Share
Return to Article DetailsThe Contents of Calcium, Chlorine, Iodine, Potassium, Magnesium, Manganese, and Sodium in Thyroid Malignant Nodules and Thyroid Tissue Adjacent to Nodules

##plugins.themes.bootstrap3.article.main##

Vladimir Zaichick

Abstract

Objective:sandBackgrounds:Thyroidmalignantnodules(TMNs)arethemostcommonendocrinecancerandthefifthmostfrequentlyoccurringtypeofmalignancies.TheetiologyandpathogenesisofTMNsmustbeconsideredasmultifactorial.Thepresentstudywasperformedtoclarifytheroleofsomechemicalelements(ChEs)intheetiologyofthesethyroiddisorders.


Methods and patients:Thyroidtissuelevelsofcalcium(Ca),chlorine(Cl),iodine(I),potassium(K),magnesium(Mg),manganese(Mn),andsodium(Na)wereprospectivelyevaluatedinmalignanttumorandtissueadjacenttotumorof41patientswithTMNs.Measurementswereperformedusingnon-destructiveinstrumentalneutronactivationanalysiswithhighresolutionspectrometryofshort-livedradionuclides.Tissuesamplesweredividedintotwoportions.OnewasusedformorphologicalstudywhiletheotherwasintendedforChEsanalysis.


Result:softhestudywereadditionallycomparedwithpreviouslyob-taineddataforthesameChEsin“normal”thyroidtissue.Results:ItwasobservedthatinmalignanttissuethemassfractionofCl,K,Mg,andNawereapproximately2.3,1.6,1.6,and1.3times,respectively,higherwhereasmassfractionofIwas25.6timeslowerthaninthenormalthyroid.InageneralsenseK,Mg,Mn,andNacontentsfoundinthe“normal”and“adjacent”groupsofthyroidtissuesampleswereverysimilar.However,inthe“adjacent”groupmeanmassfractionsofClandIwere1.57and1.73times,respectively,higher,whilemeanvalueofCacontentalmost2timeslowerthaninthe“normal”group.InmalignanttumorCa,Cl,andKcontentswereapproximately2.8,1.4,and1.7times,respectively,higher,whileIcontent43.5timeslowerthanin“adjacent”groupoftissuesamples.were very similar. However, in the “adjacent” group mean mass fractions of Cl and I were 1.57 and 1.73 times, respectively, higher, while mean value of Ca content almost 2 times lower than in the “normal” group. In malignant tumor Ca, Cl, and K contents were approximately 2.8, 1.4, and 1.7 times, respectively, higher, while I content 43.5 times lower than in “adjacent” group of tissue samples.


Conclusions: From results obtained, it was possible to conclude that the common characteristics of TMNs in comparison with “normal” thyroid and visually “intact” thyroid tissue adjacent to malignant tumors were elevated levels of Cl and K, as well as drastically reduced level of I. It was supposed that elevated levels of Cl and K, as well as drastically reduced level of I in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules

Abstract

Objective:sandBackgrounds:Thyroidmalignantnodules(TMNs)arethemostcommonendocrinecancerandthefifthmostfrequentlyoccurringtypeofmalignancies.TheetiologyandpathogenesisofTMNsmustbeconsideredasmultifactorial.Thepresentstudywasperformedtoclarifytheroleofsomechemicalelements(ChEs)intheetiologyofthesethyroiddisorders.


Methods and patients:Thyroidtissuelevelsofcalcium(Ca),chlorine(Cl),iodine(I),potassium(K),magnesium(Mg),manganese(Mn),andsodium(Na)wereprospectivelyevaluatedinmalignanttumorandtissueadjacenttotumorof41patientswithTMNs.Measurementswereperformedusingnon-destructiveinstrumentalneutronactivationanalysiswithhighresolutionspectrometryofshort-livedradionuclides.Tissuesamplesweredividedintotwoportions.OnewasusedformorphologicalstudywhiletheotherwasintendedforChEsanalysis.


Result:softhestudywereadditionallycomparedwithpreviouslyob-taineddataforthesameChEsin“normal”thyroidtissue.Results:ItwasobservedthatinmalignanttissuethemassfractionofCl,K,Mg,andNawereapproximately2.3,1.6,1.6,and1.3times,respectively,higherwhereasmassfractionofIwas25.6timeslowerthaninthenormalthyroid.InageneralsenseK,Mg,Mn,andNacontentsfoundinthe“normal”and“adjacent”groupsofthyroidtissuesampleswereverysimilar.However,inthe“adjacent”groupmeanmassfractionsofClandIwere1.57and1.73times,respectively,higher,whilemeanvalueofCacontentalmost2timeslowerthaninthe“normal”group.InmalignanttumorCa,Cl,andKcontentswereapproximately2.8,1.4,and1.7times,respectively,higher,whileIcontent43.5timeslowerthanin“adjacent”groupoftissuesamples.were very similar. However, in the “adjacent” group mean mass fractions of Cl and I were 1.57 and 1.73 times, respectively, higher, while mean value of Ca content almost 2 times lower than in the “normal” group. In malignant tumor Ca, Cl, and K contents were approximately 2.8, 1.4, and 1.7 times, respectively, higher, while I content 43.5 times lower than in “adjacent” group of tissue samples.


