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Thyroid disease in pregnancy: new insights in diagnosis and clinical management

Nature Reviews Endocrinology volume 13, pages 610–622 (2017)Cite this article

Subjects

Key Points

  • Studies published during the past decade have enabled researchers to gain new insights into the diagnosis, physiology and treatment of thyroid disease during pregnancy.

  • The previously recommended TSH cut-offs of 2.5 mU/l or 3.0 mU/l are too low and are likely to lead to overdiagnosis and overtreatment of thyroid disease during pregnancy.

  • The combination of thyroid peroxidase-antibody positivity and a high concentration of TSH seems to synergistically increase the risk of adverse pregnancy outcomes.

  • Substantial new evidence supports the important role of thyroid hormone for fetal neurodevelopment.

  • New studies indicate that in patients treated with levothyroxine, titration to thyroid hormone concentrations in the higher end of the normal range might carry a risk of overtreatment.

  • Particularly during early pregnancy, treatment with methimazole (thiamazole) or propylthiouracil might increase the risk of fetal anomalies, and clinicians should consider the cessation of low-dose regimens.

Abstract

Adequate thyroid hormone availability is important for an uncomplicated pregnancy and optimal fetal growth and development. Overt thyroid disease is associated with a wide range of adverse obstetric and child development outcomes. An increasing number of studies now indicate that milder forms of thyroid dysfunction are also associated with these adverse pregnancy outcomes. The definitions of both overt and subclinical thyroid dysfunction have changed considerably over the past few years, as new data indicate that the commonly used fixed upper limits of 2.5 mU/l or 3.0 mU/l for thyroid-stimulating hormone (TSH) are too low to define an abnormal thyroid function. Furthermore, some studies now show that the reference ranges are not necessarily the best cut-off for identifying pregnancies at high risk of adverse outcomes. In addition, data suggest that thyroid peroxidase autoantibody positivity and high or low concentrations of human chorionic gonadotropin seem to have a more prominent role in the interpretation of thyroid dysfunction than previously thought. Data on the effects of thyroid disease treatment are lacking, but some studies indicate that clinicians should be aware of the potential for overtreatment with levothyroxine. Here, we put studies from the past decade on reference ranges for TSH, determinants of thyroid dysfunction, risks of adverse outcomes and options for treatment into perspective. In addition, we provide an overview of the current views on thyroid physiology during pregnancy and discuss strategies to identify high-risk individuals who might benefit from levothyroxine treatment.

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Figure 1: Changes in thyroid physiology during pregnancy.
Figure 2: Thyroidal response to human chorionic gonadotropin (hCG) stimulation in women who are thyroid peroxidase antibody (TPOAb) negative and women who are TPOAb positive.
Figure 3: Proposed longitudinal effects of the differences in the thyroidal response to human chorionic gonadotropin (hCG) stimulation.
Figure 4: Association between maternal free T4 concentrations during early pregnancy and child IQ and cortical volume as well as postulated treatment strategies.
Figure 5: Thyroid-related substances and crossing of the placental barrier.

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Acknowledgements

The authors' research work was supported by a clinical fellowship from The Netherlands Organisation for Health Research and Development (ZonMw), project number 90700412 to R.P. Peeters.

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Authors and Affiliations

  1. Department of Internal Medicine, Erasmus Medical Center, Postbus 2040, Rotterdam, 3000 CA, The Netherlands

    Tim I. M. Korevaar, Marco Medici, Theo J. Visser & Robin P. Peeters

  2. Academic Center for Thyroid Diseases, Erasmus Medical Center, Postbus 2040, Rotterdam, 3000 CA, The Netherlands

    Tim I. M. Korevaar, Marco Medici, Theo J. Visser & Robin P. Peeters

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Contributions

T.I.M.K. and R.P.P. wrote the first draft of the manuscript, after which all authors contributed equally to researching the data for the article, discussion of content, writing the article and reviewing and/or editing the manuscript.

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Correspondence to Tim I. M. Korevaar.

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T.I.M.K. has received lecture fees from Berlin-Chemie, Goodlife Healthcare and Excemed. R.P.P. has received lecture fees from Goodlife Healthcare. The other authors declare no competing interests.

Supplementary information

Supplementary information S1 (table)

Reference ranges for TSH and FT4 during early pregnancy worldwide. (PDF 148 kb)

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Glossary

Subclinical hypothyroidism

Defined as a high TSH concentration (>97.5th percentile) with a normal free T4 concentration (2.5th to 97.5th percentiles).

Hypothyroxinaemia

Defined as a normal TSH concentration (2.5th to 97.5th percentiles) with a low free T4 (<2.5th percentile; but in some cases <5th percentile).

Mental score

Determined by the outcome of standardized neurodevelopment tests, such as the WISC, and is a reflection of child IQ.

Psychomotor score

The outcome of standardized neurodevelopment tests, such as the WISC, and reflects the psychomotor development of the child, including the child's achievement of developmental milestones.

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Korevaar, T., Medici, M., Visser, T. et al. Thyroid disease in pregnancy: new insights in diagnosis and clinical management. Nat Rev Endocrinol 13, 610–622 (2017). https://doi.org/10.1038/nrendo.2017.93

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