FULL JOURNAL TITLE
Alexander, Pearce, et al., 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum. Thyroid. DOI: 10.1089/thy.2016.0457
American Thyroid Association Task Force Updates Guidelines on Thyroid Disease and Pregnancy
Kimberly Dorris, Executive Director/CEO
Graves’ Disease and Thyroid Foundation
If you are planning a pregnancy, currently pregnant, or in the postpartum period, it’s important to stay up to date on the latest guidelines on thyroid disease and pregnancy. A task force from the American Thyroid Association (ATA) has reviewed the latest research and distilled it into a new publication: “2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.” The task force was co-chaired by Dr. Erik K. Alexander (Brigham and Women’s Hospital, Harvard Medical School) and Dr. Elizabeth N. Pearce (Boston University School of Medicine) and included Dr. Gregory A. Brent (VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA), Dr. Rosalind S. Brown (Boston Children’s Hospital, Harvard Medical School), Dr. Herbert Chen (University of Alabama at Birmingham), Dr. Chrysoula Dosiou (Stanford University School of Medicine), Dr. William A. Grobman (Northwestern University), Dr. Peter Laurberg (Aalborg University Hospital, Denmark), Dr. John H. Lazarus (Cardiff University, Cardiff, United Kingdom), Dr. Susan J. Mandel (Perelman School of Medicine, University of Pennsylvania), Dr. Robin P. Peeters (Rotterdam Thyroid Center, Erasmus Medical Center, The Netherlands) and Dr. Scott Sullivan ( Medical University of South Carolina).
The new guidelines (updated from a prior edition from 2011) are available free on the website of Thyroid, the official peer-reviewed journal of the ATA, published by Mary Ann Liebert, Inc., publishers. “With an estimated 300,000 pregnancies impacted by thyroid disease in the United States annually, these guidelines coalesce the best available evidence into clear clinical recommendations, and will improve the health of many, many mothers and newborns alike,” note Dr. Alexander and Dr. Pearce. The guidelines were reviewed in advance and endorsed by a number of medical associations as well as patient groups, including the Graves’ Disease & Thyroid Foundation.
Thyroid dysfunction is a potential factor in infertility, possibly due to irregular menstrual cycles. The new guidelines recommend TSH testing for all women seeking treatment for infertility, with levothyroxine recommended for cases of overt hypothyroidism. For subclinical hypothyroidism (normal T3 and T4 values, with abnormally high TSH), the task force notes that there is insufficient evidence to determine whether levothyroxine can improve fertility, although states that treatment with a low dose of levothyroxine “may be considered in this setting given its ability to prevent progression to more significant hypothyroidism once pregnancy is achieved.” Treatment of subclinical hypothyroidism is recommended for women who are undergoing IVF or ICSI fertility treatments, with a goal of reducing TSH to less than 2.5 mU/L. Low-dose levothyroxine therapy “may be considered” in women who are using assisted reproductive techniques and test positive for thyroid peroxidase antibodies (TPOAbs), which are often present in Hashimoto’s thyroiditis.
The task force recommends that women who are currently being treated for hypothyroidism and are planning a pregnancy undergo TSH testing, with a goal of achieving a TSH between the lower end of the reference range and no more than 2.5 mU/L prior to conception.
For women with thyrotoxicosis due to an overactive thyroid nodule, balancing maternal and fetal thyroid function during pregnancy can be challenging; in these cases, ablative therapy (surgery or RAI) might be recommended prior to conception.
Women who are being treated for Graves’ disease are advised to postpone pregnancy planning until thyroid function is stabilized, as indicated by two normal tests at least one month apart, with no change in medication dosing. The guidelines note that, “Women with GD seeking future pregnancy should be counseled regarding the complexity of disease management during future gestation, including the association of birth defects with antithyroid drug (ATD) use. Preconception counseling should review the risks and benefits of all treatment options and the patient’s desired timeline to conception.” These treatment options include antithyroid medications, radioactive iodine, and thyroidectomy. Patients who choose radioactive iodine are advised to delay pregnancy by at least six months (and not attempt conception until thyroid levels are stable) and should be aware that increased antibody levels following treatment can potentially affect the fetus.
