Involvement of essential trace elements in the pathogenesis of thyroid diseases: diagnostic markers and analytical methods for determination

AIM. To study the role of iodine, selenium and zinc in the pathogenesis of iodine deficiency and autoimmune thyroid diseases and scientifically substantiate the choice of security biomarkers and analytical methods for determination.

MATERIALS AND METHODS. Serum iodine (I), selenium (Se), and zinc (Zn) concentrations were measured using inductively coupled plasma ionization tandem mass spectrometry (Agilent 8900 ICP-MS Triple Quad); by chemiluminescent immunoassay on an automatic analyzer Architect i2000 — TSH and AT-TPO in blood serum; by enzyme immunoassay — ZnT8A; biochemical method — ALP, SOD1 in 1150 people aged from 18 to 65 years (the average age of the subjects was 40±5 years). Ultrasound of the thyroid gland was performed in the supine position using a portable ultrasound machine LOGIQe with a multifrequency linear sensor 10–15 MHz; during the study, the volume of the thyroid gland, the presence of nodules and their characteristics according to the TIRADS classification, the structure of the thyroid gland and its echogenicity were assessed.

RESULTS. In our study, the median serum iodine concentration was 60.68 μg/L (n=1150), with no significant difference between sexes. In 2%, the level of iodine in the blood serum was less than 30 mcg/l. Among the samples obtained (n=57), 19% were found to have a reduced iodine content in the lipophilic fraction — less than 10% of the total. In these samples, additional studies were performed on TSH, total and free T3 and T4 fractions. As a result, all indicators fell within the normal range, which indicates that there was no effect on thyroid function from a decrease in iodine content in the lipophilic fraction. In a comparative analysis of our previously obtained results of determining iodine in urine using the cerium-arsenite method and the inductively coupled plasma mass spectrometry method, it was found that both methods are generally comparable. The median selenium concentration was 83.38 µg/l, which corresponds to the reference values. The proportion of individuals with serum selenium levels less than 40 μg/L was 2.2%. A comparative analysis of groups of patients with serum selenium concentrations of less than 100 µg/l and more than 100 µg/l was carried out; in the group with low-normal selenium levels, the incidence of autoimmune thyroid pathology is 5% higher than in the comparison group. 60.3% of the adult population had zinc levels less than 1000 μg/L. The median serum zinc concentration was 632.9 μg/L. In regions with zinc deficiency, the incidence of autoimmune diseases (AI) of the thyroid gland and nodular / multinodular goiter is on average 10% higher than in regions with optimal zinc supply. There was no relationship between the content of zinc in the blood serum and antibodies to the zinc transporter (ZnT8A), alkaline phosphatase (ALP) and superoxide dismutase (SOD1), including in comparison of the data obtained in carriers of AT-TPO and in the comparison group (among carriers of AT-TPO: the median concentration of zinc was 644.4 μg/l, SOD1 — 117.2 ng/ml, ALP — 70.3 U/l, antibodies to ZnT8A — 249.8; in the comparison group — median zinc concentration — 744.6 μg/l, SOD1 — 102.4 ng/ml, ALP — 66.1 U/l, antibodies to ZnT8A — 242).

Thus, based on the data obtained, the relationship between thyroid pathology and micronutrient deficiencies was confirmed. No convincing evidence has been obtained on the study of additional diagnostic markers of Zn deficiency, which casts doubt on the advisability of their determination in routine practice. The ICP-MS method made it possible to propose its own reference values for I, Se, Zn and is comparable to the cerium-arsenite method in sensitivity and specificity when studying I in urine. However, due to technical features and limitations in sample size, the study population requires further improvement.

1. Troshina EA, Senyushkina ES, Ioutsi VA, Nikankina LV. Issledovanie mikroelementov syvorotki krovi v sopostavlenii so strukturnofunkcional’nymi harakteristikami zoba i nositel’stvom antitireoidnyh antitel v ryade regionov Rossii. Voprosy pitaniya. 2022;91(6):85–91 (In Russ.)] doi: https://doi.org/10.33029/0042-8833-2022-91-6-00-00

2. Qing Zhou, Shuai Xue, Li Zhang, Guang Chen. Trace elements and the thyroid. Front Endocrinol (Lausanne). 2022;13:904889. doi: https://doi.org/10.3389/fendo.2022.904889

3. Mikronutrienty protiv koronavirusov / IYu Torshin, OA Gromova. Pod red. A.G. Chuchalina. Moskva: GEOTAR-Media, 2020. — 112 s. (In Russ.)]

4. Tam E, Keats EC, Rind F, Das JK, Bhutta AZA. Micronutrient supplementation and fortifi cation interventions on health and development outcomes among children under-fi ve in low- and middle-income countries: a systematic re view and meta-analysis. Nutrients. 2020;12(2):289. doi: https://doi.org/10.3390/nu12020289

5. Senyushkina ES, Troshina EА. The role of zinc in the synthesis and metabolism of thyroid hormones. Clinical and experimental thyroidology. 2020;16(3):25-30. (In Russ.)] doi: https://doi.org/10.14341/ket12697

6. Troshina EA, Platonova NM, Abdulhabirova FM, Gerasimov GA. Jododeficitnye zabolevaniya v Rossijskoj Federacii: vremya prinyatiya reshenij / Pod red. II Dedova, G.A. Mel’nichenko. — M.: OAO «Konti-Print»; 2012. 232 s. (In Russ.)]

