Aging Clinical and Experimental Research

, Volume 30, Issue 9, pp 1059–1070 | Cite as

Associations between age and 50 trace element contents and relationships in intact thyroid of males

  • Vladimir ZaichickEmail author
  • Sofia Zaichick
Original Article



It is unclear why a prevalence of thyroid dysfunction is higher in the elderly as compared to the younger population. An excess or deficiency of trace element contents in thyroid may play important role in goitre- and carcinogenesis of gland.


To examine the variation with age of the mass fraction of 50 trace elements in intact (normal) male thyroid.


Samples of thyroid parenchyma obtained from 72 healthy males (mean age 37.8 years, range 2–80 years) was investigated. Measurements were performed using a combination of non-destructive and destructive methods: instrumental neutron activation analysis and inductively coupled plasma mass spectrometry, respectively. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for trace element analysis.


There is a statistically significant increase in Cd and Se mass fraction, as well as a decrease in Al, Be, Dy, Ga, Gd, Li, Mn, U, and Y mass fraction in the normal thyroid of male during a lifespan. Moreover, a disturbance of intra-thyroidal chemical element relationships (correlations) with increasing age was found.


Our findings suggest that, at least, a goitrogenic and carcinogenic effect of Cd overload and Mn deficiency in the thyroid of old males may be assumed. Many trace elements in human thyroid behave themselves as antagonists or synergists. Therefore, an age-related disturbance in correlations between Mn and other trace element mass fractions in thyroid parenchyma may also contribute to harmful effects on the gland.


Age-related changes in intra-thyroidal trace element contents and disturbances in trace element relationships are involved in goitre- and carcinogenesis.


Thyroid Chemical elements Age-related changes Neutron activation analysis Inductively coupled plasma mass spectrometry 



We are grateful to Dr. Yu. Choporov, Head of the Forensic Medicine Department of City Hospital, Obninsk, for supplying thyroid samples. We are also grateful to Dr. Karandaschev V., Dr. Nosenko S., and Moskvina I., Institute of Microelectronics Technology and High Purity Materials, Chernogolovka, Russia, for their help in ICP-MS analysis.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest aside from grant funding stated above.

Informed Consent

For this type of study formal consent is not required.

Statement of human and animal rights.

All 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 comparable ethical standards.

Supplementary material

40520_2018_906_MOESM1_ESM.docx (33 kb)
Supplementary material 1 (DOCX 33 KB)


