Thyroid dysfunction: how concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer

  • Maryam Rezaei
  • Seyed Yoosef Javadmoosavi
  • Borhan MansouriEmail author
  • Nammam Ali Azadi
  • Omid Mehrpour
  • Samaneh Nakhaee
Research Article


This study was conducted to evaluate the levels of trace metals Fe, Cr, Co, Cd, Cu, Ni, Hg, Zn, and Pb in healthy individuals and patients with thyroid disease (hyperthyroidism, hypothyroidism, and cancerous). The serum levels of 110 participants living in Birjand City, east of Iran, were collected and analyzed using ICP-MS (Agilent 7900). Results showed that the concentration levels of Cr, Co, Zn, Cd, and Pb were significantly higher at case-patients (p < 0.05), but the levels of Fe, Ni, and Hg were similar between healthy and patient subjects (p > 0.05). In patients with high or low thyroid activity, strong mutual correlations between Cr, Ni, and Fe were noticeable (p < 0.05). In hypothyroid patients, no significant correlation between Zn and Hg, Co, and Cd was found, but Zn was moderately and positively correlated with other trace metals. The moderate negative correlations between Cd-Cr (p = − 0.46) and Cd-Fe (p = − 0.43) were also observed. Logistic regression analysis showed that the effect of Cr, Co, Pb, Cu, Zn, and Cd was significant in developing hyperthyroidism and hypothyroidism; whereas, in patients with thyroid cancer, the effect of Cr, Cd, and Pb was found to be significant. In conclusion, our findings suggest that toxic metals such as Pb, Cd, and Cr can increase the risk of developing hypothyroidism and thyroid cancer, but more research is needed to evaluate the potential toxicity mechanisms of Pb, Cd, and Cr.


Thyroid diseases Lead Chromium Cadmium Copper Zinc Cobalt 



The authors would like to appreciate M Amirabadizadeh and H Ataei, who provided logistic for chemicals and samples. Moreover, the authors thank Dr. J Afrifa for their nice comments in improving the manuscript.

Funding information

This study has been carried out with financial support from Birjand University of Medical Sciences (Grant number: 1397/4809).


