The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, enzymes involved in thyroid hormone metabolism, regulation of redox state and protection from oxidative damage. Selenium content in selenium-sensitive tissues such as the liver, kidney or muscle and expression of nonessential selenoproteins, such as the glutathione peroxidases GPx1 and GPx3, is controlled by nutritional supply. The thyroid gland is, however, largely independent from dietary selenium intake and thyroid selenoproteins are preferentially expressed. As a consequence, no explicit effects on thyroid hormone profiles are observed in healthy individuals undergoing selenium supplementation. However, low selenium status correlates with risk of goiter and multiple nodules in European women. Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined. The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenium supplementation, which might primarily disrupt self-amplifying cycles of the endocrine–immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens. Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system–thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction.
Selenium is needed for biosynthesis of selenoproteins, including thyroid hormone metabolizing enzymes (iodothyronine deiodinases), hydrogen peroxide degrading enzymes (glutathione peroxidases) and enzymes affecting endoplasmic reticulum function
Endogenous pathways ensure that the thyroid gland and thyroid selenoproteins are exceptionally well supplied with selenium and largely resistant to selenium deficiency
Selenium status declines and selenoprotein biosynthesis is impaired in inflammatory diseases, which potentially necessitates supplementation with this trace element
Selenium supplementation trials in patients with Hashimoto thyroiditis successfully reduced autoantibody concentrations and improved selenium status and quality of life
However, not all selenium supplementation trials have been successful and the underlying mechanisms of the selenium effects and the major parameters controlling trial outcome are unknown
Selenium supplementation is hypothesized to improve functioning of both thyrocytes and immune cells, thereby rectifying the derailed interaction of lymphocytes with thyroid autoantigens in selenium-deficient patients
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Kryukov, G. V. et al. Characterization of mammalian selenoproteomes. Science 300, 1439–1443 (2003).
Small-Howard, A. et al. Supramolecular complexes mediate selenocysteine incorporation in vivo. Mol. Cell Biol. 26, 2337–2346 (2006).
Allmang, C., Wurth, L. & Krol, A. The selenium to selenoprotein pathway in eukaryotes: more molecular partners than anticipated. Biochim. Biophys. Acta 1790, 1415–1423 (2009).
Xu, X. M. et al. Biosynthesis of selenocysteine on its tRNA in eukaryotes. PLoS Biol. 5, e4 (2007).
Aeby, E. et al. The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes. Proc. Natl Acad. Sci. USA 106, 5088–5092 (2009).
Duntas, L. H. Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm. Metab. Res. 41, 443–447 (2009).
Gärtner, R. Selenium and thyroid hormone axis in critical ill states: an overview of conflicting view points. J. Trace Elem. Med. Biol. 23, 71–74 (2009).
Papp, L. V., Lu, J., Holmgren, A. & Khanna, K. K. From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid. Redox Signal 9, 775–806 (2007).
Shchedrina, V. A., Zhang, Y., Labunskyy, V. M., Hatfield, D. L. & Gladyshev, V. N. Structure-function relations, physiological roles, and evolution of mammalian ER-resident selenoproteins. Antioxid. Redox Signal 12, 839–849 (2010).
Schomburg, L. Genetics and phenomics of selenoenzymes—how to identify an impaired biosynthesis? Mol. Cell Endocrinol. 322, 114–124 (2010).
Dumitrescu, A. M., Di Cosmo, C., Liao, X. H., Weiss, R. E. & Refetoff, S. The syndrome of inherited partial SBP2 deficiency in humans. Antioxid. Redox Signal 12, 905–920 (2010).
McCann, J. C. & Ames, B. N. Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. Faseb J. 25, 1793–1814 (2011).
Rayman, M. P. The importance of selenium to human health. Lancet 356, 233–241 (2000).
Fairweather-Tait, S. J. et al. Selenium in human health and disease. Antioxid. Redox Signal 14, 1337–1383 (2011).
