Modulation of Thyroid Hormone Concentrations in Serum of Rats Coadministered with Perchlorate and Iodide-Deficient Diet

  • Tatsuya Kunisue
  • Jeffrey W. Fisher
  • Kurunthachalam KannanEmail author


Perchlorate can perturb thyroid hormone (TH) homeostasis by competitive inhibition of iodide uptake by the thyroid gland. Until recently, the effects of perchlorate on TH homeostasis were examined by measuring serum concentrations of THs by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis they are compromised by lack of adequate specificity. In this study, we determined the concentrations of six THs: l-thyroxine (T4), 3,3′,5-triiodo-l-thyronine (T3), 3,3′,5′-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine, 3,3′-diiodo-l-thyronine, and 3-iodo-l-thyronine in the serum of rats administered perchlorate by isotope (13C6-T4)-dilution liquid chromatography–tandem mass spectrometry. The method recoveries for THs spiked into a serum matrix were between 97.0% and 115%, with a coefficient of variation of 2.1% to 9.4%. Rats were placed on an iodide-deficient or iodide-sufficient diet for 2.5 months, and for the last 2 weeks of that period they were provided drinking water either without or with perchlorate (10 mg/kg body weight/day). No significant differences in serum concentrations of T3 and T4 were observed between rats given iodide-deficient and iodide-sufficient diets for 2 or 2.5 months. After 24 h of perchlorate exposure, significantly lower concentrations of T3 and T4 were found in the serum of rats administered the iodide-deficient diet but not in rats administered the iodide-sufficient diet. However, after 2 weeks of perchlorate exposure, TH levels in rats fed the iodide-sufficient diet were also significantly lower than those in control rats. Our results suggest that perchlorate affects TH homeostasis and that such effects are more pronounced under iodide-deficient nutrition.


Thyroid Hormone Perchlorate Thyroid Gland Flow Injection Analysis System Provide Drinking Water 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was supported by USEPA STAR Cooperative Agreement R832134 and by a biomonitoring grant (Grant No. 1U38EH000464-01) from the Centers for Disease Control and Prevention (CDC), Atlanta, GA, United States. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC.


