Skip to main content
SpringerLink
Log in

Endocrinopathy of the Critically Ill

  • Chapter
  • First Online:
Post-Intensive Care Syndrome

Part of the book series: Lessons from the ICU ((LEICU))

Abstract

During critical illness, marked neuroendocrine alterations develop in response to the severe stress. This neuroendocrine response to critical illness is biphasic. The acute phase is characterized by hypercortisolism, hypersecretion of growth hormone uncoupled from insulin-like growth factor-I, and suppression of thyroid and gonadal axes. These changes favor endogenous substrate release, while postponing costly anabolism, and are generally considered adaptive. The chronic phase is characterized by overall diminished hypothalamic output, leading to ineffective stimulation of the pituitary gland and an ongoing state of pronounced hypercatabolism. It is presumed that the neuroendocrine disturbances of prolonged critical illness, or their non-recovery, could contribute to the development of the post-intensive care syndrome. Strategies attempting to counteract these changes have mostly failed, but combined administration of hypothalamic releasing factors has shown to reactivate the neuroendocrine axes. Whether this intervention is able to improve short-term recovery, as well as long-term rehabilitation, needs thorough investigation in appropriately designed, adequately powered randomized controlled clinical trials.

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 49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 64.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 89.99
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. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992;267(9):1244–52.

    Article  CAS  PubMed  Google Scholar 

  2. Van den Berghe G, de Zegher F, Bouillon R. Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab. 1998;83(6):1827–34.

    PubMed  Google Scholar 

  3. Vanhorebeek I, Langouche L, Van den Berghe G. Endocrine aspects of acute and prolonged critical illness. Nat Clin Pract Endocrinol Metab. 2006;2(1):20–31.

    Article  CAS  PubMed  Google Scholar 

  4. Dos Santos C, Hussain SN, Mathur S, Picard M, Herridge M, Correa J, et al. Mechanisms of chronic muscle wasting and dysfunction after an intensive care unit stay. A pilot study. Am J Respir Crit Care Med. 2016;194(7):821–30.

    Article  CAS  PubMed  Google Scholar 

  5. Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293–304.

    Article  CAS  PubMed  Google Scholar 

  6. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  Google Scholar 

  8. van den Berghe G, Weekers F, Baxter RC, Wouters P, Iranmanesh A, Bouillon R, et al. Five-day pulsatile gonadotropin-releasing hormone administration unveils combined hypothalamic-pituitary-gonadal defects underlying profound hypoandrogenism in men with prolonged critical illness. J Clin Endocrinol Metab. 2001;86(7):3217–26.

    PubMed  Google Scholar 

  9. 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.

    PubMed  Google Scholar 

  10. Kargi AY, Merriam GR. Diagnosis and treatment of growth hormone deficiency in adults. Nat Rev Endocrinol. 2013;9(6):335–45.

    Article  CAS  PubMed  Google Scholar 

  11. Puche JE, Castilla-Cortázar I. Human conditions of insulin-like growth factor-I (IGF-I) deficiency. J Transl Med. 2012;10:224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet. 2015;386(9996):913–27.

    Article  CAS  PubMed  Google Scholar 

  13. Parsaik AK, Singh B, Roberts RO, Pankratz S, Edwards KK, Geda YE, et al. Hypothyroidism and risk of mild cognitive impairment in elderly persons: a population-based study. JAMA Neurol. 2014;71(2):201–7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pandharipande PP, Girard TD, Ely EW. Long-term cognitive impairment after critical illness. N Engl J Med. 2014;370(2):185–6.

    PubMed  Google Scholar 

  15. Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, et al. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014;190(4):410–20.

    Article  PubMed  Google Scholar 

  16. Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Annu Rev Physiol. 2005;67:259–84.

    Article  CAS  PubMed  Google Scholar 

  17. Hellman L, Nakada F, Curti J, Weitzman ED, Kream J, Roffwarg H, et al. Cortisol is secreted episodically by normal man. J Clin Endocrinol Metab. 1970;30(4):411–22.

