, Volume 17, Issue 2, pp 183–196 | Cite as

Selenoproteins in human body: focus on thyroid pathophysiology

  • Ana Valea
  • Carmen Emanuela Georgescu
Review Article


Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves’ orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.


Selenium Selenoproteins Selenocysteine Iodothyronine deiodinases Chronic autoimmune Hashimoto’s thyroiditis Differentiated thyroid cancer Graves’ disease Orbitopathy Malignancy 


CHEK2 gene

Checkpoint kinase


Deoxyribonucleic Acid


Iodothyronine deiodinases


Elongation factor of Sec


Glutathione peroxidases


Methionine-R-sulfoxide reductase 1


Sodium-iodide symporter


Pituitary adenylate cyclase-activating polypeptide


Polymerase chain reaction


Polymerase chain reaction-restriction fragment length polymorphism


Paired box 8


Reactive oxygen species








Selenocysteine-insertion sequence


SECIS Binding protein


Selenoprotein P1


Selenoprotein N


Selenoprotein S


Selenocysteine synthase


Single nucleotide polymorphism


Selenophosphate synthetase 2


Thioredoxin reductases


Thioredoxin reductase 2






Thyroid stimulating hormone


TSH receptor autoantibodies


Antithyroperoxidase antibody


Antithyroglobulin antibodies


Thyroid patient-reported outcome


Thioredoxin/thioredoxin reductase-1


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Varlamova EG, Cheremushkina IV (2017) Contribution of mammalian selenocysteine-containing proteins to carcinogenesis. J Trace Elem Med Biol 39:76–85PubMedCrossRefGoogle Scholar
  2. 2.
    Patrick L (2004) Selenium biochemistry and cancer: a review of the literature. Altern Med Rev 9(3):239–258PubMedGoogle Scholar
  3. 3.
    Skowronska-Jozwiak E (2015) The effect of selenium on thyroid physiology and pathology. Thyroid Res 8(Suppl 1):A23PubMedCentralCrossRefGoogle Scholar
  4. 4.
    Kieliszek M, Błażejak S (2016) Current knowledge on the importance of selenium in food for living organisms: a review. Molecules 21(5).
  5. 5.
    Papp LV, Holmgren A, Khanna KK (2010) Selenium and selenoproteins in health and disease. Antioxid Redox Signal 12(7):793–795PubMedCrossRefGoogle Scholar
  6. 6.
    Bubenik JL, Miniard AC, Driscoll DM (2014) Characterization of the UGA-recoding and SECIS-binding activities of SECIS-binding protein 2. RNA Biol 11(11):1402–1413PubMedCrossRefGoogle Scholar
  7. 7.
    Schweizer U, Fradejas-Villar N (2016) Why 21 ? The significance of selenoproteins for human health revealed by inborn errors of metabolism. FASEB J 30(11):3669–3681PubMedCrossRefGoogle Scholar
  8. 8.
    Barrett CW, Short SP, Williams CS (2017) Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut. Cell Mol Life Sci 74(4):607–616PubMedCrossRefGoogle Scholar
  9. 9.
    Brigelius-Flohé R, Flohé L (2017) Selenium and redox signaling. Arch Biochem Biophys 617:48–59PubMedCrossRefGoogle Scholar
  10. 10.
    Kryukov GV, Castellano S, Novoselov SV et al (2003) Characterization of mammalian selenoproteomes. Science 300(5624):1439–1443PubMedCrossRefGoogle Scholar
  11. 11.
    Gladyshev VN, Arnér ES, Berry MJ et al (2016) Selenoprotein gene nomenclature. J Biol Chem 291(46):24036–24040PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Kieliszek M, Błażejak S (2013) Selenium: significance, and outlook for supplementation. Nutrition 29(5):713–718PubMedCrossRefGoogle Scholar
  13. 13.
    Pitts MW, Hoffmann PR (2017) Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis. Cell Calcium S0143-4160(17):30047–30047. CrossRefGoogle Scholar
  14. 14.
    Labunskyy VM, Hatfield DL, Gladyshev VN (2014) Selenoproteins: molecular pathways and physiological roles. Physiol Rev 94(3):739–777PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Aaseth J, Alexander J, Bjørklund G et al (2016) Treatment strategies in Alzheimer's disease: a review with focus on selenium supplementation. Biometals 29(5):827–839PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Steinbrenner H, Speckmann B, Klotz LO (2016) Selenoproteins: antioxidant selenoenzymes and beyond. Arch Biochem Biophys 595:113–119PubMedCrossRefGoogle Scholar