  1. 1.
    Gesing A (2015) The thyroid gland and the process of aging. Thyroid Res 8(Suppl 1):A8CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Mitrou P, Raptis SA, Dimitriadis G (2011) Thyroid disease in older people. Maturitas 70:5–9CrossRefPubMedGoogle Scholar
  3. 3.
    Kwong N, Medici M, Angell TE et al (2015) The influence of patient age on thyroid nodule formation, multinodularity, and thyroid cancer risk. J Clin Endocrinol Metab 100:434–440CrossRefGoogle Scholar
  4. 4.
    Mazzaferri E (1993) Management of a solitary thyroid nodule. NEJM 328:553–559CrossRefPubMedGoogle Scholar
  5. 5.
    Smailyte G, Miseikyte-Kaubriene E, Kurtinaitis J (2006) Increasing thyroid cancer incidence in Lithuania in 1978–2003. BMC Cancer 11:284CrossRefGoogle Scholar
  6. 6.
    Olinski R, Siomek A, Rozalski R et al (2007) Oxidative damage to DNA and antioxidant status in aging and age-related diseases. Acta Biochim Pol 54:11–26PubMedGoogle Scholar
  7. 7.
    Minelli A, Bellezza I, Conte C et al (2009) Oxidative stress-related aging: a role for prostate cancer? Biochim Biophys Acta 1795:83–91PubMedGoogle Scholar
  8. 8.
    Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38:96–109CrossRefPubMedGoogle Scholar
  9. 9.
    Järup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182CrossRefPubMedGoogle Scholar
  10. 10.
    Zaichick V, Zaichick S (1999) Role of zinc in prostate cancerogenesis. In: Anke M et al (eds) Mengen und Spurenelemente, 19 Arbeitstagung. Friedrich-Schiller-Universitat, Jena, pp 104–115Google Scholar
  11. 11.
    Zaichick V (2004) INAA and EDXRF applications in the age dynamics assessment of Zn content and distribution in the normal human prostate. J Radioanal Nucl Chem 262:229–234CrossRefGoogle Scholar
  12. 12.
    Zaichick V (2006) Medical elementology as a new scientific discipline. J Radioanal Nucl Chem 269:303–309CrossRefGoogle Scholar
  13. 13.
    Toyokuni S (2008) Molecular mechanisms of oxidative stress-induced carcinogenesis: from epidemiology to oxygenomics. IUBMB Life 60:441–447CrossRefPubMedGoogle Scholar
  14. 14.
    Gupte A, Mumper RJ (2009) Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treat Rev 35:32–46CrossRefPubMedGoogle Scholar
  15. 15.
    Lee JD, Wu SM, Lu LY et al (2009) Cadmium concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans. Taiwan yi zhi 108:554–559CrossRefPubMedGoogle Scholar
  16. 16.
    Zaichick V, Tsyb A, Vtyurin BM (1995) Trace elements and thyroid cancer. Analyst 120:817–821CrossRefPubMedGoogle Scholar
  17. 17.
    Zaichick V, Choporov Yu (1996) Determination of the natural level of human intra-thyroid iodine by instrumental neutron activation analysis. J Radioanal Nucl Chem 207:153–161CrossRefGoogle Scholar
  18. 18.
    Zaichick V, Zaichick S (1997) Normal human intrathyroidal iodine. Sci Total Environ 206:39–56CrossRefPubMedGoogle Scholar
  19. 19.
    Zaichick V (1998) Iodine excess and thyroid cancer. J Trace Elem Exp Med 11:508–509Google Scholar
  20. 20.
    Zaichick V (1998) In vivo and in vitro application of energy-dispersive XRF in clinical investigations: experience and the future. J Trace Elem Exp Med 11:509–510Google Scholar
  21. 21.
    Zaichick V, Iljina T (1998) Dietary iodine supplementation effect on the rat thyroid 131I blastomogenic action. In: Anke M et al (eds) Die Bedentung der Mengen- und Spurenelemente. 18. Arbeitstangung. Friedrich-Schiller-Universität, Jena, pp 294–306Google Scholar
  22. 22.
    Zaichick V, Zaichick S (1999) Energy-dispersive X-ray fluorescence of iodine in thyroid puncture biopsy specimens. J Trace Microprobe Tech 17:219–232Google Scholar
  23. 23.
    Zaichick V (1999) Human intrathyroidal iodine in health and non-thyroidal disease. In: Abdulla M et al (eds) New aspects of trace element research. Smith-Gordon and Nishimura, London and Tokyo, pp 114–119Google Scholar
  24. 24.
    Zaichick V (2000) Relevance of, and potentiality for in vivo intrathyroidal iodine determination. Ann N Y Acad Sci 904:630–632CrossRefPubMedGoogle Scholar
  25. 25.
    Zhu H, Wang N, Zhang Y et al (2010) Element contents in organs and tissues of Chinese adult men. Health Phys 98:61–73CrossRefPubMedGoogle Scholar