    Article  CAS  PubMed  Google Scholar 

  18. Kovács KJ. CRH: the link between hormonal-, metabolic- and behavioral responses to stress. J Chem Neuroanat. 2013;54:25–33.

    Article  PubMed  CAS  Google Scholar 

  19. Hammond GL. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol. 2016;230(1):R13–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol. 2013;132(5):1033–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dorin RI, Ferries LM, Roberts B, Qualls CR, Veldhuis JD, Lisansky EJ. Assessment of stimulated and spontaneous adrenocorticotropin secretory dynamics identifies distinct components of cortisol feedback inhibition in healthy humans. J Clin Endocrinol Metab. 1996;81(11):3883–91.

    CAS  PubMed  Google Scholar 

  22. Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, et al. Reduced cortisol metabolism during critical illness. N Engl J Med. 2013;368(16):1477–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Vermes I, Beishuizen A, Hampsink RM, Haanen C. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natriuretic hormone. J Clin Endocrinol Metab. 1995;80(4):1238–42.

    CAS  PubMed  Google Scholar 

  24. Boonen E, Meersseman P, Vervenne H, Meyfroidt G, Guïza F, Wouters PJ, et al. Reduced nocturnal ACTH-driven cortisol secretion during critical illness. Am J Physiol Endocrinol Metab. 2014;306(8):E883–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vassiliadi DA, Dimopoulou I, Tzanela M, Douka E, Livaditi O, Orfanos SE, et al. Longitudinal assessment of adrenal function in the early and prolonged phases of critical illness in septic patients: relations to cytokine levels and outcome. J Clin Endocrinol Metab. 2014;99(12):4471–80.

    Article  CAS  PubMed  Google Scholar 

  26. Boonen E, Van den Berghe G. Cortisol metabolism in critical illness: implications for clinical care. Curr Opin Endocrinol Diabetes Obes. 2014;21(3):185–92.

    Article  CAS  PubMed  Google Scholar 

  27. Siebig S, Meinel A, Rogler G, Klebl E, Wrede CE, Gelbmann C, et al. Decreased cytosolic glucocorticoid receptor levels in critically ill patients. Anaesth Intensive Care. 2010;38(1):133–40.

    Article  CAS  PubMed  Google Scholar 

  28. van den Akker EL, Koper JW, Joosten K, de Jong FH, Hazelzet JA, Lamberts SW, et al. Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis. Intensive Care Med. 2009;35(7):1247–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Peeters RP, Hagendorf A, Vanhorebeek I, Visser TJ, Klootwijk W, Mesotten D, et al. Tissue mRNA expression of the glucocorticoid receptor and its splice variants in fatal critical illness. Clin Endocrinol. 2009;71(1):145–53.

    Article  CAS  Google Scholar 

  30. Perogamvros I, Ray DW, Trainer PJ. Regulation of cortisol bioavailability--effects on hormone measurement and action. Nat Rev Endocrinol. 2012;8(12):717–27.

    Article  CAS  PubMed  Google Scholar 

  31. Boonen E, Bornstein SR, Van den Berghe G. New insights into the controversy of adrenal function during critical illness. Lancet Diabetes Endocrinol. 2015;3(10):805–15.

    Article  CAS  PubMed  Google Scholar 

  32. Boonen E, Langouche L, Janssens T, Meersseman P, Vervenne H, De Samblanx E, et al. Impact of duration of critical illness on the adrenal glands of human intensive care patients. J Clin Endocrinol Metab. 2014;99(11):4214–22.

    Article  CAS  PubMed  Google Scholar 

  33. Fletcher SN, Kennedy DD, Ghosh IR, Misra VP, Kiff K, Coakley JH, et al. Persistent neuromuscular and neurophysiologic abnormalities in long-term survivors of prolonged critical illness. Crit Care Med. 2003;31(4):1012–6.