  17. 17.
    Zhang X, Zhang L, Zhu JH, Cheng WH (2016) Nuclear selenoproteins and genome maintenance. IUBMB Life 68(1):5–12PubMedCrossRefGoogle Scholar
  18. 18.
    Rayman MP (2012) Selenium and human health. Lancet 379(9822):1256–1268PubMedCrossRefGoogle Scholar
  19. 19.
    Soriano-Garcia M (2004) Organoselenium compounds as potential therapeutic and chemopreventive agents: a review. Curr Med Chem 11(12):1657–1669PubMedCrossRefGoogle Scholar
  20. 20.
    Zhou J, Huang K, Lei XG (2013) Selenium and diabetes-evidence from animal studies. Free Radic Biol Med 65:1548–1556PubMedCrossRefGoogle Scholar
  21. 21.
    Brigelius-Flohé R, Banning A, Schnurr K (2003) Selenium-dependent enzymes in endothelial cell function. Antioxid Redox Signal 5(2):205–215PubMedCrossRefGoogle Scholar
  22. 22.
    Mangiapane E, Pessione A, Pessione E (2014) Selenium and selenoproteins: an overview on different biological systems. Curr Protein Pept Sci 15(6):598–607PubMedCrossRefGoogle Scholar
  23. 23.
    Qin HB, Zhu JM, Liang L, Wang MS, Su H (2013) The bioavailability of selenium and risk assessment for human selenium poisoning in high-Se areas, China. Environ Int 52:66–74PubMedCrossRefGoogle Scholar
  24. 24.
    Lacka K, Szeliga A (2015) Significance of selenium in thyroid physiology and pathology. Pol Merkur Lekarski 38(228):348–353PubMedGoogle Scholar
  25. 25.
    Mehdi Y, Hornick JL, Istasse L, Dufrasne I (2013) Selenium in the environment, metabolism and involvement in body functions. Molecules 18(3):3292–3311PubMedCrossRefGoogle Scholar
  26. 26.
    Kipp AP, Strohm D, Brigelius-Flohé R et al (2015) Revised reference values for selenium intake. J Trace Elem Med Biol 32:195–199PubMedCrossRefGoogle Scholar
  27. 27.
    Roman Viñas B, Ribas Barba L et al (2011) Projected prevalence of inadequate nutrient intakes in Europe. Ann Nutr Metab 59(2–4):84–95. PubMedCrossRefGoogle Scholar
  28. 28.
    Olza J, Aranceta-Bartrina J, González-Gross M et al (2017) Reported dietary intake and food sources of zinc, selenium, and vitamins A, E and C in the Spanish population: findings from the ANIBES study. Nutrients 9(7).
  29. 29.
    Jolnes GD, Droz B, Greve P, Gottschalk P, Poffet D, McGrath SP, Seneviratne SI, Smith P, Winkel LH (2017) Selenium deficiency risk predicted to increase under future climate change. Proc Natl Acad Sci U S A 114(11):2848–2853. CrossRefGoogle Scholar
  30. 30.
    Guastamacchia E, Giagulli VA, Licchelli B, Triggiani V (2015) Selenium and iodine in autoimmune thyroiditis. Endocr Metab Immune Disord Drug Targets 15(4):288–292PubMedCrossRefGoogle Scholar
  31. 31.
    Schomburg L (2011) Selenium, selenoproteins and the thyroid gland. Nat Rev Endocrinology 8(3):160–171PubMedCrossRefGoogle Scholar
  32. 32.
    Carroll L, Davies MJ, Pattison DI (2015) Reaction of low-molecular-mass organoselenium compounds (and their sulphur analogues) with inflammation-associated oxidants. Free Radic Res 49(6):750–767PubMedCrossRefGoogle Scholar
  33. 33.
    Speckmann B, Grune T (2015) Epigenetic effects of selenium and their implications for health. Epigenetics 10(3):179–190PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Schweizer U, Steegborn C (2015) New insights into the structure and mechanism of iodothyronine deiodinases. J Mol Endocrinol 55(3):R37–R52PubMedCrossRefGoogle Scholar
  35. 35.
    Joseph J, Loscalzo J (2013) Selenistasis: epistatic effects of selenium on cardiovascular phenotype. Nutrients 5(2):340–358PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Jain RB (2014) Thyroid function and serum copper, selenium, and zinc in general U.S. population. Biol Trace Elem Res 159(1–3):87–98PubMedCrossRefGoogle Scholar
  37. 37.
