Pregnancy induces significant physiological changes in the endocrine system, including alterations in thyroid function and iodine metabolism. Central sensitivity to thyroid hormones (TH) and urinary iodine levels are two essential factors that influence maternal and fetal health. This study explores the relationship between central sensitivity to thyroid hormones and changes in urinary iodine during pregnancy. We examine how these factors are interconnected, considering the unique metabolic demands during pregnancy and the potential effects on maternal and fetal thyroid health. We find that while both thyroid hormone sensitivity and urinary iodine levels fluctuate throughout pregnancy, their interplay can significantly affect pregnancy outcomes, particularly in iodine-deficient populations.

Thyroid hormones, Pregnancy, Iodine deficiency

Bianco, A.C.; Salvatore, D.; Gereben, B.; Berry, M.J.; Larsen, P.R. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 2002, 23, 38–89. [Google Scholar] [CrossRef] [PubMed]

Glinoer, D. The regulation of thyroid function in pregnancy: Pathways of endocrine adaptation from physiology to pathology. Endocr. Rev. 1997, 18, 404–433. [Google Scholar] [CrossRef]

Koukkou, E.; Kravaritis, S.; Mamali, I.; Markantes, G.G.; Michalaki, M.; Adonakis, G.G.; Georgopoulos, N.A.; Markou, K.B. No increase in renal iodine excretion during pregnancy: A telling comparison between pregnant women and their spouses. Hormones 2014, 13, 375–381. [Google Scholar] [CrossRef] [PubMed]

Croce, L.; Chiovato, L.; Tonacchera, M.; Petrosino, E.; Tanda, M.L.; Moleti, M.; Magri, F.; Olivieri, A.; Pearce, E.N.; Rotondi, M. Iodine status and supplementation in pregnancy: An overview of the evidence provided by meta-analyses. Rev. Endocr. Metab. Disord. 2023, 24, 241–250. [Google Scholar] [CrossRef]

Chandra, M.; Paray, A.A. Natural Physiological Changes during Pregnancy. Yale J. Biol. Med. 2024, 97, 85–92. [Google Scholar] [CrossRef] [PubMed]

Zuñiga, L.F.F.; Muñoz, Y.S.; Pustovrh, M.C. Thyroid hormones: Metabolism and transportation in the fetoplacental unit. Mol. Reprod. Dev. 2022, 89, 526–539. [Google Scholar] [CrossRef]

Geno, K.A.; Nerenz, R.D. Evaluating thyroid function in pregnant women. Crit. Rev. Clin. Lab. Sci. 2022, 59, 460–479. [Google Scholar] [CrossRef]

Laclaustra, M.; Moreno-Franco, B.; Lou-Bonafonte, J.M.; Mateo-Gallego, R.; Casasnovas, J.A.; Guallar-Castillon, P.; Cenarro, A.; Civeira, F. Impaired Sensitivity to Thyroid Hormones Is Associated with Diabetes and Metabolic Syndrome. Diabetes Care 2019, 42, 303–310. [Google Scholar] [CrossRef]

Sun, H.; Zhou, Y.; Liu, J.; Wang, Y.; Wang, G. Maternal pre-pregnancy obesity modifies the association between first-trimester thyroid hormone sensitivity and gestational Diabetes Mellitus: A retrospective study from Northern China. Diabetol. Metab. Syndr. 2023, 15, 212. [Google Scholar] [CrossRef]

Zhao, X.; Sun, J.; Yuan, N.; Zhang, X. Relationship between the Central and Peripheral Thyroid Sensitivity Indices and Fetal Macrosomia: A Cohort Study of Euthyroid Pregnant Women in China. Diagnostics 2023, 13, 2013. [Google Scholar] [CrossRef]

Li, S.; Wu, Y.; Zhang, S.-J.; Li, G.; Xiang, Y.T.; Zhang, W.-Z.; Pan, W.-J.; Chen, W.-Q.; Hao, Y.-T.; Ling, W.-H.; et al. Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone—Analyses based on the Huizhou mother-infant cohort. Front. Endocrinol. 2022, 13, 937430. [Google Scholar] [CrossRef]

Yuan, S.; Liu, C.; Liu, Z.; Wang, J.; Xu, Y.; Shi, J. Correlation between thyroid function indices and urine iodine levels in patients with nodular goiter. Am. J. Transl. Res. 2023, 15, 4147–4154. [Google Scholar]

Pearce, E.N.; Caldwell, K.L. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status. Am. J. Clin. Nutr. 2016, 104 (Suppl. S3), 898S–901S. [Google Scholar] [CrossRef]

Koukkou, E.G.; Ilias, I.; Mamalis, I.; Markou, K.B. Pregnant Greek Women May Have a Higher Prevalence of Iodine Deficiency than the General Greek Population. Eur. Thyroid. J. 2017, 6, 26–30. [Google Scholar] [CrossRef]

Dunn, J.T.; Crutchfield, H.E.; Gutekunst, R.; Dunn, A.D. Two simple methods for measuring iodine in urine. Thyroid 1993, 3, 119–123. [Google Scholar] [CrossRef]

Tukey, J.W. Exploratory Data Analysis; Addison-Wesley Publishing Company: Reading, MA, USA, 1977; pp. 43–49. [Google Scholar]

Kyrilli, A.; Unuane, D.; Poppe, K.G. Thyroid autoimmunity and pregnancy in euthyroid women. Best Pract. Res. Clin. Endocrinol. Metab. 2023, 37, 101632. [Google Scholar] [CrossRef]

Di Bonito, P.; Corica, D.; Marzuillo, P.; Di Sessa, A.; Licenziati, M.R.; Faienza, M.F.; Calcaterra, V.; Franco, F.; Maltoni, G.; Valerio, G.; et al. Sensitivity to thyroid hormones and reduced glomerular filtration in children and adolescents with overweight or obesity. Horm. Res. Paediatr. 2023, 97, 383–387. [Google Scholar] [CrossRef]

Liu, X.; Li, Y.; Chai, Y.; Zhang, Y.; Zhang, L.; Zhang, H. Thyroid function and thyroid homeostasis parameters are associated with increased urinary albumin excretion in euthyroid individuals over 60 years old from NHANES. Front. Endocrinol. 2024, 14, 1285249. [Google Scholar] [CrossRef]

Shi, C.; Liu, X.; Du, Z.; Tian, L. Impaired Sensitivity to Thyroid Hormones is Associated with the Risk of Diabetic Nephropathy in Euthyroid Patients with Type 1 Diabetes Mellitus. Diabetes Metab. Syndr. Obes. 2024, 17, 611–618. [Google Scholar] [CrossRef]

Yang, W.; Jin, C.; Wang, H.; Lai, Y.; Li, J.; Shan, Z. Subclinical hypothyroidism increases insulin resistance in normoglycemic people. Front. Endocrinol. 2023, 14, 1106968. [Google Scholar] [CrossRef]

Alonso, S.P.; Valdés, S.; Maldonado-Araque, C.; Lago, A.; Ocon, P.; Calle, A.; Castaño, L.; Delgado, E.; Menéndez, E.; Franch-Nadal, J.; et al. Thyroid hormone resistance index and mortality in euthyroid subjects: Di@bet.es study. Eur. J. Endocrinol. 2022, 186, 95–103. [Google Scholar] [CrossRef]