  1. Afrifa J, Ogbordjor WD, Duku-Takyi R (2018) Variation in thyroid hormone levels is associated with elevated blood mercury levels among artisanal small-scale miners in Ghana. Plos One 13:e0203335. CrossRefGoogle Scholar
  2. Aziz MA, Habil NY, AKS D (2016) Effectiveness of zinc supplementation in regulating serum hormonal and inflammatory status in hypothyroidism patients. Med J Babylon 13:347–353Google Scholar
  3. Baltaci AK, Dundar TK, Aksoy F, Mogulkoc R (2017) Changes in the serum levels of trace elements before and after the operation in thyroid cancer patients. Biol Trace Elem Res 175:57–64. CrossRefGoogle Scholar
  4. Barysheva ES (2018) Experimental simulation of the effects of essential and toxic trace elements on thyroid function. Bull Exp Biol Med 164:439–441. CrossRefGoogle Scholar
  5. Brandão-Neto J, Silva CAB, Shuhama T, SilvaJA, Oba L (2001) Renal handling of zinc in insulin-dependent diabetes mellitus patients. BioMetals 14:75–80CrossRefGoogle Scholar
  6. Bocca B, Madeddu R, Asara Y, Tolu P, Marchal JA, Forte G (2011) Assessment of reference ranges for blood Cu, Mn, Se and Zn in a selected Italian population. J Trace Elem Med Biol 25:19–26. CrossRefGoogle Scholar
  7. Buha A, Matovic V, Antonijevic B, Bulat Z, Curcic M, Renieri EA, Tsatsakis AM, Schweitzer A, Wallace D (2018) Overview of cadmium thyroid disrupting effects and mechanisms. Int J Mol Sci 19:1501CrossRefGoogle Scholar
  8. Bulat Z, Duki´c-Cosic D, Antonijevic B, Buha A, Bulat P, Pavlovic Z, Matovic V (2017) Can zinc supplementation ameliorate cadmium-induced alterations in the bioelement content in rabbits? Arh Hig Rada Toksikol 68:38–45CrossRefGoogle Scholar
  9. Chen A, Kim SS, Chung E, Dietrich KN (2012) Thyroid hormones in relation to lead, mercury, and cadmium exposure in the National Health and Nutrition Examination Survey, 2007–2008. Environ Health Perspect 121:181–186. CrossRefGoogle Scholar
  10. Chung HK, Nam JS, Ahn CW, Lee YS, Kim KR (2016) Some elements in thyroid tissue are associated with more advanced stage of thyroid cancer in Korean women. Biol Trace Elem Res 171:54–62. CrossRefGoogle Scholar
  11. Cooper DS (2003) Hyperthyroidism. Lancet:459–468Google Scholar
  12. Dhawan D, Singh B, Chand B, Singh N, Mangal PC (1995) X-ray fluorescence in the assessment of inter-elemental interaction in rat liver following lead treatment. Bio Metals 8:105–110Google Scholar
  13. Dundar B, Öktem F, Arslan MK, Delibas N, Baykal B, Arslan Ç, Gultepe M, Ilhan IE (2006) The effect of long-term low-dose lead exposure on thyroid function in adolescents. Environ Res 101:140–145. CrossRefGoogle Scholar
  14. Ebrahim AM, Eltayeb M, Benker B, Grill P, Attahir M, Osman A, Elsadig M, Michalke B (2011) Study on some trace element contents in serum and nail samples obtained from Sudanese subjects. Biol Trace Elem Res 144:225–233. CrossRefGoogle Scholar
  15. Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K (2008) Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism. Biol Trace Elem Res 123:1–7. CrossRefGoogle Scholar
  16. Fallahzadeh RA, Khosravi R, Dehdashti B, Ghahramani E, Omidi F, Adli A, Miri M (2018) Spatial distribution variation and probabilistic risk assessment of exposure to chromium in ground water supplies; a case study in the east of Iran. FCT. 115:260–266. CrossRefGoogle Scholar
  17. Ferrari SM, Fallahi P, AntonelliA., Benvenga S (2017) Environmental issues in thyroid diseases. Front Endocrinol 8:50.
  18. Gil F, Hernández AF, Márquez C, Femia P, Olmedo P, López-Guarnido O, Pla A (2011) Biomonitorization of cadmium, chromium, manganese, nickel and lead in whole blood, urine, axillary hair and saliva in an occupationally exposed population. Sci Total Environ 409:1172–1180. CrossRefGoogle Scholar
