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Cadmium Exposure was Associated with Sex-Specific Thyroid Dysfunction: Consistent Evidence from Two Independent Cross-Sectional Studies Based on Urinary and Blood Cadmium Measurements

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Abstract

Population-based studies on the association between cadmium (Cd) exposure and thyroid function are limited and have shown conflicting results. Two independent cross-sectional studies using different Cd biomarkers were carried out in six rural areas with different soil Cd levels in China. Thyroid dysfunction was defined based on levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4). Multivariable linear regression, multiple logistic regression, and restrictive cubic splines models were used to estimate the association between Cd and thyroid dysfunction. For both of the two independent studies, higher Cd levels were observed to be associated with lower TSH levels and higher risk of thyroid dysfunction. The negative relationship between urinary Cd and TSH was found in both total participants (β =  − 0.072, p = 0.008) and males (β =  − 0.119, p = 0.020) but not in females; however, the negative relationship between blood Cd and TSH was only found in females (β =  − 0.104, p = 0.024). Higher urinary Cd was associated with higher risk of thyroid dysfunction (OR = 1.77, p = 0.031), while higher blood Cd was associated with higher risk of thyroid dysfunction (OR = 1.95, p = 0.011). Results from the two independent cross-sectional studies consistently suggested that higher Cd levels were associated with sex-specific thyroid dysfunction.

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References

  1. Genchi G, Sinicropi MS, Lauria G et al (2020) The effects of cadmium toxicity. Int J Environ Res Public Health 17:3782. https://doi.org/10.3390/ijerph17113782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ma Y, Ran D, Shi X et al (2021) Cadmium toxicity: a role in bone cell function and teeth development. Sci Total Environ 769:144646. https://doi.org/10.1016/j.scitotenv.2020.144646

  3. Ministry of Environmental Protection of the People's Republic of China (MEP) (2014). National Soil Pollution Investigation Bulletin. Land and Resources Communication, 2014(8):26-29 (in Chinese)

  4. Clemens S, Ma JF (2016) Toxic heavy metal and metalloid accumulation in crop plants and foods. Annu Rev Plant Biol 67:489–512. https://doi.org/10.1146/annurev-arplant-043015-112301

    Article  CAS  PubMed  Google Scholar 

  5. Xu F-F, Song J, Li Y-Q et al (2021) Bioaccessibility and bioavailability adjusted dietary exposure of cadmium for local residents from a high-level environmental cadmium region. J Hazard Mater 420:126550. https://doi.org/10.1016/j.jhazmat.2021.126550

    Article  CAS  PubMed  Google Scholar 

  6. Flannery BM, Schaefer HR, Middleton KB (2022) A scoping review of infant and children health effects associated with cadmium exposure. Regul Toxicol Pharmacol RTP 131:105155. https://doi.org/10.1016/j.yrtph.2022.105155

    Article  CAS  PubMed  Google Scholar 

  7. Garner R, Levallois P (2016) Cadmium levels and sources of exposure among canadian adults. Health Rep 27:10–18

    PubMed  Google Scholar 

  8. Pérez R, Doménech E, Conchado A et al (2018) Influence of diet in urinary levels of metals in a biomonitoring study of a child population of the valencian region (spain). Sci Total Environ 618:1647–1657. https://doi.org/10.1016/j.scitotenv.2017.10.011

    Article  CAS  PubMed  Google Scholar 

  9. Wu X, Liang Y, Jin T et al (2008) Renal effects evolution in a Chinese population after reduction of cadmium exposure in rice. Environ Res 108:233–238. https://doi.org/10.1016/j.envres.2008.02.011

    Article  CAS  PubMed  Google Scholar 

  10. Lafuente A (2013) The hypothalamic-pituitary-gonadal axis is target of cadmium toxicity. an update of recent studies and potential therapeutic approaches. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 59:395–404. https://doi.org/10.1016/j.fct.2013.06.024

    Article  CAS  Google Scholar 

  11. Jonklaas J, Razvi S (2019) Reference intervals in the diagnosis of thyroid dysfunction: treating patients not numbers. Lancet Diabetes Endocrinol 7:473–483. https://doi.org/10.1016/S2213-8587(18)30371-1

    Article  PubMed  Google Scholar 

  12. Kar Anand (2022) Cadmium toxicity could be a cause for thyroid problem. J Environ Biol 43(5):i–ii. https://doi.org/10.22438/jeb/43/5/editorial

