The effect of selenium deficiency on thyroid deiodinase activity and the severity of oxidative stress in autoimmune thyroid diseases: a review of the literature
Keywords:
selenoproteins, glutathione peroxidase, thioredoxin reductase, Hashimoto’s thyroiditis, Graves' disease, trace element supplementationAbstract
Background. Selenium is a trace element of crucial importance for thyroid physiology, acting mainly through its incorporation into functionally specialised proteins, including the iodothyronine deiodinases and several enzymes engaged in antioxidant defence. Growing clinical and experimental data link suboptimal selenium status with an increased risk of autoimmune thyroid diseases (AITDs), particularly Hashimoto's thyroiditis, Graves' disease and postpartum thyroid dysfunction.
Methods. A structured search of the PubMed/MEDLINE database was performed using keywords related to selenium, deiodinases, oxidative stress and autoimmune thyroid disorders. The analysis primarily included English-language articles, with one regionally relevant Polish publication. Priority was given to randomised controlled trials, meta-analyses and large observational studies. Animal studies were included only where human data were insufficient.
Results. Selenium deficiency lowers DIO1 and DIO2 activity, impairing peripheral conversion of thyroxine to the active triiodothyronine. A concurrent decline in glutathione peroxidase and thioredoxin reductase activity promotes oxidative stress in thyrocytes and may amplify immune-mediated tissue injury. Clinical trials show that selenium supplementation (100–200 µg/day) can reduce anti-thyroid peroxidase antibody titres in Hashimoto's thyroiditis, improve mild Graves' orbitopathy and decrease postpartum thyroid dysfunction in women with positive thyroid antibodies.
Conclusions. Adequate selenium status is essential for thyroid hormone homeostasis and for limiting oxidative damage in AITDs. Selenium supplementation may benefit certain patients, particularly those in selenium-deficient populations. Nevertheless, its narrow therapeutic window and considerable genetic variability in selenium metabolism require individualised supplementation.
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Bano I, Hassan MF, Kieliszek M. A comprehensive review of selenium as a key regulator in thyroid health. Biol Trace Elem Res. 2025;203(12):6466–6480. https://doi.org/10.1007/s12011-025-04653-7. PMID: 40358914.
Maia LB, Maiti BK, Moura I, Moura JJG. Selenium—more than just a fortuitous sulfur substitute in redox biology. Molecules. 2023;29(1):120. https://doi.org/10.3390/molecules29010120. PMID: 38202704.
Wang F, Li C, Li S, Cui L, Zhao J, Liao L. Selenium and thyroid diseases. Front Endocrinol. 2023;14:1133000. https://doi.org/10.3389/fendo.2023.1133000.
Zhang Y, Zhang Q, Wei B, Wang W, Chen X, Ding W, et al. SEPHS2 loss reprograms cancer metabolism from oxidative phosphorylation to gluconeogenesis via PCK1 stabilization. Cell Rep. 2026;45(5):117297. https://doi.org/10.1016/j.celrep.2026.117297. PMID: 42035418.
Kieliszek M, Bano I. Selenium as an important factor in various disease states—a review. EXCLI J. 2022;21:948–966. https://doi.org/10.17179/excli2022-5137. PMID: 36172072.
Mojadadi A, Au A, Salah W, Witting P, Ahmad G. Role for selenium in metabolic homeostasis and human reproduction. Nutrients. 2021;13(9):3256. https://doi.org/10.3390/nu13093256. PMID: 34579133.
Kochman J, Jakubczyk K, Bargiel P, Janda-Milczarek K. The influence of oxidative stress on thyroid diseases. Antioxidants (Basel). 2021;10(9):1442. https://doi.org/10.3390/antiox10091442. PMID: 34573074.