    Article  PubMed  Google Scholar 

  34. Lipiner-Friedman D, Sprung CL, Laterre PF, Weiss Y, Goodman SV, Vogeser M, et al. Adrenal function in sepsis: the retrospective Corticus cohort study. Crit Care Med. 2007;35(4):1012–8.

    Article  PubMed  Google Scholar 

  35. Pastores SM, Annane D, Rochwerg B, ESICM atCGTFoSa. Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency (CIRCI) in Critically Ill Patients (Part II): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Crit Care Med. 2018;46(1):146–8.

    Article  PubMed  Google Scholar 

  36. Annane D, Sébille V, Troché G, Raphaël JC, Gajdos P, Bellissant E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA. 2000;283(8):1038–45.

    Article  CAS  PubMed  Google Scholar 

  37. Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009;301(22):2362–75.

    Article  CAS  PubMed  Google Scholar 

  38. Sprung CL, Caralis PV, Marcial EH, Pierce M, Gelbard MA, Long WM, et al. The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med. 1984;311(18):1137–43.

    Article  CAS  PubMed  Google Scholar 

  39. Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378:797.

    Article  CAS  PubMed  Google Scholar 

  40. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111–24.

    Article  CAS  PubMed  Google Scholar 

  41. Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354(16):1671–84.

    Article  CAS  PubMed  Google Scholar 

  42. Meduri GU, Marik PE, Chrousos GP, Pastores SM, Arlt W, Beishuizen A, et al. Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med. 2008;34(1):61–9.

    Article  CAS  PubMed  Google Scholar 

  43. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003;348(8):727–34.

    Article  CAS  PubMed  Google Scholar 

  44. Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287(2):236–40.

    Article  CAS  PubMed  Google Scholar 

  45. Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Arch Surg. 2008;143(12):1222–6.

    Article  CAS  PubMed  Google Scholar 

  46. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–77.

    Article  PubMed  Google Scholar 

  47. Hässig A, Wen-Xi L, Stampfli K. Stress-induced suppression of the cellular immune reactions: on the neuroendocrine control of the immune system. Med Hypotheses. 1996;46(6):551–5.

    Article  PubMed  Google Scholar 

  48. Ebeling P, Koivisto VA. Physiological importance of dehydroepiandrosterone. Lancet. 1994;343(8911):1479–81.

    Article  CAS  PubMed  Google Scholar 

  49. Findling JW, Waters VO, Raff H. The dissociation of renin and aldosterone during critical illness. J Clin Endocrinol Metab. 1987;64(3):592–5.

    Article  CAS  PubMed  Google Scholar 

  50. Schelling G. Effects of stress hormones on traumatic memory formation and the development of posttraumatic stress disorder in critically ill patients. Neurobiol Learn Mem. 2002;78(3):596–609.

    Article  CAS  PubMed  Google Scholar 

  51. Hauer D, Weis F, Krauseneck T, Vogeser M, Schelling G, Roozendaal B. Traumatic memories, post-traumatic stress disorder and serum cortisol levels in long-term survivors of the acute respiratory distress syndrome. Brain Res. 2009;1293:114–20.

    Article  CAS  PubMed  Google Scholar 

  52. Weis F, Kilger E, Roozendaal B, de Quervain DJ, Lamm P, Schmidt M, et al. Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. J Thorac Cardiovasc Surg. 2006;131(2):277–82.

    Article  CAS  PubMed  Google Scholar 

  53. Kok L, Hillegers MH, Veldhuijzen DS, Cornelisse S, Nierich AP, van der Maaten JM, et al. The effect of dexamethasone on symptoms of posttraumatic stress disorder and depression after cardiac surgery and intensive care admission: longitudinal follow-up of a randomized controlled trial. Crit Care Med. 2016;44(3):512–20.