  26. 26.
    Vlasova ZA (1969) Dynamics of trace element contents in thyroid gland in connection with age and atherosclerosis, vol 80. In: Proceedings of the Leningrad institute of doctor advanced training, pp 135–144Google Scholar
  27. 27.
    Kortev AI, Dontsov GI, Lyascheva AP (1972) Bio-elements in human pathology. Middle-Ural Publishing-House, SverdlovskGoogle Scholar
  28. 28.
    Kamenev VF (1963) Trace element contents in the thyroid gland of adult person. In: Trace elements in agriculture and medicine. Ulan-Ude, Russia, pp 12–16Google Scholar
  29. 29.
    Kosta L, Zelenko V, Ravnik V et al (1974) Trace elements in human thyroid with special reference to the observed accumulation of mercury following long-term exposure. In: Comparative studies of food and environmental contamination. IAEA, Vienna, pp 541–550Google Scholar
  30. 30.
    Reddy SB, Charles MJ, Kumar MR et al (2002) Trace elemental analysis of adenoma and carcinoma thyroid by PIXE method. Nucl Instrum Methods Phys Res B Beam Interact Mater Atoms 196:333–339CrossRefGoogle Scholar
  31. 31.
    Boulyga SF, Zhuk IV, Lomonosova EM et al (1997) Determination of microelements in thyroids of the inhabitants of Belarus by neutron activation analysis using the k0-method. J Radioanal Nucl Chem 222:11–14CrossRefGoogle Scholar
  32. 32.
    Zakutinskiy DI, Parfeynov UyD, Selivanova LN (1962) Handbook on the toxicology of radioisotopes. Meditcinskaya Literatura, MoscowGoogle Scholar
  33. 33.
    Tipton IH, Cook MJ (1963) Trace elements in human tissue. Part II. Adult subjects from the United States. Health Phys 9:103–145CrossRefPubMedGoogle Scholar
  34. 34.
    Remiz AM (1962) Endemic goiter and trace elements in Kabardino-Balkaria АSSR. In: In: All-Union conference on endocrinology. Medgiz, Moscow, pp 330–331Google Scholar
  35. 35.
    Uetani M, Kobayashi E, Suwazono Y et al (2006) Tissue cadmium (Cd) concentrations of people living in a Cd polluted area, Japan. Biometals 19:521–525CrossRefPubMedGoogle Scholar
  36. 36.
    Katoh Y, Sato T, Yamamoto Y (2002) Determination of multielement concentrations in normal human organs from the Japanese. Biol Trace Elem Res 90:57–70CrossRefPubMedGoogle Scholar
  37. 37.
    Salimi J, Moosavi K, Vatankhah S, Yaghoobi A (2004) Investigation of heavy trace elements in neoplastic and non-neoplastic human thyroid tissue: a study by proton-induced X-ray emissions. Iran J Radiat Res 1:211–216Google Scholar
  38. 38.
    Yamagata N (1962) The concentration of common cesium and rubidium in human body. J Radiat Res 3:9–30CrossRefPubMedGoogle Scholar
  39. 39.
    Ataulchanov IA (1969) Age-related changes of manganese, cobalt, coper, zinc, and iron contents in the endocrine glands of females. Probl Endocrinol 15:98–102Google Scholar
  40. 40.
    Belozerov ES (1965) Content of Ga trace element in some human tissues and organs, including thyroid gland. Zdravoohr Turkm 4:15–16Google Scholar
  41. 41.
    Teraoka H (1981) Distribution of 24 elements in the internal organs of normal males and the metallic workers in Japan. Arch Environ Health 36:155–165CrossRefPubMedGoogle Scholar
  42. 42.
    Reytblat MA, Kropacheyv AM (1967) Some trace elements in the normal thyroid of Perm Prikam’e inhabitants. Proc Perm Med Inst 78:157–164Google Scholar
  43. 43.
    Boulyga SF, Becker JS, Malenchenko AF et al (2000) Application of ICP-MS for multielement analysis in small sample amounts of pathological thyroid tissue. MCA 134:215–222Google Scholar
  44. 44.
    Fuzailov YuM (1981) Reaction of human and animal thyroids in the conditions of antimony sub-region of the Fergana valley. IX All-union conference on trace elements in biology, Kishinev, pp 58–62Google Scholar
  45. 45.
    Kvicala J, Havelka J, Zeman J (1991) Determination of some trace elements in the thyroid gland by INAA. J Radioanal Nucl Chem 149:267–274CrossRefGoogle Scholar
  46. 46.
    Forssen A (1972) Inorganic elements in the human body. Ann Med Exp Biol Fenn 50:99–162PubMedGoogle Scholar
  47. 47.
    Soman SD, Joseph KT, Raut SJ (1970) Studies of major and trace element content in human tissues. Health Phys 19:641–656CrossRefPubMedGoogle Scholar
  48. 48.