Conclusions: From results obtained, it was possible to conclude that the common characteristics of TMNs in comparison with “normal” thyroid and visually “intact” thyroid tissue adjacent to malignant tumors were elevated levels of Cl and K, as well as drastically reduced level of I. It was supposed that elevated levels of Cl and K, as well as drastically reduced level of I in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules

Keyword : Chemical elements, Neutron activation analysis, Thyroid, Thyroid malignant nodules

How to Cite
Zaichick, V. . (2022). Return to Article DetailsThe Contents of Calcium, Chlorine, Iodine, Potassium, Magnesium, Manganese, and Sodium in Thyroid Malignant Nodules and Thyroid Tissue Adjacent to Nodules. Journal of Medical Case Reports and Reviews, 5(02). Retrieved from http://jmcrr.info/index.php/jmcrr/article/view/106
  Submitted
Feb 11, 2022
Published
Feb 11, 2022
Abstract Views
110
PDF Downloads
38
XML Downloads
1
HTML Downloads
6
ePub Downloads
24

Introduction

Thyroid malignant nodules (TMNs) are the most common endocrine cancer and the fifth most frequently occurring type of malignancies 1 .2 The incidence of TMNs has increased worldwide over the past four decades. TMNs are divided into three main histological types: differentiated (papillary and follicular thyroid cancer), undifferentiated (poorly differentiated and anaplastic thyroid cancer, and medullary thyroid cancer, arising from C cells of thyroid 3 . For over 20th century, there was the dominant opinion that TMNs is the simple consequence of iodine deficiency 4 . However, it was found that TMNs is a frequent disease even in those countries and regions where the population is never exposed to iodine shortage. Moreover, it was shown that iodine excess has severe consequences on human health and associated with the presence of TMNs 5, 6, 7, 8 . It was also demonstrated that besides the iodine deficiency and excess many other dietary, environmental, and occupational factors are associated with the TMNs incidence 9, 10, 11 . Among these factors a disturbance of evolutionary stable input of many chemical elements (ChEs) in human body after industrial revolution plays a significant role in etiology of TMNs 12 .

Besides iodine, many other ChEs have also essential physiological functions 13 . Essential or toxic (goitrogenic, mutagenic, carcinogenic) properties of ChEs depend on tissue-specific need or tolerance, respectively 13 . Excessive accumulation or an imbalance of the ChEs may disturb the cell functions and may result in cellular proliferation, degeneration, death, benign or malignant transformation 13, 14, 15 .

In our previous studies the complex of in vivo and in vitro nuclear analytical and related methods was developed and used for the investigation of iodine and other ChEs contents in the normal and pathological thyroid 16, 17, 18, 19, 20, 21, 22 . Iodine level in the normal thyroid was investigated in relation to age, gender and some non-thyroidal diseases 23, 24 . After that, variations of many ChEs content with age in the thyroid of males and females were studied and age- and gender-dependence of some ChEs was observed 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 . Furthermore, a significant difference between some ChEs contents in colloid goiter, thyroiditis, and thyroid adenoma in comparison with normal thyroid was demonstrated 42, 43, 44, 45, 46 .

To date, the etiology and pathogenesis of TMNs must be considered as multifactorial. The present study was performed to find out differences in ChEs contents between the group of cancerous tissues and tissue adjacent to tumor, as well as to clarify the role of some ChEs in the etiology of TMNs. Having this in mind, the aim of this exploratory study was to examine differences in the content of calcium (Ca), chlorine (Cl), iodine (I), potassium (K), magnesium (Mg), manganese (Mn), and sodium (Na) in nodular and adjacent to nodules tissues of thyroids with TMNs using a non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides (INAA-SLR), and to compare the levels of these ChEs in two groups (tumor and adjacent to tumor tissues) of the cohort of TMNs samples. Moreover, for understanding a possible role of ChEs in etiology and pathogenesis of TMNs results of the study were compared with previously obtained data for the same ChEs in “normal” thyroid tissue 42, 43, 44, 45, 46 .

Patients and method

All patients with TMNs (n=41, mean age M�SD was 46�15 years, range 16-75) were hospitalized in the Head and Neck Department of the Medical Radiological Research Centre (MRRC), Obninsk.. Thick-needle puncture biopsy of suspicious nodules of the thyroid was performed for every patient, to permit morphological study of thyroid tissue at these sites and to estimate their trace element contents. In all cases the diagnosis has been confirmed by clinical and morphological results obtained during studies of biopsy and resected materials. Histological conclusions for malignant tumors were: 25 papillary adenocarcinomas, 8 follicular adenocarcinomas, 7 solid carcinomas, and 1 reticulosarcoma. Tissue samples of tumor and visually intact tissue adjacent to tumor were taken from resected materials.

