Abstract

Phthalates are ubiquitous in different environmental exposure media around the world. Recent years, issues on the relationships of phthalates and endocrine disorders raise attention. Evidence of thyroid disruption as a result of phthalates expose among euthyroid participants with diabetes is very limited. We aimed to evaluate the association between phthalate and thyroid function, and to explore whether thyroid autoimmunity mediated this association. Concurrent urine and blood samples were collected from 538 participant in METAL study. We measured urinary concentrations of ten phthalate metabolites (urinary creatinine adjusted), along with serum levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Euthyroidism was defined as TSH within normal range. After adjusting for age, sex (only with the entire sample), BMI and smoking status, linear regression analyses showed exactly opposite directional results among men and women. TSH levels were negatively associated with mono-2-ethyl-5-carboxypentylphthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexylphthalate (MEOHP), mono-2-carboxymethyl-hexyl phthalate (MCMHP) and sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHPm) in men, but positively associated with monoisobutylphthalate (MiBP) and mono-n-butylphthalate (MnBP) in women. Meanwhile, FT4 was positively associated with mono-2-ethylhexylphthalate percentage (%MEHP) in men, but negatively associated with MnBP, MEOHP and MCMHP in women. Further, in women, TPOAb was increasing along with the increased level of MEHP and %MEHP. In the mediation analysis, TPOAb demonstrated a mediating effect whereby MEHP or %MEHP had a positive effect on TSH and a negative effect on FT4 only in women (all P<0.05). We got a conclusion that among euthyroid participants with diabetes, urinary phthalate metabolites maybe associated with altered TSH, FT4 and TPOAb levels in different direction in men and women. Further, our present study maybe the first to suggest that TPOAb might be a potential mediator of the association between phthalate metabolites and thyroid function in women.

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