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
In a study from the Netherlands, Pop and associates2 found impaired psychomotor function in 22 infants (age 10 months) whose mothers had had FT4 below the 10th percentile at 12 weeks of gestation, compared with 194 infants whose mothers had normal readings. When these children were reevaluated at 2 years, no neurodevelopmental delay was found in the infants whose mothers had a spontaneously increased free thyroxine level after the first trimester.
There is much speculation about precisely when thyroid hormone is critical for fetal brain development. The study by Pop and associates2 would suggest it is important after the first trimester. That study also recommends exogenous thyroxine for FT4 values below 0.96 ng/mL (12 pmol/L).
In Italy, Vermiglio and coworkers11 conducted behavioral and neuropsychological testing in 27 children at ages 18 to 36 months and again at 8 to 10 years. Mothers of 16 of these children were from a moderately iodine-deficient area (group A), and the mothers of 11 children were from a marginally iodine-sufficient area and were monitored with thyroid function tests in the first trimester (group B). Attention-deficit and hyperactivity disorders were more prevalent in group A.
Two studies published in 2006 also suggest that maternal free thyroxine levels in the first trimester of pregnancy correlate with impaired neonatal behavior at 3 months, and impaired mental development at ages 6, 9, and 12 months.3,4
Thyroid disorders affect approximately 5% of the general population, two thirds of them women.17 Subclinical hypothyroidism occurs in an additional 4.3%, and subclinical hyperthyroidism in 0.7%.
In pregnancy, subclinical disease is present in 3.6% of women; overt hypothyroidism, in 2.5%; and overt hyperthyroidism, in 0.2%. In addition, thyroid disease affects 5% to 9% of postpartum women.14
No consensus on whom to test or what test is best
There is no clear agreement about which population should be targeted for screening or what test to use. Most medical societies do not recommend routine screening, including the American College of Obstetricians and Gynecologists, which recommends TSH testing only in women with a history of thyroid disease and in women with “symptoms” (but does not specify which symptoms or how many symptoms warrant testing). A majority of organizations agree that all high-risk women should be tested when pregnancy is planned or as soon as pregnancy is confirmed.
TABLE 5
Comparison of screening recommendations highlights lack of consensus (and, in pregnancy, the absence of guidance)
| YEAR | ORGANIZATION | NONPREGNANT STATE | PREGNANCY |
|---|---|---|---|
| 1994 | American Association of Clinical Endocrinologists (AACE), American Academy of Family Physicians | Periodic assessment via thyroid function tests in older women | No recommendation |
| 1998 | American College of Physicians | Office screening of women >50 years of age | No recommendation |
| 2000 | American Thyroid Association (ATA) | Measure TSH every 5 years in women age 35 and older (probably men also) | No recommendation |
| 2002 | American College of Obstetricians and Gynecologists | Measure TSH every 5 years in women age 65 and older | No screening recommended |
| 2003 | Institute of Medicine | Screening is not cost-effective in Medicare population | No recommendation |
| 2004 | United States Preventive Services Task Force | Routine screening of children and adults is not recommended | No recommendation |
| 2004 | AACE, ATA, the Endocrine Society Consensus Group | No population-based screening, but “aggressive case finding” in women at high risk and those over age 60 | Do not support routine testing; recommend “aggressive case finding” and screening pregnant women at high risk |
Proponents of routine screening argue that it may limit health risks to children and save money in the long run, and they point out that thyroid disease is easy to treat with pills. Opponents note that no cost-benefit analysis has been performed, the benefits of treating mild disease are unclear, and screening a large population could be a significant expense ($40–100 per person) and would necessitate a lifelong commitment to daily medication in asymptomatic patients.
As a diagnostic test, the TSH immunoassay has 98% sensitivity and 92% specificity, and the current third-generation test lacks biases between methods and does not require method-specific reference ranges. However, it has low predictive value as a screening test (7–25%), possibly because of multiple confounding variables. Despite being the “gold standard,” it can lead to falsely positive results.
TABLE 6
What makes a TSH measurement falsely high or low?
| ELEVATED TSH | LOW TSH |
|---|---|
| Recovery from nonthyroidal illness | Euthyroid sick syndrome |
| Late evening TSH surge | Recovery from normal pregnancy |
| Assay variability | |
| Adrenal insufficiency | |
| Drugs: metoclopramide, amiodarone, cholecystographic dye (sodium ipodate) | Drugs: glucocorticoids, dopamine |
As for the value of FT4 alone as a screening test, we lack sufficient data on its utility. Another problem is that equilibrium dialysis, the most accurate and reliable laboratory method to measure FT4, is too technically complex and expensive for routine use. The most widely used 2-step radioimmunoassay is automated, but different methods are used by different commercial laboratories, cutoffs vary for every laboratory, and the results are sensitive to abnormal binding-protein states such as pregnancy in a method-specific manner. Tandem mass spectrometry is as reliable as equilibrium dialysis, but is not yet readily available.12