“Normal” thyroids for the control group samples were removed at necropsy from 105 deceased (mean age 44�21 years, range 2-87), who had died suddenly. The majority of deaths were due to trauma. A histological examination in the control group was used to control the age norm conformity, as well as to confirm the absence of micro-nodules and latent cancer.

All studies were approved by the Ethical Committees of MRRC. All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments, or with comparable ethical standards. Informed consent was obtained from all individual participants included in the study

All tissue samples obtained from tumors and visually intact tissue adjacent to tumors were divided into two portions using a titanium scalpel to prevent contamination by ChEs of stainless steel 47 . One was used for morphological study while the other was intended for ChEs analysis. After the samples intended for ChEs analysis were weighed, they were freeze-dried and homogenized 48 . The pounded samples weighing about 10 mg (for biopsy) and 100 mg (for resected materials) were used for ChEs measurement by INAA-SLR.

To determine contents of the ChE by comparison with a known standard, biological synthetic standards (BSS) prepared from phenol-formaldehyde resins were used 49 . In addition to BSS, aliquots of commercial, chemically pure compounds were also used as standards. Ten sub-samples of certified reference material (CRM) of the International Atomic Energy Agency (IAEA) IAEA H-4 (animal muscle) weighing about 100 mg were treated and analyzed in the same conditions as thyroid samples to estimate the precision and accuracy of results.

The content of Ca, Cl, I, K, Mg, Mn, and Na were determined by INAA-SLR using a horizontal channel equipped with the pneumatic rabbit system of the WWR-c research nuclear reactor (Branch of Karpov Institute, Obninsk). Details of used nuclear reactions, radionuclides, gamma-energies, spectrometric unit, sample preparation, and the quality control of results were presented in our earlier publications concerning the INAA-SLR of ChEs contents in human thyroid, scalp hair, and prostate 27, 28, 50 .51 52

A dedicated computer program for INAA-SLR mode optimization was used 53 . All thyroid samples for ChEs analysis were prepared in duplicate, and mean values of ChEs contents were used in final calculation. Using Microsoft Office Excel software, a summary of the statistics, including, arithmetic mean, standard deviation, standard error of mean, minimum and maximum values, median, percentiles with 0.025 and 0.975 levels was calculated for ChEs contents in malignant and adjacent to tumor tissue of thyroids with TMNs. Data for “normal” thyroid were taken from our previous publications 42, 43, 44, 45, 46 . The difference in the results between three groups of samples (“normal”, “tumor”, and “adjacent”) was evaluated by the parametric Student’s t-test and non-parametric Wilcoxon-Mann-Whitney U-test.

Results

Table:1 presents certain statistical parameters (arithmetic mean, standard deviation, standard error of mean, minimal and maximal values, median, percentiles with 0.025 and 0.975 levels) of theCa, Cl, I, K, Mg, Mn, and Na mass fraction in “normal”, “tumor”, and “adjacent” groups of thyroid tissue samples.

The ratios of means and the comparison of mean values of Ca, Cl, I, K, Mg, Mn, and Na mass fractions in pairs of sample groups such as “normal” and “tumor”, “normal” and “adjacent”, and also “adjacent” and “tumor” are presented in Table 2, 3, and 4, respectively.

Discussion

As was shown before 27, 28, 50, 51, 52 good agreement of the Ca, Cl, I, K, Mg, Mn, and Na contents in CRM IAEA H-4 samples analyzed by INAA-SLR with the certified data of this CRM indicates acceptable accuracy of the results obtained in the study of thyroid tissue samples presented in Tables 1–4.

From Table 2, it is observed that in malignant tissue the mass fraction of Cl, K, Mg, and Na are approximately 2.3, 1.6, 1.6, and 1.3 times, respectively, higher whereas mass fraction of I is 25.6 times lower than in the normal thyroid. Thus, if we accept the ChEs contents in thyroid glands of the “normal” group as a norm, we have to conclude that with a malignant transformation the Cl, I, K, Mg, and Na contents in thyroid tissue significantly changed. In a general sense K, Mg, Mn, and Na contents found in the “normal” and “adjacent” groups of thyroid tissue samples were very similar (Table 3). However, in the “adjacent” group mean mass fractions of Cl and I were 1.57 and 1.73 times, respectively, higher, while mean value of Ca content was 2 times lower than in the “normal” group. Significant changes of tumor ChEs contents in comparison with thyroid tissue adjacent to tumor were found for Ca (increase), Cl (increase), I (decrease), and K (increase). In malignant tumor Ca, Cl, and K contents were approximately 2.8, 1.4, and 1.7 times, respectively, higher, while I content 43.5 times lower than in “adjacent” group of tissue samples (Table 4). Thus, from results obtained, it was possible to conclude that the common characteristics of TMNs in comparison with “normal” thyroid and visually “intact” thyroid tissue adjacent to malignant tumors were elevated levels of Cl and K, as well as drastically reduced level of I (Tables 2 and 4). 54 55 56 57 58

Table 1 Some statistical parameters of, Ca, Cl, I, K, Mg, Mn, and Na mass fraction (mg/kg, dry mass basis) in normal thyroid and thyroid cancer (tumor and “intact” thyroid tissue adjacent to tumor)

M – arithmetic mean, SD – standard deviation, SEM – standard error of mean, Min – minimum value, Max – maximum value, P 0.025 – percentile with 0.025 level, P 0.975 – percentile with 0.975 level.

