; p<0.05). While gestational age at delivery was similar in all RTHβ pregnancies, the NlFe had a lower birth body weight than the AfFe (2.3±0.1 vs. 3.1±0.2 kg; p<0.01). Cord blood TSH in NlFe was undetectable (<0.1 mU/L) but was 9.51 mU/L (2.2-10; range in normal neonates) in AfFe, which indicates that the thyroid function in NlFe could be restricted during pregnancy, but not in AfFe. Cord blood FT4 levels were similar in NlFe and AfFe (98.4±16.4 vs. 89.5±9.4% ULN). However, FT3 levels were significantly higher in NlFe than in AfFe (67.7±3.0 vs. 42.0±9.6% ULN; p<0.05) and represented ∼68, and ∼42% of the serum maternal FT3 level at birth, respectively. NlMo carrying either AfFe or NlFe showed similar TSH and FT3 levels during pregnancies. However, from weeks 33 to 40, FT4 levels were lower when carrying an AfFe than when carrying a NlFe (51.8±2.8 vs. 62.5±3.2% ULN; p<0.001). Our findings indicate that maternal thyroid function are influenced by THRB genotype of the fetus. The quantitation of placental and fetal TH transporters, deiodinases, and TH metabolites could provide insights into the mechanisms involved. Presentation: Friday, June 16, 2023