Toulis, K. A., Anastasilakis, A. D., Tzellos, T. G., Goulis, D. G. & Kouvelas, D. Selenium supplementation in the treatment of Hashimoto's thyroiditis: a systematic review and a meta-analysis. Thyroid 20, 1163–1173 (2010).
Rosai, J., Kuhn, E. & Carcangiu, M. L. Pitfalls in thyroid tumour pathology. Histopathology 49, 107–120 (2006).
Klonisch, T., Hoang-Vu, C. & Hombach-Klonisch, S. Thyroid stem cells and cancer. Thyroid 19, 1303–1315 (2009).
Fagman, H. & Nilsson, M. Morphogenetics of early thyroid development. J. Mol. Endocrinol. 46, R33–R42 (2010).
Song, Y. et al. Association of duoxes with thyroid peroxidase and its regulation in thyrocytes. J. Clin. Endocrinol. Metab. 95, 375–382 (2010).
Senou, M. et al. A coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid. J. Clin. Endocrinol. Metab. 95, 4021–4030 (2010).
Laurberg, P., Bülow Pedersen, I., Knudsen, N., Ovesen, L. & Andersen, S. Environmental iodine intake affects the type of nonmalignant thyroid disease. Thyroid 11, 457–469 (2001).
Linke, M., Jordans, S., Mach, L., Herzog, V. & Brix, K. Thyroid stimulating hormone upregulates secretion of cathepsin B from thyroid epithelial cells. Biol. Chem. 383, 773–784 (2002).
Vassart,, G. & Dumont, J. E. The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr. Rev. 13, 596–611 (1992).
Levy, O. et al. Characterization of the thyroid Na+/I– symporter with an anti-COOH terminus antibody. Proc. Natl Acad. Sci. USA 94, 5568–5573 (1997).
Kero, J. et al. Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development. J. Clin. Invest. 117, 2399–2407 (2007).
Herzog, V., Berndorfer, U. & Saber, Y. Isolation of insoluble secretory product from bovine thyroid: extracellular storage of thyroglobulin in covalently cross-linked form. J. Cell Biol. 118, 1071–1083 (1992).
Friedrichs, B. et al. Thyroid functions of mouse cathepsins B, K, and L. J. Clin. Invest. 111, 1733–1745 (2003).
Björkman, U. & Ekholm, R. Generation of H2O2 in isolated porcine thyroid follicles. Endocrinology 115, 392–398 (1984).
Corvilain, B., van Sande, J., Laurent, E. & Dumont, J. E. The H2O2-generating system modulates protein iodination and the activity of the pentose phosphate pathway in dog thyroid. Endocrinology 128, 779–785 (1991).
Chan, E. C., Jiang, F., Peshavariya, H. M. & Dusting, G. J. Regulation of cell proliferation by NADPH oxidase-mediated signaling: potential roles in tissue repair, regenerative medicine and tissue engineering. Pharmacol. Ther. 122, 97–108 (2009).
Rada, B. et al. Role of Nox2 in elimination of microorganisms. Semin. Immunopathol. 30, 237–253 (2008).
Savina, A. et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 126, 205–218 (2006).
Hultqvist, M., Olsson, L. M., Gelderman, K. A. & Holmdahl, R. The protective role of ROS in autoimmune disease. Trends Immunol. 30, 201–208 (2009).
Leto, T. L., Morand, S., Hurt, D. & Ueyama, T. Targeting and regulation of reactive oxygen species generation by Nox family NADPH oxidases. Antioxid. Redox Signal 11, 2607–2619 (2009).
Grasberger, H. & Refetoff, S. Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. J. Biol. Chem. 281, 18269–18272 (2006).
Fortunato, R. S. et al. Functional consequences of dual oxidase-thyroperoxidase interaction at the plasma membrane. J. Clin. Endocrinol. Metab. 95, 5403–5411 (2010).
Pachucki, J., Wang, D., Christophe, D. & Miot, F. Structural and functional characterization of the two human ThOX/Duox genes and their 5′-flanking regions. Mol. Cell Endocrinol. 214, 53–62 (2004).
Grasberger, H. Defects of thyroidal hydrogen peroxide generation in congenital hypothyroidism. Mol. Cell Endocrinol. 322, 99–106 (2010).
Maruo, Y. et al. Transient congenital hypothyroidism caused by biallelic mutations of the dual oxidase 2 gene in Japanese patients detected by a neonatal screening program. J. Clin. Endocrinol. Metab. 93, 4261–4267 (2008).
Weyemi, U. et al. Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues. Endocr. Relat Cancer 17, 27–37 (2010).
Filomeni, G., Rotilio, G. & Ciriolo, M. R. Disulfide relays and phosphorylative cascades: partners in redox-mediated signaling pathways. Cell Death Differ. 12, 1555–1563 (2005).
Schweizer, U., Chiu, J. & Köhrle, J. Peroxides and peroxide-degrading enzymes in the thyroid. Antioxid. Redox Signal 10, 1577–1592 (2008).
Ekholm, R. & Bjorkman, U. Glutathione peroxidase degrades intracellular hydrogen peroxide and thereby inhibits intracellular protein iodination in thyroid epithelium. Endocrinology 138, 2871–2878 (1997).
Weetman, A. P. Autoimmune thyroid disease. Autoimmunity 37, 337–340 (2004).
McCombe, P. A., Greer, J. M. & Mackay, I. R. Sexual dimorphism in autoimmune disease. Curr. Mol. Med. 9, 1058–1079 (2009).
Vanderpump, M. P. & Tunbridge, W. M. Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid 12, 839–847 (2002).
Weetman, A. P. The genetics of autoimmune thyroid disease. Horm. Metab. Res. 41, 421–425 (2009).
Prummel, M. F., Strieder, T. & Wiersinga, W. M. The environment and autoimmune thyroid diseases. Eur. J. Endocrinol. 150, 605–618 (2004).
Chen, C. R. et al. Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice and appear after thyroglobulin antibodies. Endocrinology 151, 4583–4593 (2010).
Pearce, E. N., Farwell, A. P. & Braverman, L. E. Thyroiditis. N. Engl. J. Med. 348, 2646–2655 (2003).
Teng, W. et al. Effect of iodine intake on thyroid diseases in China. N. Engl. J. Med. 354, 2783–2793 (2006).
Zois, C. et al. High prevalence of autoimmune thyroiditis in schoolchildren after elimination of iodine deficiency in northwestern Greece. Thyroid 13, 485–489 (2003).
Ban, Y. & Tomer, Y. Genetic susceptibility in thyroid autoimmunity. Pediatr. Endocrinol. Rev. 3, 20–32 (2005).
Duthoit, C. et al. Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity? Biochem. J. 360, 557–562 (2001).
Burek, C. L. & Rose, N. R. Autoimmune thyroiditis and ROS. Autoimmun. Rev. 7, 530–537 (2008).
Niethammer, P., Grabher, C., Look, A. T. & Mitchison, T. J. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459, 996–999 (2009).
Hartikainen, H. Biogeochemistry of selenium and its impact on food chain quality and human health. J. Trace Elem. Med. Biol. 18, 309–318 (2005).
Combs, G. F. Jr. Selenium in global food systems. Br. J. Nutr. 85, 517–547 (2001).
Hurst, R. et al. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am. J. Clin. Nutr. 91, 923–931 (2010).
Xia, Y. et al. Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects. Am. J. Clin. Nutr. 92, 525–531 (2010).
Forceville, X. et al. Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit. Care Med. 26, 1536–1544 (1998).
Seiler, W. O. Clinical pictures of malnutrition in ill elderly subjects. Nutrition 17, 496–498 (2001).
Rannem, T., Ladefoged, K., Hylander, E., Hegnhøj, J. & Staun, M. Selenium depletion in patients with gastrointestinal diseases: are there any predictive factors? Scand. J. Gastroenterol. 33, 1057–1061 (1998).
Schomburg, L. & Köhrle, J. On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Mol. Nutr. Food Res. 52, 1235–1246 (2008).
Tonelli, M. et al. Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med. 7, 25 (2009).