Characteristically, elevated or reduced levels of ChEs observed in thyroid nodules are discussed in terms of their potential role in the initiation and promotion of these thyroid lesions. In other words, using the low or high levels of the ChEs in affected thyroid tissues researchers try to determine the role of the deficiency or excess of each ChE in the etiology and pathogenesis of thyroid diseases. In our opinion, abnormal levels of many ChEs in TMNs could be and cause, and also effect of thyroid tissue transformation. From the results of such kind studies, it is not always possible to decide whether the measured decrease or increase in ChEs level in pathologically altered tissue is the reason for alterations or vice versa. According to our opinion, investigation of ChEs contents in thyroid tissue adjacent to malignant nodules and comparison obtained results with ChEs levels typical of “normal” thyroid gland may give additional useful information on the topic because these data show conditions of tissue in which TMNs were originated and developed.

Table 2 Differences between mean values (M±SEM) of Ca, Cl, I, K, Mg, Mn, and Na mass fraction (mg/kg, dry mass basis) in normal thyroid and thyroid cancer (tumor)

M – arithmetic mean, SEM – standard error of mean, Statistically significant values are in bold.

Table 3 3. Differences between mean values (M±SEM) of Ca, Cl, I, K, Mg, Mn, and Na mass fraction (mg/kg, dry mass basis) in normal thyroid and “intact” thyroid tissue adjacent to tumor

M – arithmetic mean, SEM – standard error of mean, Statistically significant values are in bold.

Table 4 Differences between mean values (M±SEM) of Ca, Cl, I, K, Mg, Mn, and Na mass fraction (mg/kg, dry mass basis) in thyroid cancer and “intact” thyroid tissue adjacent to tumor

M – arithmetic mean, SEM – standard error of mean, Statistically significant values are in bold.

Chlorine and sodium: Cl and Na are ubiquitous, extracellular electrolytes essential to more than one metabolic pathway. In the body, Cl and Na mostly present as sodium chloride. Therefore, as usual, there is a correlation between Na and Cl contents in tissues and fluids of human body. Because Cl is halogen like I, in the thyroid gland the biological behavior of chloride has to be similar to the biological behavior of iodide. The main source of natural Cl for human body is salt in food and chlorinated drinking water. Environment (air, water and food) polluted by artificial nonorganic Cl-contained compounds, for example such as sodium chlorate (NaClO3), and organic Cl-contained compounds, for example such as polychlorinated biphenyls (PCBs) and dioxin, is other source. There is a clear association between using chlorinated drinking water, levels NaClO3, PCBs and dioxin in environment and thyroid disorders, including cancer [54-58}. Thus, on the one hand, the accumulated data suggest that Cl level in thyroid tissue might be responsible for TMNs development. However, on the other hand, it is well known that Cl and Na mass fractions in human tissue samples depend mainly on the extracellular water volume 59 . Tumors and adjacent to tumors thyroid tissues can be more vascularized than normal thyroid. Because blood is extracellular liquid, it is possible to speculate that more intensive vascularization could be the reason for elevated levels of Cl and Na in TMNs and adjacent tissue. If that is the case, the equilibrium between Cl and Na increases has to be, however, in comparison with “normal” thyroid the change of Cl level in tumors and adjacent tissue is significantly higher than change of Na level. Thus, it is possible to assume that an excessive accumulation of Cl in thyroid tissue is involved in TMNs etiology. Overall, the elevated levels of Cl in thyroid tissue could possibly be explored as risk factor of TMNs.

Iodine: Nowadays it was well established that iodine deficiency or excess has severe consequences on human health and associated with the presence of TMNs 4, 5, 6, 7, 8, 60, 61, 62, 63 . In present study elevated level of I in thyroid tissue adjacent to malignant tumor and drastically reduced I mass fraction in cancerous tissue was found in comparison with “normal” thyroid.

Compared to other soft tissues, the human thyroid gland has higher levels of I, because this element plays an important role in its normal functions, through the production of thyroid hormones (thyroxin and triiodothyronine) which are essential for cellular oxidation, growth, reproduction, and the activity of the central and autonomic nervous system. As was shown in present study, malignant transformation is accompanied by a significant loss of tissue-specific functional features, which leads to a drastically reduction in I content associated with functional characteristics of the human thyroid tissue. Because the malignant part of gland stopped to produce thyroid hormones, the rest “intact” part of thyroid tries to compensate thyroid hormones deficiency and work more intensive than usual. The intensive work may explain elevated level of I in thyroid tissue adjacent to malignant tumor.

Drastically reduced level of I content in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules, because, as was found in our ealier studies, thyroid benign trasformation (goiter, thyroiditis, and adenoma) is accompanied by a little loss of I accumulation [42-46].