Thyroid Function Testing and Pregnancy
Trimester-specific ranges for thyroid function testing are recommended during pregnancy, due to typical increases of T4 and suppression of TSH in the first trimester. Variations that occur due to race, ethnicity, iodine intake, the presence or absence of thyroid antibodies, and even body mass index can make development of these ranges challenging. The guidelines note that ideally, the reference range should be tailored to a specific population as well as the specific process used by the test manufacturer.
Hypothyroidism and Pregnancy
Untreated hypothyroidism during pregnancy is associated with an increased risk of a number of adverse outcomes, including premature birth, low birth weight, lower offspring IQ, and even pregnancy loss.
Pregnant women who are euthyroid, but have positive TPOAbs, may develop hypothyroidism prior to delivery. To ensure timely treatment, the task force recommends TSH testing at the time pregnancy is confirmed and every four weeks until mid-pregnancy, when thyroid function tends to stabilize. Treatment of overt hypothyroidism is always recommended during pregnancy, and therapy is also recommended for subclinical hypothyroidism in TPOAb-positive women. The guidelines note that the recommended treatment is oral levothyroxine; combination therapy using T3 or desiccated thyroid is not recommended during pregnancy.
The task force also states that administration of 25-50 micrograms of levothyroxine “may be considered” in women who are TPOAb-positive, but euthyroid, and who have a prior history of pregnancy loss.
The guidelines recommend that women with overt or subclinical hypothyroidism, as well as those at risk for hypothyroidism, undergo TSH testing every four weeks until mid-pregnancy and at least once near 30 weeks gestation.
Women who are already taking thyroid hormone replacement at the time pregnancy is confirmed (or even suspected) should contact their provider immediately; the task force recommends independently increasing the dose of their replacement hormone by taking two additional tablets weekly of their current daily dose. Follow-up testing will determine if the dose needs to be further adjusted as pregnancy progresses.
Thyrotoxicosis and Pregnancy
Women can also experience thyrotoxicosis (excessive levels of thyroid hormone) during pregnancy. If left untreated, adverse affects noted in the new guidelines include “pregnancy loss, pregnancy-induced hypertension, prematurity, low birth weight, intrauterine growth restriction, stillbirth, thyroid storm, and maternal congestive heart failure.”
Common causes of thyrotoxicosis during pregnancy are Graves’ disease, an autoimmune condition, gestational transient thyrotoxicosis, and overactive thyroid nodules. Receiving a correct diagnosis is critical, as this will affect treatment options. Findings that point to gestational transient thyrotoxicosis include no prior history of thyroid disease, and absence of goiter or eye findings, mild symptoms of thyrotoxicosis, and vomiting. A blood test can confirm the presence of antibodies (TRAb) that cause Graves’ disease, and an ultrasound can identify the presence of nodules. Although a radioactive iodine uptake & scan can distinguish between Graves’ disease and other causes of thyrotoxicosis, this procedure is not recommended during pregnancy.
Gestational transient thyrotoxicosis often resolves itself after the first half of pregnancy, although management of dehydration is needed, and hospitalization may be required. Beta blockers may be considered for relief of symptoms, but ATD are not needed.
Dealing with overactive nodules during pregnancy is challenging, as treatment with ATDs in the mother can potentially cause hypothyroidism in the fetus. Therefore, the task force recommends using a low dose of ATDs, with the goal of keeping the mother’s Free T4 at or slightly above the reference range.
The standard treatment options for Graves’ disease come with special considerations during pregnancy. Radioactive iodine is never an option for pregnant women. Thyroid surgery is only recommended during the second trimester and for specific situations, particularly women who are unable to take antithyroid medications.
Antithyroid medications come with an increased risk of birth defects, although PTU generally has a lower risk than methimazole, and is the recommended medication during the first trimester. (The task force did not make a recommendation on switching back to methimazole after the first trimester. Although MMI comes with a reduced risk of liver issues, the medications are not doseequivalent, so finding the “sweet spot” dose with the new medication could take some time).
Within the first days of an absent or weak menstrual period, women who are taking ATDs are advised to contact their provider to discuss thyroid function testing and potential dose adjustments.
Block-replace therapy, which involves giving large doses of ATDs in conjunction with replacement hormone, is not recommended during pregnancy, due to the risk of fetal hypothyroidism. However, this approach may be used in rare cases where the mother is hypothyroid after RAI or surgery, but maternal antibodies are causing hyperthyroidism in the fetus. The ATDs will pass through the placenta to calm the fetal hyperthyroidism, while the replacement hormone will keep the mother’s thyroid levels stable.