Vanderpas, J. Nutritional epidemiology and thyroid hormone metabolism. Annu. Rev. Nutr. 26, 293–322 (2006).
Contempre, B., Le Moine, O., Dumont, J. E., Denef, J. F. & Many, M. C. Selenium deficiency and thyroid fibrosis. A key role for macrophages and transforming growth factor beta (TGF-beta). Mol. Cell Endocrinol. 124, 7–15 (1996).
Köhrle, J., Jakob, F., Contempré, B. & Dumont, J. E. Selenium, the thyroid, and the endocrine system. Endocr. Rev. 26, 944–984 (2005).
Arthur, J. R. The glutathione peroxidases. Cell. Mol. Life Sci. 57, 1825–1835 (2000).
Bianco, A. C. & Larsen, P. R. Cellular and structural biology of the deiodinases. Thyroid 15, 777–786 (2005).
Kuiper, G. G., Kester, M. H., Peeters, R. P. & Visser, T. J. Biochemical mechanisms of thyroid hormone deiodination. Thyroid 15, 787–798 (2005).
Schweizer, U., Weitzel, J. M. & Schomburg, L. Think globally: act locally. New insights into the local regulation of thyroid hormone availability challenge long accepted dogmas. Mol. Cell Endocrinol. 289, 1–9 (2008).
Galton, V. A., Schneider, M. J., Clark, A. S. & St. Germain, D. L. Life without thyroxine to 3, 5, 3′-triiodothyronine conversion: studies in mice devoid of the 5′-deiodinases. Endocrinology 150, 2957–2963 (2009).
Schneider, M. J. et al. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 147, 580–589 (2006).
Streckfuss, F. et al. Hepatic deiodinase activity is dispensable for the maintenance of normal circulating thyroid hormone levels in mice. Biochem. Biophys. Res. Commun. 337, 739–745 (2005).
Ng, L. et al. A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory function. Endocrinology 150, 1952–1960 (2009).
Ng, L. et al. Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors. J. Neurosci. 30, 3347–3357 (2010).
Dayan, C. M. & Panicker, V. Novel insights into thyroid hormones from the study of common genetic variation. Nat. Rev. Endocrinol. 5, 211–218 (2009).
Hall, J. A. & Bianco, A. C. Triumphs of the thyroid despite lesser conversion. Endocrinology 150, 2502–2504 (2009).
Bates, J. M., Spate, V. L., Morris, J. S., St. Germain, D. L. & Galton, V. A. Effects of selenium deficiency on tissue selenium content, deiodinase activity, and thyroid hormone economy in the rat during development. Endocrinology 141, 2490–2500 (2000).
Behne, D., Hilmert, H., Scheid, S., Gessner, H. & Elger, W. Evidence for specific selenium target tissues and new biologically important selenoproteins. Biochim. Biophys. Acta 966, 12–21 (1988).
Wingler, K., Böcher, M., Flohé, L., Kollmus, H. & Brigelius-Flohé, R. mRNA stability and selenocysteine insertion sequence efficiency rank gastrointestinal glutathione peroxidase high in the hierarchy of selenoproteins. Eur. J. Biochem. 259, 149–157 (1999).
Schomburg, L. & Schweizer, U. Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. Biochim. Biophys. Acta 1790, 1453–1462 (2009).
Hill, K. E., Lyons, P. R. & Burk, R. F. Differential regulation of rat liver selenoprotein mRNAs in selenium deficiency. Biochem. Biophys. Res. Commun. 185, 260–263 (1992).
Bermano, G. et al. Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats. Biochem. J. 311 (Pt 2), 425–430 (1995).
Gross, M., Oertel, M. & Köhrle, J. Differential selenium-dependent expression of type I 5′-deiodinase and glutathione peroxidase in the porcine epithelial kidney cell line LLC-PK1. Biochem. J. 306 (Pt 3), 851–856 (1995).
Beckett, G. J. & Arthur, J. R. Selenium and endocrine systems. J. Endocrinol. 184, 455–465 (2005).
Brigelius-Flohé, R. et al. Functions of GI-GPx: lessons from selenium-dependent expression and intracellular localization. Biofactors 14, 101–106 (2001).
Dittrich, A. M. et al. Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice. Eur. Respir. J. 35, 1148–1154 (2010).
Howie, A. F., Walker, S. W., Akesson, B., Arthur, J. R. & Beckett, G. J. Thyroidal extracellular glutathione peroxidase: a potential regulator of thyroid-hormone synthesis. Biochem. J. 308 (Pt 3), 713–717 (1995).
Schmutzler, C. et al. Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3. Biol. Chem. 388, 1053–1059 (2007).
Conrad, M., Schneider, M., Seiler, A. & Bornkamm, G. W. Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals. Biol. Chem. 388, 1019–1025 (2007).
Burk, R. F. & Hill, K. E. Regulation of selenoproteins. Annu. Rev. Nutr. 13, 65–81 (1993).
Allan, C. B., Lacourciere, G. M. & Stadtman, T. C. Responsiveness of selenoproteins to dietary selenium. Annu. Rev. Nutr. 19, 1–16 (1999).
Brigelius-Flohé, R. Glutathione peroxidases and redox-regulated transcription factors. Biol. Chem. 387, 1329–1335 (2006).
Krohn, K., Maier, J. & Paschke, R. Mechanisms of disease: hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors. Nat. Clin. Pract Endocrinol. Metab. 3, 713–720 (2007).
Poncin, S. et al. Oxidative stress in the thyroid gland: from harmlessness to hazard depending on the iodine content. Endocrinology 149, 424–433 (2008).
Ashton, K. et al. Methods of assessment of selenium status in humans: a systematic review. Am. J. Clin. Nutr. 89, 2025S–2039S (2009).
Schomburg, L. et al. Synthesis and metabolism of thyroid hormones is preferentially maintained in selenium-deficient transgenic mice. Endocrinology 147, 1306–1313 (2006).
Ban, Y. et al. Linkage analysis of thyroid antibody production: evidence for shared susceptibility to clinical autoimmune thyroid disease. J. Clin. Endocrinol. Metab. 93, 3589–3596 (2008).
Wiebolt, J., Koeleman, B. P. & van Haeften, T. W. Endocrine autoimmune disease: genetics become complex. Eur. J. Clin. Invest. 40, 1144–1155 (2010).
Ioannidis, J. P., Castaldi, P. & Evangelou, E. A compendium of genome-wide associations for cancer: critical synopsis and reappraisal. J. Natl Cancer Inst. 102, 846–858 (2010).
Gudmundsson, J. et al. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat. Genet. 41, 460–464 (2009).
Lescure, A., Rederstorff, M., Krol, A., Guicheney, P. & Allamand, V. Selenoprotein function and muscle disease. Biochim. Biophys. Acta 1790, 1569–1574 (2009).
Schweizer, U., Dehina, N. & Schomburg, L. Disorders of selenium metabolism and selenoprotein function. Curr. Opin. Pediatr. 23, 429–435 (2011).
Petit, N. et al. Selenoprotein N.: an endoplasmic reticulum glycoprotein with an early developmental expression pattern. Hum. Mol. Genet. 12, 1045–1053 (2003).
Castets, P. et al. Satellite cell loss and impaired muscle regeneration in selenoprotein N. deficiency. Hum. Mol. Genet. 20, 694–704 (2011).
Agamy, O. et al. Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy. Am. J. Hum. Genet. 87, 538–544 (2010).
Wirth, E. K. et al. Neuronal selenoprotein expression is required for interneuron development and prevents seizures and neurodegeneration. FASEB J. 24, 844–852 (2010).
Copeland, P. R., Fletcher, J. E., Carlson, B. A., Hatfield, D. L. & Driscoll, D. M. A novel RNA binding protein, SBP2, is required for the translation of mammalian selenoprotein mRNAs. EMBO J. 19, 306–314 (2000).
