Hyperthyroidism in pregnancy: evidence and hypothesis in fetal programming and development

Abstract

The management of hyperthyroidism in pregnant patients has been a topic of raised clinical awareness for decades. It is a strong recommendation that overt hyperthyroidism of Graves’ disease in pregnant women should be treated to prevent complications. The consequences of hyperthyroidism in pregnancy are less studied than hypothyroidism, and a literature review illustrates that the main burden of evidence to support current clinical guidance emerges from early observations of severe complications in Graves’ disease patients suffering from untreated hyperthyroidism in the pregnancy. On the other hand, the more long-term consequences in children born to mothers with hyperthyroidism are less clear. A hypothesis of fetal programming by maternal hyperthyroidism implies that excessive levels of maternal thyroid hormones impair fetal growth and development. Evidence from experimental studies provides clues on such mechanisms and report adverse developmental abnormalities in the fetal brain and other organs. Only few human studies addressed developmental outcomes in children born to mothers with hyperthyroidism and did not consistently support an association. In contrast, large observational human studies performed within the last decade substantiate a risk of teratogenic side effects to the use of antithyroid drugs in early pregnancy. Thus, scientific and clinical practice are challenged by the distinct role of the various exposures associated with Graves’ disease including the hyperthyroidism per se, the treatment, and thyroid autoimmunity. More basic and clinical studies are needed to extend knowledge on the effects of each exposure, on the potential interaction between exposures and with other determinants, and on the underlying mechanisms.

Hyperthyroidism in pregnancy: design and methodology of a Danish multicenter study

“…Hyperthyroidism in pregnant women has long been a matter of concern [15]. Evidence to support the adverse effects of uncontrolled hyperthyroidism in pregnant women with GD dates nearly a century back to reports in the 1920s to 1940s, which was before the development of ATDs, illustrating the severe consequences of the disease for mother and child when left untreated during pregnancy [16].…”

The Influence of Triclosan on the Thyroid Hormone System in Humans - A Systematic Review

“…Total T3 and T4 reach a plateau around gestational week 20, but until this point, T4 and thyroxine-binding globulin levels are constantly changing and exhibit wide individual variation ( 49 , 50 ). Therefore, the associations may vary considerably according to the measurement time point and it is possible that the effect of triclosan also varies over the course of pregnancy ( 44 , 51 ).…”

Associations between hyperthyroidism and adverse obstetric and neonatal outcomes: A study of a population database including almost 17,000 women with hyperthyroidism

“…All our findings, as other findings that have been reported in the literature, may be attributed to hyperthyroidism per se, to the presence of maternal autoantibodies, or the antithyroid medications. 5,11 Treating hyperthyroidism during pregnancy is considered complicated due to the teratogenic effects of both antithyroid medications methimazole and propylthiouracil, and hepatotoxicity. 27 Our study has several limitations.…”

“…[5][6][7][8][9][10] These guidelines also noted that the fetuses in mothers with hyperthyroidism are at increased risks of intrauterine growth restriction, low birth weight, fetal and neonatal hyperthyroidism, and intrauterine death. 5,10 In a review by Andersen and Andersen, 11 fetal exposure to high levels of thyroid hormones was also reported to have an influence later in life, in a process called "fetal programming." In a meta-analysis from 2020 that included 29 studies, epilepsy and neurodevelopmental disorders in the offspring were associated with maternal hyperthyroidism.…”