    Article  CAS  PubMed  Google Scholar 

  54. Yehuda R, Hoge CW, McFarlane AC, Vermetten E, Lanius RA, Nievergelt CM, et al. Post-traumatic stress disorder. Nat Rev Dis Primers. 2015;1:15057.

    Article  PubMed  Google Scholar 

  55. Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016;150(5):1129–40.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dettling-Ihnenfeldt DS, Wieske L, Horn J, Nollet F, van der Schaaf M. Functional recovery in patients with and without intensive care unit-acquired weakness. Am J Phys Med Rehabil. 2017;96(4):236–42.

    Article  PubMed  Google Scholar 

  57. Ho KK, O’Sullivan AJ, Hoffman DM. Metabolic actions of growth hormone in man. Endocr J. 1996;43(Suppl):S57–63.

    Article  CAS  PubMed  Google Scholar 

  58. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19(6):717–97.

    CAS  PubMed  Google Scholar 

  59. Mesotten D, Van den Berghe G. Changes within the GH/IGF-I/IGFBP axis in critical illness. Crit Care Clin. 2006;22(1):17–28.

    Article  CAS  PubMed  Google Scholar 

  60. Defalque D, Brandt N, Ketelslegers JM, Thissen JP. GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors. Am J Phys. 1999;276(3 Pt 1):E565–72.

    CAS  Google Scholar 

  61. Baxter RC. Changes in the IGF-IGFBP axis in critical illness. Best Pract Res Clin Endocrinol Metab. 2001;15(4):421–34.

    Article  CAS  PubMed  Google Scholar 

  62. Van den Berghe G, de Zegher F, Veldhuis JD, Wouters P, Awouters M, Verbruggen W, et al. The somatotropic axis in critical illness: effect of continuous growth hormone (GH)-releasing hormone and GH-releasing peptide-2 infusion. J Clin Endocrinol Metab. 1997;82(2):590–9.

    PubMed  Google Scholar 

  63. Van den Berghe G, de Zegher F, Baxter RC, Veldhuis JD, Wouters P, Schetz M, et al. Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone secretagogues. J Clin Endocrinol Metab. 1998;83(2):309–19.

    PubMed  Google Scholar 

  64. Van den Berghe G, Baxter RC, Weekers F, Wouters P, Bowers CY, Veldhuis JD. A paradoxical gender dissociation within the growth hormone/insulin-like growth factor I axis during protracted critical illness. J Clin Endocrinol Metab. 2000;85(1):183–92.

    PubMed  Google Scholar 

  65. Hadley JS, Hinds CJ. Anabolic strategies in critical illness. Curr Opin Pharmacol. 2002;2(6):700–7.

    Article  CAS  PubMed  Google Scholar 

  66. Pichard C, Kyle U, Chevrolet JC, Jolliet P, Slosman D, Mensi N, et al. Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study. Crit Care Med. 1996;24(3):403–13.

    Article  CAS  PubMed  Google Scholar 

  67. Koea JB, Breier BH, Douglas RG, Gluckman PD, Shaw JH. Anabolic and cardiovascular effects of recombinant human growth hormone in surgical patients with sepsis. Br J Surg. 1996;83(2):196–202.

    Article  CAS  PubMed  Google Scholar 

  68. Gamrin L, Essén P, Hultman E, McNurlan MA, Garlick PJ, Wernerman J. Protein-sparing effect in skeletal muscle of growth hormone treatment in critically ill patients. Ann Surg. 2000;231(4):577–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med. 1999;341(11):785–92.

    Article  CAS  PubMed  Google Scholar 

  70. Ruokonen E, Takala J. Dangers of growth hormone therapy in critically ill patients. Curr Opin Clin Nutr Metab Care. 2002;5(2):199–209.

    Article  CAS  PubMed  Google Scholar 

  71. Yarwood GD, Ross RJ, Medbak S, Coakley J, Hinds CJ. Administration of human recombinant insulin-like growth factor-I in critically ill patients. Crit Care Med. 1997;25(8):1352–61.