    Rijntjes E, Scholz PM, Mugesh G, Kohrle J (2013) Se- and se-based thiouracil and methimazole analogues exert different inhibitory mechanisms on type 1 and type 2 deiodinases. Eur Thyroid J 2:252–258PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Schweizer U, Schlicker C, Braun D, Köhrle J, Steegborn C (2014) Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism. Proc Natl Acad Sci U S A 111(29):10526–10531PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Mondal S, Raja K, Schweizer U, Mugesh G (2016) Chemistry and biology in the biosynthesis and action of thyroid hormones. Angew Chem Int Ed Engl 55(27):7606–7630PubMedCrossRefGoogle Scholar
  40. 40.
    Ciavardelli D, Bellomo M, Crescimanno C, Vella V (2014) Type 3 deiodinase: role in cancer growth, stemness, and metabolism. Front Endocrinol (Lausanne) 5:215. eCollection 2014CrossRefGoogle Scholar
  41. 41.
    Tanguy Y, Falluel-Morel A, Arthaud S et al (2011) The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes. Endocrinology 152(11):4322–4335PubMedCrossRefGoogle Scholar
  42. 42.
    Triggiani V, Tafaro E, Giagulli VA et al (2009) Role of iodine, selenium and other micronutrients in thyroid function and disorders. Endocr Metab Immune Disord Drug Targets 9(3):277–294PubMedCrossRefGoogle Scholar
  43. 43.
    Puig-Domingo M, Vila L (2013) The implications of iodine and its supplementation during pregnancy in fetal brain development. Curr Clin Pharmacol 8(2):97–109PubMedCrossRefGoogle Scholar
  44. 44.
    Eskes SA, Endert E, Fliers E et al (2014) Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies. Clin Endocrinol 80(3):444–451CrossRefGoogle Scholar
  45. 45.
    Winther KH, Bonnema SJ, Cold F et al (2015) Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population. Eur J Endocrinol 172(6):657–667PubMedCrossRefGoogle Scholar
  46. 46.
    Liu Y, Huang H, Zeng J, Sun C (2013) Thyroid volume, goiter prevalence, and selenium levels in an iodine-sufficient area: a cross-sectional study. BMC Public Health 13:1153PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Rasmussen LB, Schomburg L, Kohrle J et al (2011) Selenium status, thyroid volume, and multiple nodule formation in an area with mild iodine deficiency. Eur J Endocrinol 164:585–590PubMedCrossRefGoogle Scholar
  48. 48.
    Doupis J, Stavrianos C, Saltiki K et al (2009) Thyroid volume, selenium levels and nutritional habits in a rural region in Albania. Hormones (Athens) 8(4):296–2302CrossRefGoogle Scholar
  49. 49.
    Knobel M (2016) Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters. J Endocrinol Investig 39(4):357–373CrossRefGoogle Scholar
  50. 50.
    Wu Q, Rayman MP, Hongjun LV et al (2015) Low population selenium status is associated with increased prevalence of thyroid disease. J Clin Endocrinol Metab 100(11):4037–4047PubMedCrossRefGoogle Scholar
  51. 51.
    Ferrari SM, Fallahi P, Antonelli A, Benvenga S (2017) Environmental issues in thyroid diseases. Front Endocrinol (Lausanne) 8:50. eCollection 2017CrossRefGoogle Scholar
  52. 52.
    Fallahi P, Ferrari SM, Vita R, Benvenga S, Antonelli A (2016) The role of human parvovirus B19 and hepatitis C virus in the development of thyroid disorders. Rev Endocr Metab Disord 17(4):529–535PubMedCrossRefGoogle Scholar
  53. 53.
    D'Aurizio F, Villalta D, Metus P, Doretto P, Tozzoli R (2015) Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases? Autoimmun Rev 14(5):363–369PubMedCrossRefGoogle Scholar
  54. 54.
    Muscogiuri G, Tirabassi G et al (2015) Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr 69(3):291–296PubMedCrossRefGoogle Scholar
  55. 55.
    Liontiris MI, Mazokopakis EE (2017) A concise review of Hashimoto thyroiditis (HT) and the importance of iodide, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Points that need more investigation. Hell J Nucl Med 20(1):51–56PubMedGoogle Scholar
  56. 56.
    Hu S, Rayman MP (2017) Multiple nutritional factors and the risk of Hashimoto’s thyroiditis. Thyroid 27(5):597–610PubMedCrossRefGoogle Scholar
  57. 57.
    Duntas LH (2015) The role of iodine and selenium in autoimmune thyroiditis. Horm Metab Res 47(10):721–726PubMedCrossRefGoogle Scholar
  58. 58.
    Yu L, Zhou L, Xu E et al (2017) Levothyroxine monotherapy versus levothyroxine and selenium combination therapy in chronic lymphocytic thyroiditis. J Endocrinol Investig.
  59. 59.
    Mahmoodianfard S, Vafa M, Golgiri F et al (2015) Effects of zinc and selenium supplementation on thyroid function in overweight and obese hypothyroid female patients: a randomized double-blind controlled trial. J Am Coll Nutr 34(5):391–399PubMedCrossRefGoogle Scholar
  60. 60.
    Parshukova O, Potolitsyna N, Shadrina V, Chernykh A, Bojko E (2014) Features of selenium metabolism in humans living under the conditions of North European Russia. Int Arch Occup Environ Health 87(6):607–614PubMedCrossRefGoogle Scholar
  61. 61.
    Leoni SG, Sastre-Perona A, De la Vieja A, Santisteban P (2016) Selenium increases thyroid-stimulating hormone-induced sodium/iodide symporter expression through thioredoxin/apurinic/apyrimidinic endonuclease 1-dependent regulation of paired box 8 binding activity. Antioxid Redox Signal 24(15):855–866PubMedCrossRefGoogle Scholar
  62. 62.
    Mondal S, Mugesh G (2017) Novel thyroid hormone analogues, enzyme inhibitors and mimetics, and their action. Mol Cell Endocrinol.
  63. 63.
    Burk RF, Hill KE (2015) Regulation of selenium metabolism and transport. Annu Rev Nutr 35:109–134PubMedCrossRefGoogle Scholar
  64. 64.
    Kurokawa S, Bellinger FP, Hill KE, Burk RF, Berry MJ (2014) Isoform-specific binding of selenoprotein P to the β-propeller domain of apolipoprotein E receptor 2 mediates selenium supply. J Biol Chem 289(13):9195–9207PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Burk RF, Hill KE, Motley AK et al (2014) Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration. FASEB J 28(8):3579–3588PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Mao J, Teng W (2013) The relationship between selenoprotein P and glucose metabolism in experimental studies. Nutrients 5(6):1937–1948PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Kurokawa S, Eriksson S, Rose KL et al (2014) Sepp1(UF) forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1. Free Radic Biol Med 69:67–76PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Nourbakhsh M, Ahmadpour F, Chahardoli B et al (2016) Selenium and its relationship with selenoprotein P and glutathioneperoxidase in children and adolescents with Hashimoto's thyroiditis and hypothyroidism. J Trace Elem Med Biol 34:10–14PubMedCrossRefGoogle Scholar
  69. 69.
    de Farias CR, Cardoso BR, de Oliveira GM (2015) A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes. J Endocrinol Investig 38(10):1065–1074CrossRefGoogle Scholar
  70. 70.
    Mazokopakis EE, Chatzipavlidou V (2007) Hashimoto’s thyroiditis and the role of selenium. Current concepts. Hell J Nucl Med 10(1):6–8PubMedGoogle Scholar
  71. 71.
    Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW (2002) Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endocrinol Metab 87(4):1687–1691PubMedCrossRefGoogle Scholar
  72. 72.
    Esposito D, Rotondi M, Accardo G et al (2017) Influence of short-term selenium supplementation on the natural course of Hashimoto's thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial. J Endocrinol Investig 40(1):83–89CrossRefGoogle Scholar
  73. 73.
    van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H (2013) Selenium supplementation for Hashimoto’s thyroiditis. Cochrane Database Syst Rev 6:CD010223. CrossRefGoogle Scholar
  74. 74.
    Pirola I, Gandossi E, Agosti B, Delbarba A, Cappelli C (2016) Selenium supplementation could restore euthyroidism in subclinical hypothyroid patients with autoimmune thyroiditis. Endokrynol Pol 67(6):567–571PubMedCrossRefGoogle Scholar
  75. 75.
    Wichman J, Winther KH, Bonnema SJ, Hegedüs L (2016) Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid 26(12):1681–1692PubMedCrossRefGoogle Scholar
  76. 76.
    Watt T, Cramon P, Hegedüs L et al (2014) The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects. J Clin Endocrinol Metab 99(10):3708–3717PubMedCrossRefGoogle Scholar
  77. 77.
    Bektas Uysal H, Ayhan M (2016) Autoimmunity affects health-related quality of life in patients with Hashimoto’s thyroiditis. Kaohsiung J Med Sci 32(8):427–433PubMedCrossRefGoogle Scholar
  78. 78.
    Cramon P, Winther KH, Watt T et al (2016) Quality-of-life impairments persist six months after treatment of Graves’ hyperthyroidism and toxic nodular goiter: a prospective cohort study. Thyroid 26(8):1010–1018PubMedCrossRefGoogle Scholar
  79. 79.
    Cramon P, Bonnema SJ, Bjorner JB et al (2015) Quality of life in patients with benign nontoxic goiter: impact of disease and treatment response, and comparison with the general population. Thyroid 25(3):284–291PubMedCrossRefGoogle Scholar
  80. 80.
    Rasmussen SL, Rejnmark L, Ebbehøj E et al (2016) High level of agreement between electronic and paper mode of administration of a Thyroid-Specific Patient-Reported Outcome, ThyPRO. Eur Thyroid J 5(1):65–72PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Muehlhausen W, Doll H, Quadri N et al (2015) Equivalence of electronic and paper administration of patient-reported outcome measures: a systematic review and meta-analysis of studies conducted between 2007 and 2013. Health Qual Life Outcomes 13:167. PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Winther KH, Watt T, Bjørner JB et al (2014) The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial. Trials 15:115PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Watt T, Hegedüs L, Groenvold M et al (2010) Validity and reliability of the novel thyroid-specific quality of life questionnaire, ThyPRO. Eur J Endocrinol 162(1):161–167PubMedCrossRefGoogle Scholar
  84. 84.
    Kachouei A, Rezvanian H, Amini M, Aminorroaya A, Moradi E (2018) The effect of levothyroxine and selenium versus levothyroxine alone on reducing the level of anti-thyroid peroxidase antibody in autoimmune hypothyroidism patients. Adv Biomed Res 7:1PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Winther KH, Wichman JE, Bonnema SJ, Hegedüs L (2017) Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis. Endocrine 55(2):376–385PubMedCrossRefGoogle Scholar
  86. 86.
    Chakrabarti SK, Ghosh S, Banerjee S, Mukherjee S, Chowdhury S (2016) Oxidative stress in hypothyroid patients and the role of antioxidant supplementation. Indian J Endocrinol Metab 20(5):674–678PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Radetti G (2014) Clinical aspects of Hashimoto’s thyroiditis. Endocr Dev 26:158–170PubMedCrossRefGoogle Scholar
  88. 88.
    Wiersinga WM (2016) Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab (Seoul) 31(2):213–222CrossRefGoogle Scholar
  89. 89.
    Nacamulli D, Petricca D, Mian C (2013) Selenium and autoimmune thyroiditis. J Endocrinol Investig 36(10 Suppl):8–14Google Scholar
  90. 90.
    Duntas LH, Benvenga S (2015) Selenium: an element for life. Endocrine 48(3):756–775. PubMedCrossRefGoogle Scholar
  91. 91.
    Bullow Pedersen I, Knudsen N et al (2013) Serum selenium is low in newly diagnosed Graves’s disease: a population-based study. Clin Endocrinol 79(4):584–590CrossRefGoogle Scholar
  92. 92.
    Khong JJ, Goldstein RF, Sanders KM et al (2014) Serum selenium status in Graves’s disease with and without orbitopathy: a case-control study. Clin Endcrinol (Oxf) 80(6):905–910CrossRefGoogle Scholar
  93. 93.
    Wertenbruch T, Wilenberg HS, Sagert C et al (2007) Serum selenium in patients with remission and relapse of Graves’s disease. Med Chem 3(3):281–284PubMedCrossRefGoogle Scholar
  94. 94.
    Dehina N, Hofmann PJ, Behrends T, Eckstein A, Schomburg L (2016) Lack of association between selenium status and disease severity and activity in patients with Graves’ ophthalmopathy. Eur Thyroid J 5(1):57–64PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Khong JJ, McNab AA, Ebeling PR, Craig JE, Selva D (2016) Pathogenesis of thyroid eye disease: review and update on molecular mechanisms. Br J Ophthalmol 100(1):142–150PubMedCrossRefGoogle Scholar
  96. 96.
    Kahaly GJ, Riedl M, König J, Diana T, Schomburg L (2017) Double-blind, placebo- controlled, randomized trial of selenium in graves hyperthyroidism. J Clin Endocrinol Metab 102(11):4333–4341. PubMedCrossRefGoogle Scholar
  97. 97.
    Wang L, Wang B, Chen SR et al (2016) Effect of selenium supplementation on recurrent hyperthyroidism caused by Graves’ disease: a prospective pilot study. Horm Metab Res 48(9):559–564PubMedCrossRefGoogle Scholar
  98. 98.
    Watt T, Cramon P, Bjorner B et al (2013) Selenium supplementation for patients with Graves’ hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial. Trials 14:119. PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Cramon P, Rasmussen ÅK, Bonnema SJ et al (2014) Development and implementation of PROgmatic: a clinical trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes. ClinTrials 11(3):344–354Google Scholar
  100. 100.
    Dharmasena A (2014) Selenium supplementation in thyroid associated ophthalmopathy: an update. Int J Ophthalmol 7(2):365–375PubMedPubMedCentralGoogle Scholar
  101. 101.
    Gupta S, Jaworska-Bieniek K, Lubinski J, Jakubowska A (2013) Can selenium be a modifier of cancer risk in CHEK2 mutation carriers? Mutagenesis 28(6):625–629PubMedCrossRefGoogle Scholar
  102. 102.
    Siołek M, Cybulski C, Gąsior-Perczak D et al (2015) CHEK2 mutations and the risk of papillary thyroid cancer. Int J Cancer 137(3):548–552PubMedCrossRefGoogle Scholar
  103. 103.
    Nettore IC, De Nisco E, Desiderio S et al (2017) Selenium supplementation modulates apoptotic processes in thyroid follicular cells. Biofactors.
  104. 104.
    Glattre E, Thomassen Y, Thoresen SO et al (1989) Prediagnostic serum selenium in a case-control study of thyroid cancer. Int J Epidemiol 18:45–49PubMedCrossRefGoogle Scholar
  105. 105.
    Shen F, Cai WS, Li JL, Feng Z, Cao J, Xu B (2015) The association between serum levels of selenium, copper, and magnesium with thyroid cancer: a meta-analysis. Biol Trace Elem Res 167(2):225–235PubMedCrossRefGoogle Scholar
  106. 106.
    Köhrle J (2013) Pathophysiological relevance of selenium. J Endocrinol Investig 36(10 Suppl):1–7Google Scholar
  107. 107.
    Mao H, Cui R, Wang X (2015) Association analysis of selenoprotein S polymorphisms in Chinese Han with susceptibility to gastric cancer. Int J Clin Exp Med 8(7):10993–10999PubMedPubMedCentralGoogle Scholar
  108. 108.
    Huang L, Shi Y, Lu F et al (2013) Association study of polymorphism on selenoprotein genes and Kashin-Beck disease and serum selenium/iodine concentration in a Tibetan population. PlosONE 8(8):e71411CrossRefGoogle Scholar
  109. 109.
    Lei R, Jiang N, Zhang Q et al (2016) Prevalence of selenium, T-2 toxin, and deoxynivalenol in Kashin-Beck disease areas in Qinghai Province, Northwest China. Biol Trace Elem Res 171(1):34–40PubMedCrossRefGoogle Scholar
  110. 110.
    Santos LR, Durães C, Mendes A et al (2014) A polymorphismin the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto’s thyroiditis susceptibility. J Clin Endocrinol Metab 99(4):E719–E723PubMedCrossRefGoogle Scholar
  111. 111.
    Li M, Liu B, Li L, Zhang C, Zhou Q (2015) Association studies of SEPS1 gene polymorphisms with Hashimoto’s thyroiditis in Han Chinese. J Hum Genet 60(8):427–433PubMedCrossRefGoogle Scholar
  112. 112.
    Xiao L, Yuan J, Yao Q et al (2017) A case-control study of selenoprotein genes polymorphisms and autoimmune thyroid diseases in a Chinese population. BMC Med Genet.
  113. 113.
    Verloop H, Dekkers OM, Peeters RP, Schoones JW, Smit JW (2014) Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans. Eur J Endocrinol 171(3):R123–R135PubMedCrossRefGoogle Scholar
