19-18: Thyroid Disease in Pregnancy

Thyroid disease is relatively common in pregnancy, and in their overt states, both hypothyroidism and hyperthyroidism have been consistently associated with adverse pregnancy outcomes. There are gestational age-specific effects that pregnancy has on thyroid function tests; failure to recognize these physiologic alterations can cause misclassification or misdiagnosis. Women who have a history of a thyroid disorder or symptoms that suggest thyroid dysfunction should be screened with thyroid function tests. Screening asymptomatic pregnant women, however, is of unproven benefit and is not currently recommended.

Overt hypothyroidism is defined by an elevated serum TSH level with a depressed FT₄ level. During pregnancy, several factors occur that affect maternal thyroid hormones: (1) Rising estrogen levels increase thyroxine binding globulin (TBG) serum concentrations, reducing FT₄ levels. (2) Placental deiodinase promotes the turnover of T₄. (3) Supplemental iron and prenatal multivitamins containing iron can bind to oral T₄ and reduce its intestinal absorption.

The most common etiology of hypothyroidism during pregnancy is Hashimoto (autoimmune) thyroiditis. Many of the symptoms of hypothyroidism mimic those of normal pregnancy, making its clinical identification difficult. Maternal hypothyroidism has consistently been associated with an increase in complications such as spontaneous abortion, preterm birth, preeclampsia, placental abruption, and impaired neuropsychological development in the offspring; the fetus is at least partially dependent on maternal T₄ for its CNS development—particularly in the second trimester. Therefore, for women who need levothyroxine, it is prudent to increase the dosages by approximately 20–30% as soon as pregnancy is confirmed. Pregnant women with overt hypothyroidism or myxedema should be treated immediately with levothyroxine at full replacement doses of 1.6 mcg/kg/day (about 100–150 mcg daily). For titration, the levothyroxine dosage may be increased according to clinical response and serum TSH, measuring serum TSH every 4–6 weeks and trying to keep the serum TSH level in a trimester-specific gestational reference range. An increase in the dose of levothyroxine may be required in the second and third trimesters. By mid-pregnancy, women require an average of 47% increase in their levothyroxine dosage.

Subclinical hypothyroidism is defined as an increased serum TSH with a normal FT₄ level. Although some studies have found associations with untoward pregnancy outcomes such as miscarriage, preterm birth, and preeclampsia, others have failed to confirm these findings. There is no evidence that treatment of subclinical hypothyroidism will prevent any of these outcomes. Early observational studies also suggested that cognitive function was impaired in offspring of women with untreated subclinical hypothyroidism. Data from an NIH-sponsored Maternal-Fetal Medicine Units Network randomized, controlled trial demonstrated no improvement in cognitive function of 5-year-olds born to women screened and treated for subclinical hypothyroidism. The ACOG and the American Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy.

Overt hyperthyroidism, defined as excessive production of thyroxine with a depressed (usually undetectable) serum TSH level, is also associated with increased risks in pregnancy. Spontaneous pregnancy loss, preterm birth, ...