    Article  CAS  PubMed  Google Scholar 

  72. Carroll PV, Jackson NC, Russell-Jones DL, Treacher DF, Sönksen PH, Umpleby AM. Combined growth hormone/insulin-like growth factor I in addition to glutamine-supplemented TPN results in net protein anabolism in critical illness. Am J Physiol Endocrinol Metab. 2004;286(1):E151–7.

    Article  CAS  PubMed  Google Scholar 

  73. Umpleby AM, Carroll PV, Russell-Jones DL, Treacher DF, Jackson NC. Glutamine supplementation and GH/IGF-I treatment in critically ill patients: effects on glutamine metabolism and protein balance. Nutrition. 2002;18(2):127–9.

    Article  CAS  PubMed  Google Scholar 

  74. Jiang J, Chen Z, Liang B, Yan J, Zhang Y, Jiang H. Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 and risk of postoperative cognitive dysfunction. Springerplus. 2015;4:787.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Pirskanen A, Kiefer JC, Hauschka SD. IGFs, insulin, Shh, bFGF, and TGF-beta1 interact synergistically to promote somite myogenesis in vitro. Dev Biol. 2000;224(2):189–203.

    Article  CAS  PubMed  Google Scholar 

  76. Klose M, Feldt-Rasmussen U. Chronic endocrine consequences of traumatic brain injury – what is the evidence? Nat Rev Endocrinol. 2018;14(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  77. Fliers E, Wiersinga WM, Swaab DF. Physiological and pathophysiological aspects of thyrotropin-releasing hormone gene expression in the human hypothalamus. Thyroid. 1998;8(10):921–8.

    Article  CAS  PubMed  Google Scholar 

  78. Fliers E, Unmehopa UA, Alkemade A. Functional neuroanatomy of thyroid hormone feedback in the human hypothalamus and pituitary gland. Mol Cell Endocrinol. 2006;251(1–2):1–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  80. Mebis L, Van den Berghe G. Thyroid axis function and dysfunction in critical illness. Best Pract Res Clin Endocrinol Metab. 2011;25(5):745–57.

    Article  CAS  PubMed  Google Scholar 

  81. Van den Berghe G. On the neuroendocrinopathy of critical illness. Perspectives for feeding and novel treatments. Am J Respir Crit Care Med. 2016;194(11):1337–48.

    Article  PubMed  Google Scholar 

  82. Van den Berghe G. Non-thyroidal illness in the ICU: a syndrome with different faces. Thyroid. 2014;24(10):1456–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Mebis L, van den Berghe G. The hypothalamus-pituitary-thyroid axis in critical illness. Neth J Med. 2009;67(10):332–40.

    CAS  PubMed  Google Scholar 

  84. 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.

    Article  CAS  PubMed  Google Scholar 

  85. 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.

    Article  CAS  PubMed  Google Scholar 

  86. 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.

    CAS  PubMed  Google Scholar 

  87. Langouche L, Vander Perre S, Marques M, Boelen A, Wouters PJ, Casaer MP, et al. 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. 2013;98(3):1006–13.

    Article  CAS  PubMed  Google Scholar 

  88. 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.

    Article  CAS  PubMed  Google Scholar 

  89. 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.

    Article  CAS  PubMed  Google Scholar 

  90. 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.

    Article  CAS  PubMed  Google Scholar 

  91. 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. 2009;161(2):243–50.

    Article  CAS  PubMed  Google Scholar 

  92. Thijssen-Timmer DC, Peeters RP, Wouters P, Weekers F, Visser TJ, Fliers E, et al. Thyroid hormone receptor isoform expression in livers of critically ill patients. Thyroid. 2007;17(2):105–12.

    Article  CAS  PubMed  Google Scholar 

  93. Ma SF, Xie L, Pino-Yanes M, Sammani S, Wade MS, Letsiou E, et al. Type 2 deiodinase and host responses of sepsis and acute lung injury. Am J Respir Cell Mol Biol. 2011;45(6):1203–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  95. Vaughan GM, Pruitt BA. Thyroid function in critical illness and burn injury. Semin Nephrol. 1993;13(4):359–70.