  19. Giray B, Arnaud J, Sayek İ, Favier A, Hıncal F (2010) Trace elements status in multinodular goiter. J Trace Elem Med Biol 24:106–110. CrossRefGoogle Scholar
  20. Hammouda F, Messaoudi I, El Hani J, Baati T, Saïd K, Kerkeni A (2008) Reversal of cadmium-induced thyroid dysfunction by selenium, zinc, or their combination in rat. Biol Trace Elem Res 126:194–203CrossRefGoogle Scholar
  21. Hanif S, Ilyas A, Shah MH (2018) Statistical evaluation of trace metals, TSH and T4 in blood serum of thyroid disease patients in comparison with controls. Biol Trace Elem Res 183:58–70. CrossRefGoogle Scholar
  22. Hassanin KMA, Abd El-Kawi SH, Hashem KS (2013) The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid. Int J Nanomed 8:1713–1720. CrossRefGoogle Scholar
  23. Hybsier S, Höfig C, Mittag J, Brabant G, Schomburg L (2015) Control of serum copper (Cu) and selenium (Se) status by thyroid hormones. Exp Clin Endocrinol Diabetes 122:12–18. CrossRefGoogle Scholar
  24. Kasperczyk A, Prokopowicz A, Dobrakowski M, Pawlas N, Kasperczyk S (2012) The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins. Biol Trace Elem Res 150:49–55CrossRefGoogle Scholar
  25. Kazi TG, Kandhro GA, Afridi HI, Kazi N, Baig JA, Arain MB, Shah AQ, Syed N, Kumar S, Kolachi NF, Khan S (2010) Interaction of copper with iron, iodine, and thyroid hormone status in goitrous patients. Biol Trace Elem Res 134:265–279. CrossRefGoogle Scholar
  26. Kolpak E, Kabrits S, Bubalo V (2015) The follicle function and thyroid gland cancer. Biol Med 7:1–6Google Scholar
  27. Krężel A, Maret W (2016) The biological inorganic chemistry of zinc ions. Arch Biochem Biophys 611:3–19. CrossRefGoogle Scholar
  28. Kuriyama C, Mori K, Nakagawa Y, Hoshikawa S, Ozaki H, Ito S, Inoue M, Ohta M, Yoshida K (2011) Erythrocyte zinc concentration as an indicator to distinguish painless thyroiditis-associated transient hypothyroidism from permanent hypothyroidism. Endocr J 58:59–63. CrossRefGoogle Scholar
  29. Laurberg P, Andersen S, Karmisholt J (2005) Cold adaptation and thyroid hormone metabolism. Horm Metab Res 37:545–549CrossRefGoogle Scholar
  30. Li J, Liu Y, Kong D, Ren S, Li N (2016) T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc. Environ Sci Pollut Res. 23:9843–9851. CrossRefGoogle Scholar
  31. Liao LM, Friesen M C, Xiang YB, Cai H, Koh DH, Ji BT, Yang G, Li HL, Locke S J, Rothman N, Zheng W, Gao YT, Shu XO, Purdue M P (2016) Occupational lead exposure and associations with selected cancers: the Shanghai Men’s and Women’s Health Study cohorts. Environ Health Perspect 124:97–103. CrossRefGoogle Scholar
  32. Liu Y, Liu S, Mao J, Piao S, Qin J, Peng S, Xie X, Guan H, Li Y, Shan Z, Teng W (2018) Serum trace elements profile in graves’ disease patients with or without orbitopathy in Northeast China. Biomed Res Int 2018:3029379. CrossRefGoogle Scholar
  33. Malandrino P, Russo M, Ronchi A, Minoia C, Cataldo D, Regalbuto C, Giordano C, Attard M, Squatrito S, Trimarchi F, Vigneri R (2016) Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination. Endocrine 53:471–479. CrossRefGoogle Scholar
  34. Manisha A, Roshan K M, Sudeep K, Imran M, Sumesh P S (2018) Study of trace elements in patients of hypothyroidism with special reference to zinc and copper. Biomed J Sci Tech Res 6:5190–5194Google Scholar
  35. Maret W (2017) Zinc in cellular regulation: The nature and significance of “zinc signals”. Int J Mol Sci 18:2285. CrossRefGoogle Scholar
  36. Meeker JD, Rossano MG, Protas B, Diamond MP, Puscheck E, Daly D, Paneth N, Wirth JJ (2009) Multiple metals predict prolactin and thyrotropin (TSH) levels in men. Environ Res 109:869–873. CrossRefGoogle Scholar
