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Managing Graves' Disease During Pregnancy: Risks and Benefits

Having Graves' hyperthyroidism during pregnancy requires a careful balancing act to reduce the risks to both mother and child; be prepared to explore treatment options well before becoming pregnant.

With  Angela M. Leung, MD, MSc

Graves’ hyperthyroidism (GH) affects fewer than 1 in 100 women pregnant women, including those with pre-existing disease and women who have newly diagnosed Graves’ thyroiditis1 When left untreated, or if insufficiently managed, Graves’ disease during pregnancy is associated with substantial adverse effects on the pregnancy such as pre-eclampsia, premature delivery, low birth weight, and even pregnancy loss 2

Establishing a diagnosis of GH in a woman who is currently pregnant presents a bit of a challenge since pregnancy alters the thyroid physiology.2 The 2017 Guidelines of the American Thyroid Association (ATA) for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum suggest results of your thyroid-function tests be assessed differently during pregnancy then when you are not pregnant.3

Counseling a couple about managing Graves'disease when pregnant. Women who have Graves' hyperthyroidism should discuss treatment options before they get pregnant if possible, and should know the risks. Photo: 123rf

Preconception Counseling for Graves' Disease Improves Outcomes 

There is no standardized way, as yet, to predict or monitor for the effects of Graves’ medical treatment on the fetus. However, any risks of harm during the pregnancy are significantly lower when Graves’ disease is adequately controlled. The most important message about treatment is that the most substantial risks that are associated with the use of antithyroid medications occur during the first trimester.

Ideally, women under treatment for Graves’ disease who intend to become pregnant should be stabilized prior to conception or should be advised to delay attempts at conception until a stable euthyroid state has been achieved, whenever possible.4

For women who opt for surgery or radioactive iodine therapy, the goal should be to achieve a stabilized thyroid hormone replacement dose, optimally for at least 6 months, prior to conception.

Even when women with Graves’ disease who are considered to be well controlled, thyroid-stimulating disease antibodies may cross the placental barrier and cause Graves’ symptoms in the developing fetus. In most cases, the symptoms of goiter, bulging eyes, and hyperthyroid will abate once the baby is no longer exposed to the antibodies, although these symptoms may persist or reoccur later in childhood.

Managing Graves’ Hyperthyroidism During Pregnancy

When Graves’ first appears or re-occurs during pregnancy, the options for treatment are more limited given the potential for negative consequences to both the mother and baby. In a recent study, the authors looked at 2,887,000 completed pregnancies linked to live-born infants over six years, using data from the Korean National Health Insurance database.5

They examined birth results for the 12,891 pregnancies exposed to ATDs during the first trimester.  and found a significantly greater occurrence of birth defects in offspring exposed to antithyroid medications compared to the babies whose mothers did not take such medication during pregnancy (7.27% vs 5.94%, respectively; P < 0.001).

In the first trimester, Dr. Seo reported that use of propylthiouracil (PTU), methimazole (MMI), or a combination of the two were associated with absolute increases in congenital malformations. In particular, 77% of women with Graves’ disease were treated with PTU, 8.7% of treated women received MMI, and 14.3% of them took a combination of PTU/MMI.5

Compared with pregnant women who received no antithyroid medication during the first trimester, the risk in those taking PTU was nearly half that of the women receiving MMI or a combination of the two medications.5

The researchers also found that the risk of congenital defects among women who switched from MMI to PTU use before conception was similar to that of women who continued to use MMI during pregnancy, even among women who switched treatments approximately three months prior to conception.5The types of congenital malformations observed in the Seo study were consistent with those observed in prior studies.6

Tim I.M. Korevaar, MD, PhD and Robin P. Peeters, MD, PhD, provided comments about the study findings,7 and they noted that “perhaps the most interesting and novel findings of the study are those showing dose-dependent effects.”

In particular, "although neither a cumulative dosage nor duration of treatment with PTU appeared to result in congenital malformations, a longer duration of treatment (> 7 weeks) with MMI was associated with an up to 68% higher (but not statistical significant) risk and a higher cumulative dosage (> 495 mg) was associated with an 87% higher risk of congenital malformations compared with a low dose (1 to 126 mg; P = 0.03)."6,7

Counseling Women of Reproductive Age to Treat Hyperthyroidism 

Experts now recommend that women who require medication to manage their Graves’ disease while pregnant should receive the lowest possible dose of PTU in order to keep maternal thyroid function at the upper limit of normality with low serum TSH in order to avoid fetal hypothyroidism.8

“As the mechanism(s) underlying how these drugs may produce [birth defects] remain incompletely understood, there may be unique susceptibilities and risk factors among different populations of women. Although these pathways still need to be fully established, the [Seo] findings are still likely to be pertinent to all women,” says Angela M. Leung, MD, MSc, assistant professor of medicine in the Division of Endocrinology, Diabetes, and Metabolism at the UCLA David Geffen School of Medicine in Los Angeles, California.

“This is an important study that provides further data regarding concerns of congenital malformations associated with the use of antithyroid drugs during early pregnancy,” she tells EndocrineWeb, and the Seo study findings are similar to those of a recent Danish epidemiologic study,9 and both are supported by the strength of large population-level databases.

However, “as the authors of the {Seo] study acknowledge, use of a prescription dataset is associated with inherent limitations, as prescribed and actual uses of the antithyroid medications may be different. Nonetheless, these data are provocative and suggest that the guidelines by various professional societies surrounding the use of antithyroid medications during preconception, pregnancy, and breastfeeding, be reexamined.”

When asked how the findings from this study might influence what women need to know when speaking with their physician, Dr. Leung says, “it is reasonable that clinicians who take care of hyperthyroid women before and during pregnancy discuss the potential risks of taking antithyroid medication while pregnant.

"Just as important, women should understand that having Graves' hyperthyroidism that goes untreated can have equally severe adverse effects on the outcome of the pregnancy, so women of reproductive age are urged to discuss all the available their options for treatment as early as possible,” she says.

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