Rovcanin B, Stojsavljevic A, Kekic D, Gopcevic K, Manojlovic D, Jovanovic M, et al. Redox status and antioxidative cofactor metals influence clinical and pathological characteristics of papillary thyroid carcinoma and colloid goiter. Biol Trace Elem Res. 2020;197(2):349–359. https://doi.org/10.1007/s12011-019-01995-x. PMID: 31811573.
Eckert JV, Rogers LK, Tipple TE, Mathias M. Selenium in the preterm infant: are we supplementing enough in this vulnerable population? Nutrients. 2026;18(8):1271. https://doi.org/10.3390/nu18081271.
National Institutes of Health Office of Dietary Supplements. Selenium—Health Professional Fact Sheet. Bethesda (MD): NIH Office of Dietary Supplements; 2024. Available from: https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
Wang M, Li B, Li S, Song Z, Kong F, Zhang X. Selenium in wheat from farming to food. J Agric Food Chem. 2021;69(51):15458–15467. https://doi.org/10.1021/acs.jafc.1c04992. PMID: 34907773.
Stefanowicz FA, Talwar D, O'Reilly DS, Dickinson N, Atkinson J, Hursthouse AS, et al. Erythrocyte selenium concentration as a marker of selenium status. Clin Nutr. 2013;32(5):837–842. https://doi.org/10.1016/j.clnu.2013.01.005. PMID: 23391458.
Hadrup N, Ravn-Haren G. Absorption, distribution, metabolism and excretion (ADME) of oral selenium from organic and inorganic sources: a review. J Trace Elem Med Biol. 2021;67:126801. https://doi.org/10.1016/j.jtemb.2021.126801.
Huang J, Xie L, Song A, Zhang C. Selenium status and its antioxidant role in metabolic diseases. Oxid Med Cell Longev. 2022;2022:7009863. https://doi.org/10.1155/2022/7009863. PMID: 35847596.
Bai S, Zhang M, Tang S, Li M, Wu R, Wan S, et al. Effects and impact of selenium on human health: a review. Molecules. 2024;30(1):50. https://doi.org/10.3390/molecules30010050. PMID: 39795109.
Seale LA, Hashimoto AC, Kurokawa S, Berry MJ. Sexual dimorphism in selenium metabolism and selenoproteins. Free Radic Biol Med. 2018;127:198–205.
EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, et al. Scientific opinion on the tolerable upper intake level for selenium. EFSA J. 2023;21(1):e07704. https://doi.org/10.2903/j.efsa.2023.7704. PMID: 36698500.
Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, et al. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2010;91(4):923–931. https://doi.org/10.3945/ajcn.2009.28169. PMID: 20181815. PMCID: PMC2844680.
Cornelis MC, Fornage M, Foy M, Xun P, Gladyshev VN, Morris S, et al. Genome-wide association study of selenium concentrations. Hum Mol Genet. 2015;24(5):1469–1477. https://doi.org/10.1093/hmg/ddu546.
Ferreira RR, Carvalho RV, Coelho LL, Gonzaga BMS, Bonecini-Almeida MDG, Garzoni LR, et al. Current understanding of human polymorphism in selenoprotein genes: a review of its significance as a risk biomarker. Int J Mol Sci. 2024;25(3):1402. https://doi.org/10.3390/ijms25031402.
Wang L, Sagada G, Wang R, Li P, Xu B, Zhang C, et al. Different forms of selenium supplementation in fish feed: the bioavailability, nutritional functions, and potential toxicity. Aquaculture. 2022;549:737819. https://doi.org/10.1016/j.aquaculture.2021.737819.
Battin EE, Zimmerman MT, Ramoutar RR, Quarles CE, Brumaghim JL. Preventing metal-mediated oxidative DNA damage with selenium compounds. Metallomics. 2011;3(5):503–512. https://doi.org/10.1039/c0mt00063a.
Bisht N, Phalswal P, Khanna PK. Selenium nanoparticles: a review on synthesis and biomedical applications. Mater Adv. 2022;3:1415–1431. https://doi.org/10.1039/D1MA00659B.
