A normal pregnancy results in a number of important physiological and hormonal changes that alter thyroid function. These changes mean that laboratory tests of thyroid function must be interpreted with caution during pregnancy. Thyroid function tests change during pregnancy due to the influence of two main hormones: human chorionic gonadotropin (hCG), the hormone that is measured in the pregnancy test and estrogen, the main female hormone. HCG can weakly turn on the thyroid and the high circulating hCG levels in the first trimester may result in a slightly low TSH. When this occurs, the TSH will be slightly decreased in the first trimester and then return to normal throughout the duration of pregnancy (see Table 1). Estrogen increases the amount of thyroid hormone binding proteins in the serum which increases the total thyroid hormone levels in the blood since >99% of the thyroid hormones in the blood are bound to these proteins. However, measurements of “Free” hormone (that not bound to protein, representing the active form of the hormone) usually remain normal. The thyroid is functioning normally if the TSH, Free T4 and Free T3 are all normal throughout pregnancy.

Size Changes. The thyroid gland can increase in size during pregnancy (enlarged thyroid = goiter). However, pregnancy-associated goiters occur much more frequently in iodine-deficient areas of the world. It is relatively uncommon in the United States, which is thought to be relatively iodine-sufficient. If very sensitive imaging techniques (ultrasound) are used, it is possible to detect an increase in thyroid volume in some women. This is usually only a 10-15% increase and is not typically apparent on physical examination by the physician. However, sometimes a significant goiter may develop and prompt the doctor to measure tests of thyroid function.

What is the interaction between the thyroid function of the mother and the baby?

For the first 10-12 weeks of pregnancy, the baby is completely dependent on the mother for the production of thyroid hormone. By the end of the first trimester, the baby’s thyroid begins to produce thyroid hormone on its own. The baby, however, remains dependent on the mother for ingestion of adequate amounts of iodine, which is essential to make the thyroid hormones. The World Health Organization recommends iodine intake of 200 micrograms/day during pregnancy to maintain adequate thyroid hormone production. The normal diet in the United States contains sufficient iodine so additional iodine supplementation is rarely necessary.

Overall, the most common cause (80-85%) of maternal hyperthyroidism during pregnancy is Graves’ disease and occurs in 1 in 1500 pregnant patients. In addition to other usual causes of hyperthyroidism, very high levels of hCG, seen in severe forms of morning sickness (hyperemesis gravidarum), may cause transient hyperthyroidism. The diagnosis of hyperthyroidism can be somewhat difficult during pregnancy, as 123I thyroid scanning is contraindicated during pregnancy due to the small amount of radioactivity, which can be concentrated by the baby’s thyroid. Consequently, diagnosis is based on a careful history, physical exam and laboratory testing.

Graves’ disease may present initially during the first trimester or may be exacerbated during this time in a woman known to have the disorder. In addition to the classic symptoms associated with hyperthyroidism, inadequately treated maternal hyperthyroidism can result in early labor and a serious complication known as pre-eclampsia. Additionally, women with active Graves’ disease during pregnancy are at higher risk of developing very severe hyperthyroidism known as thyroid storm. Graves’ disease often improves during the third trimester of pregnancy and may worsen during the post partum period.

What are the risks of Graves’ Disease/hyperthyroidism to the baby?

The risks to the baby from Graves’ disease are due to one of three possible mechanisms:

  1. Uncontrolled maternal hyperthyroidism: Uncontrolled maternal hyperthyroidism has been associated with fetal tachycardia (fast heart rate), small for gestational age babies, prematurity, stillbirths and possibly congenital malformations. This is another reason why it is important to treat hyperthyroidism in the mother.

  2. Extremely high levels of thyroid stimulating immunogloblulins (TSI): Graves’ disease is an autoimmune disorder caused by the production of antibodies that stimulate thyroid gland referred to as thyroid stimulating immunoglobulins (TSI). These antibodies do cross the placenta and can interact with the baby’s thyroid. Although uncommon (2-5% of cases of Graves’ disease in pregnancy), high levels of maternal TSI’s, have been known to cause fetal or neonatal hyperthyroidism. Fortunately, this typically only occurs when the mother’s TSI levels are very high (many times above normal). Measuring TSI in the mother with Graves’ disease is often done in the third trimester.

    In the mother with Graves’ disease requiring antithyroid drug therapy, fetal hyperthyroidism due to the mother’s TSI is rare, since the antithyroid drugs also cross the placenta. Of potentially more concern to the baby is the mother with prior treatment for Graves’ disease (for example radioactive iodine or surgery) who no longer requires antithyroid drugs. It is very important to tell you doctor if you have been treated for Graves’ Disease in the past so proper monitioring can be done to ensure the baby remains healthy during the pregnancy.

  3. Anti-thyroid drug therapy (ATD). Methimazole (Tapazole) or propylthiouracil (PTU) are the ATDs available in the United States for the treatment of hyperthyroidism. Both of these drugs cross the placenta and can potentially impair the baby’s thyroid function and cause fetal goiter. Historically, PTU has been the drug of choice for treatment of maternal hyperthyroidism, possibly because transplacental passage may be less than with Tapazole. However, recent studies suggest that both drugs are safe to use during pregnancy. It is recommended that the lowest possible dose of ATD be used to control maternal hyperthyroidism to minimize the development of hypothyroidism in the baby or neonate. Neither drug appears to increase the general risk of birth defects. Overall, the benefits to the baby of treating a mother with hyperthyroidism during pregnancy outweigh the risks if therapy is carefully monitored.

What are the treatment options for a pregnant woman with Graves’ Disease/hyperthyroidism?

Mild hyperthyroidism (slightly elevated thyroid hormone levels, minimal symptoms) often is monitored closely without therapy as long as both the mother and the baby are doing well. When hyperthyroidism is severe enough to require therapy, anti-thyroid medications are the treatment of choice, with PTU being the historical drug of choice. The goal of therapy is to keep the mother’s free T4 and free T3 levels in the high-normal range on the lowest dose of antithyroid medication. Targeting this range of free hormone levels will minimize the risk to the baby of developing hypothyroidism or goiter. Maternal hypothyroidism should be avoided. Therapy should be closely monitored during pregnancy. This is typically done by following thyroid function tests (TSH and thyroid hormone levels) monthly.

In patients who cannot be adequately treated with anti-thyroid medications (i.e. those who develop an allergic reaction to the drugs), surgery is an acceptable alternative. Surgical removal of the thyroid gland is only very rarely recommended in the pregnant woman due to the risks of both surgery and anesthesia to the mother and the baby.
Radioiodine is contraindicated to treat hyperthyroidism during pregnancy since it readily crosses the placenta and is taken up by the baby’s thyroid gland. This can cause destruction of the gland and result in permanent hypothyroidism.

Beta-blockers can be used during pregnancy to help treat significant palpitations and tremor due to hyperthyroidism. They should be used sparingly due to reports of impaired fetal growth associated with long ¬term use of these medications. Typically, these drugs are only required until the hyperthyroidism is controlled with anti-thyroid medications.

What is the natural history of Graves’ Disease after delivery?

Graves’ disease typically worsens in the postpartum period, usually in the first 3 months after delivery. Higher doses of anti-thyroid medications are frequently required during this time. At usual, close monitoring of thyroid function tests is necessary.

Yes. PTU is the drug of choice because it is highly protein bound. Consequently, lower amounts of PTU cross into breast milk compared to Tapazole. It is important to note that the baby will require periodic assessment of his/her thyroid function to ensure maintenance of normal thyroid status. PTU has a recent FDA warning as a risk to the patient regarding liver failure, but the pregnancy survival supercedes the risk. the patient has been advised