Thyroglobulin as a Functional Biomarker of Iodine Status in a Cohort Study of Pregnant Women in the United Kingdom

Background: Though iodine deficiency in pregnancy is a matter of public-health concern, a functional measure of iodine status is lacking. The thyroid-specific protein thyroglobulin (Tg), which reflects thyroid size, has shown promise as a functional measure in studies of children and adults, but data in pregnancy are sparse. In a cohort of mildly to moderately iodine-deficient pregnant women, this study aimed to explore whether serum Tg is a sensitive functional biomarker of iodine status and to examine longitudinal change in Tg with gestational age. Method: A total of 230 pregnant women were recruited at an antenatal clinic at 12 weeks of gestation to the Selenium in PRegnancy INTervention study, in Oxford, United Kingdom. Repeated measures of urinary iodine-to-creatinine ratio, serum thyrotropin (TSH), and Tg at 12, 20, and 35 weeks of gestation were made. Women were dichotomized by their iodine-to-creatinine ratio (<150 or ≥150 μg/g) to group them broadly as iodine deficient or iodine sufficient. Women with thyroid antibodies were excluded; data and samples were available for 191 women. Results: Median Tg concentrations were 21, 19, and 23 μg/L in the first, second, and third trimesters, respectively. In a linear mixed model, controlling for confounders, Tg was higher in the <150 μg/g group than it was in the ≥150 μg/g group (p < 0.001) but there was no difference in TSH (p = 0.27). Gestational week modified the effect of iodine status on TSH (p = 0.01) and Tg (p = 0.012); Tg did not increase with gestational week in the ≥150 μg/g group, but it did in the <150 μg/g group, and TSH increased more steeply in the <150 μg/g group. Conclusions: Low iodine status (<150 μg/g) in pregnancy is associated with higher serum Tg, suggesting that the thyroid is hyperstimulated by iodine deficiency, which causes it to enlarge. Tg is a more sensitive biomarker of iodine status in pregnancy than is TSH.