Therapy Insight: Management of Graves' disease during pregnancy

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Nature Clinical Practice Endocrinology &#38 Metabolism (Impact Factor: 7.55). 07/2007; 3(6):470-8. DOI: 10.1038/ncpendmet0508
Source: PubMed


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 (131)I-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.

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    • "Antithyroid drugs (ATDs), radioactive iodine ( 131 I), or surgical excision of the thyroid gland are the major treatment options for controlling hyperthyroidism. During pregnancy, radioactive iodine treatment is contraindicated and surgery is recommended only when the hyperthyroid condition is refractory to ATDs (Abalovich et al., 2007; Chan and Mandel, 2007). Thus, ATDs are the treatment of choice for active Graves' disease during gestation. "
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    ABSTRACT: Background: Propylthiouracil (PTU) and methimazole (MMI) are antithyroid drugs used to treat hyperthyroidism. Despite the widespread use of PTU and MMI during pregnancy, modest clinical data and less animal data are available on the teratogenic potential of these drugs. Methods: We evaluated the teratogenicity of in utero exposure to PTU or MMI in mice and rats. First, pregnant C57Bl/6 mice were treated daily with PTU (10 or 100 mg/kg), MMI (2 or 20 mg/kg), or vehicle from gestation day (GD) 6 to 16. GD 18 fetuses were evaluated for gross and histopathological abnormalities. Next, pregnant Sprague-Dawley rats were treated daily with PTU (50 or 100 mg/kg), MMI (10 or 20 mg/kg), or vehicle from GD 6 to 19, followed by evaluation for gross and histopathological abnormalities at GD 20. Results: In mice treated with PTU or MMI, no significant histopathological abnormalities or external gross malformations, and no adverse effects on placental weight, litter size, resorption rates, or fetal weight were observed at GD 18. In rats, no adverse effects on litter size, placental weights, or maternal body weights were observed with either PTU or MMI treatment. PTU treatment (50 and 100 mg/kg) and MMI (10 mg/kg) treatment resulted in a decrease in crown-rump length in rat fetuses but no external gross malformations or histopathological abnormalities were observed. Conclusion: We did not observe either gross external malformations or histopathological malformations in mice or rats treated long-term with high doses of PTU or MMI during pregnancy.
    Birth Defects Research Part B Developmental and Reproductive Toxicology 08/2014; 101(4). DOI:10.1002/bdrb.21113 · 0.77 Impact Factor
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    • "Although exacerbations early in pregnancy are sometimes observed [141] once the first trimester is passed the immune suppression of pregnancy sets in, the Treg cells increase their effectiveness, and the disease very often abates. The aggravation of thyrotoxicosis in the first part of pregnancy is probably secondary to the added effects of hCG which itself can cause gestational thyrotoxicosis [141–143]. In keeping with this scenario, TSHR-Abs reach their lowest point at the time of delivery [144, 145]. "
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    ABSTRACT: Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum.
    Journal of Thyroid Research 04/2013; 2013(1):182472. DOI:10.1155/2013/182472
    • "This can occur even if the mother is on low-dose antithyroid drugs, because of the exquisite sensitivity of the fetus to antithyroid drugs. The neonatal goiter and hypothyroidism normalizes in a few days time so that most often the confirmatory tests will come back normal even if TSH is high on screening.[1314] "
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    ABSTRACT: Transient thyroid function abnormalities in the new born which revert back to normal after varying periods of time are mostly identified in the neonatal screening tests for thyroid and are becoming more common because of the survival of many more premature infants. It can be due to factors primarily affecting the thyroid-like iodine deficiency or excess, maternal thyroid-stimulating hormone receptor (TSHR) antibodies, maternal use of antithyroid drugs, DUOX 2 (dual oxidase 2) mutations, and prematurity or those that affect the pituitary-like untreated maternal hyperthyroidism, prematurity, and drugs. Most of these require only observation, whereas some, such as those due to maternal TSHR antibodies may last for upto three-to-six months and may necessitate treatment. Isolated hyperthyrotropinemia (normal Tetraiodothyronine (T4) and high Thyroid Stimulating hormone (TSH)) may persist as subclinical hypothyroidism in childhood. Transient hypothyroxinemia (low T4 and normal TSH) is very common in premature babies. The recognition of these conditions will obviate the risks associated with unnecessary thyroxine supplementation in childhood and parental concerns of a life long illness in their offspring.
    07/2011; 15(Suppl 2):S117-20. DOI:10.4103/2230-8210.83345
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