    Article  Google Scholar 

  13. Jadhao AG, Paul PL, Rao PD (1994) Effect of cadmium chloride on the pituitary, thyroid and gonads in the catfish, Clarias batrachus (Linn.). Funct Dev Morphol 4:39–44

    CAS  PubMed  Google Scholar 

  14. Sun N, Wang H, Ju Z, Zhao H (2018) Effects of chronic cadmium exposure on metamorphosis, skeletal development, and thyroid endocrine disruption in Chinese toad Bufo gargarizans tadpoles. Environ Toxicol Chem 37:213–223. https://doi.org/10.1002/etc.3947

    Article  CAS  PubMed  Google Scholar 

  15. Sola E, Moyano P, Flores A et al (2022) Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption. Environ Toxicol Pharmacol 90:103791. https://doi.org/10.1016/j.etap.2021.103791

    Article  CAS  PubMed  Google Scholar 

  16. Yoshizuka M, Mori N, Hamasaki K et al (1991) Cadmium toxicity in the thyroid gland of pregnant rats. Exp Mol Pathol 55:97–104. https://doi.org/10.1016/0014-4800(91)90021-o

    Article  CAS  PubMed  Google Scholar 

  17. Liu Z-M, Chen GG, Shum CKY et al (2007) Induction of functional MT1 and MT2 isoforms by calcium in anaplastic thyroid carcinoma cells. FEBS Lett 581:2465–2472. https://doi.org/10.1016/j.febslet.2007.04.049

    Article  CAS  PubMed  Google Scholar 

  18. Chen Y, Zhou C, Bian Y et al (2023) Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling. Ecotoxicol Environ Saf 249:114376. https://doi.org/10.1016/j.ecoenv.2022.114376

    Article  CAS  PubMed  Google Scholar 

  19. Buha A, Matovic V, Antonijevic B et al (2018) Overview of cadmium thyroid disrupting effects and mechanisms. Int J Mol Sci 19:1501. https://doi.org/10.3390/ijms19051501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Peana M, Pelucelli A, Chasapis CT et al (2022) Biological effects of human exposure to environmental cadmium. Biomolecules 13:36. https://doi.org/10.3390/biom13010036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rasic-Milutinovic Z, Jovanovic D, Bogdanovic G et al (2016) Potential influence of selenium, copper, zinc and cadmium on L-thyroxine substitution in patients with Hashimoto thyroiditis and hypothyroidism. Exp Clin Endocrinol Diabetes 125:79–85. https://doi.org/10.1055/s-0042-116070

    Article  CAS  PubMed  Google Scholar 

  22. Rezaei M, Javadmoosavi SY, Mansouri B et al (2019) Thyroid dysfunction: how concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer. Environ Sci Pollut Res 26:35787–35796. https://doi.org/10.1007/s11356-019-06632-7

    Article  CAS  Google Scholar 

  23. Uetani M, Kobayashi E, Suwazono Y et al (2006) Tissue cadmium (Cd) concentrations of people living in a Cd polluted area, Japan. Biometals Int J Role Met Ions Biol Biochem Med 19:521–525. https://doi.org/10.1007/s10534-005-5619-0

    Article  CAS  Google Scholar 

  24. Chen Y, Xiang Q, Wang N et al (2022) Are ethnic differences, urinary iodine status, lead and cadmium exposure associated with thyroid autoimmunity and hypothyroid status? Cross-Sectional Study BMJ Open 12:e056909. https://doi.org/10.1136/bmjopen-2021-056909

    Article  PubMed  Google Scholar 

  25. Nie X, Chen Y, Chen Y et al (2017) Lead and cadmium exposure, higher thyroid antibodies and thyroid dysfunction in Chinese women. Environ Pollut 230:320–328. https://doi.org/10.1016/j.envpol.2017.06.052

    Article  CAS  PubMed  Google Scholar 

  26. Chung SM, Moon JS, Yoon JS et al (2019) Sex-specific effects of blood cadmium on thyroid hormones and thyroid function status: Korean nationwide cross-sectional study. J Trace Elem Med Biol 53:55–61. https://doi.org/10.1016/j.jtemb.2019.02.003

    Article  CAS  PubMed  Google Scholar 

  27. White AJ, O’Brien KM, Jackson BP, Karagas MR (2018) Urine and toenail cadmium levels in pregnant women: a reliability study. Environ Int 118:86–91. https://doi.org/10.1016/j.envint.2018.05.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ke S, Cheng X-Y, Li H et al (2015) Body burden of cadmium and its related factors: a large-scale survey in China. Sci Total Environ 511:649–654. https://doi.org/10.1016/j.scitotenv.2015.01.014

