Understanding the Pathogenesis of Gestational Hypothyroidism

^{School of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, China,}

^{Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China,}

^{Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China,}

Edited by: Qi Chen, The University of Auckland, New Zealand

Reviewed by: Yolanda De Rijke, Erasmus Medical Center, Netherlands; Stefania Triunfo, BCNatal, Spain; Weiping Teng, First Affiliated Hospital of Anhui Medical University, China

*Correspondence: Qiongjie Zhou, nc.gro.yykcf@2371eijgnoiquohz; Xiaotian Li, moc.361@555ilnaitoaix

This article was submitted to Reproduction, a section of the journal Frontiers in Endocrinology

Edited by: Qi Chen, The University of Auckland, New Zealand

Reviewed by: Yolanda De Rijke, Erasmus Medical Center, Netherlands; Stefania Triunfo, BCNatal, Spain; Weiping Teng, First Affiliated Hospital of Anhui Medical University, China

Received 2021 Jan 14; Accepted 2021 Apr 1.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Pregnancy is a complex state with many endocrinological challenges to a woman’s physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual.

Keywords: gestational hypothyroidism, subclinical hypothyroidism, pregnancy, thyroid disorders, placenta, estrogen, iodine, levothyroxine

Abstract

*RCT, Randomised Controlled Trial; TSH, Thyroid-Stimulating Hormone; fT4, Free Thyroxine; SCH, Subclinical Hypothyroidism; IH, Isolated Hypothyroxinemia; TPOAb (+), Thyroid Peroxidases antibodies.

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