Re: “Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum” by Alexander et al. ( Thyroid 2017;27:315–389)

Dear Editor:

We read with interest the recent guidelines provided by the American Thyroid Association (ATA) for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Regarding selenium (Se), the guidelines state that “Se supplementation is not recommended for the treatment of thyroid peroxidase antibody (TPOAb)-positive women during pregnancy.” In addition, a higher risk for developing type 2 diabetes mellitus (T2D) with Se is suggested, which potentially increases the risk-to-benefit ratio (1).

Some comments might be of interest. Se is an essential element for human reproduction, associated with favorable birth outcomes (2 –4). Its sufficiency status, assessed by serum selenoprotein concentrations, has been negatively associated with the risk of developing gestational diabetes mellitus (GDM) (2 –4). A meta-analysis of observational studies showed that Se concentrations are lower in women with GDM, as well as in pregnant women with impaired glucose tolerance, compared to normoglycemic pregnant women, mainly during the third trimester (2). With respect to the effect of Se supplementation on glucose metabolism, few studies exist. At a dose of 200 μg/day, Se seems to be beneficial for glucose homeostasis (as indicated by the reduction in fasting plasma glucose concentrations and insulin sensitivity indexes) and oxidative stress reduction during pregnancy (as indicated by elevation in plasma glutathione and significant reduction in plasma malondialdehyde concentrations) (3). A randomized controlled trial supplemented a British pregnant population of relatively low baseline Se status (whole blood Se concentrations: 103 μg/L) with low-dose Se (60 μg/day) from 12–14 weeks to the end of gestation. There was no effect on plasma adiponectin concentrations, an established biomarker of insulin resistance (4). Furthermore, in the two studies cited by the ATA 2017 guidelines, no increased risk in obstetrical complications, such as GDM, was reported in the Se-treated pregnant women compared to the controls (1).

Regarding the association between Se and T2D, this seems to be complex and dependent on the status of the population studied. A recent meta-analysis of five observational studies (13,460 participants from the United States and Europe) found a U-shaped dose–response relationship between serum Se and T2D. Se concentrations were positively associated with T2D in populations with relatively low (<97.5 μg/L) or high serum Se concentrations (>132.5 μg/L), whereas at intermediate concentrations (97.5–132.5 μg/L), no association with T2D was found (5).

In conclusion, even though a clear benefit of Se supplementation during pregnancy regarding thyroid autoimmunity has not been proven, its benefits on glucose metabolism seem to outweigh the potential risks. Therefore, the phrase “patients treated with Se could be at higher risk for developing T2D” could be removed from the ATA guidelines. We believe that a recommendation such as “insufficient evidence exists to determine conclusively whether Se supplementation is beneficial for the treatment of TPOAb-positive women during pregnancy” would summarize the existing data in a more accurate way.