    Article  CAS  PubMed  Google Scholar 

  29. Sun H, Wang D, Zhou Z et al (2016) Association of cadmium in urine and blood with age in a general population with low environmental exposure. Chemosphere 156:392–397. https://doi.org/10.1016/j.chemosphere.2016.05.013

    Article  CAS  PubMed  Google Scholar 

  30. Gao S, Jin Y, Hall KS et al (2007) Selenium level and cognitive function in rural elderly Chinese. Am J Epidemiol 165:955–965. https://doi.org/10.1093/aje/kwk073

    Article  PubMed  Google Scholar 

  31. Liu H, Su L, Chen X et al (2021) Higher blood cadmium level is associated with greater cognitive decline in rural Chinese adults aged 65 or older. Sci Total Environ 756:144072. https://doi.org/10.1016/j.scitotenv.2020.144072

    Article  CAS  PubMed  Google Scholar 

  32. Wang Y, Zhang P, Chen X et al (2019) Multiple metal concentrations and gestational diabetes mellitus in Taiyuan. China Chemosphere 237:124412. https://doi.org/10.1016/j.chemosphere.2019.124412

    Article  CAS  PubMed  Google Scholar 

  33. Chen H, Yang X, Wang P et al (2018) Dietary cadmium intake from rice and vegetables and potential health risk: a case study in Xiangtan, southern China. Sci Total Environ 639:271–277. https://doi.org/10.1016/j.scitotenv.2018.05.050

    Article  CAS  PubMed  Google Scholar 

  34. Zou Y, Wang D, Cheng X et al (2021) Reference intervals for thyroid-associated hormones and the prevalence of thyroid diseases in the Chinese population. Ann Lab Med 41:77–85. https://doi.org/10.3343/alm.2021.41.1.77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liu Y, Shan Z, Endocrine Metabolic Diseases Group of the Chinese Geriatrics Society, Thyroid Group of the Chinese Society of Endocrinology, Chinese Medical Association (2021) Expert consensus on diagnosis and treatment for elderly with thyroid diseases in China (2021). Aging Med Milton NSW 4:70–92. https://doi.org/10.1002/agm2.12165

    Article  Google Scholar 

  36. Friberg L, International Programme on Chemical Safety, Weltgesundheitsorganisation (1992) Cadmium. World Health Organization, Geneva

  37. Satarug S, Vesey DA, Gobe GC (2017) Current health risk assessment practice for dietary cadmium: data from different countries. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 106:430–445. https://doi.org/10.1016/j.fct.2017.06.013

    Article  CAS  Google Scholar 

  38. Wasserstein RL, Lazar NA (2016) The ASA Statement on p -values: context, process, and purpose. Am Stat 70:129–133. https://doi.org/10.1080/00031305.2016.1154108

    Article  Google Scholar 

  39. Yorita Christensen KL (2013) Metals in blood and urine, and thyroid function among adults in the United States 2007–2008. Int J Hyg Environ Health 216:624–632. https://doi.org/10.1016/j.ijheh.2012.08.005

    Article  CAS  PubMed  Google Scholar 

  40. Chen A, Kim SS, Chung E, Dietrich KN (2013) 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. https://doi.org/10.1289/ehp.1205239

    Article  CAS  PubMed  Google Scholar 

  41. Iijima K, Otake T, Yoshinaga J et al (2007) Cadmium, lead, and selenium in cord blood and thyroid hormone status of newborns. Biol Trace Elem Res 119:10–18. https://doi.org/10.1007/s12011-007-0057-1

    Article  CAS  PubMed  Google Scholar 

  42. Rosati MV, Montuori L, Caciari T et al (2016) Correlation between urinary cadmium and thyroid hormones in outdoor workers exposed to urban stressors. Toxicol Ind Health 32:1978–1986. https://doi.org/10.1177/0748233715602833

    Article  CAS  PubMed  Google Scholar 

  43. Ramadan MA, Saif Eldin AS (2022) Effect of occupational cadmium exposure on the thyroid gland and associated inflammatory markers among workers of the electroplating industry. Toxicol Ind Health 38:210–220. https://doi.org/10.1177/07482337221085046

    Article  CAS  PubMed  Google Scholar 

  44. Gustin K, Barman M, Skröder H et al (2021) Thyroid hormones in relation to toxic metal exposure in pregnancy, and potential interactions with iodine and selenium. Environ Int 157:106869. https://doi.org/10.1016/j.envint.2021.106869