  114. 114.
    Miller JC, Thomson CD, Williams SM et al (2012) Influence of the glutathione peroxidase 1 Pro200Leu polymorphism on the response of glutathione peroxidase activity to selenium supplementation: a randomized controlled trial. Am J Clin Nutr 96(4):923–931PubMedCrossRefGoogle Scholar
  115. 115.
    Mao J, Vanderlelie JJ, Perkins AV, Redman CW, Ahmadi KR, Rayman MP (2016) Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women. Am J Clin Nutr 103(1):100–106PubMedCrossRefGoogle Scholar
  116. 116.
    Hellwege JN, Palmer ND, Ziegler JT et al (2014) Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics. Gene 534(1):33–39PubMedCrossRefGoogle Scholar
  117. 117.
    Wang Y, Yang X, Zheng Y et al (2013) The SEPS1 G-105A polymorphism is associated with risk of spontaneous preterm birth in a Chinese population. PLoS One 8(6):e65657. PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Crosley LK, Bashir S, Nicol F, Arthur JR, Hesketh JE, Sneddon AA (2013) The single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: interaction with selenium and fatty acids. Mol Nutr Food Res 57(12):2185–2194PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Li XX, Guan HJ, Liu JP et al (2015) Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study. Blood Coagul Fibrinolysis 26(2):131–135PubMedCrossRefGoogle Scholar
  120. 120.
    Kilic MK, Yesilkaya Y, Tezcan K et al (2016) The association between thyroid volume, L-thyroxine therapy and hepatocyte growth factor levels among patients with euthyroid and hypothyroid goitrous and non-goitrous Hashimoto’s thyroiditis versus healthy subjects. Endocr Res 41(2):110–115PubMedCrossRefGoogle Scholar
  121. 121.
    Felicetti F, Catalano MG, Fortunati N (2017) Thyroid autoimmunity and cancer. Front Horm Res 48:97–109PubMedCrossRefGoogle Scholar
  122. 122.
    Fiore E, Latrofa F, Vitti P (2015) Iodine, thyroid autoimmunity and cancer. Eur Thyroid J 4(1):26–35PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Lipinski B (2016) Sodium selenite as an anti-cancer agent. Anticancer Agents Med ChemGoogle Scholar
  124. 124.
    Vinceti M, Filippini T, Cilloni S et al (2017) Health risk assessment of environmental selenium: emerging evidence and challenges. (Review) Mol Med Rep 15(5):3323–3335PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Misra S, Boylan M, Selvam A, Spallholz JE, Björnstedt M (2015) Redox-active selenium compounds-from toxicity and cell death to cancer treatment. Nutrients 7(5):3536–3556PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Ogawa-Wong AN, Berry MJ, Seale LA (2016) Selenium and metabolic disorders: an emphasis on type 2 diabetes risk. Nutrients 8(2):80. PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Wrobel JK, Power R, Toborek M (2016) Biological activity of selenium: revisited. IUBMB Life 68(2):97–105PubMedCrossRefGoogle Scholar
  128. 128.
    Köhrle J (2015) Selenium and the thyroid. Curr Opin Endocrinol Diabetes Obes 22(5):392–401PubMedCrossRefGoogle Scholar
  129. 129.
    Schwingshackl L, Boeing H, Stelmach-Mardas M et al (2017) Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials. Adv Nutr 8(1):27–39PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Schwingshackl L, Hoffmann G, Buijsse B et al (2015) Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials. Syst Rev 4:34. PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Sabino P, Stranges S, Strazzullo P (2013) Does selenium matter in cardiometabolic disorders? A short review of the evidence. J Endocrinol Investig 36(10 Suppl):21–27Google Scholar
  132. 132.
    Rees K, Hartley L, Day C, Flowers N, Clarke A, Stranges S (2013) Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 1:CD009671Google Scholar
  133. 133.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2012) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 3:CD007176. CrossRefGoogle Scholar
  134. 134.
    Alehagen U, Aaseth J (2015) Selenium and coenzyme Q10 interrelationship in cardiovascular diseases—a clinician’s point of view. J Trace Elem Med Biol 31:157–162PubMedCrossRefGoogle Scholar
  135. 135.
    Alfthan G, Eurola M, Selenium Working Group et al (2015) Effects of nationwide addition of selenium to fertilizers on foods, and animal and human health in Finland: from deficiency to optimal selenium status of the population. J Trace Elem Med Biol 31:142–147PubMedCrossRefGoogle Scholar
  136. 136.
    Poblaciones MJ, Rodrigo S, Santamaria O, Chen Y, McGrath SP (2014) Selenium accumulation and speciation in biofortified chickpea (Cicer arietinum L.) under Mediterranean conditions. J Sci Food Agric 94(6):1101–1106PubMedCrossRefGoogle Scholar
  137. 137.
    De Vita P, Platani C, Fragasso M et al (2017) Selenium-enriched durum wheat improves the nutritional profile of pasta without altering its organoleptic properties. Food Chem 214:374–382PubMedCrossRefGoogle Scholar
  138. 138.
    Lipinski B (2016) Redox-active selenium in health and disease: a conceptual review. Mini Rev Med ChemGoogle Scholar
  139. 139.
    Poblaciones MJ, Rodrigo S, Santamaría O, Chen Y, McGrath SP (2014) Agronomic selenium biofortification in Triticum durum under Mediterranean conditions: from grain to cooked pasta. Food Chem 146:378–384PubMedCrossRefGoogle Scholar
  140. 140.
    Poblaciones MJ, Rodrigo SM, Santamaría O (2013) Evaluation of the potential of peas (Pisumsativum L.) to be used in selenium biofortification programs under Mediterranean conditions. Biol Trace Elem Res 151(1):132–137PubMedCrossRefGoogle Scholar
  141. 141.
    Pietinen P, Männistö S, Valsta LM, Sarlio-Lähteenkorva S (2010) Nutrition policy in Finland. Public Health Nutr 13(6A):901–906PubMedCrossRefGoogle Scholar
  142. 142.
    Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP (2013) Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 159(12):824–834PubMedCrossRefGoogle Scholar
  143. 143.
    Weekley CM, Harris HH (2013) Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem Soc Rev 42(23):8870–8894PubMedCrossRefGoogle Scholar
  144. 144.
    Golabek T, Bukowczan J, Sobczynski R, Leszczyszyn J, Chlosta PL (2016) The role of micronutrients in the risk of urinary tract cancer. Arch Med Sci 12(2):436–447PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Potter JD (2014) The failure of cancer chemoprevention. Carcinogenesis 35(5):974–982PubMedCrossRefGoogle Scholar
  146. 146.
    Golabek T, Powroźnik J, Chłosta P, Dobruch J, Borówka A (2015) The impact of nutrition in urogenital cancers. Arch Med Sci 11(2):411–418PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2008) Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev 3:CD00418. CrossRefGoogle Scholar
  148. 148.
    Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, Hurst R (2011) Selenium in human health and disease. Antioxid Redox Signal 14(7):1337–1383PubMedCrossRefGoogle Scholar
  149. 149.
    Prabhu KS, Lei XG (2016) Selenium. Adv Nutr 7(2):415–417PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velázquez-Villoria Á, Galofré JC (2015) Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol 2015:249125. PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Bartalena L, Baldeschi L, Boboridis K et al (2016) The 2016 European Thyroid Association/European Group on Graves’ orbitopathy guidelines for the management of Graves’ orbitopathy. Eur Thyroid J 5:9–26PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Jonklaas J, Bianco AC, Bauer AJ et al (2014) Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid 24(12):1670–1751PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Ana Valea
    • 1
    • 2
    • 3
  • Carmen Emanuela Georgescu
    • 1
    • 2
  1. 1.Department of EndocrinologyIuliu Hatieganu University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.Endocrinology ClinicClinical County HospitalCluj-NapocaRomania
  3. 3.Cluj-NapocaRomania

Personalised recommendations