title: Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan Environmental Survey for Toxicants (TEST) 2013.
abstract: BACKGROUND
  Previous epidemiologic and toxicological studies provide some inconsistent evidence that exposure to phthalates may affect thyroid function and growth hormone homeostasis.
  
  
  OBJECTIVE
  To assess the relations between exposure to phthalates and indicators of thyroid function and growth hormone homeostasis disturbances both among adults and minors.
  
  
  METHODS
  We conducted a population-based cross-sectional study of 279 Taiwanese adults (≥18 years old) and 79 minors (<18 years old) in 2013. Exposure assessment was based on urinary biomarkers, 11 phthalate metabolites measured by using online liquid chromatography/tandem mass spectrometry. Indicators of thyroid function included serum levels of thyroxine (T4), free T4, triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin (TBG). Growth hormone homeostasis was measured as the serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3). We applied multivariate linear regression models to examine these associations after adjusting for covariates.
  
  
  RESULTS
  Among adults, serum T4levels were negatively associated with urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate (β=-0.028, P=0.043) and the sum of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolite (β=-0.045, P=0.017) levels. Free T4levels were negatively associated with urinary mono-ethylhexyl phthalate (MEHP) (β=-0.013, P=0.042) and mono-(2-ethyl-5-oxohexyl) phthalate (β=-0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (β=0.014, P=0.037) after adjustment for age, BMI, gender, urinary creatinine levels, and TBG levels. Postive associations between urinary MEHP levels and IGF-1 levels (β=0.033, P=0.006) were observed. Among minors, free T4was positively associated with urinary mono benzyl phthalate levels (β=0.044, P=0.001), and IGF-1 levels were negatively associated with the sum of urinary DEHP metabolite levels (β=-0.166, P=0.041) after adjustment for significant covariance and IGFBP3.
  
  
  CONCLUSIONS
  Our results are consistent with the hypothesis that exposure to phthalates influences thyroid function and growth hormone homeostasis.
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Han-Bin
authors.initials: HB
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Division of Preventive Medicine and Health Service Research, Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
authors.affiliation: Research Center for Environmental Trace Toxic Substances, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jung-Wei
authors.initials: JW
authors.lastname: Chang
authors.affiliation: National Environmental Health Research Center, National Institute of Environmental Health Science, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hung-Che
authors.initials: HC
authors.lastname: Chiang
authors.affiliation: National Environmental Health Research Center, National Institute of Environmental Health Science, National Health Research Institutes, Miaoli, Taiwan; Institution of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan.
authors.forename: Yue Leon
authors.initials: YL
authors.lastname: Guo
authors.affiliation: Center for Environmental and Respiratory Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Jouni J K
authors.initials: JJ
authors.lastname: Jaakkola
authors.affiliation: National Environmental Health Research Center, National Institute of Environmental Health Science, National Health Research Institutes, Miaoli, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Safety, Health and Environmental Engineering, National United University, Taiwan.
authors.forename: Po-Chin
authors.initials: PC
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003430:Cross-Sectional Studies; D004051:Diethylhexyl Phthalate / Q000378:metabolism / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006706:Homeostasis; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000633:toxicity* / Q000652:urine; D013624:Taiwan; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000097:blood
chemical_list: D004785:Environmental Pollutants; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D010795:Phthalic Acids; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I; C032279:phthalic acid; D004051:Diethylhexyl Phthalate; D013974:Thyroxine
keywords: Biomonitoring; Growth hormone; Phthalate metabolites; Taiwanese; Thyroid hormones