Papp, L. V. et al. SECIS-binding protein 2 promotes cell survival by protecting against oxidative stress. Antioxid Redox Signal 12, 797–808 (2010).
Dumitrescu, A. M. et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat. Genet. 37, 1247–1252 (2005).
Di Cosmo, C. et al. Clinical and molecular characterization of a novel selenocysteine insertion sequence-binding protein 2 (SBP2) gene mutation (R128X). J. Clin. Endocrinol. Metab. 94, 4003–4009 (2009).
Schomburg, L. et al. Selenium supplementation fails to correct the selenoprotein synthesis defect in subjects with SBP2 gene mutations. Thyroid 19, 277–281 (2009).
Ferreira Azevedo, M. et al. Selenoprotein-related disease in a young girl caused by nonsense mutations in the SBP2 gene. J. Clin. Endocrinol. Metab. 95, 4066–4071 (2010).
Schoenmakers, E. et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J. Clin. Invest. 120, 4220–4235 (2010).
Steinnes, E. Soils and geomedicine. Environ. Geochem. Health 31, 523–535 (2009).
Arthur, J. R. Selenium supplementation: does soil supplementation help and why? Proc. Nutr. Soc. 62, 393–397 (2003).
Rayman, M. P. et al. Randomized controlled trial of the effect of selenium supplementation on thyroid function in the elderly in the United Kingdom. Am. J. Clin. Nutr. 87, 370–378 (2008).
Thomson, C. D., Campbell, J. M., Miller, J., Skeaff, S. A. & Livingstone, V. Selenium and iodine supplementation: effect on thyroid function of older New Zealanders. Am. J. Clin. Nutr. 90, 1038–1046 (2009).
Hawkes, W. C. et al. High-selenium yeast supplementation in free-living North American men: no effect on thyroid hormone metabolism or body composition. J. Trace Elem. Med. Biol. 22, 131–142 (2008).
Combs, G. F. Jr. et al. Effects of selenomethionine supplementation on selenium status and thyroid hormone concentrations in healthy adults. Am. J. Clin. Nutr. 89, 1808–1814 (2009).
Moreno-Reyes, R. et al. Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy. Am. J. Clin. Nutr. 78, 137–144 (2003).
Angstwurm, M. W., Schopohl, J. & Gaertner, R. Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients. Eur. J. Endocrinol. 151, 47–54 (2004).
Berger, M. M. et al. Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial. Intensive Care Med. 27, 91–100 (2001).
McKenzie, R. C., Rafferty, T. S. & Beckett, G. J. Selenium: an essential element for immune function. Immunol. Today 19, 342–345 (1998).
Arthur, J. R., McKenzie, R. C. & Beckett, G. J. Selenium in the immune system. J. Nutr. 133, 1457S–1459S (2003).
Hoffmann, P. R. & Berry, M. J. The influence of selenium on immune responses. Mol. Nutr. Food Res. 52, 1273–1280 (2008).
Duntas, L. H. Selenium and the thyroid: a close-knit connection. J. Clin. Endocrinol. Metab. 95, 5180–5188 (2010).
Angstwurm, M. W., Schottdorf, J., Schopohl, J. & Gärtner, R. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Crit. Care Med. 27, 1807–1813 (1999).
Sakr, Y. et al. Time course and relationship between plasma selenium concentrations, systemic inflammatory response, sepsis, and multiorgan failure. Br. J. Anaesth. 98, 775–784 (2007).
Renko, K. et al. Down-regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice. FASEB J. 23, 1758–1765 (2009).
Angstwurm, M. W. et al. Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit. Care Med. 35, 118–126 (2007).
Forceville, X. X. et al. Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study. Crit. Care 11, R73 (2007).
Wang, Z. et al. A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 32, 140–146 (2009).
Schomburg, L. A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 33, 554–555; author reply 555–556 (2010).
Schomburg, L. Selenium in intensive care (SIC) study: the XX files are still unresolved. Crit. Care Med. 35, 995–996; author reply 996–997 (2007).
