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Non-Thyroidal Illness

Living reference work entry
Part of the Endocrinology book series (ENDOCR)

Abstract

The non-thyroidal illness syndrome (NTIS) is a term used to describe alterations in thyroid function tests observed in critically ill patients in the absence of intrinsic thyroid disease. Several studies have demonstrated that it has a high prevalence among hospitalized patients and it is significantly associated with the severity and the outcome of the disease. In the last decades there has been a shift in our view of the pathogenetic mechanisms underlying the syndrome. It has been increasingly recognized that alterations in the hypothalamus and the pituitary play a predominant role in the pathogenesis of NTIS, whereas the contribution of peripheral pathways, such as deiodinase activity, does not seem to be as significant as considered in the past. The majority of studies agree that treatment with thyroid hormone (TH) is not beneficial. However, TH may be reserved as an option for high-risk patients with very low TH levels and protracted disease, in whom some degree of hypothyroidism may be present.

Keywords

Non-thyroidal illness syndrome Low T3 syndrome Euthyroid sick syndrome Deiodinases Critical illness 

References

  1. Acker CG, Singh AR, Flick RP, Bernardini J, Greenberg A, Johnson JP. A trial of thyroxine in acute renal failure. Kidney Int. 2000;57(1):293–8.CrossRefPubMedGoogle Scholar
  2. Afandi B, Schussler GC, Arafeh AH, Boutros A, Yap MG, Finkelstein A. Selective consumption of thyroxine-binding globulin during cardiac bypass surgery. Metabolism. 2000;49(2):270–4.CrossRefPubMedGoogle Scholar
  3. Alevizaki M, Synetou M, Xynos K, Pappa T, Vemmos KN. Low triiodothyronine: a strong predictor of outcome in acute stroke patients. Eur J Clin Investig. 2007;37(8):651–7.CrossRefGoogle Scholar
  4. Alexopoulou O, Beguin C, De Nayer P, Maiter D. Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol. 2004;150(1):1–8.CrossRefPubMedGoogle Scholar
  5. Alkemade A, Unmehopa UA, Wiersinga WM, Swaab DF, Fliers E. Glucocorticoids decrease thyrotropin-releasing hormone messenger ribonucleic acid expression in the paraventricular nucleus of the human hypothalamus. J Clin Endocrinol Metab. 2005;90(1):323–7.CrossRefPubMedGoogle Scholar
  6. Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002;87(3):1068–72.CrossRefPubMedGoogle Scholar
  7. Arrojo EDR, Bianco AC. Type 2 deiodinase at the crossroads of thyroid hormone action. Int J Biochem Cell Biol. 2011;43(10):1432–41.CrossRefGoogle Scholar
  8. Bayer MF. Effect of heparin on serum free thyroxine linked to post-heparin lipolytic activity. Clin Endocrinol. 1983;19(5):591–6.CrossRefGoogle Scholar
  9. Beck-Peccoz P, Mariotti S. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Physiology of the hypothalamic-pituitary-thyroid axis. South Dartmouth: Endotext; 2000.Google Scholar
  10. Bennett-Guerrero E, Jimenez JL, White WD, D’Amico EB, Baldwin BI, Schwinn DA. Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomized, double-blind, placebo- controlled trial. Duke T3 study group. JAMA. 1996;275(9):687–92.CrossRefPubMedGoogle Scholar
  11. Berger MM, Reymond MJ, Shenkin A, Rey F, Wardle C, Cayeux C, et al. Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial. Intensive Care Med. 2001;27(1):91–100.CrossRefPubMedGoogle Scholar
  12. Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest. 2006;116(10):2571–9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Boelen A, Kwakkel J, Thijssen-Timmer DC, Alkemade A, Fliers E, Wiersinga WM. Simultaneous changes in central and peripheral components of the hypothalamus-pituitary-thyroid axis in lipopolysaccharide-induced acute illness in mice. J Endocrinol. 2004;182(2):315–23.CrossRefPubMedGoogle Scholar
  14. Boelen A, Kwakkel J, Vos XG, Wiersinga WM, Fliers E. Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor beta2 mRNA expression in mice. J Endocrinol. 2006;190(2):537–44.CrossRefPubMedGoogle Scholar
  15. Boelen A, Boorsma J, Kwakkel J, Wieland CW, Renckens R, Visser TJ, et al. Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes in response to acute bacterial infection. Thyroid. 2008;18(10):1095–103.CrossRefPubMedGoogle Scholar
  16. Boelen A, Kwakkel J, Fliers E. Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev. 2011;32(5):670–93.CrossRefPubMedGoogle Scholar
  17. Boelen A, van Beeren M, Vos X, Surovtseva O, Belegri E, Saaltink DJ, et al. Leptin administration restores the fasting-induced increase of hepatic type 3 deiodinase expression in mice. Thyroid. 2012;22(2):192–9.CrossRefPubMedGoogle Scholar
  18. Bornstein SR, Torpy DJ, Chrousos GP, Licinio J, Engelmann L. Leptin levels are elevated despite low thyroid hormone levels in the “euthyroid sick” syndrome. J Clin Endocrinol Metab. 1997;82(12):4278–9.PubMedGoogle Scholar
  19. Brabant A, Brabant G, Schuermeyer T, Ranft U, Schmidt FW, Hesch RD, et al. The role of glucocorticoids in the regulation of thyrotropin. Acta Endocrinol. 1989;121(1):95–100.PubMedGoogle Scholar
  20. Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122(9):3035–43.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Brent GA, Hershman JM. Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. J Clin Endocrinol Metab. 1986;63(1):1–8.CrossRefPubMedGoogle Scholar
  22. den Brinker M, Joosten KF, Visser TJ, Hop WC, de Rijke YB, Hazelzet JA, et al. Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins. J Clin Endocrinol Metab. 2005;90(10):5613–20.CrossRefGoogle Scholar
  23. Burger A, Nicod P, Suter P, Vallotton MB, Vagenakis P, Braverman L. Reduced active thyroid hormone levels in acute illness. Lancet. 1976;1(7961):653–5.CrossRefPubMedGoogle Scholar
  24. Chopra IJ. Simultaneous measurement of free thyroxine and free 3,5,3′-triiodothyronine in undiluted serum by direct equilibrium dialysis/radioimmunoassay: evidence that free triiodothyronine and free thyroxine are normal in many patients with the low triiodothyronine syndrome. Thyroid. 1998;8(3):249–57.CrossRefPubMedGoogle Scholar
  25. Chopra IJ, Teco GN, Mead JF, Huang TS, Beredo A, Solomon DH. Relationship between serum free fatty acids and thyroid hormone binding inhibitor in nonthyroid illnesses. J Clin Endocrinol Metab. 1985;60(5):980–4.CrossRefPubMedGoogle Scholar
  26. De Groot LJ. Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006;22(1):57–86.vi.CrossRefPubMedGoogle Scholar
  27. Escobar-Morreale HF, Obregon MJ, Hernandez A, Escobar del Rey F, Morreale de Escobar G. Regulation of iodothyronine deiodinase activity as studied in thyroidectomized rats infused with thyroxine or triiodothyronine. Endocrinology. 1997;138(6):2559–68.CrossRefGoogle Scholar
  28. Everts ME, de Jong M, Lim CF, Docter R, Krenning EP, Visser TJ, et al. Different regulation of thyroid hormone transport in liver and pituitary: its possible role in the maintenance of low T3 production during nonthyroidal illness and fasting in man. Thyroid. 1996;6(4):359–68.CrossRefPubMedGoogle Scholar
  29. Fekete C, Lechan RM. Negative feedback regulation of hypophysiotropic thyrotropin-releasing hormone (TRH) synthesizing neurons: role of neuronal afferents and type 2 deiodinase. Front Neuroendocrinol. 2007;28(2–3):97–114.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Fekete C, Lechan RM. Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr Rev. 2014;35(2):159–94.CrossRefPubMedGoogle Scholar
  31. Fekete C, Gereben B, Doleschall M, Harney JW, Dora JM, Bianco AC, et al. Lipopolysaccharide induces type 2 iodothyronine deiodinase in the mediobasal hypothalamus: implications for the nonthyroidal illness syndrome. Endocrinology. 2004;145(4):1649–55.CrossRefPubMedGoogle Scholar
  32. Fekete C, Sarkar S, Christoffolete MA, Emerson CH, Bianco AC, Lechan RM. Bacterial lipopolysaccharide (LPS)-induced type 2 iodothyronine deiodinase (D2) activation in the mediobasal hypothalamus (MBH) is independent of the LPS-induced fall in serum thyroid hormone levels. Brain Res. 2005;1056(1):97–9.CrossRefPubMedGoogle Scholar
  33. Fliers E, Guldenaar SE, Wiersinga WM, Swaab DF. Decreased hypothalamic thyrotropin-releasing hormone gene expression in patients with nonthyroidal illness. J Clin Endocrinol Metab. 1997;82(12):4032–6.PubMedGoogle Scholar
  34. Forestier E, Vinzio S, Sapin R, Schlienger JL, Goichot B. Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: the Alsanut study. Eur J Endocrinol. 2009;160(2):207–14.CrossRefPubMedGoogle Scholar
  35. Gerard AC, Boucquey M, van den Hove MF, Colin IM. Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1alpha/IFN-gamma, an effect partially mediated by nitric oxide. Am J Physiol Endocrinol Metab. 2006;291(2):E242–53.CrossRefPubMedGoogle Scholar
  36. Hampton J. Thyroid gland disorder emergencies: thyroid storm and myxedema coma. AACN Adv Crit Care. 2013;24(3):325–32.CrossRefPubMedGoogle Scholar
  37. Hansen PS, Brix TH, Sorensen TI, Kyvik KO, Hegedus L. Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins. J Clin Endocrinol Metab. 2004;89(3):1181–7.CrossRefPubMedGoogle Scholar
  38. Harris AR, Fang SL, Azizi F, Lipworth L, Vagenakis AG, Barverman LE. Effect of starvation on hypothalamic-pituitary-thyroid function in the rat. Metabolism. 1978;27(9):1074–83.CrossRefPubMedGoogle Scholar
  39. Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009;23(6):793–800.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Janssen R, Zuidwijk MJ, Muller A, van Mil A, Dirkx E, Oudejans CB, et al. MicroRNA 214 is a potential regulator of thyroid hormone levels in the mouse heart following myocardial infarction, by targeting the thyroid-hormone-inactivating enzyme deiodinase type III. Front Endocrinol (Lausanne). 2016;7:22.Google Scholar
  41. Jirasakuldech B, Schussler GC, Yap MG, Drew H, Josephson A, Michl J. A characteristic serpin cleavage product of thyroxine-binding globulin appears in sepsis sera. J Clin Endocrinol Metab. 2000;85(11):3996–9.CrossRefPubMedGoogle Scholar
  42. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on thyroid hormone replacement. Thyroid. 2014;24(12):1670–751.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kaptein EM, Robinson WJ, Grieb DA, Nicoloff JT. Peripheral serum thyroxine, triiodothyronine and reverse triiodothyronine kinetics in the low thyroxine state of acute nonthyroidal illnesses. A noncompartmental analysis. J Clin Invest. 1982;69(3):526–35.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Kwakkel J, Chassande O, van Beeren HC, Wiersinga WM, Boelen A. Lacking thyroid hormone receptor beta gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness. J Endocrinol. 2008;197(1):151–8.CrossRefPubMedGoogle Scholar
  45. Kwakkel J, van Beeren HC, Ackermans MT, Platvoet-Ter Schiphorst MC, Fliers E, Wiersinga WM, et al. Skeletal muscle deiodinase type 2 regulation during illness in mice. J Endocrinol. 2009;203(2):263–70.CrossRefPubMedGoogle Scholar
  46. Larsen PR. Salicylate-induced increases in free triiodothyronine in human serum. Evidence of inhibition of triiodothyronine binding to thyroxine-binding globulin and thyroxine-binding prealbumin. J Clin Invest. 1972;51(5):1125–34.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Lim CF, Docter R, Visser TJ, Krenning EP, Bernard B, van Toor H, et al. Inhibition of thyroxine transport into cultured rat hepatocytes by serum of nonuremic critically ill patients: effects of bilirubin and nonesterified fatty acids. J Clin Endocrinol Metab. 1993;76(5):1165–72.PubMedGoogle Scholar
  48. Marks SD. Nonthyroidal illness syndrome in children. Endocrine. 2009;36(3):355–67.CrossRefPubMedGoogle Scholar
  49. McKeown DW, Bonser RS, Kellum JA. Management of the heartbeating brain-dead organ donor. Br J Anaesth. 2012;108(Suppl 1):i96–107.CrossRefPubMedGoogle Scholar
  50. Mebis L, Langouche L, Visser TJ, Van den Berghe G. The type II iodothyronine deiodinase is up-regulated in skeletal muscle during prolonged critical illness. J Clin Endocrinol Metab. 2007;92(8):3330–3.CrossRefPubMedGoogle Scholar
  51. Mebis L, Paletta D, Debaveye Y, Ellger B, Langouche L, D’Hoore A, et al. Expression of thyroid hormone transporters during critical illness. Eur J Endocrinol. 2009a;161(2):243–50.CrossRefPubMedGoogle Scholar
  52. Mebis L, Debaveye Y, Ellger B, Derde S, Ververs EJ, Langouche L, et al. Changes in the central component of the hypothalamus-pituitary-thyroid axis in a rabbit model of prolonged critical illness. Crit Care. 2009b;13(5):R147.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Miller J, Carney P. Central hypothyroidism with oxcarbazepine therapy. Pediatr Neurol. 2006;34(3):242–4.CrossRefPubMedGoogle Scholar
  54. Moshage H. Cytokines and the hepatic acute phase response. J Pathol. 1997;181(3):257–66.CrossRefPubMedGoogle Scholar
  55. Novitzky D, Mi Z, Sun Q, Collins JF, Cooper DK. Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis. Transplantation. 2014;98(10):1119–27.CrossRefPubMedGoogle Scholar
  56. Oetting A, Yen PM. New insights into thyroid hormone action. Best Pract Res Clin Endocrinol Metab. 2007;21(2):193–208.CrossRefPubMedGoogle Scholar
  57. Ohzeki T, Hanaki K, Motozumi H, Ohtahara H, Ishitani N, Urashima H, et al. Efficacy of bromocriptine administration for selective pituitary resistance to thyroid hormone. Horm Res. 1993;39(5–6):229–34.CrossRefPubMedGoogle Scholar
  58. Osborn DA, Hunt RW. Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2007;1:CD005948.Google Scholar
  59. Pappa TA, Vagenakis AG, Alevizaki M. The nonthyroidal illness syndrome in the non-critically ill patient. Eur J Clin Investig. 2011;41(2):212–20.CrossRefGoogle Scholar
  60. Peeters RP, Wouters PJ, Kaptein E, van Toor H, Visser TJ, Van den Berghe G. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab. 2003;88(7):3202–11.CrossRefPubMedGoogle Scholar
  61. Peeters RP, van der Geyten S, Wouters PJ, Darras VM, van Toor H, Kaptein E, et al. Tissue thyroid hormone levels in critical illness. J Clin Endocrinol Metab. 2005;90(12):6498–507.CrossRefPubMedGoogle Scholar
  62. Pingitore A, Galli E, Barison A, Iervasi A, Scarlattini M, Nucci D, et al. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008;93(4):1351–8.CrossRefPubMedGoogle Scholar
  63. Plikat K, Langgartner J, Buettner R, Bollheimer LC, Woenckhaus U, Scholmerich J, et al. Frequency and outcome of patients with nonthyroidal illness syndrome in a medical intensive care unit. Metabolism. 2007;56(2):239–44.CrossRefPubMedGoogle Scholar
  64. van der Poll T, Van Zee KJ, Endert E, Coyle SM, Stiles DM, Pribble JP, et al. Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man. J Clin Endocrinol Metab. 1995;80(4):1341–6.PubMedGoogle Scholar
  65. Portman MA, Slee A, Olson AK, Cohen G, Karl T, Tong E, et al. Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis. Circulation. 2010;122(11 Suppl):S224–33.CrossRefPubMedPubMedCentralGoogle Scholar
  66. Rodriguez-Perez A, Palos-Paz F, Kaptein E, Visser TJ, Dominguez-Gerpe L, Alvarez-Escudero J, et al. Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock. Clin Endocrinol. 2008;68(5):821–7.CrossRefGoogle Scholar
  67. Rothwell PM, Lawler PG. Prediction of outcome in intensive care patients using endocrine parameters. Crit Care Med. 1995;23(1):78–83.CrossRefPubMedGoogle Scholar
  68. Sacca L. Heart failure as a multiple hormonal deficiency syndrome. Circ Heart Fail. 2009;2(2):151–6.CrossRefPubMedGoogle Scholar
  69. Samuels MH, Henry P, Ridgway EC. Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion. J Clin Endocrinol Metab. 1992;74(1):217–22.PubMedGoogle Scholar
  70. Schneider MJ, Fiering SN, Thai B, Wu SY, St Germain E, Parlow AF, et al. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology. 2006;147(1):580–9.CrossRefPubMedGoogle Scholar
  71. Schonberger W, Grimm W, Emmrich P, Gempp W. Thyroid administration lowers mortality in premature infants. Lancet. 1979;2(8153):1181.CrossRefPubMedGoogle Scholar
  72. Schulman RC, Mechanick JI. Metabolic and nutrition support in the chronic critical illness syndrome. Respir Care. 2012;57(6):958–77. discussion 77-8.CrossRefPubMedGoogle Scholar
  73. Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, et al. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. J Clin Invest. 2008;118(3):975–83.PubMedPubMedCentralGoogle Scholar
  74. Spratt DI, Frohnauer M, Cyr-Alves H, Kramer RS, Lucas FL, Morton JR, et al. Physiological effects of nonthyroidal illness syndrome in patients after cardiac surgery. Am J Physiol Endocrinol Metab. 2007;293(1):E310–5.CrossRefPubMedGoogle Scholar
  75. Tang KT, Braverman LE, DeVito WJ. Tumor necrosis factor-alpha and interferon-gamma modulate gene expression of type I 5′-deiodinase, thyroid peroxidase, and thyroglobulin in FRTL-5 rat thyroid cells. Endocrinology. 1995;136(3):881–8.CrossRefPubMedGoogle Scholar
  76. Uchiyama A, Kushima R, Watanabe T, Kusuda S. Effect of l-thyroxine supplementation on infants with transient hypothyroxinemia of prematurity at 18 months of corrected age: randomized clinical trial. J Pediatr Endocrinol Metab. 2015;28(1–2):177–82.PubMedGoogle Scholar
  77. Van den Berghe G. Non-thyroidal illness in the ICU: a syndrome with different faces. Thyroid. 2014;24(10):1456–65.CrossRefPubMedPubMedCentralGoogle Scholar
  78. Van den Berghe G, Wouters P, Weekers F, Mohan S, Baxter RC, Veldhuis JD, et al. Reactivation of pituitary hormone release and metabolic improvement by infusion of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness. J Clin Endocrinol Metab. 1999;84(4):1311–23.PubMedGoogle Scholar
  79. Van den Berghe G, Baxter RC, Weekers F, Wouters P, Bowers CY, Iranmanesh A, et al. The combined administration of GH-releasing peptide-2 (GHRP-2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP-2 alone. Clin Endocrinol. 2002;56(5):655–69.CrossRefGoogle Scholar
  80. Vella KR, Ramadoss P, Lam FS, Harris JC, Ye FD, Same PD, et al. NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways. Cell Metab. 2011;14(6):780–90.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Vigersky RA, Filmore-Nassar A, Glass AR. Thyrotropin suppression by metformin. J Clin Endocrinol Metab. 2006;91(1):225–7.CrossRefPubMedGoogle Scholar
  82. de Vries EM, Fliers E, Boelen A. The molecular basis of the non-thyroidal illness syndrome. J Endocrinol. 2015;225(3):R67–81.CrossRefPubMedGoogle Scholar
  83. Wajner SM, Goemann IM, Bueno AL, Larsen PR, Maia AL. IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. J Clin Invest. 2011;121(5):1834–45.CrossRefPubMedPubMedCentralGoogle Scholar
  84. Walley AJ, Asher JE, Froguel P. The genetic contribution to non-syndromic human obesity. Nat Rev Genet. 2009;10(7):431–42.CrossRefPubMedGoogle Scholar
  85. Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol. 2010;205(1):1–13.CrossRefPubMedGoogle Scholar
  86. Winther KH, Bonnema SJ, Cold F, Debrabant B, Nybo M, Cold S, et al. Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population. Eur J Endocrinol. 2015;172(6):657–67.CrossRefPubMedGoogle Scholar
  87. Wu SY, Green WL, Huang WS, Hays MT, Chopra IJ. Alternate pathways of thyroid hormone metabolism. Thyroid. 2005;15(8):943–58.CrossRefPubMedGoogle Scholar
  88. Yu J, Koenig RJ. Regulation of hepatocyte thyroxine 5′-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome. J Biol Chem. 2000;275(49):38296–301.CrossRefPubMedGoogle Scholar
  89. Yu J, Koenig RJ. Induction of type 1 iodothyronine deiodinase to prevent the nonthyroidal illness syndrome in mice. Endocrinology. 2006;147(7):3580–5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Section of Endocrinology, Diabetes and Metabolism, Department of MedicineThe University of ChicagoChicagoUSA
  2. 2.Endocrine Unit, Department of Medical Therapeutics, Alexandra Hospital, School of MedicineNational Kapodistrian UniversityAthensGreece

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