{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:47:06Z","timestamp":1781606826090,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["Grant No 6066532"],"award-info":[{"award-number":["Grant No 6066532"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 \u00b5g\/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 \u00b5g\/L) and Ni - fT3 pair (0.397-66.8 \u00b5g\/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1145153","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:50:03Z","timestamp":1695289803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Nickel as a potential disruptor of thyroid function: benchmark modelling of human data"],"prefix":"10.3389","volume":"14","author":[{"given":"Djurdjica","family":"Maric","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Baralic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Javorac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mandic-Rajcevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milos","family":"Zarkovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Antonijevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Djukic-Cosic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zorica","family":"Bulat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra Buha","family":"Djordjevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3390\/ijerph17030679","article-title":"Nickel: human health and environmental toxicology","volume":"17","author":"Genchi","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"B2","article-title":"A Review of Its Sources and Environmental Toxicology","volume":"15","author":"Cempel","year":"2006","journal-title":"Pol. J. Environ. Stud."},{"key":"B3","doi-asserted-by":"publisher","first-page":"9:e12230","DOI":"10.7717\/peerj.12230","article-title":"Nickel stress-tolerance in plant-bacterial associations","author":"Pishchik","year":"2021","journal-title":"PeerJ"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.matpr.2021.06.278","article-title":"Effect of heavy metals: an overview","volume":"51","author":"Kiran","year":"2022","journal-title":"Mater Today Proc"},{"key":"B5","volume-title":"Toxicological profile for nickel","year":"2005"},{"key":"B6","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3390\/toxics10030148","article-title":"Nickel\u2019s role in pancreatic ductal adenocarcinoma: potential involvement of microRNAs","volume":"10","author":"Mortoglou","year":"2022","journal-title":"Toxics"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu200","article-title":"Nickel exposure is associated with the prevalence of type 2 diabetes in Chinese adults","volume":"44","author":"Liu","year":"2015","journal-title":"Int J Epidemiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"112034","DOI":"10.1016\/j.ecoenv.2021.112034","article-title":"Research progress on the effects of nickel on hormone secretion in the endocrine axis and on target organs","volume":"213","author":"Yang","year":"2021","journal-title":"Ecotoxicol Environ Saf."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1080\/10934529.2012.672114","article-title":"Reproductive toxicology of nickel \u2013 review","volume":"47","author":"Forgacs","year":"2012","journal-title":"J Environ Sci Health Part A."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201601116","article-title":"Chemistry and biology in the biosynthesis and action of thyroid hormones","volume":"55","author":"Mondal","year":"2016","journal-title":"Angew Chem Int Ed"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2018.18","article-title":"Global epidemiology of hyperthyroidism and hypothyroidism","volume":"14","author":"Taylor","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6754","DOI":"10.1038\/s41598-017-07004-2","article-title":"Metabolic syndrome is associated with an increased incidence of subclinical hypothyroidism \u2013 a cohort study","volume":"7","author":"Chang","year":"2017","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-019-01825-0","article-title":"The association between thyroid injury and apoptosis, and alterations of bax, bcl-2, and caspase-3 mRNA\/Protein expression induced by nickel sulfate in wistar rats","volume":"195","author":"Liu","year":"2020","journal-title":"Biol Trace Elem Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2018.10.038","article-title":"Associations of blood metal exposure with thyroid hormones in Chinese pregnant women: a cross-sectional study","volume":"121","author":"Guo","year":"2018","journal-title":"Environ Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0246748","article-title":"Mercury in the human thyroid gland: potential implications for thyroid cancer, autoimmune thyroiditis, and hypothyroidism","volume":"16","author":"Pamphlett","year":"2021","journal-title":"PloS One"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-015-0581-2","article-title":"Systemic nickel allergic syndrome as an immune-mediated disease with an increased risk for thyroid autoimmunity","volume":"50","author":"Andrioli","year":"2015","journal-title":"Endocrine"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2017.4658","article-title":"Update: use of the benchmark dose approach in risk assessment","volume":"15","author":"Hardy","year":"2017","journal-title":"EFSA J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.5937\/arhfarm71-34280","article-title":"Cadmium levels in human breast tissue and estradiol serum levels: is there a connection","volume":"71","author":"Buha-\u0110or\u0111evi\u0107","year":"2021","journal-title":"Arh Za Farm"},{"key":"B19","doi-asserted-by":"publisher","first-page":"107313","DOI":"10.1016\/j.envint.2022.107313","article-title":"Benchmark dose approach in investigating the relationship between blood metal levels and reproductive hormones: data set from human study","volume":"165","author":"Barali\u0107","year":"2022","journal-title":"Environ Int"},{"key":"B20","doi-asserted-by":"publisher","first-page":"120428","DOI":"10.1016\/j.envpol.2022.120428","article-title":"Exploring the endocrine disrupting potential of lead through benchmark modelling \u2013 study in humans","volume":"316","author":"Javorac","year":"2023","journal-title":"Environ pollut"},{"key":"B21","doi-asserted-by":"publisher","first-page":"114283","DOI":"10.1016\/j.envres.2022.114283","article-title":"Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: possible role of arsenic as a metabolic disruptor","volume":"215","author":"\u0110uki\u0107-\u0106osi\u0107","year":"2022","journal-title":"Environ Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/26895293.2022.2128439","article-title":"Puzzling relationship between levels of toxic metals in blood and serum levels of reproductive hormones: benchmark dose approach in cross-sectional study","volume":"15","author":"Mari\u0107","year":"2022","journal-title":"Life"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.5937\/arhfarm72-40122","article-title":"Exposure to mercury and thyroid function: is there a connection","volume":"72","author":"Mari\u0107","year":"2022","journal-title":"Arh Za Farm"},{"key":"B24","article-title":"SPINA thyr","author":"Dietrich","year":"2021","journal-title":"Zenodo"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00057\/abstract","article-title":"Calculated parameters of thyroid homeostasis: emerging tools for differential diagnosis and clinical research","volume":"7","author":"Dietrich","year":"2016","journal-title":"Front Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1744595","article-title":"Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with parkinson\u2019s disease","volume":"131","author":"Tan","year":"2021","journal-title":"Int J Neurosci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/351864","article-title":"TSH and thyrotropic agonists: key actors in thyroid homeostasis","volume":"2012","author":"Dietrich","year":"2012","journal-title":"J Thyroid Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1472-6823-8-13","article-title":"The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome","volume":"8","author":"Dietrich","year":"2008","journal-title":"BMC Endocr Disord"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2021.09.012","article-title":"Dose-dependent toxicological effects in rats following a 90-day dietary exposure to PCB-156 include retinoid disruption","volume":"107","author":"Vieira Silva","year":"2022","journal-title":"Reprod Toxicol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/risa.13324","article-title":"A review of recent advances in benchmark dose methodology","volume":"39","author":"Jensen","year":"2019","journal-title":"Risk Anal"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2012.06.015","article-title":"Low-dose effects and nonmonotonic dose\u2013responses of endocrine disrupting chemicals: has the case been made","volume":"64","author":"Rhomberg","year":"2012","journal-title":"Regul Toxicol Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30129-7","article-title":"Endocrine-disrupting chemicals: implications for human health","volume":"8","author":"Kahn","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1210\/er.2011-1050","article-title":"Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses","volume":"33","author":"Vandenberg","year":"2012","journal-title":"Endocr Rev"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-019-02547-x","article-title":"Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures","volume":"93","author":"Hernandez","year":"2019","journal-title":"Arch Toxicol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2018.12.043","article-title":"Hormetic neurobehavioral effects of low dose toxic chemical mixtures in real-life risk simulation (RLRS) in rats","volume":"125","author":"Tsatsakis","year":"2019","journal-title":"Food Chem Toxicol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-021-02815-x","article-title":"Protective effects of selenium and zinc against nickel chloride\u2013induced hormonal changes and oxidative damage in thyroid of pregnant rats","volume":"200","author":"Salah","year":"2022","journal-title":"Biol Trace Elem Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s10661-013-3415-9","article-title":"Biomonitoring of cadmium, chromium, nickel and arsenic in general population living near mining and active industrial areas in southern Tunisia","volume":"186","author":"Khlifi","year":"2014","journal-title":"Environ Monit Assess."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2006.08.001","article-title":"Biomonitoring of 37 trace elements in blood samples from inhabitants of northern Germany by ICP\u2013MS","volume":"20","author":"Heitland","year":"2006","journal-title":"J Trace Elem Med Biol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-019-06632-7","article-title":"Thyroid dysfunction: how concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer","volume":"26","author":"Rezaei","year":"2019","journal-title":"Environ Sci pollut Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1023\/B:BIOM.0000045732.91261.e2","article-title":"Environmental epidemiological study and estimation of benchmark dose for renal dysfunction in a cadmium-polluted area in China","volume":"17","author":"Jin","year":"2004","journal-title":"BioMetals"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1080\/15376510701623888","article-title":"Application of benchmark dose for occupational epidemiology in lead exposure","volume":"18","author":"Lin","year":"2008","journal-title":"Toxicol Mech Methods"},{"key":"B42","doi-asserted-by":"publisher","first-page":"116519","DOI":"10.1016\/j.envpol.2021.116519","article-title":"A benchmark dose analysis for urinary cadmium and type 2 diabetes mellitus","volume":"273","author":"Shi","year":"2021","journal-title":"Environ pollut"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6521","DOI":"10.3390\/ijms22126521","article-title":"Environmental factors affecting thyroid-stimulating hormone and thyroid hormone levels","volume":"22","author":"Babi\u0107 Leko","year":"2021","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1145153\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:50:07Z","timestamp":1695289807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1145153\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,20]]},"references-count":43,"alternative-id":["10.3389\/fendo.2023.1145153"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1145153","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,20]]},"article-number":"1145153"}}