  37. Memon NS, Kazi TG, Afridi HI, Baig JA, Arain SS, Sahito OM, Baloch S, Waris M (2016) Evaluation of calcium and lead interaction, in addition to their impact on thyroid functions in hyper and hypothyroid patients. Environ Sci Pollut Res 23:878–886. CrossRefGoogle Scholar
  38. Mendy A, Gasana J, Vieira ER (2013) Low blood lead concentrations and thyroid function of American adults. Int J Environ Health Res 23:461–473. CrossRefGoogle Scholar
  39. Petering HG, Choudhury H, Stemmer KL (1979) Some effects of oral ingestion of cadmium on zinc, copper, and iron metabolism. Environ Health Perspect 28:97–106. CrossRefGoogle Scholar
  40. Porcheron G, Garenaux A, Proulx J, Sabri M, Dozois C (2013) Iron, copper, zinc, and manganese transport and regulation in pathogenic enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence. Front Cell Infect Microbiol 3:90. CrossRefGoogle Scholar
  41. Rana SVS (2014) Perspectives in endocrine toxicity of heavy metals—a review. Biol Trace Elem Res 160:1–14. CrossRefGoogle Scholar
  42. Severo JS, Morais JBS, de Freitas TEC, Andrade ALP, Feitosa MM, Fontenelle LC, do Nascimento Marreiro D (2019) The role of zinc in thyroid hormones metabolism. Int J Vitamin Nut Res 89: 80-88.CrossRefGoogle Scholar
  43. Sherif MM, Mohammed YS, Zedan HAEM, Kheder MAE, Mohammed AHAES (2017) Toxic effect of some heavy metals (cadmium and lead) on thyroid function. Egypt J Hosp Med 69:2512–2516. CrossRefGoogle Scholar
  44. Sirchia R, Longo A, Luparello C (2008) Cadmium regulation of apoptotic and stress response genes in tumoral and immortalized epithelial cells of the human breast. Biochimie 90:1578–1590CrossRefGoogle Scholar
  45. Stojsavljević A, Trifković J, Rasić-Milutinović Z, Jovanović D, Bogdanović G, Mutić J, Manojlović D (2018) Determination of toxic and essential trace elements in serum of healthy and hypothyroid respondents by ICP-MS: a chemometric approach for discrimination of hypothyroidism. J Trace Elem Med Biol 48:134–140. CrossRefGoogle Scholar
  46. Stojsavljević A, Rovčanin B, Krstić Đ, Borković-Mitić S, Paunović I, Kodranov I, Manojlović D (2019) Evaluation of trace metals in thyroid tissues: comparative analysis with benign and malignant thyroid diseases. Ecotoxicol Environ Safe 183:109479CrossRefGoogle Scholar
  47. Unnikrishnan AG, Menon UV (2011) Thyroid disorders in India: an epidemiological perspective. Indian. J Endocrinol Metab 15:S78–S81.
  48. Vigneri R, Malandrino P, Gianì F, Russo M, Vigneri P (2017) Heavy metals in the volcanic environment and thyroid cancer. Mol Cell Endocrinol 457:73–80. CrossRefGoogle Scholar
  49. Wagner MS, Wajner SM, Maia AL (2008) The role of thyroid hormone in testicular development and function. J Endocrinol 199:351–365. CrossRefGoogle Scholar
  50. Yu J (2014) Endocrine disorders and the neurologic manifestations. Ann Pediatr Endocrinol Metab 19:184–190.
  51. Zaichick VY, Tsyb AF, Vtyurin BM (1995) Trace elements and thyroid cancer. Analyst. 120:817–821CrossRefGoogle Scholar
  52. Zhang C, Wu HB, Cheng MX, Wang L, Gao CB, Huang F (2019) Association of exposure to multiple metals with papillary thyroid cancer risk in China. Environ Sci Pollut Res:1–13Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical Toxicology and Drug Abuse Research Center (MTDRC)Birjand University of Medical SciencesBirjandIran
  2. 2.Student Research CommitteeBirjand University of Medical SciencesBirjandIran
  3. 3.Substance Abuse Prevention Research Center, Health InstituteKermanshah University of Medical SciencesKermanshahIran
  4. 4.Biostatistics Department, Faculty of Public HealthIran University of Medical SciencesTehranIran
  5. 5.Rocky Mountain Poison and Drug CenterDenverUSA

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