Sentkowska A, Pyrzyńska K. The influence of synthesis conditions on the antioxidant activity of selenium nanoparticles. Molecules. 2022;27(8):2486. https://doi.org/10.3390/molecules27082486.
Tan Y, Zhang F, Cao J, Feng L, Xie B, Gao L, et al. GPX1-driven selenium nanoplatform reprograms MAMs-mediated organelle crosstalk to reverse inflammatory adipose expansion in thyroid eye disease. Theranostics. 2025 Aug 30;15(18):9601-9622. https://doi.org/10.7150/thno.117582. PMID: 41041063; PMCID: PMC12486268.
Zou X, Jiang Z, Li L, Huang Z. Selenium nanoparticles coated with pH responsive silk fibroin complex for fingolimod release and enhanced targeting in thyroid cancer. Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):83-95. https://doi.org/10.1080/21691401.2021.1871620. PMID: 33438446.
Köhrle J. Selenium, iodine and iron—essential trace elements for thyroid hormone synthesis and metabolism. Int J Mol Sci. 2023;24(4):3393. https://doi.org/10.3390/ijms24043393. PMID: 36834802.
Gladyshev VN, Arnér ES, Berry MJ, Brigelius-Flohé R, Bruford EA, Burk RF, et al. Selenoprotein gene nomenclature. J Biol Chem. 2016;291(46):24036–24040. https://doi.org/10.1074/jbc.M116.756155.
Pitts MW, Hoffmann PR. Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis. Cell Calcium. 2018;70:76–86. https://doi.org/10.1016/j.ceca.2017.05.001.
Labunskyy VM, Hatfield DL, Gladyshev VN. Selenoproteins: molecular pathways and physiological roles. Physiol Rev. 2014;94(3):739–777. https://doi.org/10.1152/physrev.00039.2013.
Minnetti M, Sada V, Feola T, Giannetta E, Pozza C, Gianfrilli D, et al. Selenium supplementation in pregnant women with autoimmune thyroiditis: a practical approach. Nutrients. 2022;14(11):2234. https://doi.org/10.3390/nu14112234. PMID: 35684035.
Gorini F, Sabatino L, Pingitore A, Vassalle C. Selenium: An Element of Life Essential for Thyroid Function. Molecules. 2021 Nov 23;26(23):7084. https://doi.org/10.3390/molecules26237084. PMID: 34885664; PMCID: PMC8658851.
De Stefano MA, Porcelli T, Schlumberger M, Salvatore D. Deiodinases in thyroid tumorigenesis. Endocr Relat Cancer. 2023;30(5):e230015. https://doi.org/10.1530/ERC-23-0015. PMID: 36862025.
Lopes SO, Mayer EM, Azevedo FM, Candido AC, Bittencourt JM, Morais DC, et al. Nutritional Status of Iodine and Association with Iron, Selenium, and Zinc in Population Studies: A Systematic Review and Meta-Analysis. Nutrients. 2025 Oct 31;17(21):3432. https://doi.org/10.3390/nu17213432. PMID: 41228503; PMCID: PMC12608380.
Köhrle J, Frädrich C. Deiodinases control local cellular and systemic thyroid hormone availability. Free Radic Biol Med. 2022 Nov 20;193(Pt 1):59-79. https://doi.org/10.1016/j.freeradbiomed.2022.09.024. Epub 2022 Oct 4. PMID: 36206932.
Sabatino L, Vassalle C, Del Seppia C, Iervasi G. Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions. Endocrinol Metab (Seoul). 2021 Oct;36(5):952-964. https://doi.org/10.3803/EnM.2021.1198. Epub 2021 Oct 21. PMID: 34674502; PMCID: PMC8566136.
Zhang F, Li X, Wei Y. Selenium and selenoproteins in health. Biomolecules. 2023;13(5):799. https://doi.org/10.3390/biom13050799. PMID: 37238669.