    Wang J, Zhu H, Ouyang L (2004) Determination of trace Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS. Spectrosc Spect Anal 24:1117–1120Google Scholar
  49. 49.
    Zaichick V (1997) Sampling, sample storage and preparation of biomaterials for INAA in clinical medicine, occupational and environmental health. In: Harmonization of health-related environmental measurements using nuclear and isotopic techniques. IAEA, Vienna, pp 123–133Google Scholar
  50. 50.
    Zaichick V (2004) Losses of chemical elements in biological samples under the dry ashing process. Mikroelem Med 5:17–22Google Scholar
  51. 51.
    Zaichick V, Zaichick S (2000) INAA applied to halogen (Br and I) stability in long-term storage of lyophilized biological materials. J Radioanal Nucl Chem 244:279–281CrossRefGoogle Scholar
  52. 52.
    Zaichick V, Zaichick S (1996) Instrumental effect on the contamination of biomedical samples in the course of sampling. Zh Anal Khim 51:1200–1205Google Scholar
  53. 53.
    Zaichick V, Tsislyak YuV (1978) A simple device for bio-sample lyophilic drying. Lab Delo 2:109–110Google Scholar
  54. 54.
    Zaichick V, Tsislyak YuV (1981) A modified adsorptive and cryogenic lyophilizer for biosample concentrations. Lab Delo 2:100–101Google Scholar
  55. 55.
    Zaichick V, Zaichick S (1997) A search for losses of chemical elements during freeze-drying of biological materials. J Radioanal Nucl Chem 218:249–253CrossRefGoogle Scholar
  56. 56.
    Zaichick V (1995) Applications of synthetic reference materials in the medical Radiological Research Centre. Fresenius J Anal Chem 352:219–223CrossRefGoogle Scholar
  57. 57.
    Zaichick S, Zaichick V (2011) The effect of age on Ag, Co, Cr, Fe, Hg, Sb, Sc, Se, and Zn contents in intact human prostate investigated by neutron activation analysis. J Appl Radiat Isot 69:827–833CrossRefGoogle Scholar
  58. 58.
    Zaichick V, Zaichick S (2013) INAA application in the assessment of Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn mass fraction in pediatric and young adult prostate glands. J Radioanal Nucl Chem 298:1559–1566CrossRefGoogle Scholar
  59. 59.
    Zaichick V, Zaichick S, Na P (2014) Relations of the Al, B, Ba, Br, Ca, Cl, Cu, Fe, K, Li, Mg, Mn, S, Si, Sr, and Zn mass fractions to morphometric parameters in pediatric and nonhyperplastic young adult prostate glands. Biometals 27:333–348CrossRefPubMedGoogle Scholar
  60. 60.
    Zaichick S, Zaichick V, Nosenko S et al (2012) Mass fractions of 52 trace elements and zinc trace element content ratios in intact human prostates investigated by inductively coupled plasma mass spectrometry. Biol Trace Elem Res 149:171–183CrossRefPubMedGoogle Scholar
  61. 61.
    Zaichick V, Zaichick S (2013) Use of neutron activation analysis and inductively coupled plasma mass spectrometry for the determination of trace elements in pediatric and young adult prostate. AJAC 4:696–706CrossRefGoogle Scholar
  62. 62.
    Zaichick V, Zaichick S (2014) Use of INAA and ICP-MS for the assessment of trace element mass fractions in adult and geriatric prostate. J Radioanal Nucl Chem 301:383–397CrossRefGoogle Scholar
  63. 63.
    Zaichick S. Zaichick V (2010) The effect of age and gender on 37 chemical element contents in scalp hair of healthy humans. Biol Trace Elem Res 134:41–54CrossRefPubMedGoogle Scholar
  64. 64.
    Korelo AM, Zaichick V (1993) Software to optimize the multielement INAA of medical and environmental samples. In: Activation analysis in environment protection. Joint Institute for Nuclear Research, Dubna, pp 326–332Google Scholar
  65. 65.
    Schroeder HA, Tipton IH, Nason AP (1972) Trace metals in man: strontium and barium. J Chron Dis 25:491–517CrossRefPubMedGoogle Scholar
  66. 66.
    Krewski D, Yokel RA, Nieboer E et al (2007) Human health risk assessment for aluminium, aluminium oxide, and aluminium hydroxide. J Toxicol Environ Health B Crit Rev 10(Suppl 1):1–269CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Ivanoff CS, Ivanoff AE, Hottel TL (2012) Gallium poisoning: a rare case report. FCT 50:212–215Google Scholar
  68. 68.