Potassium: An uncontrollable cell proliferation characterize the malignant tumors. Therefore, morphological structures of TMNs differ from the structure of normal thyroid parenchyma. Because K is mainly an intracellular electrolyte, an elevated level of K content in cancerous tissue in comparison with “normal” and “adjacent” tissue might reflect increase of ratio “mass of transformed thyroid cell – mass of follicular colloid” in the malignant tumors. Nevertheless, the accumulation of K in neoplastic thyroids could possibly be explored for diagnosis of TMNs.

Magnesium: Mg is abundant in the human body. This element is essential for the functions of more than 300 enzymes (e.g. alkaline phosphatases, ATP-ases, phosphokinases, the oxidative phosphorylation pathway). It plays a crucial role in many cell functions such as energy metabolism, protein and DNA syntheses, and cytoskeleton activation. Moreover, Mg plays a central role in determining the clinical picture associated with thyroid disease 64 . Experimental data have shown that high doses of magnesium increase the activity of the thyroid gland 65 . Magnesium deficiency can influence bioavailability and tissue distribution of selenium which then appears diminished 66 . From these data, one can conclude that Mg is involved in the thyroid function. If so, significant reduction in Mg content cam be associate with TMNs, because malignant transformation is accompanied by a loss of thyroid-specific functional features. However, it is well known that malignant tumors have an usually higher Mg levels than do normal tissues 67, 68, 69, 70, 71, 72, 73 , possibly caused by the "retention" of Mg by the tumor 74 , as a result of the high Mg requirement of growing cells. In addition, cultured proliferating cells have long been known to contain more magnesium than quiescent cells, and experimental conditions that decreased magnesium availability affected cell proliferation rate 75 . Thus, the elevated levels of Mg in neoplastic thyroids could possibly be explored for diagnosis of TMNs.

Limitations: This study has several limitations. Firstly, analytical techniques employed in this study measure only seven ChEs (Ca, Cl, I, K, Mg, Mn, and Na) mass fractions. Future studies should be directed toward using other analytical methods which will extend the list of ChE investigated in “normal” thyroid and in pathologically altered tissue. Secondly, the sample size of TMNs group was relatively small and prevented investigations of ChEs contents in this group using differentials like gender, histological types of TMNs, tumor functional activity, stage of disease, and dietary habits of patients with TMNs. Lastly, generalization of our results may be limited to Russian population. Despite these limitations, this study provides evidence on many ChEs level alteration in malignant tumor and adjacent to tumor tissue and shows the necessity to continue ChEs research of TMNs.

Conclusion

In this work, ChEs analysis was carried out in the tissue samples of TMNs using INAA-SLR. It was shown that INAA-SLR is an adequate analytical tool for the non-destructive determination of Ca, Cl, I, K, Mg, Mn, and Na content in the tissue samples of human thyroid in norm and pathology, including needle-biopsy specimens. It was observed that in malignant tissue the mass fraction of Cl, K, Mg, and Na were approximately 2.3, 1.6, 1.6, and 1.3 times, respectively, higher whereas mass fraction of I was 25.6 times lower than in the normal thyroid. In a general sense K, Mg, Mn, and Na contents found in the “normal” and “adjacent” groups of thyroid tissue samples were very similar. However, in the “adjacent” group mean mass fractions of Cl and I were 1.57 and 1.73 times, respectively, higher, while mean value of Ca content almost 2 times lower than in the “normal” group. In malignant tumor Ca, Cl, and K contents were approximately 2.8, 1.4, and 1.7 times, respectively, higher, while I content 43.5 times lower than in “adjacent” group of tissue samples. Thus, from results obtained, it was possible to conclude that the common characteristics of TMNs in comparison with “normal” thyroid and visually “intact” thyroid tissue adjacent to malignant tumors were elevated levels of Cl and K, as well as drastically reduced level of I. It was supposed that elevated levels of Cl and K, as well as drastically reduced level of I in cancerous tissue could possibly be explored for differential diagnosis of benign and malignant thyroid nodules.

References

  1. Laha D, Nilubol N, Boufraqech M. New therapies for advanced thyroid cancer. Front Endocrinol (Lausanne) 2020;11:82 ..
  2. X-ray fluorescence analysis of bromine for the estimation of extracellular water Zaichick V. J Appl Radiat Isot.1998;49(12):1165-1174.
  3. Evaluation of bromine, calcium, chlorine, iodine, potassium, magnesium, manganese, and sodium content in the thyroid adenomas using neutron activation analysis Zaichick V. Journal of Carcinogenesis & Mutagenesis.2021;12(366):1-8.
  4. Association between female subclinical hypothyroidism and inadequate quantities of some intra-thyroidal chemical elements investigated by X-ray fluorescence and neutron activation analysis Zaichick V, Zaichick S. Gynaecology and Perinatology.2018;2(4):340-355.
  5. Effect of age on chemical element contents in female thyroid investigated by some nuclear analytical methods Zaichick V, Zaichick S. MicroMedicine.2018;6(1):47-61.
  6. Trace-metal analysis of cancerous and non-cancerous human tissues Mulay I L, Roy R, Knox B E, Suhr N H, Delaney W E. J Natl Cancer Inst.1971;47:1-13.
  7. Red blood cell, serum and tissue magnesium levels in subjects with laryngeal carcinoma Szmeja Z, Koenczewska H. J Otorhinolaryngol Relat Spec.1983;45:102-107.
  8. The effect of age on Br, Ca, Cl, K, Mg, Mn, and Na mass fraction in pediatric and young adult prostate glands investigated by neutron activation analysis Zaichick V, Zaichick S. Appl Radiat Isot.2013;82:145-151.
  9. Thyroid nodules: Advances in evaluation and management Kant R, Davis A, Verma V. Am Fam Physician.2020;102(5):298-304.
  10. Magnesium and cancer: Clinical data Collery P, Anghileri L J, Coudoux P, Durlach J. Magnesium Bull.1981;3:11-20.
  11. Dietary Intake of Endocrine Disrupting Substances Presents in Environment and Their Impact on Thyroid Function Sokal A, Jarmakiewicz-Czaja S, Tabarkiewicz J, Filip R. Nutrients.2021;13(3):867-867.
  12. Se, and Zn contents in intact thyroid of females investigated by neutron activation analysis Zaichick V, Zaichick S, Age Ag Co Cr Fe Hg Rb Sb Sc. J Gerontol Geriatr Med.2017;3:15-15.
  13. Medical elementology as a new scientific discipline Zaichick V. J Radioanal Nucl Chem.2006;269:303-309.
  14. Relationship between magnesium, cancer and carcinogenic or anticancer metals Durlach J, Bara M, Guiet-Bara A, Collery P. Anticancer Res.1986;6:1353-1361.
  15. Investigation of association between the high risk of female subclinical hypothyroidism and inadequate quantities of intra-thyroidal trace elements using neutron activation and inductively coupled plasma mass spectrometry Zaichick V, Zaichick S. Acta Scientific Medical Sciences.2018;2(9):23-37.
  16. Nutritional status and follicular-derived thyroid cancer: An update Barrea L, Gallo M, Ruggeri R M, Giacinto Di, Sesti P, Prinzi F, Adinolfi N, Barucca V, Renzelli V, Muscogiuri V, Colao G, Baldelli A, R. Crit Rev Food Sci Nutr.2021;61(1):25-59.
  17. INAA application in the age dynamics assessment of Br, Ca, Cl, K, Mg, Mn, and Na content in the normal human prostate Zaichick S, Zaichick V. J Radioanal Nucl Chem.2011;288(1):197-202.
  18. Environmental Factors Affecting Thyroid-Stimulating Hormone and Thyroid Hormone Levels Leko M B, Gunjača I, Pleić N, Zemunik T. Int J Mol Sci.2021;22(12):6521-6521.
  19. Se, and Zn contents in intact thyroid of males investigated by neutron activation analysis Zaichick V, Zaichick S, Age Ag Co Cr Fe Hg Rb Sb Sc. Curr Trends Biomedical Eng Biosci.2017;4(4):555644-555644.
  20. Human intrathyroidal iodine in health and non-thyroidal disease Zaichick V, M.Abdulla, M.Bost, S.Gamon, P.Arnaud, G.Chazot). London: Smith-Gordon. New aspects of trace element research.1999;:114-119.
  21. Changes in bioavailability and tissue distribution of selenium caused by magnesium deficiency in rats Jiménez A. J Am Coll Nutr.1997;16:175-180.
  22. Associations between age and 50 trace element contents and relationships in intact thyroid of males Zaichick V, Zaichick S. Aging Clin Exp Res.2018;30(9):1059-1070.
  23. Association between iodine intake, thyroid function, and papillary thyroid cancer: A case-control study Kim K, Cho S W, Park Y J, Lee K E, Lee D-W, Park S K. Endocrinol Metab (Seoul).2021;36(4):790-799.
  24. Iodine status in the colombian population and the impact of universal salt iodization: a double-edged sword? Vargas-Uricoechea Р, Pinzón-Fernández M V, Bastidas-Sánchez B E, Jojoa-Tobar E, Ramírez-Bejarano L E, Murillo-Palacios J. J Nutr Metab.2019;:6239243-6239243.
  25. Age-related changes of Br, Ca, Cl, I, K, Mg, Mn, and Na contents in intact thyroid of males investigated by neutron activation analysis Zaichick V, Zaichick S. J Aging Age Relat Dis.2017;1(1):1002-1002.
  26. Age-related changes of some trace element contents in intact thyroid of males investigated by energy dispersive X-ray fluorescent analysis Zaichick V, Zaichick S. MOJ Gerontol Ger.2017;1(5):28-28.
  27. Energy-dispersive X-ray fluorescence of iodine in thyroid puncture biopsy specimens Zaichick V, Zaichick S. J Trace Microprobe Tech.1999;17(2):219-232.
  28. Comparison between Bromine, Calcium, Chlorine, Iodine, Potassium, Magnesium, Manganese, and Sodium Contents in Macro and Micro Follicular Colloid Goiter Zaichick V. Innovare Journal of Medical Sciences.2021;9(6):5-9.
  29. Applications of synthetic reference materials in the medical Radiological Research Centre Zaichick V. Fresenius J Anal Chem.1995;352:219-223.
  30. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms Beyersmann D, Hartwig A. Arch Toxicol.2008;82(8):493-512.
  31. Neutron activation and X-ray fluorescent analysis in study of association between age and chemical element contents in thyroid of males Zaichick V, Zaichick S. Op Acc J Bio Eng Bio Sci.2018;2(4):202-212.
  32. Investigation of association between the high risk of female subclinical hypothyroidism and inadequate quantities of twenty intra-thyroidal chemical elements Zaichick V, Zaichick S. Clin Res: Gynecol Obstet.2018;1(1):1-18.
  33. Iodine status and thyroid function in a group of seaweed consumers in Norway Aakre I, Evensen L T, Kjellevold M, Dahl L, Henjum S, Alexander J, Madsen L, Markhus M W. Nutrients.2020;12(11):3483-3483.
  34. Neutron-activation analysis in the study of the behavior of iodine in the organism Zaĭchik V, Yus Raibukhin, Melnik A D, Cherkashin V I. Med Radiol (Mosk).1970;15(1):33-36.
  35. Intrathyroid iodine in the diagnosis of thyroid cancer Zaĭchik V, Matveenko E G, Vtiurin B M, Medvedev V S. Vopr Onkol.1982;28(3):18-24.
  36. Possible role of inadequate quantities of intra-thyroidal cobalt, rubidium and zinc in the etiology of female subclinical hypothyroidism Zaichick V, Zaichick S. Womens Health Sci J.2018;2(1):108-108.
  37. Instrumental effect on the contamination of biomedical samples in the course of sampling Zaichick V, Zaichick S. The Journal of Analytical Chemistry.1996;51(12):1200-1205.
  38. Comparison between Bromine, Calcium, Chlorine, Iodine, Potassium, Magnesium, Manganese, and Sodium Contents in Normal Thyroid and Thyroid with Hashimoto's thyroiditis Zaichick V. J Clin Res Oncol.2021;4(1):1-7.
  39. Toxicology and carcinogenesis studies of sodium chlorate (Cas No. 7775-09-9) in F344/N rats and B6C3F1 mice (drinking water studies) Natl Toxicol Program Tech Rep Ser.2005;517:1-255.
  40. Association between age and twenty chemical element contents in intact thyroid of males Zaichick V, Zaichick S. SM Gerontol Geriatr Res.2018;2(1):1014-1014.
  41. Consequences of excess iodine Leung A M, Braverman L E. Nat Rev Endocrinol.2014;10(3):136-142.
  42. Risk assessment of toxic and essential trace metals on the thyroid health at the tissue level: The significance of lead and selenium for colloid goiter disease Stojsavljević A, Rovčanin B, Krstić D, Borković-Mitić S, Paunović I, Diklić A, Gavrović-Jankulović M, Manojlović D. Expo Health; 2019.
  43. Magnesium and tumors: Ally or foe? Wolf F I, Cittadini Arm, Maier A M. Cancer Treatment Reviews.2009;35(4):378-382.
  44. Variation with age of chemical element contents in females’ thyroids investigated by neutron activation analysis and inductively coupled plasma atomic emission spectrometry Zaichick V, Zaichick S. J Biochem Analyt Stud.2018;3(1):1-10.
  45. Age-related changes of some trace element contents in intact thyroid of females investigated by energy dispersive X-ray fluorescent analysis Zaichick V, Zaichick S. Trends Geriatr Healthc.;2017(1):31-38.
  46. Possible role of inadequate quantities of intra-thyroidal bromine, rubidium and zinc in the etiology of female subclinical hypothyroidism Zaichick V, Zaichick S. EC Gynaecology.2018;7(3):107-115.
  47. Environmental epigenetics in metal exposure Martinez-Zamudio R, Ha H C. Epigenetics.2011;6(7):820-827.
  48. Epidemiology of endometriosis and its comorbidities Parazzini F, Esposito G, Tozzi L, Tozzi S. Eur J Obstet Gynecol Reprod Biol.2017;209:3-7.
  49. Software to optimize the multielement INAA of medical and environmental samples Korelo A M, Zaichick V. Activation Analysis in Environment Protection.1993;:326-332.
