Detection of preoperative serum trace elements in thyroid tumors

Introduction

The global incidence of thyroid tumors has experienced a striking upward trend in recent years, which is attributed to the more widespread use of neck and chest imaging in asymptomatic patients (1). Most thyroid tumors are benign, and approximately 10% of thyroid tumors have the potential to progress to thyroid cancers. In accordance with the 2022 World Health Organization Classification of Thyroid Tumors, there are primarily three types of benign thyroid tumors, including thyroid nodules (TNs), nodular goiter, and thyroid adenoma (2). TNs are a common benign proliferative disease of the thyroid gland, with an overall prevalence of approximately 25% in the general population. Their prevalence varies substantially according to demographic factors such as age and gender, as well as the presence of risk factors. Nodular goiter, an enlargement of the thyroid gland, is a common endocrine abnormality. Currently, the incidence of this disease is steadily increasing, with up to 10% of the worldwide population affected (3). Multinodular goiter may be associated with environmental pollutants, genetic susceptibility and other intrinsic factors. Thyroid adenoma represents another common benign thyroid neoplasm, which typically manifests as a solitary TN in approximately 4% of adults (4). Thyroid cancer, a major endocrine malignancy, accounts for approximately 3–4% of all cancers, and its incidence has risen exponentially over the years (5). In 2020, there were 586,202 newly diagnosed cases of thyroid cancer worldwide, and the global incidence rate among females was 10.2 per 100,000, approximately 3 times that among males (6). Consistently, the number of thyroid cancer cases in China increased by 289.6% from 1990 to 2019 (7). This rising trend may be attributed to multiple factors beyond overdiagnosis, including environmental exposures and genetic predisposition. Among thyroid cancers, papillary thyroid carcinoma (PTC) is the most common histological subtype, accounting for approximately 85–90% of all cases (8).

Some trace elements, such as calcium (Ca), magnesium (Mg), iron (Fe), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), are essential for maintaining the hormonal balance of the thyroid gland (9). Trace elements constitute the essential structural components of thyroid hormones and are critical for the metabolism and function of the thyroid gland (10). Appropriate metabolism of thyroid hormones maintains internal homeostasis within the human body. Adverse physiological conditions, harmful lifestyles, and imbalances of trace metals may increase individual susceptibility to goiter and other thyroid disorders, including TNs, thyroid adenoma, and thyroid carcinoma (11).

Additionally, other toxic elements in the external environment, such as nickel (Ni), arsenic (As), platinum (Pt), molybdenum (Mo), cadmium (Cd), titanium (Ti), and lead (Pb), may cause various thyroid diseases. In the well-vascularized thyroid tissue, some heavy metals (such as Cu, Pb, Cd) generally accumulate with varying affinities and exhibit distinct half-lives (12). Based on the current state of knowledge, exposure to heavy metals, including cadmium and lead, may be an important factor contributing to the progression of thyroid cancer (13). Moreover, it has been indicated that environmental exposure to toxic Pb poses a substantial risk to human health (14). Accumulation of Pb in the thyroid gland leads to structural damage of follicular cells and subsequent thyroid dysfunction. Chronic Pb exposure is associated with disruption certain endocrine levels, such as significantly higher free T3 and trend of higher T3.

Although extensive studies have investigated the association between serum trace elements and the developments of thyroid tumors, no consistent consensus has been reached. Some studies reported that serum Ca and Mg are associated with the TNs (15). While others found that serum Zn and Se levels in PTC and follicular carcinoma are lower than that in healthy individuals (16). Therefore, our study aims to investigate the correlation between serum trace elements and the occurrence of thyroid tumors, providing a valuable insight into the differential diagnosis of thyroid tumors. We present this article in accordance with the STARD reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0171/rc).

Methods

Patients and sample collection

This was a retrospective observational study on thyroid tumors. From December 2025 to February 2026, we collected 130 patients with thyroid tumors admitted to Beijing Tongren Hospital, Capital Medical University. Inclusion criteria included: (I) availability of complete clinical data; (II) no history of prior special treatments such as radiotherapy, chemotherapy, or hormone replacement therapy; and (III) postoperative pathology confirming of benign thyroid tumors or PTC with clear pathological staging, and the diagnosis of PTC followed the 5th edition of the World Health Organization classification system. Exclusion criteria were as follows: (I) incomplete clinical data; (II) severe comorbidities or organ disorders, including cardiovascular system diseases, liver diseases, kidney diseases, other infectious diseases, and other cancers. The tumor-lymph node-metastasis (TNM) staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer classification system.

