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Therapy Insight: management of Graves' disease during pregnancy

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 470–478 (2007)Cite this article

Abstract

The diagnosis of Graves' disease in pregnancy can be complex because of normal gravid physiologic changes in thyroid hormone metabolism. Mothers with active Graves' disease should be treated with antithyroid drugs, which impact both maternal and fetal thyroid function. Optimally, the lowest possible dose should be used to maintain maternal free thyroxine levels at or just above the upper limit of the normal nonpregnant reference range. Fetal thyroid function depends on the balance between the transplacental passage of thyroid-stimulating maternal antibodies and thyroid-inhibiting antithyroid drugs. Elevated levels of serum maternal anti-TSH-receptor antibodies early in the third trimester are a risk factor for fetal hyperthyroidism and should prompt evaluation of the fetal thyroid by ultrasound, even in women with previously ablated Graves' disease. Maternal antithyroid medication can be modulated to treat fetal hyperthyroidism. Serum TSH and either total or free thyroxine levels should be measured in fetal cord blood at delivery in women with active Graves' disease, and those with a history of 131I-mediated thyroid ablation or thyroidectomy who have anti-TSH-receptor antibodies. Neonatal thyrotoxicosis can occur in the first few days of life after clearance of maternal antithyroid drug, and can last for several months, until maternal antibodies are also cleared.

Key Points

  • First-line therapy for Graves' disease during pregnancy includes antithyroid drugs (preferably propylthiouracil)

  • Prescribed doses should be as low as possible to maintain maternal serum free T4 levels at or just above the upper limit of the normal nonpregnant range, or total T4 levels at 1.5-times the normal nonpregnant reference range

  • If continued administration of antithyroid medication is not possible, second-trimester thyroidectomy can be considered; patients should receive β-adrenergic blockade and iodide therapy preoperatively

  • All women with active Graves' disease, and levothyroxine-replaced patients with a history of 131I-mediated ablation or thyroidectomy, should have their anti-TSH-receptor antibody (TRAb) levels measured at 26–28 weeks gestation to evaluate the risk for fetal hyperthyroidism

  • To assess fetal thyroid function, fetal ultrasound at 28–32 weeks should be performed if there is evidence of active maternal Graves' disease (elevated maternal TRAb levels, or maternal requirement for antithyroid medication)

  • Serum TSH and total T4 or free T4 concentrations should be measured in fetal cord blood at delivery in women with active Graves' disease or positive TRAb screen after 131I-mediated ablation or thyroidectomy

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Figure 1: Serum total T4 and free T4 levels by trimester
Figure 2: Serum TSH concentrations by trimester
Figure 3: Differentiation between fetal hypothyroidism and hyperthyroidism in the presence of a fetal goiter

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Acknowledgements

GW Chan is supported by NIH grant 2-T32-DK007314-26. We thank C Spencer for supplying the data used for Figure 1. Désirée Lie, University of California, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. in the Division of Endocrinology, Department of Medicine, GW Chan is a Fellow, and SJ Mandel is Associate Professor of Medicine and Radiology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.,

    Grace W Chan & Susan J Mandel

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Correspondence to Susan J Mandel.

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Chan, G., Mandel, S. Therapy Insight: management of Graves' disease during pregnancy. Nat Rev Endocrinol 3, 470–478 (2007). https://doi.org/10.1038/ncpendmet0508

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