Mittag, J., Behrends, T., Hoefig, C., Vennström, B. & Schomburg, L. Thyroid hormones regulate selenoprotein expression and selenium status in mice. PLOS ONE 5, e12931 (2010).
Look, M. P. et al. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection. Biol. Trace Elem. Res. 56, 31–41 (1997).
Misso, N. L., Powers, K. A., Gillon, R. L., Stewart, G. A. & Thompson, P. J. Reduced platelet glutathione peroxidase activity and serum selenium concentration in atopic asthmatic patients. Clin. Exp. Allergy 26, 838–847 (1996).
Sammalkorpi, K., Valtonen, V., Alfthan, G., Aro, A. & Huttunen, J. Serum selenium in acute infections. Infection 16, 222–224 (1988).
Nichol, C. et al. Changes in the concentrations of plasma selenium and selenoproteins after minor elective surgery: further evidence for a negative acute phase response? Clin. Chem. 44, 1764–1766 (1998).
Beck, M. A., Levander, O. A. & Handy, J. Selenium deficiency and viral infection. J. Nutr. 133, 1463S–1467S (2003).
Mizock, B. A. Immunonutrition and critical illness: an update. Nutrition 26, 701–707 (2010).
Joffe, A. et al. Nutritional support for critically ill children. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD005144 doi:10.1002/14651858.CD005144.pub2 (2009).
Carcillo, J. et al. Rationale and design of the pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial. JPEN J. Parenter. Enteral Nutr. 33, 368–374 (2009).
Hardy, G., Menendez, A. M. & Manzanares, W. Trace element supplementation in parenteral nutrition: pharmacy, posology, and monitoring guidance. Nutrition 25, 1073–1084 (2009).
Beckett, G. J. et al. Inter-relationships between selenium and thyroid hormone metabolism in the rat and man. J. Trace Elem. Electrolytes Health Dis. 5, 265–267 (1991).
Kucharzewski, M., Braziewicz, J., Majewska, U. & Gozdz, S. Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases. Biol. Trace Elem. Res. 88, 25–30 (2002).
Gärtner, R., Gasnier, B. C., Dietrich, J. W., Krebs, B. & Angstwurm, M. W. Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J. Clin. Endocrinol. Metab. 87, 1687–1691 (2002).
Duntas, L. H., Mantzou, E. & Koutras, D. A. Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur. J. Endocrinol. 148, 389–393 (2003).
Turker, O., Kumanlioglu, K., Karapolat, I. & Dogan, I. Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J. Endocrinol. 190, 151–156 (2006).
Karanikas, G. et al. No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis. Thyroid 18, 7–12 (2008).
Nacamulli, D. et al. Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis. Clin. Endocrinol. (Oxf.) 73, 535–539 (2010).
Negro, R. et al. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J. Clin. Endocrinol. Metab. 92, 1263–1268 (2007).
Bahn, R. S. Graves' ophthalmopathy. N. Engl. J. Med. 362, 726–738 (2010).
Bartalena, L. et al. Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy. Thyroid 18, 333–346 (2008).
Marcocci, C. et al. Selenium and the course of mild Graves' orbitopathy. N. Engl. J. Med. 364, 1920–1931 (2011).
Xia, Y., Hill, K. E., Byrne, D. W., Xu, J. & Burk, R. F. Effectiveness of selenium supplements in a low-selenium area of China. Am. J. Clin. Nutr. 81, 829–834 (2005).
Burk, R. F., Norsworthy, B. K., Hill, K. E., Motley, A. K. & Byrne, D. W. Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol. Biomarkers Prev. 15, 804–810 (2006).
Bleys, J., Navas-Acien, A. & Guallar, E. Serum selenium and diabetes in U. S. adults. Diabetes Care 30, 829–834 (2007).
Stranges, S. et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann. Intern. Med. 147, 217–223 (2007).
Stranges, S. et al. Higher selenium status is associated with adverse blood lipid profile in British adults. J. Nutr. 140, 81–87 (2010).
Rayman, M. P., Stranges, S., Griffin, B. A., Pastor-Barriuso, R. & Guallar, E. Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. Ann. Intern. Med. 154, 656–665 (2011).