In addition, 51 age-matched healthy individuals undergoing routine physical examinations were selected as the control group, with no TNs confirmed by ultrasound. These subjects had no history of cardiovascular diseases, liver diseases, kidney diseases, diabetes, hypertension, malignant tumors, or pregnancy.

Before surgery, 3 mL of fasting peripheral venous blood samples were collected. Routine serum testing included measurement of clinical biochemical parameters and thyroid function indicators. The remaining serum was stored at −80 ℃ for subsequent trace element analysis.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Academic Ethics Committee of Beijing Tongren Hospital, Capital Medical University (approval No. TREC2026-KY004). Informed consent was obtained for publication of this study.

Detection of clinical biochemical and thyroid function indicators

Clinical biochemical parameters, including serum glucose (GLU), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine (CRE), and thyroid function indicators, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), and thyroid peroxidase antibody (TPO-Ab), were determined using a Beckman AU5811 biochemical analyzer and a Beckman DXI800 chemiluminescent immunoassay analyzer with their corresponding reagents (Beckman Coulter Inc., Brea, CA), respectively.

Detection of trace elements based on the ICP-QMS-1

Serum levels of 15 trace elements (Ca, Mg, Fe, Mn, Co, Cu, Zn, Se, Ni, As, Pt, Mo, Cd, Ti, Pb) were measured using a Clin-ICP-QMS-I instrument (Bioyong Technologies Inc.) and its corresponding reagents. The instrument was operated in accordance with standard operating procedures (SOP). For each trace element, six-level calibration solutions were utilized for instrument calibration. The correlation coefficients of the calibration curves ranged between 0.991 and 1.000, indicating good linearity. The working parameters of the instrument are shown in Table 1. All samples were tested in triplicate; therefore, the average value of the three replicate results was used for statistical analysis. Additionally, the coefficient of variation (CV) for each trace element was required to be less than 10%. If the CV exceeded this threshold, the sample was retested. Moreover, two-level quality controls were tested simultaneously for every trace element, and the results of the quality controls were required to be within the control ranges.

Statistical analysis

Statistical analysis was performed using SPSS 22.0 software, and all figures were generated with GraphPad Prism 8.0. Continuous data with a normal distribution was presented as mean ± standard deviation (SD), and analysis of variance (ANOVA) was used for multi-group comparisons. Non-normally distributed continuous data was expressed as median and interquartile range (IQR). The Mann-Whitney U test was used for comparisons between two groups, and the Kruskal-Wallis H test was applied for multi-group comparisons. Spearman’s correlation analysis was performed to investigate the association between serum trace elements. Categorical data were presented as cases (percentages), and the Chi-square test was used for inter-group comparisons. Logistic regression analysis was performed to identify risk factors for thyroid tumors. Receiver operating characteristic (ROC) curve analysis was applied to assess the predictive value of these risk factors for thyroid tumor, with a higher area under the curve (AUC) indicating better predictive performance. Furthermore, DeLong’s test was performed to compare the AUCs of the best single marker and the combined model, validating that the combination provided a significant improvement. A value of P<0.05 was considered statistically significant.

Results

Patient characteristics

Based on postoperative pathological results, a total of 130 patients were collected, including 54 benign thyroid tumor cases and 76 PTC cases. Simultaneously, 51 age-matched healthy individuals were selected as the control group. The general characteristics of the patients were shown in Table 2. Among the three groups, no significant differences were observed in gender (P=0.32) and age (P=0.13). In the benign thyroid tumor group, there were 13 cases of TNs, 35 cases of thyroid nodular goiter, and 6 cases of thyroid adenoma. In the PTC group, 54 cases (71.05%) had a tumor diameter ≤2 cm, with 22 cases (28.95%) >2 cm. Regarding tumor staging, 64 cases (84.21%) were in stages 1–2, and 12 cases (15.79%) were in stages 3–4. Lymph node metastasis was absent in 40 cases (52.63%) and present in 36 cases (47.37%). The healthy control group included 51 individuals, consisting of 20 males and 31 females, aged 23–60 years.

The levels of preoperative serum clinical biochemical and thyroid function indicators among the three groups

There were no significant differences in the clinical biochemical parameters (including serum GLU, liver function indicators ALT and AST, and renal function indicators UREA and CRE) among the three groups, as shown in Table 3. Similarly, no significant differences were observed in FT3, FT4, TSH and TPO-Ab levels across the three groups. However, the level of TG-Ab in the PTC group was significantly higher than those in the benign thyroid tumor and the control groups.

Results of preoperative serum trace elements among the three groups

All the results of preoperative serum trace elements among the three groups were shown in Table 4. Among the 15 trace elements, there were significant differences in preoperative serum Ca, Mg, Cu, Zn, Se, and Mo among the three groups (P<0.05). About the remaining 9 trace elements, no significant differences were found. In addition, according to the results of the Mann-Whitney U test, serum levels of Ca, Mg, Cu, Zn, Se, and Mo in the benign thyroid tumor and PTC groups were significantly higher compared with those in the healthy control group (Figure 1). However, no significant difference in these 6 trace elements was observed between the benign thyroid tumor and PTC groups.

Figure 1 Serum Ca (A), Mg (B), Cu (C), Zn (D), Se (E) and Mo (F) levels in patients with thyroid tumor and the control group. *, P<0.05; **, P<0.01; ***, P<0.001; ns, not significant. Ca, calcium; Cu, copper; Mg, magnesium; Mo, molybdenum; PTC, papillary thyroid carcinoma; Se, selenium; Zn, zinc.

Therefore, we combined the serum trace elements results of the benign thyroid tumor and PTC groups, which were called the thyroid tumor group. The preoperative serum trace element results between the thyroid tumor group and the control group were shown in Table 5. Among these 6 trace elements, serum Zn level in the thyroid tumor group was significantly higher than that in the control group, with an increase of approximately 37.47%. Serum Mo and Cu levels in the thyroid tumor group increased by 18.52% and 17.62%, respectively. The elevation degree of serum Ca in the thyroid tumor group was the lowest, which was only 9.78% higher than that in the control group (all P<0.05).

Among these 6 trace elements, significant correlations were observed between any two elements following Spearman’s correlation analysis (Table 6). However, the correlation coefficients between each pair of these trace elements in the thyroid tumor group was lower than those in the control group. For example, the correlation coefficient between serum Ca and Mg levels was 0.871 in the thyroid tumor group, while it was 0.915 in the control group. This difference in correlation strength may be attributed to the varying degrees of elevation of these 6 trace elements in the thyroid tumor group.

Analysis of thyroid tumor risk using univariate and multivariate logistic regression

The results of logistic regression analysis in patients with thyroid tumors are presented in Table 7. The relationships between these 6 trace elements (serum Ca, Mg, Cu, Zn, Se, and Mo) and dependent variable (presence or absence of thyroid tumors) were analyzed. In univariate logistic regression analysis, serum Ca, Mg, Cu, Zn, Se, and Mo were correlated with the presence of thyroid tumors. However, in the multivariate logistic regression analysis, only serum Cu [odds ratio (OR), 1.004; 95% confidence interval (CI): 1.002–1.008; P=0.02] and Zn (OR, 1.009; 95% CI: 1.005–1.013; P<0.001) were identified as independent risk factors for thyroid tumors.

Enhanced efficacy in the combined assessment of Cu and Zn for differential diagnosis of thyroid tumors and the control group

To further evaluate the diagnostic efficacy of serum Cu and Zn levels in differentiating patients with thyroid tumors from the control group, we employed ROC curve analysis. The results showed that the area under the ROC curve for serum Cu in distinguishing patients with thyroid tumors from controls was 0.720 (95% CI: 0.642–0.797; sensitivity, 63.1%; specificity, 76.5%; P<0.001). The AUC for serum Zn for differentiating thyroid tumors from controls were 0.781 (95% CI: 0.715–0.847; sensitivity, 63.1%; specificity, 88.2%; P<0.001), as presented in Table 8. When the two markers were combined for diagnostic evaluation, the AUC increased to 0.783 (95% CI: 0.718–0.848), with a sensitivity of 56.2% and specificity of 98.0% (P<0.001) (Figure 2). However, the combination of serum Cu and Zn did not offer a significant improvement, as confirmed by DeLong’s test.

Figure 2 ROC curve analysis of diagnostic efficacy of serum Cu, Zn, and the combination of serum Cu and Zn. AUC, area under the curve; Cu; ROC, receiver operating characteristic.