  50. Determination of twenty chemical element contents in normal and goitrous thyroid using X-ray fluorescent and neutron activation analysis Zaichick V. World Journal of Advanced Research and Reviews.2021;11(02):130-176.
  51. Zaichick S, Zaichick V. INAA application in the age dynamics assessment of Br, Ca, Cl, K, Mg, Mn, and Na content in the normal human prostate. J Radioanal Nucl Chem 2011;288(1):197-202. ..
  52. Zaichick V, Zaichick S. The effect of age on Br, Ca, Cl, K, Mg, Mn, and Na mass fraction in pediatric and young adult prostate glands investigated by neutron activation analysis. Appl Radiat Isot 2013;82:145-151. ..
  53. Korelo AM, Zaichick V. Software to optimize the multielement INAA of medical and environmental samples. In: Activation Analysis in Environment Protection. Dubna, Russia: Joint Institute for Nuclear Research, 1993:326-332 ..
  54. Leko MB, Gunjača I, Pleić N, Zemunik T. Environmental Factors Affecting Thyroid-Stimulating Hormone and Thyroid Hormone Levels. Int J Mol Sci 2021;22(12):6521 ..
  55. Schwartz GG, Klug MG. Thyroid Cancer Incidence Rates in North Dakota are Associated with Land and Water Use. Int J Environ Res Public Health. 2019;16(20):3805. ..
  56. National Toxicology Program. Toxicology and carcinogenesis studies of sodium chlorate (Cas No. 7775-09-9) in F344/N rats and B6C3F1 mice (drinking water studies). Natl Toxicol Program Tech Rep Ser 2005;517:1-255. ..
  57. Parazzini F, Esposito G, Tozzi L, Tozzi S. Epidemiology of endometriosis and its comorbidities. Eur J Obstet Gynecol Reprod Biol 2017;209:3-7. ..
  58. Sokal A, Jarmakiewicz-Czaja S, Tabarkiewicz J, Filip R. Dietary Intake of Endocrine Disrupting Substances Presents in Environment and Their Impact on Thyroid Function. Nutrients 2021;13(3):867. ..
  59. Zaichick V. X-ray fluorescence analysis of bromine for the estimation of extracellular water. J Appl Radiat Isot. 1998;49(12):1165-9. ..
  60. Kant R, Davis A, Verma V. Thyroid nodules: Advances in evaluation and management. Am Fam Physician 2020;102(5):298-304. ..
  61. Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol 2014;10(3):136-142. ..
  62. Lee J-H, Hwang Y, Song R-Y, Yi JW, Yu HW, Kim S-J, Chai YJ, ChoiJY, Lee KE, Park SK. Relationship between iodine levels and papillary thyroid carcinoma: A systematic review and meta-analysis. Head Neck 2017;39(8):1711-1718. ..
  63. Aakre I, Evensen LT, Kjellevold M, Dahl L, Henjum S, Alexander J, Madsen L, Markhus MW. Iodine status and thyroid function in a group of seaweed consumers in Norway. Nutrients 2020;12(11):3483. ..
  64. Moncayo R, Moncayo H. Applying a systems approach to thyroid physiology: Looking at the whole with a mitochondrial perspective instead of judging single TSH values or why we should know more about mitochondria to understand metabolism. BBA Clin 2017;7:127-140. ..
  65. Chandra A.K. Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats. Indian J Exp Biol 2014;52:787-792. ..
  66. Jiménez A. Changes in bioavailability and tissue distribution of selenium caused by magnesium deficiency in rats. J Am Coll Nutr 1997;16:175-180. ..
  67. Durlach J, Bara M, Guiet-Bara A, Collery P. Relationship between magnesium, cancer and carcinogenic or anticancer metals. Anticancer Res 1986;6:1353-1361. ..
  68. Mulay IL, Roy R, Knox BE, Suhr NH, Delaney WE. Trace-metal analysis of cancerous and non-cancerous human tissues. J Natl Cancer Inst 1971;47:1-13. ..
  69. Anghileri LJ, Miller ES, Robinette J, Prasad KN, Lagerborg VA. Calcium metabolism in tumors. II. Calcium, magnesium and phosphorus in human and animal tumors. Oncology 1971;25:193-209. ..
  70. Digiesi V, Bandinelli R, Bisceglie P, Santoro E. Magnesium in tumoral tissues, in the muscle and serum of subjects suffering from neoplasia. Biochem Med 1983;29:360-363. ..
  71. Szmeja Z, Koenczewska H. Red blood cell, serum and tissue magnesium levels in subjects with laryngeal carcinoma. J Otorhinolaryngol Relat Spec 1983;45:102-107. ..
  72. Ranade SS, Panday VK. Major metals in human cancer: calcium, magnesium, sodium and potassium. Sci Total Environm 1985;41:79-89. ..
  73. Taylor JS, Vigneron DB, Murphy-Boesch J Nelson S., Kessler HB, Coia L, Curran W, Brown TR.. Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T. Proc Natl Acad Sci USA 1991;88:6810-6814. ..
  74. Collery P, Anghileri LJ, Coudoux P, Durlach J. Magnesium and cancer: Clinical data. Magnesium Bull 1981;3:11-20. ..
  75. Wolf FI, Cittadini ARM, Maier AM. Magnesium and tumors: Ally or foe? Cancer Treatment Reviews 2009;35(4):378-382. ..

##plugins.themes.bootstrap3.article.details##

Section
Articles

Cited by

AllSince 2017
Citations11
h-index11
i10-index00