COMMENTARY

Pregnant With Thyroid Disease? 5 Treatment Changes to Know About

Caroline T. Nguyen, MD,

Disclosures

August 12, 2021

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Much can change in a woman's life as she prepares for and lives through pregnancy, including treatment for existing conditions. How is management different for patients with Hashimoto thyroiditis, Graves disease, or thyroid cancer who are pregnant or planning to become pregnant? Here are five important treatment changes to know about.

1. Switch patients on T4 and T3 to levothyroxine.

The majority of patients on thyroid hormone supplementation take levothyroxine (LT4), which consists of thyroxine, the inactive form of thyroid hormone. A small percentage of patients take desiccated thyroid hormone or a combination of synthetic T4 and liothyronine (T3), the active form of thyroid hormone. Patients taking formulations with T3 who are interested in becoming pregnant need to be counseled and made aware that LT4 is the gold standard for treatment of hypothyroidism in pregnancy.

Thyroid hormone is essential for normal pregnancy and fetal brain development. During early gestation, placental and fetal development relies almost entirely on maternal thyroid hormone, as fetal hypothalamic-pituitary-thyroid maturation does not occur until after 18 weeks of gestation.

Because the fetal central nervous system is relatively impermeable to T3, the majority of fetal T3 is derived from conversion of maternal T4. Thyroid preparations that contain T4 and T3, such as desiccated thyroid hormone, have a relative excess of T3 to T4 (ie, a ratio of T4 to T3 of 4.2:1, compared with 14:1 in the human thyroid gland) and have the potential risk for insufficient transfer of maternal T4 to the fetal brain.

Patients who are taking desiccated thyroid hormone or combination therapy with synthetic T4 and T3 should be switched to LT4 well in advance of when they would like to conceive because the medication dose may require adjustments.

2. Increase the thyroid hormone replacement dose by 20%-30%.

In patients without thyroid disease, the thyroid gland becomes larger during pregnancy in response to stimulation from thyroid-stimulating hormone (TSH) and placental human chorionic gonadotropin to produce more thyroid hormone to meet the increased demand for the fetus. Patients with hypothyroidism from chronic autoimmune thyroiditis, thyroidectomy, or radioactive iodine ablation need to increase their thyroid hormone replacement dose accordingly to meet this increased demand.

During preconception counseling, advise patients to notify their physicians immediately once they are pregnant to have thyroid function tests checked. They should also be instructed to self-increase their LT4 dose once they realize they are pregnant.

Patients can take an extra two pills per week once they become pregnant. For example, if a patient is taking 100 µg daily before pregnancy, she can increase her dose to two tabs of 100 µg on Monday and Wednesday. This is equivalent to a 20%-30% increase in weekly dose.

The increase in thyroid hormone requirement can occur very early in pregnancy, yet many patients don't realize that they are pregnant until well into the first trimester and may have difficulty seeing their physician or having lab tests done immediately. This has been especially true this past year.

Monitor thyroid function tests approximately every 4 weeks until mid-gestation, when increased thyroid hormone requirements tend to plateau. Patients can then be monitored periodically thereafter, and at least once after 30 weeks of gestation.

3. Treat patients with Graves disease who require antithyroid drugs with PTU in the first trimester.

The majority of patients with Graves disease in pregnancy are treated with antithyroid drugs. Two that are typically used are methimazole (MMZ) and propylthiouracil (PTU). MMZ is most commonly used in nonpregnant patients because it can be dosed once daily, compared with three times daily for PTU. PTU is also associated with an increased risk for hepatotoxicity.

Discuss with patients how Graves disease and treatment with antithyroid drugs can potentially affect the pregnancy and the fetus. Ideally, antithyroid drugs should be avoided in pregnancy, although this is not always possible because of the patient's timeline for pregnancy or preferences regarding definitive treatment (ie, surgery or radioactive iodine ablation).

The lowest dose of antithyroid drug needed to maintain thyroxine levels in the upper limit of normal should be used during pregnancy to avoid overtreatment of the fetus and increased risk for side effects. Both MMZ and PTU are associated with congenital malformations in pregnancy, with a prevalence of 2%-4%. However, PTU is preferred in the first trimester because the potential congenital malformations associated with it are considered less severe than those associated with MMZ and are more likely to be surgically correctable.

For women who are contemplating pregnancy, consider switching from MMZ to PTU once the patient is no longer on contraception. Many patients do not realize that they are pregnant until well into the first trimester, and weeks may pass before they can be seen by a physician.

The fetus is most susceptible to the potential side effects of antithyroid drugs between weeks 6 and 10, when organ systems are forming. Switching to PTU before pregnancy would help avoid fetal exposure to MMZ in early pregnancy.

4. For patients with thyroid cancer, maintain the same degree of TSH suppression as before pregnancy.

For women with thyroid cancer who are interested in becoming pregnant, post–thyroid cancer treatment risk stratification can help guide patient management and prognosis during pregnancy.

Women who are considered low risk — those who have no detectable residual cancerous tissue or tumor markers before pregnancy — do well during and after pregnancy and do not appear to be at increased risk for tumor recurrence. For those with persistent structural or biochemical disease, pregnancy may be a stimulus for thyroid cancer growth. These patients who are higher risk require monitoring throughout pregnancy with biochemical testing and ultrasound imaging.

TSH suppression therapy is an important component of thyroid cancer management, especially in patients with persistent biochemical or structural disease. In pregnancy, the majority of studies have not demonstrated an increased risk for maternal or fetal complications associated with subclinical hyperthyroidism. Of note, in women without any history of thyroid disease, TSH levels can be below the normal reference range in pregnancy. Therefore, the same degree of TSH suppression maintained before pregnancy can be safely continued during pregnancy. In patients with persistent structural disease, the recommendation is to maintain the TSH level < 0.1 mU/L.

To maintain pre-conception degrees of suppression, women who have undergone thyroidectomy will need an increase in their thyroid hormone dose because of the greater demand for thyroid hormone in pregnancy.

5. Monitor thyroid hormone levels for at least 1 year postpartum

Women should be restarted on their pre-pregnancy dose of LT4 at delivery. Levels should then be checked at 6 weeks postpartum and adjusted as needed. Women who were taking desiccated thyroid hormone or combination LT4 and T3 before pregnancy can switch back to their previous regimens. However, those who are contemplating a future pregnancy may prefer to continue with LT4 therapy alone.

Five percent of women and 50% of those with thyroid peroxidase antibodies (TPO-Ab) may develop postpartum thyroiditis (PPT). Of note, those who are TPO-Ab positive but who remain euthyroid during pregnancy are four times more likely to develop PPT than those who require LT4 supplementation.

PPT typically occurs about 6-12 weeks postpartum and entails an initial hyperthyroid phase, which lasts a few weeks to months, followed by a brief euthyroid phase and then a hypothyroid phase. The majority of patients eventually return to a euthyroid state by 1 year postpartum.

Treatment is not generally necessary because PPT is transient and self-resolving. However, for some very symptomatic women, beta-blockers and LT4 supplementation may have a role. PPT may take 7-12 months to resolve. Physicians must be sure to monitor these patients even after the postpartum period because 20%-50% of women may develop permanent hypothyroidism and require thyroid supplementation. Thirty percent to 70% of women with PPT may develop PPT again in a future pregnancy.

Women with Graves disease who go into remission in the latter part of pregnancy are at risk for recurrence in the postpartum period as the immune system reconstitutes. These women will need to be restarted on antithyroid drugs, usually MMZ. Women taking MMZ can breastfeed safely, although doses of MMZ should be kept to < 20 mg daily.

Some women may have new-onset Graves disease in the postpartum period. A study from Japan reported that in 40% of women aged 20-39 years with Graves disease, the condition was diagnosed in the postpartum period.

Graves disease must be distinguished from the hyperthyroid phase of PPT because the latter does not require treatment with antithyroid drugs. Onset of hyperthyroidism after 4-6 months postpartum would suggest Graves disease, along with any physical exam findings, such as Graves ophthalmopathy or goiter. Obtaining thyroid-stimulating immunoglobulin levels or TSH receptor antibody titers may also be helpful if the diagnosis remains unclear; these values would be elevated in Graves disease but not in PPT.

Caroline T. Nguyen, MD, is an assistant professor of clinical medicine at the Keck School of Medicine of USC. Her clinical and research interests are focused on thyroid disorders in pregnancy. She has published numerous articles and has been an invited speaker at national conferences.

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