    CAS  PubMed  Google Scholar 

  96. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506–17.

    Article  CAS  PubMed  Google Scholar 

  97. Hermans G, Casaer MP, Clerckx B, Güiza F, Vanhullebusch T, Derde S, et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. Lancet Respir Med. 2013;1(8):621–9.

    Article  PubMed  Google Scholar 

  98. Van den Berghe G. Endocrine evaluation of patients with critical illness. Endocrinol Metab Clin N Am. 2003;32(2):385–410.

    Article  CAS  Google Scholar 

  99. 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.

    Article  CAS  PubMed  Google Scholar 

  100. Becker RA, Vaughan GM, Ziegler MG, Seraile LG, Goldfarb IW, Mansour EH, et al. Hypermetabolic low triiodothyronine syndrome of burn injury. Crit Care Med. 1982;10(12):870–5.

    Article  CAS  PubMed  Google Scholar 

  101. Wu T, Flowers JW, Tudiver F, Wilson JL, Punyasavatsut N. Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatr. 2006;6:12.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Wiersinga WM. Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nat Rev Endocrinol. 2014;10(3):164–74.

    Article  CAS  PubMed  Google Scholar 

  103. Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab. 2008;4(12):683–94.

    Article  CAS  PubMed  Google Scholar 

  104. Mechanick JI, Nierman DM. Gonadal steroids in critical illness. Crit Care Clin. 2006;22(1):87–103.. vii

    Article  CAS  PubMed  Google Scholar 

  105. Spratt DI. Altered gonadal steroidogenesis in critical illness: is treatment with anabolic steroids indicated? Best Pract Res Clin Endocrinol Metab. 2001;15(4):479–94.

    Article  CAS  PubMed  Google Scholar 

  106. Bulger EM, Jurkovich GJ, Farver CL, Klotz P, Maier RV. Oxandrolone does not improve outcome of ventilator dependent surgical patients. Ann Surg. 2004;240(3):472–8; discussion 8-80.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Gervasio JM, Dickerson RN, Swearingen J, Yates ME, Yuen C, Fabian TC, et al. Oxandrolone in trauma patients. Pharmacotherapy. 2000;20(11):1328–34.

    Article  CAS  PubMed  Google Scholar 

  108. Van den Berghe G, de Zegher F, Veldhuis JD, Wouters P, Gouwy S, Stockman W, et al. Thyrotrophin and prolactin release in prolonged critical illness: dynamics of spontaneous secretion and effects of growth hormone-secretagogues. Clin Endocrinol. 1997;47(5):599–612.

    Article  Google Scholar 

  109. Van den Berghe G, de Zegher F. Anterior pituitary function during critical illness and dopamine treatment. Crit Care Med. 1996;24(9):1580–90.

    Article  PubMed  Google Scholar 

  110. Van den Berghe G, de Zegher F, Wouters P, Schetz M, Verwaest C, Ferdinande P, et al. Dehydroepiandrosterone sulphate in critical illness: effect of dopamine. Clin Endocrinol. 1995;43(4):457–63.

    Article  Google Scholar 

  111. Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med. 1995;333(25):1688–94.

    Article  CAS  PubMed  Google Scholar 

  112. Vinclair M, Broux C, Faure P, Brun J, Genty C, Jacquot C, et al. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med. 2008;34(4):714–9.

    Article  PubMed  Google Scholar 

  113. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med. 1984;310(22):1415–21.

    Article  CAS  PubMed  Google Scholar 

  114. Lamberts SW, Bons EG, Bruining HA, de Jong FH. Differential effects of the imidazole derivatives etomidate, ketoconazole and miconazole and of metyrapone on the secretion of cortisol and its precursors by human adrenocortical cells. J Pharmacol Exp Ther. 1987;240(1):259–64.