    Zaichick S, Zaichick V, Karandashev V et al (2011) Accumulation of rare earth elements in human bone within the lifespan. Metallomics 3:186–194CrossRefPubMedGoogle Scholar
  69. 69.
    Mulware SJ (2013) Trace elements and carcinogenicity: a subject in review. Biotech 3:85–96CrossRefPubMedGoogle Scholar
  70. 70.
    Waisberg M, Joseph P, Hale B et al (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192:95–117CrossRefPubMedGoogle Scholar
  71. 71.
    Jancic SA, Stosic BZ (2014) Cadmium effects on the thyroid gland. Vitam Horm 94:391–425CrossRefPubMedGoogle Scholar
  72. 72.
    Hartwig A (2013) Cadmium and cancer. Met Ions Life Sci 11:491–507CrossRefPubMedGoogle Scholar
  73. 73.
    Harari F, Bottai M, Casimiro E et al (2015) Exposure to lithium and cesium through drinking water and thyroid function during pregnancy: a prospective cohort study. Thyroid 25:1199–1208CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Zaichick S, Zaichick V, Karandashev V et al (2011) The effect of age on the lithium content in prostate of healthy men. In: Interaction of neutrons with nuclei. Joint Institute for Nuclear Research, Dubna, pp 337–341Google Scholar
  75. 75.
    Soldin OP, Aschner M (2007) Effects of manganese on thyroid hormone homeostasis. Neurotoxicology 28:951–956CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Aschner JL, Aschner M (2005) Nutritional aspects of manganese homeostasis. Mol Asp Med 26:353–362CrossRefGoogle Scholar
  77. 77.
    Hasegawa S, Koshikawa M, Takahashi I et al (2008) Alterations in manganese, copper, and zinc contents, and intracellular status of the metal-containing superoxide dismutase in human mesothelioma cells. J Trace Elem Med Biol 22:248–255CrossRefPubMedGoogle Scholar
  78. 78.
    Watts DL (1989) The nutritional relationships of the thyroid. Orthomol Med 4:165–169Google Scholar
  79. 79.
    Aaseth J, Frey H, Glattre E et al (1990) Selenium concentrations in the human thyroid gland. Biol Trace Elem Res 24:147–152CrossRefPubMedGoogle Scholar
  80. 80.
    Winde F, Erasmus E, Geipel G (2017) Uranium contaminated drinking water linked to leukaemia—revisiting a case study from South Africa taking alternative exposure pathways into account. Sci Total Environ 574:400–421CrossRefPubMedGoogle Scholar
  81. 81.
    Banning A, Benfer M (2017) Drinking water uranium and potential health effects in the German Federal State of Bavaria. Int J Environ Res Public Health 14:1–10CrossRefGoogle Scholar
  82. 82.
    Snow ET (1992) Metal carcinogenesis: mechanistic implications. Pharmacol Ther 53:31–65CrossRefPubMedGoogle Scholar
  83. 83.
    Toyokuni S (2009) Role of iron in carcinogenesis: cancer as a ferrotoxic disease. Cancer Sci 100:9–16CrossRefPubMedGoogle Scholar
  84. 84.
    Martinez-Zamudio R, Ha HC (2011) Environmental epigenetics in metal exposure. Epigenetics 6:820–827CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Tokar EJ, Benbrahim-Tallaa L, Waalkes MP (2011) Metal ions in human cancer development. Met Ions Life Sci 8:375–401PubMedGoogle Scholar
  86. 86.
    Tchounwou PB, Yedjou CG, Patlolla AK et al (2012) Heavy metal toxicity and the environment. EXS 101:133–164PubMedPubMedCentralGoogle Scholar
  87. 87.
    Koedrith P, Kim H, Weon JI et al (2013) Toxicogenomic approaches for understanding molecular mechanisms of heavy metal mutagenicity and carcinogenicity. Int J Hyg Environ Health 216:587–598CrossRefPubMedGoogle Scholar
  88. 88.
    Tabrez S, Priyadarshini M, Priyamvada S et al (2014) Gene–environment interactions in heavy metal and pesticide carcinogenesis. Mutat Res 760:1–9CrossRefGoogle Scholar
  89. 89.
    Zaichick V, Zaichick S, Rossmann M (2016) Intracellular calcium excess as one of the main factors in the etiology of prostate cancer. AIMS Mol Sci 3:635–647CrossRefGoogle Scholar
  90. 90.
    Zaichick V, Zaichick S, Wynchank S (2016) Intracellular zinc excess as one of the main factors in the etiology of prostate cancer. J Anal Oncol 5:124–131CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Radionuclide Diagnostics DepartmentMedical Radiological Research CentreObninskRussia
  2. 2.Laboratory of Dr. Gabriela CaraveoPiso, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

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