    Article  CAS  PubMed  Google Scholar 

  45. Luo J, Hendryx M (2014) Relationship between blood cadmium, lead, and serum thyroid measures in US adults – the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Int J Environ Health Res 24:125–136. https://doi.org/10.1080/09603123.2013.800962

    Article  CAS  PubMed  Google Scholar 

  46. Jacquet A, Arnaud J, Hininger-Favier I et al (2018) Impact of chronic and low cadmium exposure of rats: sex specific disruption of glucose metabolism. Chemosphere 207:764–773. https://doi.org/10.1016/j.chemosphere.2018.05.099

    Article  CAS  PubMed  Google Scholar 

  47. Zhang L, Wang H, Abel GM et al (2019) The effects of gene-environment interactions between cadmium exposure and apolipoprotein E4 on memory in a mouse model of Alzheimer’s disease. Toxicol Sci 173:189–201. https://doi.org/10.1093/toxsci/kfz218

    Article  PubMed Central  Google Scholar 

  48. Ya J, Xu Y, Wang G, Zhao H (2021) Cadmium induced skeletal underdevelopment, liver cell apoptosis and hepatic energy metabolism disorder in Bufo gargarizans larvae by disrupting thyroid hormone signaling. Ecotoxicol Environ Saf 211:111957. https://doi.org/10.1016/j.ecoenv.2021.111957

    Article  CAS  PubMed  Google Scholar 

  49. Lafuente A, Cano P, Esquifino A (2003) Are cadmium effects on plasma gonadotropins, prolactin, ACTH, GH and TSH levels, dose-dependent? Biometals Int J Role Met Ions Biol Biochem Med 16:243–250. https://doi.org/10.1023/a:1020658128413

    Article  CAS  Google Scholar 

  50. Caride A, Fernández-Pérez B, Cabaleiro T et al (2010) Cadmium chronotoxicity at pituitary level: effects on plasma ACTH, GH, and TSH daily pattern. J Physiol Biochem 66:213–220. https://doi.org/10.1007/s13105-010-0027-5

    Article  CAS  PubMed  Google Scholar 

  51. Hammouda F, Messaoudi I, El Hani J et al (2008) Reversal of cadmium-induced thyroid dysfunction by selenium, zinc, or their combination in rat. Biol Trace Elem Res 126:194–203. https://doi.org/10.1007/s12011-008-8194-8

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors express thanks to all the involved staff from the Chinese local cooperative hospitals and Centers for Disease Control and Prevention for their effort.

Funding

This research was supported by grants from the National Key Research and Development Program of China (2018YFC1801102) and (2018YFC1801105) and the National Institutes of Health of USA (R01AG019181). Author Liqin Su has received during the preparation of this manuscript.

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Authors and Affiliations

  1. China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing, 100050, China

    Ranqi Shao, Liqin Su, Xu Han, Ting Wang & Jiao Luo

  2. Jiangsu Key Laboratory for Organic Waste Utilization, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, 210095, China

    Peng Wang, Jun Dai & Yi Gu

  3. Yuhu Center for Disease Control and Prevention, Xiangtan, 411100, China

    Lifang Deng

  4. Changde Center for Disease Control and Prevention, Changde, 415000, China

    Jingping Liu

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  1. Ranqi Shao
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  4. Xu Han
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Contributions

All authors contributed to the study conception and design. The first draft of the manuscript was written by Ranqi Shao and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ranqi Shao: investigation, data curation, data analysis, software, formal analysis, writing original draft, visualization.

Liqin Su: conceptualization, funding acquisition, resources, project administration, supervision, writing—review and editing.

Peng Wang: funding acquisition, resources, project administration, supervision.

Xu Han: validation, measurement, investigation, supervision.

Ting Wang: investigation, measurement, data curation.

Jun Dai: investigation, measurement, data curation.

Yi Gu: investigation, measurement, data curation.

Jiao Luo: data curation, visualization.

Lifang Deng: investigation, supervision.

Jingping Liu: investigation, supervision.

Corresponding author

Correspondence to Liqin Su.

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Shao, R., Su, L., Wang, P. et al. Cadmium Exposure was Associated with Sex-Specific Thyroid Dysfunction: Consistent Evidence from Two Independent Cross-Sectional Studies Based on Urinary and Blood Cadmium Measurements. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04176-7

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