Broome, C. S. et al. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am. J. Clin. Nutr. 80, 154–162 (2004).
Hoffmann, F. W. et al. Dietary selenium modulates activation and differentiation of CD4+ T cells in mice through a mechanism involving cellular free thiols. J. Nutr. 140, 1155–1161 (2010).
Xue, H. et al. Selenium upregulates CD4(+)CD25(+) regulatory T cells in iodine-induced autoimmune thyroiditis model of NOD.H-2(h4) mice. Endocr. J. 57, 595–601 (2010).
Vunta, H. et al. The anti-inflammatory effects of selenium are mediated through 15-deoxy-Delta12, 14-prostaglandin J2 in macrophages. J. Biol. Chem. 282, 17964–17973 (2007).
Arner, E. S. Focus on mammalian thioredoxin reductases--important selenoproteins with versatile functions. Biochim. Biophys. Acta 1790, 495–526 (2009).
Lee, B. C. & Gladyshev, V. N. The biological significance of methionine sulfoxide stereochemistry. Free Radic Biol. Med. 50, 221–227 (2011).
Lee, B. C., Dikiy, A., Kim, H. Y. & Gladyshev, V. N. Functions and evolution of selenoprotein methionine sulfoxide reductases. Biochim. Biophys. Acta (2009).
Weiskopf, D. et al. Oxidative stress can alter the antigenicity of immunodominant peptides. J. Leukoc. Biol. 87, 165–172 (2010).
Ye, Y., Shibata, Y., Yun, C., Ron, D. & Rapoport, T. A. A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429, 841–847 (2004).
Curran, J. E. et al. Genetic variation in selenoprotein S. influences inflammatory response. Nat. Genet. 37, 1234–1241 (2005).
Sutherland, A., Kim, D. H., Relton, C., Ahn, Y. O. & Hesketh, J. Polymorphisms in the selenoprotein S. and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer. Genes Nutr. 5, 215–223 (2010).
Ribeiro dos Santos, L., Neves, C., Lima, J., Canedo, P. & Soares, P. Study of a polymorphism in the promoter region of the SEPS1 gene and risk of hashimoto thyroiditis. abstract P016 [online], (2009).
Verma, S. et al. Selenoprotein k knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. J. Immunol. 186, 2127–2137 (2011).
Vunta, H. et al. Selenium attenuates pro-inflammatory gene expression in macrophages. Mol. Nutr. Food Res. 52, 1316–1323 (2008).
Stoedter, M., Renko, K., Hög, A. & Schomburg, L. Selenium controls the sex-specific immune response and selenoprotein expression during the acute-phase response in mice. Biochem. J. 429, 43–51 (2010).
Tsai, S. J. et al. Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation. Biochemistry 48, 4838–4845 (2009).
Mazokopakis, E. E. et al. Effects of 12 months treatment with L-selenomethionine on serum anti-TPO levels in patients with Hashimoto's thyroiditis. Thyroid 17, 609–612 (2007).
Kvicala, J. et al. Effect of selenium supplementation on thyroid antibodies. Journal of Radioanalytical and Nuclear Chemistry 280, 275–279 (2009).
Bonfig, W., Gartner, R. & Schmidt, H. Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis. Scientific World Journal 10, 990–996 (2010).
The author expresses his gratitude to Drs Josef Köhrle, Ulrich Schweizer, Peter J. Hofmann, Birgit Hollenbach, Axel Schomburg and Jazmin Chiu-Ugalde for helpful discussions and critical remarks on the manuscript. Research in the author's laboratory is supported by the German Cancer Aid (Deutsche Krebshilfe, 10-1792 Scho2), Berlin-Brandenburg School for Regenerative Therapies (BSRT) and the Deutsche Forschungsgemeinschaft DFG (GraKo 1208/2, Scho 849/2-2).
The author declares no competing financial interests.
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Schomburg, L. Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol 8, 160–171 (2012). https://doi.org/10.1038/nrendo.2011.174
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