What you need to know about thyroid disorders in pregnancy
Managing overt disorders is straightforward, but even subclinical disease warrants heightened scrutiny
IN THIS ARTICLE
Another consideration: The physiologic changes in pregnancy render the cutoffs for the nongravid state inapplicable. TSH is lower in pregnancy, whereas the FT4 level is probably slightly increased or unchanged (TT4 is 1.5 times the prepregnancy value).
The normal reference values in each trimester of pregnancy from iodine-sufficient, autoimmune thyroid antibody-negative women are becoming available for TSH,12 as are nomograms that adjust for fetal number and gestational age.12 The measurement of FT4 still needs to be standardized across laboratories (method-specific, trimester-specific, and, possibly, population-specific reference ranges) for pregnancy.
How to manage subclinical thyroid disorders
In the nonpregnant state, subclinical hyperthyroidism should be treated in the following groups if the abnormal thyroid levels persist beyond 4 to 12 weeks and the TSH level is less than 0.1 mIU/L:
- High-risk women: postmenopausal or over age 60
- Low-risk women with cardiac disease, low bone density, or nodular thyroid disease.
If the TSH level is between 0.1 and 0.5 mIU/L, treatment is recommended for high-risk women with cardiac disease, low bone density, or nodular thyroid disease.
Subclinical hypothyroidism with a TSH level of 4.5 to 10 mIU/L need not be treated even in an elderly woman or a patient with a high antibody titer. Treatment of any woman is beneficial when the TSH level exceeds 10 mIU/L because it can ease symptoms, reduce low-density lipoprotein cholesterol, and prevent progression to overt disease. However, treatment may not lower morbidity and mortality and carries a roughly 20% risk of causing subclinical hyperthyroidism. It also involves a lifelong commitment to daily medication.
How to treat subclinical hypothyroidism in pregnancy
It is clear that overt hypothyroidism warrants treatment in both the pregnant and nonpregnant states, but the management of subclinical disease remains controversial. No trials have assessed the benefits of thyroid hormone replacement on the neuropsychological development of the newborn. Expert opinion suggests that women be treated if they are planning a pregnancy, are already pregnant, or have high TSH or low FT4.
Until we have more data, pregnant women and those planning a pregnancy should be treated with levothyroxine (starting at 2 μg/kg/day) if they are found to have elevated TSH or low FT4.
Two studies will answer questions about effects in pregnancy
The Controlled Antenatal Thyroid Screening (CATS) study will be completed in 2009, and the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units (NICHD-MFMU) study will conclude in 2014. The CATS study screened 22,000 pregnant women in the United Kingdom before 16 weeks’ gestation. Half these women were treated with levothyroxine in pregnancy if they had a TSH measurement above the 97.5th percentile or FT4 below the 2.5th percentile, and half had their blood samples stored and tested only after delivery.14 Cutoff values were derived from previously obtained antenatal sera from well-dated pregnancies, and were adjusted after every 2,000 to 3,000 samples.
The CATS study was conducted in an iodine-sufficient area with a median urinary iodine excretion of 100 μg/L (range: 11–240 μg/L). Each group contained 400 women with subclinical hypothyroidism (52% had low FT4, 45% had high TSH, and 3% had both). Antithyroid peroxidase antibodies were present in 50% of women with elevated TSH but in only 10% of women with low FT4. Neuropsychological development in their children is being tested at 3 years of age.
The NICHD-MFMU study plans to screen 110,000 women at 14 centers over 2 years, and will randomize roughly 1,000 women to thyroxine treatment or placebo. They plan to assess intellectual development of the infants yearly for 5 years, and test the mothers for postpartum thyroid dysfunction and follow them at 1 and 5 years to detect the rate of progression to overt hypothyroidism.
Postpartum dysfunction can be transient or permanent
Postpartum thyroid dysfunction (PPTD) is an autoimmune disorder that occurs at 13 to 19 weeks postpartum, affects 1 in 12 women worldwide, and is usually associated with psychiatric symptomatology.15
PPTD also is strongly associated with antithyroid peroxidase antibodies (TPOAbs).16 Premawardhana and colleagues found that 10% of women are TPOAbs-positive in the first trimester; of these, 50% develop PPTD. Of the women with PPTD, 20% to 30% develop permanent hypothyroidism, and an additional 30% to 40% develop it by 7 years. In contrast, only 5% of women without PPTD progress to overt disease by 7 years. These findings have generated considerable controversy about routine screening for PPTD. Proponents argue that PPTD is highly prevalent, linked to considerable morbidity, is easily diagnosed with relatively inexpensive tests, and is easy to treat effectively. Critics note the lack of consensus on the best screening test (thyroid function test versus TPOAbs), optimal timing of screening (early pregnancy or postpartum), and lack of high-quality, prospective cost-benefit analyses. The NICHD-MFMU hopes to resolve these controversies.