Kieliszek M, Sapazhenkava K. The Promising Role of Selenium and Yeast in the Fight Against Protein Amyloidosis. Biol Trace Elem Res. 2025 Mar;203(3):1251-1268. https://doi.org/10.1007/s12011-024-04245-x. Epub 2024 Jun 3. PMID: 38829477; PMCID: PMC11872778.
Kieliszek M. Selenium: From Redox Signaling to Interactions with the Gut Microbiome. Biol Trace Elem Res. 2026 May 1. https://doi.org/10.1007/s12011-026-05132-3. Epub ahead of print. PMID: 42062664.
Wąsowicz W, Gromadzińska J, Rydzyński K, Tomczak J. Selenium status of low-selenium area residents: Polish experience. Toxicol Lett. 2003;137(1–2):95–101. https://doi.org/10.1016/s0378-4274(02)00382-2. PMID: 12505435.
Wu Q, Rayman MP, Lv H, Schomburg L, Cui B, Gao C, et al. Low population selenium status is associated with increased prevalence of thyroid disease. J Clin Endocrinol Metab. 2015;100(11):4037–4047. https://doi.org/10.1210/jc.2015-2222. PMID: 26305620.
Derumeaux H, Valeix P, Castetbon K, Bensimon M, Boutron-Ruault MC, Arnaud J, et al. Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. Eur J Endocrinol. 2003;148(3):309–315. https://doi.org/10.1530/eje.0.1480309. PMID: 12611611.
Pirola I, Gandossi E, Agosti B, Delbarba A, Cappelli C. Selenium supplementation could restore euthyroidism in subclinical hypothyroid patients with autoimmune thyroiditis. Endokrynol Pol. 2016;67(6):567–571. https://doi.org/10.5603/EP.2016.0064. PMID: 28042649.
Ortarzewska M, Nijakowski K, Jankowski J, Sawicka-Gutaj N, Ruchała M, Surdacka A. Periodontal disease in patients with thyroid diseases: a systematic review with meta-analysis. Adv Med Sci. 2024;69(2):289–295. https://doi.org/10.1016/j.advms.2024.06.003. PMID: 38908794.
Czarnywojtek A, Florek E, Pietrończyk K, Sawicka-Gutaj N, Ruchała M, Ronen O, et al. The role of vitamin D in autoimmune thyroid diseases: a narrative review. J Clin Med. 2023;12(4):1452. https://doi.org/10.3390/jcm12041452. PMID: 36835987.
Duntas LH. The caprices of a trace element: selenium's considerable effects on Hashimoto's thyroiditis, though few on Graves' disease. Eur Thyroid J. 2026;15(1):ETJ260009. https://doi.org/10.1530/ETJ-26-0009. PMID: 41677203.
Bogusławska J, Godlewska M, Gajda E, Piekiełko-Witkowska A. Cellular and molecular basis of thyroid autoimmunity. Eur Thyroid J. 2022;11(1):e210024. https://doi.org/10.1530/ETJ-21-0024. PMID: 34981746.
Li JR, Hong FY, Zeng JY, Huang GL. Functional interleukin-17 receptor A are present in the thyroid gland in intractable Graves disease. Cell Immunol. 2013;281(1):85–90. https://doi.org/10.1016/j.cellimm.2013.02.002. PMID: 23501056.
Zuo Y, Li Y, Gu X, Lei Z. The correlation between selenium levels and autoimmune thyroid disease: a systematic review and meta-analysis. Ann Palliat Med. 2021;10(4):4398–4408. https://doi.org/10.21037/apm-21-449. PMID: 33894732.
He H, Jiang Y, Qiu J, Shen F, Qian D, Meng L. Role of interleukin 17 and T helper cells 17 cells as a new immune target and signalling in the pathogenesis and treatment of autoimmune thyroid diseases. Ann Med. 2025;57(1):2586216. https://doi.org/10.1080/07853890.2025.2586216. PMID: 41243116.
