Association of mild-to-moderate iodine deficiency with thyroid function - a systematic review and meta-analysis.

Background: The only known function of iodine in the human body is as a component of thyroid hormones. Thus, all consequences of iodine deficiency should be mediated through altered thyroid hormone production. While it is well established that severe iodine deficiency affects thyroid hormone production, the association between mild-to-moderate iodine deficiency and thyroid function remains unclear.

Objective: To review and summarize observational studies that examine the association between mild-to-moderate iodine deficiency and thyroid hormone function in the general population, including infants, children, adolescents, adults, pregnant and lactating women.

Methods: Systematic searches of the literature were performed in November 2022 and repeated in February 2024 utilizing the Medline Ovid, Embase Ovid, and Cochrane Central databases. Mild-to-moderate iodine deficiency was defined as a median urinary iodine concentration (UIC) of 20-100 μg/L in children, adolescents, and general adults, and 50-150 μg/L in pregnant women. Thyroid function outcomes included TSH, (f)T3, and (f)T4, and clinical thyroid dysfunction entities.

Results: A total of 72 studies were included: 59 cross-sectional, 12 repeated cross-sectional (longitudinal), and one cohort study. Populations studied included infants, children, and adolescents (n=7); women of reproductive age, including lactating women (n=5); general adults (n=20); and pregnant women (n=43). Most studies reported no clear association between iodine status and thyroid function across all groups. For all population groups, most studies found no clear association between iodine status and thyroid function. Meta-analyses for eight studies in pregnant women showed no difference in TSH, fT4, or fT3 for those with mild-to-moderate iodine deficiency vs. adequate status [mean difference (95% CI): TSH, 0.03 (-0.05, 0.12) mIU/L; fT4, -0.20 (-0.94, 0.53) pmol/L; fT3, 0.05 (-0.14, 0.03) pmol/L].

Conclusion: No clear association between mild-to-moderate iodine deficiency with thyroid function in the different population groups was found.

Registry number for systematic review: Registered at www.crd.york.ac.uk/PROSPERO as CRD42022360447.

Statement of significance: This is the first systematic review to provide a comprehensive overview of observational studies investigating the association between mild-to-moderate iodine deficiency and thyroid function in the general population, including infants, children, adolescents, adults, pregnant and lactating women.