The correlation of serum trace elements and TG-Ab in the thyroid tumor and the control groups

Based on the Beckman DXI800 analyzer, the reference interval of serum TG-Ab ranged from 0 to 4 IU/mL. So, the result with a TG-Ab value >4 IU/mL was considered TG-Ab positive. In the thyroid tumor group, there were 27 TG-Ab-positive patients and 103 TG-Ab-negative patients, whereas all individuals in the control group were TG-Ab negative. As shown in Figure 3, serum Cu levels in TG-Ab-positive patients were significantly higher than those in TG-Ab-negative patients (P<0.01).

Figure 3 Serum Cu levels in patients with TG-Ab negative and TG-Ab positive. **, P<0.01. Cu, copper; TG-Ab, thyroglobulin antibody.

Discussion

The incidence of TNs is steadily increasing. In this study, we focused on the differences in preoperative serum trace elements between the thyroid tumor and the control group and aimed to investigate the correlation between serum trace elements and the occurrence of thyroid tumors. Our results demonstrated that the concentrations of preoperative serum trace elements (Ca, Mg, Cu, Zn, Se, and Mo) might be correlated with thyroid tumors and not associated with the benign or malignant nature of thyroid tumors.

Of all the correlations identified in this study, the association between Ca and Mg appeared to be particularly noteworthy. Spearman’s correlation analysis showed that the correlation coefficients were 0.871 in the thyroid tumor group and 0.915 in the control group, respectively, which was consistent with the findings of Kuzan A and the relationship of Ca-Mg was 0.782 (14). Ca plays a critical role in the pathogenesis of thyroid diseases. Mg is involved in maintaining nucleic acids structural stability and participates in DNA replication, transcription, and repair. Serum Mg levels are closely associated with thyroid cancer, and malignant tissues generally exhibit higher Mg levels compared with normal tissues (10). In our study, univariate logistic regression analysis indicated that serum Ca and Mg levels were correlated with the presence of thyroid tumors. However, in multivariate logistic regression analysis, serum Ca and Mg were not identified as independent risk factors for thyroid tumors. Conversely, Ma et al. reported that high serum Ca and Mg concentrations emerged as consistent risk factors for TNs in both genders (17).

Cu and Zn are essential micrometals involved in the normal functioning of the thyroid gland, and alterations in their concentrations have been found during cancer development. These two metals participate in metabolism associated with protection against oxidative stress. Cu can stimulate the production of thyroid hormones and studies have found that Cu is positively correlated with thyroid hormones (18). In another 2024 study, Lv et al. reported that participants with TNs exhibited significantly higher Cu concentrations (P=0.002) and lower Fe concentrations (P=0.02) compared with the control group (19). High concentrations of Cu can cause DNA damage and lipid peroxidation via toxic free radicals. Furthermore, lines of evidence from clinical research indicates that elevated serum Cu levels are positively associated with the presence of thyroid autoantibodies (20), which was consistent with the result of our research. While, there was still other studies which indicated that Cu was not associated with thyroid autoimmune inflammation and thyroid autoantibodies (21).

Zn plays a role in the production and activation of the thyroid hormones. Zn can also affect thyroid volume and the volume of thyroid was positively correlated with Zn concentration (22). Numerous studies have explored the relationship between Zn and thyroid hormone levels, and both hypothyroidism and hyperthyroidism are reportedly associated with low Zn concentrations (23). Zn deficient diet and low serum Zn concentrations can cause changes in the thyroid gland structure and in the metabolism of thyroid hormones. In contrast, in our study, serum Zn levels in the thyroid tumors (including the benign thyroid tumor and PTC) were higher than those in the healthy individuals. In an iodine-adequate area of Guangdong, Zeng et al. also reported that subjects with higher levels of Zn, Mg and Cu had increased risks of the prevalence of TNs (24), which was consistent with our results. Additionally, in our study, serum Zn had higher diagnostic efficiency on the differential diagnosis of TNs and the control group, with an ROC of 0.781. This indicates that serum Zn may serve as a useful adjunct for the diagnosis of thyroid tumors.

