An Inverse Relationship Between Weight and Free Thyroxine During Early Gestation Among Women Treated for Hypothyroidism

Abstract

Background:

Following treatment sufficient to normalize thyrotropin (TSH), nonpregnant hypothyroid adults display higher free thyroxine (FT₄) concentrations than a reference population. Our aim is to determine whether FT₄ concentrations are higher during pregnancy among women treated for hypothyroidism and whether their weight is associated with FT₄ levels. Weight/FT₄ relationships have not previously been reported in treated hypothyroid adults (either pregnant or nonpregnant).

Methods:

Thyroid-related measurements were available from over 10,000 women at two early pregnancy time periods from the FaSTER (First and Second Trimester Evaluation of Risk for Fetal aneuploidy) trial (1999–2002). All women were receiving routine prenatal care. Present analyses were restricted to 9267 reference women and 306 treated, hypothyroid women with TSH between the 2nd and 98th reference percentiles. We compared FT₄ values between those groups at 11–14 and 15–18 weeks' gestation, using linear regression to estimate FT₄/maternal weight relationships, after accounting for treatment and other potential covariates.

Results:

In comparison to reference women, median FT₄ values and percent of FT₄ values ≥95th reference percentile were significantly higher in treated women at both 11–14 and 15–18 weeks' gestation (p<0.001) overall and after stratification by weight into tertiles. Among both treated and reference women, median FT₄ decreased monotonically with increasing weight, regardless of anti-thyroperoxidase antibody status. Maternal age, maternal weight, and treatment status were important predictors of FT₄ levels (p<0.001, defined by partial r ² values of 1% or higher). Anti-thyroperoxidase antibody status, TSH values (after logarithmic transformation), and all interaction terms were well below an r ² of 1%. FT₄ levels were 1.45 pmol/L higher in treated than reference women, independent of other factors. Maternal age and weight reduced FT₄ levels by 0.0694 pmol/L/y and 0.0208 pmol/L/kg, respectively.

Conclusions:

FT₄ concentrations are higher among treated hypothyroid pregnant women than among reference women, and higher maternal weight is associated with lower FT₄ levels, regardless of treatment status. This inverse relationship is not associated with higher TSH levels. While no immediate clinical implications are attached to the current observations, increased peripheral deiodinase activity in the presence of higher weight might explain these findings. Further investigation appears worthy of attention.