  1. Beckett GJ, Nicol F, Rae PWH, Beech S, Guo Y, Arthur JR (1993) Effects of combined iodine and selenium deficiency on thyroid hormone metabolism in rats. Am J Clin Nutr 57(Suppl):240S–243SGoogle Scholar
  2. Bianco AC, Kim BW (2006) Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest 116:2571–2579CrossRefGoogle Scholar
  3. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23:38–89CrossRefGoogle Scholar
  4. Blount BC, Pirkle JL, Osterloh JD, Valentin-Blasini L, Caldwell KL (2006) Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States. Environ Health Perspect 114:1865–1871Google Scholar
  5. Blount BC, Valentin-Blasini L, Osterloh JD, Mauldin JP, Pirkle JL (2007) Perchlorate exposure of the US population, 2001–2002. J Expo Sci Environ Epidemiol 17:400–407CrossRefGoogle Scholar
  6. Charnley G (2008) Perchlorate: overview of risks and regulation. Food Chem Toxicol 46:2307–2315CrossRefGoogle Scholar
  7. Delange F (2000) The role of iodine in brain development. Proc Nutr Soc 59:75–79CrossRefGoogle Scholar
  8. Dohán O, Portulano C, Basquin C, Reyna-Neyra A, Amzel LM, Carrasco N (2007) The Na+/I symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate. Proc Natl Acad Sci USA 104:20250–20255CrossRefGoogle Scholar
  9. Fisher JW, Campbell J, Muralidhara S, Bruckner JV, Ferguson D, Mumtaz M et al (2006) Effect of PCB 126 on hepatic metabolism of thyroxine and perturbations in the hypothalamic-pituitary-thyroid axis in the rat. Toxicol Sci 90:87–95CrossRefGoogle Scholar
  10. Gilbert ME, Sui L (2008) Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat. Environ Health Perspect 116:752–760CrossRefGoogle Scholar
  11. Greer MA, Goodman G, Pleus RC, Greer SE (2002) Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans. Environ Health Perspect 110:927–937CrossRefGoogle Scholar
  12. Gu J, Soldin OP, Soldin SJ (2007) Simultaneous quantification of free triiodothyronine and free thyroxine by isotope dilution tandem mass spectrometry. Clin Biochem 40:1386–1391CrossRefGoogle Scholar
  13. Hantson A-L, De Meyer M, Guérit N (2004) Simultaneous determination of endogenous and 13C-labelled thyroid hormones in plasma by stable isotope dilution mass spectrometry. J Chromatogr B 807:185–192CrossRefGoogle Scholar
  14. Hopley CJ, Stokes P, Webb KS, Baynham M (2004) The analysis of thyroxine in human serum by an ‘exact matching’ isotope dilution method with liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 18:1033–1038CrossRefGoogle Scholar
  15. Kannan K, Praamsma ML, Oldi JF, Kunisue T, Sinha RK (2009) Occurrence of perchlorate in drinking water, groundwater, surface water and human saliva from India. Chemosphere 76:22–26CrossRefGoogle Scholar
  16. Kirk AB, Martinelango PK, Tian K, Dutta A, Smith EE, Dasgupta PK (2005) Perchlorate and iodide in dairy and breast milk. Environ Sci Technol 39:2011–2017CrossRefGoogle Scholar
  17. Kunisue T, Fisher JW, Fatuyi B, Kannan K (2010) A method for the analysis of six thyroid hormones in thyroid gland by liquid chromatography-tandem mass spectrometry. J Chromatogr B 878:1725–1730CrossRefGoogle Scholar
  18. Kunisue T, Fisher JW, Kannan K (2011) Determination of six thyroid hormones in the brain and thyroid gland using isotope-dilution liquid chromatography/tandem mass spectrometry. Anal Chem 83:417–424CrossRefGoogle Scholar
  19. Murray CW, Egan SK, Kim H, Beru N, Bolger PM (2008) US Food and Drug Administration’s Total Diet Study: dietary intake of perchlorate and iodine. J Expo Sci Environ Epidemiol 18:571–580CrossRefGoogle Scholar
  20. Oldi JF, Kannan K (2009) Analysis of perchlorate in human saliva by liquid chromatography–tandem mass spectrometry. Environ Sci Technol 43:142–147CrossRefGoogle Scholar
  21. Siglin JC, Mattie DR, Dodd DE, Hildebrandt PK, Baker WH (2000) A 90-day drinking water toxicity study in rats of the environmental contaminant ammonium perchlorate. Toxicol Sci 57:61–74CrossRefGoogle Scholar
  22. Soldin OP, Soldin SJ (2011) Thyroid hormone testing by tandem mass spectrometry. Clin Biochem 44:89–94CrossRefGoogle Scholar
  23. Soldin OP, Braverman LE, Lamm SH (2001) Perchlorate clinical pharmacology and human health: a review. Ther Drug Monit 23:316–331CrossRefGoogle Scholar
  24. Soldin OP, Tractenberg RE, Soldin SJ (2004) Differences between measurements of T4 and T3 in pregnant and nonpregnant women using isotope dilution tandem mass spectrometry and immunoassays: are there clinical implications? Clin Chim Acta 347:61–69CrossRefGoogle Scholar
  25. Soldin SJ, Soukhova N, Janicic N, Jonklaas J, Soldin OP (2005) The measurement of free thyroxine by isotope dilution tandem mass spectrometry. Clin Chim Acta 358:113–118CrossRefGoogle Scholar
  26. Soukhova N, Soldin OP, Soldin SJ (2004) Isotope dilution tandem mass spectrometric method for T4/T3. Clin Chim Acta 343:185–190CrossRefGoogle Scholar
  27. Tai SS-C, Sniegoski LT, Welch MJ (2002) Candidate reference method for total thyroxine in human serum: use of isotope-dilution liquid chromatography-mass spectrometry with electrospray ionization. Clin Chem 48:637–642Google Scholar
  28. Tai SS-C, Bunk DM, White EV, Welch MJ (2004) Development and evaluation of a reference measurement procedure for the determination of total 3,3′,5-triiodothyronine in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry. Anal Chem 76:5092–5096CrossRefGoogle Scholar
  29. Tikkanen MW (2006) Development of a drinking water regulation for perchlorate in California. Anal Chim Acta 567:20–25CrossRefGoogle Scholar
  30. Tonacchera M, Pinchera A, Dimida A, Ferrarini E, Agretti P, Vitti P et al (2004) Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. Thyroid 14:1012–1019CrossRefGoogle Scholar
  31. Urbansky ET (2002) Perchlorate as an environmental contaminant. Environ Sci Pollut Res 9:187–192CrossRefGoogle Scholar
  32. Wang D, Stapleton HM (2010) Analysis of thyroid hormones in serum by liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 397:1831–1839CrossRefGoogle Scholar
  33. Wolff J (1998) Perchlorate and the thyroid gland. Pharmacol Rev 50:89–105Google Scholar
  34. York RG, Funk KA, Girard MF, Mattie D, Strawson JE (2003) Oral (drinking water) developmental toxicity study of ammonium perchlorate in Sprague-Dawley rats. Int J Toxicol 22:453–464Google Scholar
  35. York RG, Lewis E, Brown WR, Girard MF, Mattie DR, Funk KA et al (2005) Refining the effects observed in a developmental neurobehavioral study of ammonium perchlorate administered orally in drinking water to rats. I. Thyroid and reproductive effects. Int J Toxicol 24:403–418CrossRefGoogle Scholar
  36. Yu KO, Narayanan L, Mattie DR, Godfrey RJ, Todd PN, Sterner TR et al (2002) The pharmacokinetics of perchlorate and its effect on the hypothalamus-pituitary-thyroid axis in the male rat. Toxicol Appl Pharmacol 182:148–159CrossRefGoogle Scholar
  37. Zhang T, Wu Q, Sun HW, Rao J, Kannan K (2010) Perchlorate and iodide in whole blood samples from infants, children, and adults in Nanchang, China. Environ Sci Technol 44:6947–6953CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Tatsuya Kunisue
    • 1
  • Jeffrey W. Fisher
    • 3
  • Kurunthachalam Kannan
    • 1
    • 2
    • 4
    Email author
  1. 1.Wadsworth CenterNew York State Department of HealthAlbanyUSA
  2. 2.Department of Environmental Health SciencesSchool of Public Health, State University of New York at AlbanyAlbanyUSA
  3. 3.Department of Environmental Health ScienceCollege of Public Health, University of GeorgiaAthensUSA
  4. 4.State Key Laboratory of Urban Water Resources and EnvironmentIJRC PTS, Harbin Institute of TechnologyHarbinChina

Personalised recommendations