Huang Z, Zhang J, Chen S, Mao M, Wang B. Expression levels of interleukin-17 and interferon-γ in peripheral blood and relationship with thyroid function in patients with Hashimoto's thyroiditis. Front Mol Biosci. 2025;12:1645736. https://doi.org/10.3389/fmolb.2025.1645736. PMID: 41113857.
Li S, Xu Q, Wang S, Peng H, Liu Y. Recent advances of trace elements in autoimmune thyroid disease. Front Immunol. 2025;16:1662521. https://doi.org/10.3389/fimmu.2025.1662521. PMID: 41383597.
Avery JC, Hoffmann PR. Selenium, Selenoproteins, and Immunity. Nutrients. 2018 Sep 1;10(9):1203. https://doi.org/10.3390/nu10091203. PMID: 30200430; PMCID: PMC6163284.
Mazokopakis EE, Papadakis JA, Papadomanolaki MG, Batistakis AG, Giannakopoulos TG, Protopapadakis EE, et al. Effects of 12 months treatment with L-selenomethionine on serum anti-TPO levels in patients with Hashimoto's thyroiditis. Thyroid. 2007;17(7):609–612. https://doi.org/10.1089/thy.2007.0040. PMID: 17696828.
Turker O, Kumanlioglu K, Karapolat I, Dogan I. Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J Endocrinol. 2006;190(1):151–156. https://doi.org/10.1677/joe.1.06661. PMID: 16837619.
Toulis KA, Anastasilakis AD, Tzellos TG, Goulis DG, Kouvelas D. Selenium supplementation in the treatment of Hashimoto's thyroiditis: a systematic review and a meta-analysis. Thyroid. 2010;20(10):1163–1173. https://doi.org/10.1089/thy.2009.0351. PMID: 20883174.
Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92(4):1263–1268. https://doi.org/10.1210/jc.2006-1821. PMID: 17284630.
Mantovani G, Isidori AM, Moretti C, Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the "SERENA study", a randomized, double-blind, placebo-controlled trial. Endocrine. 2019;66(3):542–550. https://doi.org/10.1007/s12020-019-01958-1. PMID: 31129812.
Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, et al. Selenium and the course of mild Graves' orbitopathy. N Engl J Med. 2011;364(20):1920–1931. https://doi.org/10.1056/NEJMoa1012985. PMID: 21591944.
Rozwandowicz AM, Stuss M, Michalska-Kasiczak M, Sewerynek E. Body composition analysis in patients with Hashimoto's disease and vitamin D deficiency. J Med Sci. 2024;93(4):e1084. https://doi.org/10.20883/medical.e1084.
Włochal M, Kucharski MA, Grzymisławski M. The effects of vitamins and trace minerals on chronic autoimmune thyroiditis. J Med Sci. 2014;83(2):167–172. https://doi.org/10.20883/medical.e63.
Socha K, Dziemianowicz M, Omeljaniuk W. Nawyki żywieniowe a stężenie selenu w surowicy u pacjentów z chorobą Hashimoto [Dietary habits and serum selenium concentrations in patients with Hashimoto's disease]. Probl Hig Epidemiol. 2012;93(4):824–827. [in Polish]
Huwiler VV, Maissen-Abgottspon S, Stanga Z, Mühlebach S, Trepp R, Bally L, et al. Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Thyroid. 2024 Mar;34(3):295-313. https://doi.org/10.1089/thy.2023.0556. Epub 2024 Feb 16. PMID: 38243784; PMCID: PMC10951571.
Sawicka-Gutaj N, Gruszczyński D, Zawalna N, Nijakowski K, Skiba A, Pochylski M, et al. Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience. Pharmacol Rep. 2024;76(1):185–194. https://doi.org/10.1007/s43440-023-00567-0. PMID: 38273183.