7. Troshina EA. Zob. M.: OOO «Izdatel’stvo «Medicinskoe informacionnoe agenstvo»; 2012. 336 s. (In Russ.)]

8. Dedov II, Platonova NM, Troshina EA, Makolina NP, Belovalova IM, Senyushkina ES, Melnichenko GA. Prevention of iodine deficiency diseases: focus on regional targeted programs. Problems of Endocrinology. 2022;68(3):16-20. (In Russ.)] doi: https://doi.org/10.14341/probl13119

9. Troshina EA, Senyushkina ES, Terekhova MA. The role of selenium in the pathogenesis of thyroid disease. Clinical and experimental thyroidology. 2018;14(4):192-205. (In Russ.)] doi: https://doi.org/10.14341/ket10157

10. Gigiena pitaniya. Rukovodstvo dlya vrachej / AA Korolev. 2-e izd., pererabot. i dop. — Moskva: GEOTAR-Media, 2021. — 576 s. (In Russ.)]

11. Nazem MR, Asadi M, Jabbari N, Allameh A. Effects of zinc supplementation on superoxide dismutase activity and gene expression, and metabolic parameters in overweight type 2 diabetes patients: A randomized, double-blind, controlled trial. Clin Biochem. 2019;69:15-20. doi: https://doi.org/10.1016/j.clinbiochem.2019.05.008

12. Makris K, Mousa C, Cavalier E. Alkaline Phosphatases: Biochemistry, Functions, and Measurement. Calcif Tissue Int. 2023. doi: https://doi.org/10.1007/s00223-022-01048-x

13. Handy DE, Loscalzo J. The role of glutathione peroxidase-1 in health and disease. Free Radic Biol Med. 2022. doi: https://doi.org/10.1016/j.freeradbiomed.2022.06.004

14. Bossowski A, Stożek K, Rydzewska M, et al. Expression of zinc transporter 8 in thyroid tissues from patients with immune and non-immune thyroid diseases. Autoimmunity. 2020;53(7):376-384. doi: https://doi.org/10.1080/08916934.2020.1815194

15. J.F. Kopp et al., Institute of Nutritional Science, Germany, 2019 K. Minakata et al., Department of Legal Medicine, Japan, 2010 Heitland P, Köster HD. Human biomonitoring of 73 elements in blood, serum, erythrocytes and urine. J Trace Elem Med Biol. 2021;64:126706. doi: https://doi.org/10.1016/j.jtemb.2020.126706

16. Troshina EA, Platonova NM, Makolina NP, Isaeva MP, Abdulhabirova FM, et al. Problema jododeficitnyh zabolevanij v Chechenskoj Respublike: ocenka tekushchego sostoyaniya i puti resheniya. V sbornike: Personalizirovannaya medicina i prakticheskoe zdravoohranenie. sbornik tezisov X (XXIX) Nacional’nogo kongressa endokrinologov s mezhdunarodnym uchastiem. Moskva, 2023. S. 200. (In Russ.)]

17. Troshina EA, Platonova NM, Makolina NP, Isaeva MP, Abdulhabirova FM, et al. Rasprostranennost’ jododeficitnyh zabolevanij v Tul’skoj oblasti: sovremennoe sostoyanie i puti resheniya problem. V sbornike: Personalizirovannaya medicina i prakticheskoe zdravoohranenie. sbornik tezisov X (XXIX) Nacional’nogo kongressa endokrinologov s mezhdunarodnym uchastiem. Moskva, 2023. S. 202. (In Russ.)]

18. Berezkin VY, Kolmykova LI, Kulieva GA. A study of iodine concentration in drinking waters of Bryansk and Oryol regions. Environ Geochem Health. 2023;45(2):299-304. doi: https://doi.org/10.1007/s10653-022-01249-1

19. Zheng H, Wei J, Wang L, et al. Effects of selenium supplementation on Graves’ disease: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2018;2018:3763565. doi: https://doi.org/10.1155/2018/3763565

20. Szeliga A, Czyzyk A, Niedzielski P, et al. Assessment of serum selenium concentration in patients with autoimmune thyroiditis in Poznan district. Pol Merkur Lekarski. 2018;45(268):150-153

21. Wang W, Mao J, Zhao J, et al. Decreased thyroid peroxidase antibody titer in response to selenium supplementation in autoimmune thyroiditis and the influence of a SEPP gene polymorphism: a prospective, multicenter study in China. Thyroid. 2018. doi: https://doi.org/10.1089/thy.2017.0230

22. Drutel A, Archambeaud F, Caron P. Selenium and the thyroid gland: more good news for clinicians. Clin Endocrinol (Oxf). 2013;78(2):155-164. doi: https://doi.org/10.1111/cen.12066

23. Ihnatowicz P, Drywień M, Wątor P, et al. The importance of nutritional factors and dietary management of Hashimoto’s thyroiditis. Annals of agricultural and environmental medicine. 2020:27(2):184-193. doi: https://doi.org/10.26444/aaem/112331

24. Mahmoodianfard S, Vafa M, Golgiri F, et al. Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled Trial. Journal of the American College of Nutrition. 2015:34(5):391-399. doi: https://doi.org/10.1080/07315724.2014.926161