The American Thyroid Association’s 2017 guidelines for diagnosing and managing thyroid disease in pregnant and postpartum women recommend a new upper limit of normal on thyroid function and a new treatment protocol for hypothyroidism. The document also discusses the limitations of free thyroxine (FT4) assays and how they should be used to measure serum free T4 in pregnant women.

The guidelines also cover screening, iodine nutrition, thyroid antibodies and pregnancy complications, thyroid disease and lactation, future research, and the treatment of thyroid disease, hypothyroidism, thyrotoxicosis, and thyroid nodules and cancer in pregnancy. 

Gestation is often the time period in which clinicians assess thyroid function. “However, accurate assessment of maternal (and fetal) thyroid function during pregnancy remains difficult, and interpretation of laboratory testing differs from the nonpregnant patient,” explained the guidelines’ authors. Reference ranges for the most popular tests, FT4 and maternal thyrotropin (TSH) aren’t always consistent among various populations, either. 

In a key change from the previous 2011 version, the guidelines’ authors decided to raise the upper limit of normal for thyroid stimulating hormone (TSH) from 2.5mIU/L to 4.0 mIU/L. Several factors guided this revision, Elizabeth Pearce, MD, MSc, an associate professor of medicine at Boston University School of Medicine and co-chair of the guideline task force, told CLN Stat

One consideration was that additional data has emerged on pregnancy cohorts worldwide. The 2011 guidelines had based the threshold of 2.5 mIU/L on research involving about 5,500 pregnant women. By comparison, studies on more than 50,000 pregnant women now exist to inform reference ranges. “In addition, cohort studies demonstrate that, although TSH >2.5 mIU/L appears to be associated with adverse obstetric effects in thyroperoxidase (TPO) antibody-positive women, such effects are not consistently observed in TPO antibody-negative women until TSH is >5-10 mIU/L,” Pearce explained. 

The authors recommend that clinicians use population- or trimester-specific reference ranges to define serum TSH in pregnant women. However, if this information isn’t available, they can defer to the new 4.0 mIU/L limit. 

Another significant change concerns the algorithm for treating subclinical hypothyroidism (SCH). The 2011 guidelines stated, “SCH has been associated with adverse maternal and fetal outcomes. However, due to the lack of randomized controlled trials there is insufficient evidence to recommend for or against universal [levothyroxine] LT4 treatment in [thyroid antibody negative] TAb− pregnant women with SCH.” Nevertheless, 2011’s recommendation had been to initiate treatment when TSH was >10 mIU/L. 

The 2017 guidelines instead suggest testing for TPO antibodies in women with mild TSH elevations in order to inform treatment decisions, according to Pearce. The authors recommend TPO antibody status evaluations in pregnant women with TSH concentrations >2.5 mU/L. The updated guidelines also offer specifics on when to use LT4 therapy for SCH in pregnancy. 

The guidelines also discussed the optimal testing methods for assessing thyroid function in pregnant women. Labs tend to favor FT4 indirect analog immunoassays, which can be conducted on automated platforms. In most instances, these tests perform fairly well as far as reporting thyroid hormone deficiencies and excesses. 

“Unfortunately, this approach is prone to inaccuracy in the setting of pregnancy because of disruption of the original equilibrium — a process dependent upon dilution, temperature, buffer composition, affinity, and the concentration of the T4 antibody reagent and the T4-binding capacity within the serum sample,” the guidelines’ authors noted. The addition of albumin to these tests is another factor that can disrupt equilibrium. 

Labs usually follow what the manufacturer says about recommendations on pregnancy ranges, although ranges can vary widely among manufacturers for these types of assays. For these reasons, “current uncertainty around FT4 estimates in pregnancy has led some to question the wisdom of relying on any FT4 immunoassays during pregnancy,” according to the guidelines. 

In the event a lab uses an FT4 assay to measure thyroid function in pregnant women, the authors recommended that labs apply assay method-specific and trimester-specific pregnancy reference ranges. 

To assess FT4 in pregnancy, the 2011 guideline had recommended online extraction/liquid chromatography/tandem mass spectrometry to measure in the dialysate or ultrafiltrate of serum samples. Because such testing isn’t widely available, this approach has since been abandoned, Pearce said. The new recommendation is to use a pregnancy-adjusted total T4 measurement or free thyroxine index whenever possible. 

The guideline also tackled the controversial issue of universal screening for thyroid disease. Some have recommended it based on the potentially serious health issues that could result from insufficient screening and detection of disease during pregnancy. 

“Such a screening mandate, however, must take the cost, effectiveness, and practical nature of any such approach into account. To date, studies evaluating this question appear to demonstrate mixed conclusions,” the authors said. 

Similar to the 2011 guideline, the updated version doesn’t recommend for or against universal TSH screening of pregnant women, due to insufficient evidence. “Aggressive case-finding is recommended in pregnancy, however, and TSH testing is recommended for all women who will undergo assisted reproduction,” Pearce said. 

For newborns, hypothyroidism screening should take place several days after birth. “The introduction of newborn screening for congenital hypothyroidism has led to the virtual elimination of intellectual impairment due to hypothyroidism so long as early and adequate postnatal levothyroxine treatment is initiated immediately,” the authors explained.