Olejarz M, Szczepanek-Parulska E, Dadej D, Sawicka-Gutaj N, Domin R, Ruchała M. IgG4 as a biomarker in Graves' orbitopathy. Mediators Inflamm. 2021;2021:5590471. https://doi.org/10.1155/2021/5590471. PMID: 34220335.
Owji N, Moradi F, Khalili MR, Jahanbani-Ardakani H. Serum selenium levels in patients with Graves' disease with or without thyroid ophthalmopathy. Endocr Pract. 2022;28(12):1216–1220. https://doi.org/10.1016/j.eprac.2022.09.001. PMID: 36116714.
Kim TH, Ko J, Kim BR, Shin DY, Lee EJ, Yoon JS. Serum selenium levels in patients with Graves' disease: associations with clinical activity and severity in a retrospective case-control study. Korean J Ophthalmol. 2022;36(1):36–43. https://doi.org/10.3341/kjo.2021.0146. PMID: 34743487.
Czarnywojtek A, Ochmańska A, Zgorzalewicz-Stachowiak M, Sawicka-Gutaj N, Matyjaszek-Matuszek B, Woźniak M, et al. Influence of SARS-CoV-2 infection on thyroid gland function: the current knowledge. Adv Clin Exp Med. 2021;30(7):747–755. https://doi.org/10.17219/acem/139622. PMID: 34286519.
Peng CC, Pearce EN. An update on thyroid disorders in the postpartum period. J Endocrinol Invest. 2022;45(8):1497–1506. https://doi.org/10.1007/s40618-022-01762-1. PMID: 35181848.
Nicholson WK, Robinson KA, Smallridge RC, Ladenson PW, Powe NR. Prevalence of postpartum thyroid dysfunction: a quantitative review. Thyroid. 2006;16(6):573–582. https://doi.org/10.1089/thy.2006.16.573.
Duntas LH. Selenium and at-risk pregnancy: challenges and controversies. Thyroid Res. 2020;13:16. https://doi.org/10.1186/s13044-020-00090-x. PMID: 33014140.
Calcaterra V, Cena H, Scavone IAM, Zambon I, Taranto S, Ricciardi Rizzo C, et al. Thyroid health and selenium: the critical role of adequate intake from fetal development to adolescence. Nutrients. 2025;17(14):2362. https://doi.org/10.3390/nu17142362. PMID: 40732987.
Kazi Tani LS, Dennouni-Medjati N, Toubhans B, Charlet L. Selenium deficiency—From soil to thyroid cancer. Appl Sci (Basel). 2020;10(15):5368. doi:10.3390/app10155368.
Hao R, Yu P, Gui L, Wang N, Pan D, Wang S. Relationship between Serum Levels of Selenium and Thyroid Cancer: A Systematic Review and Meta-Analysis. Nutr Cancer. 2023;75(1):14-23. https://doi.org/10.1080/01635581.2022.2115082. Epub 2022 Aug 22. PMID: 35996814.
de Oliveira Maia M, Batista BAM, Sousa MP, de Souza LM, Maia CSC. Selenium and thyroid cancer: a systematic review. Nutr Cancer. 2020;72(8):1255-1263. https://doi.org/10.1080/01635581.2019.1679194. Epub 2019 Oct 22. PMID: 31635488.
Kazi Tani LS, Dennouni-Medjati N, Medjahedi A, Rahou Z, Harek Y, Dali-Sahi M, et al. Selenium deficiency as potential risk factor for thyroid carcinoma: Results from a Western Algerian population. J Trace Elem Med Biol. 2026;95:127882. doi:10.1016/j.jtemb.2026.127882.
Ge S, Zhao J, Yao J, Fu H, Tian Y, Shan Y, et al. The association between serum selenium levels and pathological features of papillary thyroid cancer in 284 patients. Front Endocrinol (Lausanne). 2023 Nov 3;14:1242250. https://doi.org/10.3389/fendo.2023.1242250. PMID: 38027150; PMCID: PMC10656612.
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