    CAS  PubMed  Google Scholar 

  115. Eigler T, Ben-Shlomo A. Somatostatin system: molecular mechanisms regulating anterior pituitary hormones. J Mol Endocrinol. 2014;53(1):R1–19.

    Article  CAS  PubMed  Google Scholar 

  116. Christy NP. Pituitary-adrenal function during corticosteroid therapy. Learning to live with uncertainty. N Engl J Med. 1992;326(4):266–7.

    Article  CAS  PubMed  Google Scholar 

  117. Whirledge S, Cidlowski JA. Glucocorticoids, stress, and fertility. Minerva Endocrinol. 2010;35(2):109–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Chidakel AR, Zweig SB, Schlosser JR, Homel P, Schappert JW, Fleckman AM. High prevalence of adrenal suppression during acute illness in hospitalized patients receiving megestrol acetate. J Endocrinol Investig. 2006;29(2):136–40.

    Article  CAS  Google Scholar 

  119. Malik KJ, Wakelin K, Dean S, Cove DH, Wood PJ. Cushing’s syndrome and hypothalamic-pituitary adrenal axis suppression induced by medroxyprogesterone acetate. Ann Clin Biochem. 1996;33. (Pt 3:187–9.

    Article  PubMed  Google Scholar 

  120. Rhodin A, Stridsberg M, Gordh T. Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term oral opioid treatment. Clin J Pain. 2010;26(5):374–80.

    Article  PubMed  Google Scholar 

  121. Sherman SI, Gopal J, Haugen BR, Chiu AC, Whaley K, Nowlakha P, et al. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med. 1999;340(14):1075–9.

    Article  CAS  PubMed  Google Scholar 

  122. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999;27(4):723–32.

    Article  CAS  PubMed  Google Scholar 

  124. Volbeda M, Wetterslev J, Gluud C, Zijlstra JG, van der Horst IC, Keus F. Glucocorticosteroids for sepsis: systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2015;41(7):1220–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, et al. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest. 2007;131(4):954–63.

    Article  CAS  PubMed  Google Scholar 

  126. Annane D, Sébille V, Bellissant E, Group G-I-S. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med. 2006;34(1):22–30.

    Article  CAS  PubMed  Google Scholar 

  127. Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, et al. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect. 2011;17(Suppl 6):E1–59.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27–72.

    Article  CAS  PubMed  Google Scholar 

  129. Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–8.

    Article  CAS  PubMed  Google Scholar 

  130. Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015;313(7):677–86.

    Article  CAS  PubMed  Google Scholar 

  131. Briel M, Bucher HC, Boscacci R, Furrer H. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database Syst Rev. 2006;(3):CD006150.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

    Nathalie Van Aerde, Lisa Van Dyck & Ilse Vanhorebeek

  2. Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

    Greet Van den Berghe

Authors
  1. Nathalie Van Aerde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa Van Dyck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilse Vanhorebeek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Greet Van den Berghe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Greet Van den Berghe .

Editor information

Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium

    Jean-Charles Preiser

  2. Respiratory and CCM, Toronto General Hospital, University of Toronto, Toronto, ON, Canada

    Margaret Herridge

  3. Medical Intensive Care Unit, AP-HP Saint-Louis Hospital, Paris, France

    Elie Azoulay

Rights and permissions

Reprints and permissions

Copyright information

© 2020 European Society of Intensive Care Medicine

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Van Aerde, N., Van Dyck, L., Vanhorebeek, I., Van den Berghe, G. (2020). Endocrinopathy of the Critically Ill. In: Preiser, JC., Herridge, M., Azoulay, E. (eds) Post-Intensive Care Syndrome. Lessons from the ICU. Springer, Cham. https://doi.org/10.1007/978-3-030-24250-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-24250-3_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-24249-7

  • Online ISBN: 978-3-030-24250-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation