Skip to main content
SpringerLink
Log in

Thyroidal Changes During Critical Illness

  • Chapter
  • First Online:
The Stress Response of Critical Illness: Metabolic and Hormonal Aspects

  • 1288 Accesses

Abstract

Patients suffering from a variety of critical illnesses present with uniform alterations within the thyroid axis with low plasma triiodothyronine (T3), but increased plasma reverse T3 (rT3). As these changes occur in the presence of low-normal thyroid stimulating hormone (TSH), this constellation is also referred to as Nonthyroidal Illness Syndrome (NTI). Both central and peripheral components of the thyroidal axis play a role in the development of NTI. Furthermore, nutritional intake can affect the extent and composition of NTI. The severity of NTI is associated with a poor prognosis, but it is still unclear whether this indicates a causal relationship, or in contrast, an adaptation to more severe illness.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Yen PM (2001) Physiological and molecular basis of thyroid hormone action. Physiol Rev 81(3):1097–1142

    CAS  PubMed  Google Scholar 

  2. Mullur R, Liu YY, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94(2):355–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Goldsmith RE, Stanbury JB, Brownell GL (1951) The effect of thyrotropin on the release of hormone from the human thyroid. J Clin Endocrinol Metab 11(10):1079–1094

    Article  CAS  PubMed  Google Scholar 

  4. Weintraub BD, Wondisford FE, Farr EA et al (1989) Pre-translational and post-translational regulation of TSH synthesis in normal and neoplastic thyrotrophs. Horm Res 32(1–3):22–24

    Article  CAS  PubMed  Google Scholar 

  5. Bodenner DL, Mroczynski MA, Weintraub BD, Radovick S, Wondisford FE (1991) A detailed functional and structural analysis of a major thyroid hormone inhibitory element in the human thyrotropin beta-subunit gene. J Biol Chem 266(32):21666–21673

    CAS  PubMed  Google Scholar 

  6. Oppenheimer JH (1968) Role of plasma proteins in the binding, distribution and metabolism of the thyroid hormones. N Engl J Med 278(21):1153–1162

    Article  CAS  PubMed  Google Scholar 

  7. Visser WE, Friesema EC, Jansen J, Visser TJ (2008) Thyroid hormone transport in and out of cells. Trends Endocrinol Metab 19(2):50–56

    Article  CAS  PubMed  Google Scholar 

  8. Zevenbergen C, Meima ME, Lima de Souza EC et al (2015) transport of iodothyronines by human l-type amino acid transporters. Endocrinology 156(11):4345–4355. doi:10.1210/en2015-1140

    Article  CAS  PubMed  Google Scholar 

  9. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 23(1):38–89

    Article  CAS  PubMed  Google Scholar 

  10. Friesema EC, Jansen J, Visser TJ (2005) Thyroid hormone transporters. Biochem Soc Trans 33(Pt 1):228–232

    Article  CAS  PubMed  Google Scholar 

  11. Cheng SY, Leonard JL, Davis PJ (2010) Molecular aspects of thyroid hormone actions. Endocr Rev 31(2):139–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Van den Berghe G (2000) Novel insights into the neuroendocrinology of critical illness. Eur J Endocrinol 143(1):1–13

    Article  PubMed  Google Scholar 

  13. Rothwell PM, Lawler PG (1995) Prediction of outcome in intensive care patients using endocrine parameters. Crit Care Med 23(1):78–83

    Article  CAS  PubMed  Google Scholar 

  14. Rothwell PM, Udwadia ZF, Lawler PG (1993) Thyrotropin concentration predicts outcome in critical illness. Anaesthesia 48(5):373–376

    Article  CAS  PubMed  Google Scholar 

  15. Romijn JA, Wiersinga WM (1990) Decreased nocturnal surge of thyrotropin in nonthyroidal illness. J Clin Endocrinol Metab 70(1):35–42

    Article  CAS  PubMed  Google Scholar 

  16. Van den Berghe G, de Zegher F, Veldhuis JD et al (1997) Thyrotropin and prolactin release in prolonged critical illness: dynamics of spontaneous secretion and effects of growth hormone-secretagogues. Clin Endocrinol (Oxf) 47(5):599–612

    Article  Google Scholar 

  17. Peeters RP, Wouters PJ, van Toor H, Kaptein E, Visser TJ, Van den Berghe G (2005) Serum rT3 and T3/rT3 are prognostic markers in critically ill patients and are associated with post-mortem tissue deiodinase activities. J Clin Endocrinol Metab 90(8):4559–4565

    Article  CAS  PubMed  Google Scholar 

  18. Refetoff S, Robin NI, Fang VS (1970) Parameters of thyroid function in serum of 16 selected vertebrate species: a study of PBI, serum T4, free T4, and the pattern of T4 and T3 binding to serum proteins. Endocrinology 86(4):793–805

    Article  CAS  PubMed  Google Scholar 

  19. Docter R, van Toor H, Krenning EP, de Jong M, Hennemann G (1993) Free thyroxine assessed with three assays in sera of patients with nonthyroidal illness and of subjects with abnormal concentrations of thyroxine-binding proteins. Clin Chem 39(8):1668–1674

    CAS  PubMed  Google Scholar 

  20. Van den Berghe G, de Zegher F, Vlasselaers D et al (1996) Thyrotropin-releasing hormone in critical illness: from a dopamine-dependent test to a strategy for increasing low serum triiodothyronine, prolactin, and growth hormone concentrations. Crit Care Med 24(4):590–595

    Article  PubMed  Google Scholar 

  21. Peeters RP, Wouters PJ, Kaptein E, van Toor H, Visser TJ, Van den Berghe G (2003) Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab 88(7):3202–3211

    Article  CAS  PubMed  Google Scholar 

  22. Boelen A, Kwakkel J, Thijssen-Timmer DC, Alkemade A, Fliers E, Wiersinga WM (2004) Simultaneous changes in central and peripheral components of the hypothalamus-pituitary-thyroid axis in lipopolysaccharide-induced acute illness in mice. J Endocrinol 182(2):315–323

    Article  CAS  PubMed  Google Scholar 

  23. Rodriguez-Perez A, Palos-Paz F, Kaptein E et al (2008) Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock. Clin Endocrinol (Oxf) 68(5):821–827

    Article  CAS  Google Scholar 

  24. Peeters RP, Geyten S, Wouters PJ et al (2005) Tissue thyroid hormone levels in critical illness. J Clin Endocrinol Metab 90(12):6498–6507

    Article  CAS  PubMed  Google Scholar 

  25. Mebis L, Paletta D, Debaveye Y et al (2009) Expression of thyroid hormone transporters during critical illness. Eur J Endocrinol 161(2):243–250

    Article  CAS  PubMed  Google Scholar 

  26. Mebis L, Langouche L, Visser TJ, Van den Berghe G (2007) The type II iodothyronine deiodinase is up-regulated in skeletal muscle during prolonged critical illness. J Clin Endocrinol Metab 92(8):3330–3333

    Article  CAS  PubMed  Google Scholar 

  27. Ma SF, Xie L, Pino-Yanes M et al (2011) Type 2 deiodinase and host responses of sepsis and acute lung injury. Am J Respir Cell Mol Biol 45(6):1203–1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mebis L, Debaveye Y, Ellger B et al (2009) Changes in the central component of the hypothalamus-pituitary-thyroid axis in a rabbit model of prolonged critical illness. Crit Care 13(5):R147

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fekete C, Gereben B, Doleschall M et al (2004) Lipopolysaccharide induces type 2 iodothyronine deiodinase in the mediobasal hypothalamus: implications for the nonthyroidal illness syndrome. Endocrinology 145(4):1649–1655

    Article  CAS  PubMed  Google Scholar 

  30. Thijssen-Timmer DC, Peeters RP, Wouters P et al (2007) Thyroid hormone receptor isoform expression in livers of critically ill patients. Thyroid 17(2):105–112

    Article  CAS  PubMed  Google Scholar 

  31. Schutz P, Bally M, Stanga Z, Keller U (2014) Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target? Swiss Med Wkly 144:w13957

    PubMed  Google Scholar 

  32. Everts ME, Jong M, Lim CF et al (1996) 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 6(4):359–368

    Article  CAS  PubMed  Google Scholar 

  33. Boelen A, Wiersinga WM, Fliers E (2008) Fasting-induced changes in the hypothalamus-pituitary-thyroid axis. Thyroid 18(2):123–129

    Article  CAS  PubMed  Google Scholar 

  34. Gardner DF, Kaplan MM, Stanley CA, Utiger RD (1979) Effect of tri-iodothyronine replacement on the metabolic and pituitary responses to starvation. N Engl J Med 300(11):579–584

    Article  CAS  PubMed  Google Scholar 

  35. Chourdakis M, Kraus MM, Tzellos T et al (2012) Effect of early compared with delayed enteral nutrition on endocrine function in patients with traumatic brain injury: an open-labeled randomized trial. JPEN J Parenter Enteral Nutr 36(1):108–116

    Article  CAS  PubMed  Google Scholar 

  36. Richmand DA, Molitch ME, O’Donnell TF (1980) Altered thyroid hormone levels in bacterial sepsis: the role of nutritional adequacy. Metabolism 29(10):936–942

    Article  CAS  PubMed  Google Scholar 

  37. Ouchi K, Matsubara S, Matsuno S (1991) Effects of supplementary parenteral nutrition on thyroid hormone patterns in surgical patients with liver cirrhosis. Nutrition 7(3):189–192

    CAS  PubMed  Google Scholar 

  38. Casaer MP, Mesotten D, Hermans G et al (2011) Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365(6):506–517

    Article  CAS  PubMed  Google Scholar 

  39. Langouche L, Vander PS, Marques M et al (2013) Impact of early nutrient restriction during critical illness on the nonthyroidal illness syndrome and its relation with outcome: a randomized, controlled clinical study. J Clin Endocrinol Metab 98(3):1006–1013

    Article  CAS  PubMed  Google Scholar 

  40. Mebis L, Eerdekens A, Guiza F et al (2012) Contribution of nutritional deficit to the pathogenesis of the nonthyroidal illness syndrome in critical illness: a rabbit model study. Endocrinology 153(2):973–984

    Article  CAS  PubMed  Google Scholar 

  41. Gielen M, Mesotten D, Wouters PJ et al (2012) Effect of tight glucose control with insulin on the thyroid axis of critically ill children and its relation with outcome. J Clin Endocrinol Metab 97(10):3569–3576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fliers E, Guldenaar SE, Wiersinga WM, Swaab DF (1997) Decreased hypothalamic thyrotropin-releasing hormone gene expression in patients with nonthyroidal illness. J Clin Endocrinol Metab 82(12):4032–4036

    CAS  PubMed  Google Scholar 

  43. Langouche L, Princen L, Gunst J, Guiza F, Derde S, Van den Berghe G (2013) Anterior pituitary morphology and hormone production during sustained critical illness in a rabbit model. Horm Metab Res 45(4):277–282

    CAS  PubMed  Google Scholar 

  44. Van den Berghe G, de Zegher F, Baxter RC et al (1998) Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone secretagogues. J Clin Endocrinol Metab 83(2):309–319

    PubMed  Google Scholar 

  45. Van den Berghe G, Wouters P, Weekers F et al (1999) 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 84(4):1311–1323

    PubMed  Google Scholar 

  46. Bacci V, Schussler GC, Kaplan TB (1982) The relationship between serum triiodothyronine and thyrotropin during systemic illness. J Clin Endocrinol Metab 54(6):1229–1235

    Article  CAS  PubMed  Google Scholar 

  47. Boelen A, Platvoet-ter Schiphorst MC, Bakker O, Wiersinga WM (1995) The role of cytokines in the lipopolysaccharide-induced sick euthyroid syndrome in mice. J Endocrinol 146(3):475–483

    Article  CAS  PubMed  Google Scholar 

  48. Van der Poll T, Romijn JA, Wiersinga WM, Sauerwein HP (1990) Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. J Clin Endocrinol Metab 71(6):1567–1572

    Article  PubMed  Google Scholar 

  49. Mooradian AD, Reed RL, Osterweil D, Schiffman R, Scuderi P (1990) Decreased serum triiodothyronine is associated with increased concentrations of tumor necrosis factor. J Clin Endocrinol Metab 71(5):1239–1242

    Article  CAS  PubMed  Google Scholar 

  50. Chopra IJ, Sakane S, Teco GN (1991) A study of the serum concentration of tumor necrosis factor-alpha in thyroidal and nonthyroidal illnesses. J Clin Endocrinol Metab 72(5):1113–1116

    Article  CAS  PubMed  Google Scholar 

  51. Van der Poll T, Van Zee KJ, Endert E et al (1995) Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man. J Clin Endocrinol Metab 80(4):1341–1346

    PubMed  Google Scholar 

  52. Van der Poll T, Endert E, Coyle SM, Agosti JM, Lowry SF (1999) Neutralization of TNF does not influence endotoxin induced changes in thyroid hormone metabolism in humans. Am J Physiol 276(2 Pt 2):R357–R362

    PubMed  Google Scholar 

  53. Van den Berghe G, de Zegher F, Lauwers P (1994) Dopamine and the sick euthyroid syndrome in critical illness. Clin Endocrinol (Oxf) 41(6):731–737

    Article  Google Scholar 

  54. Faglia G, Ferrari C, Beck-Peccoz P, Spada A, Travaglini P, Ambrosi B (1973) Reduced plasma thyrotropin response to thyrotropin releasing hormone after dexamethasone administration in normal subjects. Horm Metab Res 5(4):289–292

    Article  CAS  PubMed  Google Scholar 

  55. Forceville X, Vitoux D, Gauzit R, Combes A, Lahilaire P, Chappuis P (1998) Selenium, systemic immune response syndrome, sepsis, and outcome in critically ill patients. Crit Care Med 26(9):1536–1544

    Article  CAS  PubMed  Google Scholar 

  56. Berger MM, Reymond MJ, Shenkin A et al (2001) Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial. Intensive Care Med 27(1):91–100

    Article  CAS  PubMed  Google Scholar 

  57. Vidart J, Wajner SM, Leite RS et al (2014) N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial. J Clin Endocrinol Metab 99(12):4537–4545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Boelen A, Kwakkel J, Fliers E (2011) Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev 32(5):670–693

    Article  CAS  PubMed  Google Scholar 

  59. Boelen A, Boorsma J, Kwakkel J et al (2008) Type 3 deiodinase is highly expressed in infiltrating neutrophilic granulocytes in response to acute bacterial infection. Thyroid 18(10):1095–1103

    Article  CAS  PubMed  Google Scholar 

  60. Kwakkel J, Surovtseva OV, de Vries EM, Stap J, Fliers E, Boelen A (2014) A novel role for the thyroid hormone-activating enzyme type 2 deiodinase in the inflammatory response of macrophages. Endocrinology 155(7):2725–2734

    Article  CAS  PubMed  Google Scholar 

  61. Brent GA, Hershman JM (1986) Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. J Clin Endocrinol Metab 63(1):1–8

    Article  CAS  PubMed  Google Scholar 

  62. Bettendorf M, Schmidt KG, Grulich-Henn J, Ulmer HE, Heinrich UE (2000) Tri-iodothyronine treatment in children after cardiac surgery: a double-blind, randomised, placebo-controlled study. Lancet 356(9229):529–534

    Article  CAS  PubMed  Google Scholar 

  63. Barrett NA, Jones A, Whiteley C, Yassin S, McKenzie CA (2012) Management of long-term hypothyroidism: a potential marker of quality of medicines reconciliation in the intensive care unit. Int J Pharm Pract 20(5):303–306

    Article  PubMed  Google Scholar 

  64. Ringel MD (2001) Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit Care Clin 17(1):59–74

    Article  CAS  PubMed  Google Scholar 

  65. Fliers E, Wiersinga WM (2003) Myxedema coma. Rev Endocr Metab Disord 4(2):137–141

    Article  PubMed  Google Scholar 

  66. Angell TE, Lechner MG, Nguyen CT, Salvato VL, Nicoloff JT, LoPresti JS (2015) Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study. J Clin Endocrinol Metab 100(2):451–459

    Article  CAS  PubMed  Google Scholar 

  67. Papi G, Corsello SM, Pontecorvi A (2014) Clinical concepts on thyroid emergencies. Front Endocrinol (Lausanne) 5:102

    Google Scholar 

Download references

Acknowledgments

Supported by the Methusalem Program of the Flemish Government (METH/14/06) to GVdB via the KU Leuven, by an ERC Advanced Grant (AdvG-2012-321670) to GVdB from the Ideas Program of the European Union seventh framework program.

Conflicts of Interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49, Leuven, B-3000, Belgium

    Lies Langouche MSc, PhD & Greet Van den Berghe MD, PhD

Authors
  1. Lies Langouche MSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Greet Van den Berghe MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Greet Van den Berghe MD, PhD .

Editor information

Editors and Affiliations

  1. Brussels, Belgium

    Jean-Charles Preiser

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Langouche, L., Van den Berghe, G. (2016). Thyroidal Changes During Critical Illness. In: Preiser, JC. (eds) The Stress Response of Critical Illness: Metabolic and Hormonal Aspects. Springer, Cham. https://doi.org/10.1007/978-3-319-27687-8_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-27687-8_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-27685-4

  • Online ISBN: 978-3-319-27687-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation