Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

BACKGROUND: Thyroglobulin, produced exclusively by the thyroid gland, has been proposed to be a more sensitive biomarker of iodine status than thyrotropin or the thyroid hormones triiodothyronine and thyroxine. However, evidence on the usefulness of thyroglobulin (Tg) to assess iodine status has not been extensively reviewed, particularly in pregnant women and adults. SUMMARY: An electronic literature search was conducted using the Cochrane CENTRAL, Web of Science, PubMed, and Medline to locate relevant studies on Tg as a biomarker of iodine status. Since urinary iodine concentration (UIC) is the recommended method to assess iodine status in populations, only studies that clearly reported both Tg and UIC were included. For the purpose of this review, a median Tg <13 μg/L and a median UIC ≥100 μg/L (UIC ≥150 μg/L for pregnant women) were used to indicate adequate iodine status. We excluded studies conducted in subjects with either known thyroid disease or those with thyroglobulin antibodies. The search strategy and selection criteria yielded 34 articles of which nine were intervention studies. The majority of studies (six of eight) reported that iodine-deficient pregnant women had a median Tg ≥13 μg/L. However, large observational studies of pregnant women, including women with adequate and inadequate iodine status, as well as well-designed intervention trials that include both Tg and UIC, are needed. In adults, the results were equivocal because iodine-deficient adults were reported to have median Tg values of either <13 or ≥13 μg/L. Only studies in school-aged children showed that iodine-sufficient children typically had a median Tg <13 μg/L. Some of the inconsistent results may be partially explained by the use of different methodological assays and failure to assess assay accuracy using a certified reference material. CONCLUSIONS: These data suggest that Tg does hold promise as a biomarker of iodine deficiency. However, it is associated with limitations. A median Tg cutoff of 13 μg/L warrants further investigation, particularly in adults or pregnant women, as there is a lack of both observational and intervention studies in these groups.