Thyroid Disease in Pregnancy

What are the normal changes in thyroid function associated with pregnancy?

1. During pregnancy, TBG production increases and an increase in TBG sialylation leads to its decreased clearance.

TBG excess leads to an increase in both serum total thyroxine (T4) and triiodothyronine (T3) concentrations, but

measurement of free hormone remains normal.

2. Beta hCG has weak thyroid-stimulating activity. Serum hCG concentrations increase soon after fertilization and

peak at 10 to 12 weeks. Serum free T4 and T3 concentrations increase slightly and the TSH will be slightly

decreased in the first trimester but return to normal throughout the duration of pregnancy.

What are the most common causes of hyperthyroidism during pregnancy?

The most common cause of maternal hyperthyroidism during pregnancy is Graves’ disease. It usually becomes less severe during the later stages of pregnancy, perhaps mediated by a change in the activity of TSH receptor antibodies from stimulatory to blocking, but may worsen during the post partum period. In addition to Grave’s disease, very high levels of hCG, seen in severe forms of morning sickness (hyperemesis gravidarum), may cause transient hyperthyroidism.

How do you diagnose hyperthyroidism during pregnancy?

The diagnosis of hyperthyroidism can be somewhat difficult during pregnancy, as radioactive iodine thyroid scanning is contraindicated during pregnancy. Consequently, diagnosis is based on a careful history, physical exam and laboratory testing. The diagnosis of hyperthyroidism in pregnant women should be based primarily on a serum TSH value <0.01>

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

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. Both propylthiouracil and methimazole cross the placenta, but PTU is associated with less congenital malformations. PTU is also less effective at controlling hyperthyroidism and therefore is less likely to affect the fetal thyroid.

In patients who cannot be adequately treated with anti-thyroid medications, surgery is a rare but 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 can cause destruction of the fetal 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 because occasional cases of neonatal growth restriction, hypoglycemia, respiratory depression, and bradycardia have been reported after maternal administration.

What are the most common causes of hypothyroidism during pregnancy?

Hypothyroidism can occur during pregnancy due to the initial presentation of Hashimoto’s thyroiditis, inadequate treatment of a woman already known to have hypothyroidism from a variety of causes, or over-treatment of a hyperthyroid woman with anti-thyroid medications.

How should a woman with hypothyroidism be treated during pregnancy?

Women need more thyroid hormone during pregnancy with the goal of therapy is to normalize the mother's serum TSH concentration. Several factors are responsible for the increased T4 requirement during pregnancy. They include weight gain and increased T4 pool size, high serum TBG concentrations, placental deiodinase activity, transfer of T4 to the fetus, and reduced gastrointestinal absorption due to iron in prenatal vitamins. Levothyroxine dose requirements may increase by as much as 50 percent during pregnancy, and the increase occurs as early as the fifth week of gestation. Given the importance of maternal euthyroidism for normal fetal cognitive development, serum TSH should be measured four to six weeks after conception, four to six weeks after any change in the dose of T4, and at least once each trimester.

References

1. Ain, K, Mori, Y, Refetoff, S. Reduced clearance rate of thyroxine binding globulin (TBG) with increased sialylation: a mechanism for estrogen-induced elevation of serum TBG concentration. Journal of Clinical Endocrinology and Metabolism 1987; 65:689.

2. Ballabio, M, Posyyachinda, M, Ekins, RP. Pregnancy-induced changes in thyroid function: role of human chorionic gonadotropin as a putative regulator of maternal thyroid. Journal of Clinical Endocrinology and Metabolism 1991; 73:824.

3. Glinoer, D, DeNayer, Ph, Lejeune, B, et al. Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits in relation to maternal thryoid stimulation during normal pregnancy. Journal of Endocrinologic Investigation 1993; 16:881.

4. Roti, E, Minelli, R, Salvi, M. Management of hyperthyroidism and hypothyroidism in the pregnant woman. Journal of Clinical Endocrinology and Metabolism 1996; 81:1679.

5. Rubin, PC. Beta-blockers in pregnancy. New England Journal of Medicine 1981; 305:1323.

6. Alexander, EK, Marqusee, E, Lawrence, J, et al. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. New England Journal of Medicine 2004; 351:241.

Category: Medicine Notes