SAT-396 - Iodine Uptake Inhibition and Thyroid Function Changes after Environmental Perchlorate Exposure: A Systematic Review

Background:
Perchlorate is a common environmental contaminant that competitively inhibits the sodium–iodide symporter, potentially impairing thyroid hormone synthesis. This effect may be amplified in individuals with iodine deficiency and in those with concurrent exposure to other iodide uptake inhibitors.

Objective:
To systematically synthesize human evidence on the association between environmental perchlorate exposure and thyroid function in adults, with emphasis on effect modification by iodine status and co-exposure to nitrate and thiocyanate.

Methods:
A systematic search of PubMed and PubMed Central identified human studies evaluating urinary perchlorate concentrations in relation to thyroid outcomes. Four articles met inclusion criteria, including two population-based cross-sectional studies and two narrative reviews providing mechanistic context. Findings were qualitatively synthesized.

Results:
In NHANES 2001–2002 (n = 2,299; ≥12 years), urinary perchlorate was not associated with serum TSH or total thyroxine (T4) in men. In women, perchlorate was a significant predictor of both thyroid outcomes. Among women with urinary iodine < 100 µg/L, perchlorate was inversely associated with total T4 (p < 0.0001) and positively associated with TSH (p = 0.001). Among women with urinary iodine ≥100 µg/L, perchlorate remained positively associated with TSH (p = 0.025) but not with T4 (p = 0.55).
In a community-based study of 2,441 non-pregnant Chinese adults (median urinary iodine 180.1 µg/L), higher urinary perchlorate was associated with lower serum free T4 (FT4), total T4 (TT4), and total T3 (TT3), and with higher TSH (all p < 0.05) after multivariable adjustment. Mixture analyses demonstrated inverse associations between combined exposure to perchlorate, nitrate, and thiocyanate and serum FT4, TT4, and FT3 using both weighted quantile sum regression and Bayesian kernel machine regression models. Thiocyanate was independently associated with lower FT3 (β = −0.04 pmol/L per log-unit increase; 95% CI: −0.06, −0.02). Mechanistic reviews corroborated sodium–iodide symporter inhibition as the primary biological pathway and identified iodine deficiency and co-exposure as key susceptibility factors.

Conclusions:
Across diverse adult populations, environmental perchlorate exposure is associated with statistically significant alterations in thyroid biomarkers, most consistently lower T4 indices and higher TSH. Effects appear strongest among women with low iodine status and in the presence of concurrent exposure to other iodide uptake inhibitors, supporting a susceptible-subgroup and mixture-exposure model of perchlorate-related thyroid disruption. Practical exposure reduction strategies include using reverse osmosis-filtered drinking water, thoroughly washing produce, and maintaining adequate iodine intake.

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