Se is another crucial element for the biosynthesis and metabolism of thyroid hormones, highly concentrated in the thyroid gland (25,26). Se deficiency impairs the conversion of T4 to T3. Furthermore, researchers have suggested that the effect of Se on thyroid size is more pronounced in iodine-rich individuals than in iodine-deficient individuals (27). Adequate Se intake is required for the normal function of thyroid cells and vascular follicular units during the biosynthesis and storage of thyroid hormones. In addition, Mo is implicated in thyroid metabolism through interaction with thyroid hormone receptors (28). Intake of Mo can induce a significant increase of histological features of transformation in thyroid follicular cells of rats (29), suggesting that Mo is capable of modulating thyroid hormone levels. Our study was performed in an iodine-sufficient area and the mean serum Se and Mo levels were higher compared with those in many other studies, which was primarily attributed to the thyroid volume and metabolism of thyroid hormones.

Nevertheless, there were limitations in the study. First, the patient cohort composition suggests a potential for selection bias. The number of cases in the benign thyroid tumor group (n=54) was smaller than that in the PTC group (n=76), whereas benign thyroid tumors are far more common in the general population. Next, we will place greater emphasis on the serum trace elements levels of patients with benign TNs. Second, the heterogeneity within the benign thyroid tumor group deserves further consideration. The benign thyroid tumors including three types (TNs, nodular goiter, and thyroid adenoma). In our study, the benign thyroid tumor group was predominantly composed of nodular goiter (35 out of 54 cases). So, this heterogeneity may result in the potential effect with increasing serum Zn and other trace element levels, which could potentially augment the observed differences compared with the control group. We acknowledge this potential confounding effect and will select the other benign thyroid tumor type excluding nodular goiter in future studies. Thirdly, there is currently no causal evidence indicating that trace elements directly contribute to tumor development, and that the tumor itself may influence the serum levels of these elements. Therefore, it is important to clearly distinguish association from causation and more emphasis should be placed on the importance of longitudinal studies. Finally, important variables such as diet, supplementation, alcohol consumption, and smoking habits, may affect serum trace element levels. These variables should be considered in future studies.

Conclusions

Our study suggests that preoperative serum trace elements (Ca, Mg, Cu, Zn, Se, and Mo) may be correlated with thyroid tumors, but they are not associated with the benign or malignant nature of thyroid tumors. Serum Zn may be performed as a useful aid for the diagnosis of thyroid tumors. In addition, serum Cu is highly correlated with the presence of thyroid autoantibodies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0171/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0171/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0171/prf

