Mixed Views on Treatment of Subclinical Hypothyroidism in Pregnancy

The benefits of treating overt hypothyroidism in women who are pregnant or planning pregnancy are clear, given its association with adverse outcomes including increased risk for premature birth, pregnancy loss, and lower offspring IQ.¹ There is less clarity regarding the maternofetal and neonatal effects of subclinical hypothyroidism (SCH), which affects an estimated 4% to 8% of reproductive-age women.¹ Research findings on the topic have been mixed, with the results of numerous studies linking SCH to outcomes such as infertility, gestational hypertension, and low birth weight, while other findings show no evidence of adverse outcomes.^1,2

Screening and Treatment of SCH in Pregnancy

There is ongoing debate about the necessity of universal screening for thyroid dysfunction in pregnancy and for levothyroxine (LT₄) treatment of SCH in women who are pregnant or planning to become pregnant. In other adult populations, guidelines strongly recommend against LT₄ therapy for SCH given a lack of demonstrated benefits, except in patients with TSH >20 mIU/L and certain patients with severe symptoms and/or aged ≤30 years.³

In pregnant women with SCH, variable results have been found in studies investigating the effects of LT₄ treatment, further calling into question whether SCH is a “disease requiring treatment or… just a biochemical diagnosis of no clinical consequences,” stated researchers in a 2018 review.¹ They noted the risks of overtreatment, such as exogenous hyperthyroidism, and the burden associated with treatment, including financial cost, ongoing healthcare utilization, and modification of daily habits as factors to consider.¹

Evidence does seem to support better reproductive outcomes with LT₄ therapy “in women with SCH undergoing artificial reproductive techniques, but not in those who are attempting natural conception,” the researchers continued, as well as a lower risk for preterm birth and pregnancy loss in women with TSH >4.0 mIU/L who receive LT₄ treatment.¹ “During a consultation, clinicians and patients should engage in a careful consideration of the current evidence in the context of the patients’ values and preferences to determine whether LT₄ therapy initiation is the best next step,”¹ they noted.

In 2017, the American Thyroid Association (ATA) published updated guidelines on the management of thyroid disease during pregnancy.⁴ Among the points regarding SCH, the “TSH upper limit was raised from 2.5 to 4.0 mIU/L when no population-based cutoff is available, and evaluation of [thyroid peroxidase antibody (TPOAb)] status was recommended in all pregnant women with TSH concentrations >2.5 mIU/L, with the result contributing to the treatment decision.”⁵

Because of a lack of clarity pertaining to the benefits of universal screening for thyroid dysfunction in pregnancy, the ATA guidelines recommend targeted screening in patients with certain risk factors (eg, signs or symptoms of thyroid dysfunction or a history of infertility).⁴ The guideline task force did not recommend either for or against universal TSH screening, except in women with known TPOAb positivity and women planning to undergo assisted reproduction. However, earlier research demonstrated that a targeted screening approach based only on high-risk criteria could miss an estimated 55% of women with autoimmune thyroiditis or hypothyroidism.⁶

Varying Guidelines and Practices

The ATA’s screening recommendations differ from those of other professional societies, including the 2012 guidelines from the Endocrine Society, which recommended LT₄ therapy in all pregnant women with SCH regardless of TPOAb status and 2015 guidelines from the American College of Obstetricians and Gynecologists, in which universal screening in pregnancy was not recommended.⁵