Funding: This study was supported by the Abbott Laboratories and Hospital Joint Fund (No. TRECKY2021-131).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0171/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Academic Ethics Committee of Beijing Tongren Hospital, Capital Medical University (approval No. TREC2026-KY004). Informed consent was obtained for publication of this study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Acosta GJ, Singh Ospina N, Brito JP. Epidemiologic changes in thyroid disease. Curr Opin Endocrinol Diabetes Obes 2024;31:184-90. [Crossref] [PubMed]
2. Jung CK, Bychkov A, Kakudo K. Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach. Endocrinol Metab (Seoul) 2022;37:703-18. [Crossref] [PubMed]
3. Mariani G, Tonacchera M, Grosso M, et al. The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 2: Nodular Goiter, Hypothyroidism, and Subacute Thyroiditis. J Nucl Med 2021;62:886-95. [Crossref] [PubMed]
4. Xu R, Wen W, Zhang Y, et al. Diagnostic significance of ultrasound characteristics in discriminating follicular thyroid carcinoma from adenoma. BMC Med Imaging 2024;24:299. [Crossref] [PubMed]
5. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
6. Pizzato M, Li M, Vignat J, et al. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet Diabetes Endocrinol 2022;10:264-72. [Crossref] [PubMed]
7. Gong Y, Jiang Q, Zhai M, et al. Thyroid cancer trends in China and its comparative analysis with G20 countries: Projections for 2020-2040. J Glob Health 2024;14:04131. [Crossref] [PubMed]
8. Weng YJ, Huang ZH, Min L. Oncological characteristics predict permanent hypoparathyroidism following total thyroidectomy for papillary thyroid carcinoma: a study from China. Gland Surg 2025;14:2424-32. [Crossref] [PubMed]
9. Wróblewski M, Wróblewska J, Nuszkiewicz J, et al. The Role of Selected Trace Elements in Oxidoreductive Homeostasis in Patients with Thyroid Diseases. Int J Mol Sci 2023;24:4840. [Crossref] [PubMed]
10. Zhou Q, Xue S, Zhang L, et al. Trace elements and the thyroid. Front Endocrinol (Lausanne) 2022;13:904889. [Crossref] [PubMed]
11. Stojsavljević A, Rovčanin B, Jagodić J, et al. Alteration of Trace Elements in Multinodular Goiter, Thyroid Adenoma, and Thyroid Cancer. Biol Trace Elem Res 2021;199:4055-65. [Crossref] [PubMed]
12. Kuzan A, Rewak-Soroczyńska J, Kardach M, et al. Multi-element analysis of metals in human pathological and unchanged thyroid glands - pilot study. Thyroid Res 2024;17:11. [Crossref] [PubMed]
13. Gianì F, Masto R, Trovato MA, et al. Heavy Metals in the Environment and Thyroid Cancer. Cancers (Basel) 2021;13:4052. [Crossref] [PubMed]
14. He JL, Wu HB, Hu WL, et al. Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: A case-control study. Int J Hyg Environ Health 2022;246:114049. [Crossref] [PubMed]
15. Xu H, Hu X, Li J, et al. The Inverse Association of Serum Magnesium with Papillary Thyroid Cancer in Thyroid Nodules: a Cross-Sectional Survey Based on Thyroidectomy Population. Biol Trace Elem Res 2023;201:3279-89. [Crossref] [PubMed]
16. Kazi Tani LS, Gourlan AT, Dennouni-Medjati N, et al. Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer. Front Med (Lausanne) 2021;8:698167. [Crossref] [PubMed]
17. Ma Q, Li Y, Yu G, et al. Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: a Cross‑sectional Study. Biol Trace Elem Res 2024;202:4357-66. [Crossref] [PubMed]
18. Hu L, Li R, Chen C, et al. Cu single sites on BO(2) as thyroid peroxidase mimicking for iodotyrosine coupling and pharmaceutical assess. Sci Bull (Beijing) 2025;70:1611-8. [Crossref] [PubMed]
19. Lv Y, Zhang L, Liu Y, et al. Serum trace elements show association with thyroperoxidase autoantibodies in Thyroid Imaging Reporting and Data System (TI-RADS) 4 nodules. Sci Rep 2024;14:19813. [Crossref] [PubMed]
20. Kravchenko V, Zakharchenko T. Thyroid hormones and minerals in immunocorrection of disorders in autoimmune thyroid diseases. Front Endocrinol (Lausanne) 2023;14:1225494. [Crossref] [PubMed]
21. Kim MJ, Kim SC, Chung S, et al. Exploring the role of copper and selenium in the maintenance of normal thyroid function among healthy Koreans. J Trace Elem Med Biol 2020;61:126558. [Crossref] [PubMed]
22. Beserra JB, Morais JBS, Severo JS, et al. Relation Between Zinc and Thyroid Hormones in Humans: a Systematic Review. Biol Trace Elem Res 2021;199:4092-100. [Crossref] [PubMed]
23. Hung KC, Yu TS, Lai YC, et al. Association Between Zinc Deficiency and Risk of Thyroid Cancer: A Multi-Institutional Cohort Study. Nutr Cancer 2026;78:247-55. [Crossref] [PubMed]
24. Zeng H, Hu Y, Luo Y, et al. The Association of Thyroid Nodules With Blood Trace Elements Identified in a Cross-Section Study. Front Nutr 2022;9:870873. [Crossref] [PubMed]
25. Bai S, Zhang M, Tang S, et al. Effects and Impact of Selenium on Human Health, A Review. Molecules 2024;30:50. [Crossref] [PubMed]
26. Dijck-Brouwer DAJ, Muskiet FAJ, Verheesen RH, et al. Thyroidal and Extrathyroidal Requirements for Iodine and Selenium: A Combined Evolutionary and (Patho)Physiological Approach. Nutrients 2022;14:3886. [Crossref] [PubMed]
27. Nagano K, Motomura Y, Bando H, et al. Thyroid dysfunction due to trace element deficiency-not only selenium but also zinc. Hormones (Athens) 2024;23:675-81. [Crossref] [PubMed]
28. Zhu Z, Li J, Peng Y, et al. Multi-metal mixture exposure and cognitive function in urban older adults: The mediation effects of thyroid hormones. Ecotoxicol Environ Saf 2025;290:117768. [Crossref] [PubMed]
29. Chung HK, Nam JS, Ahn CW, et al. Some Elements in Thyroid Tissue are Associated with More Advanced Stage of Thyroid Cancer in Korean Women. Biol Trace Elem Res 2016;171:54-62. [Crossref] [PubMed]