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Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis?

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Abstract

There is ongoing controversy as to whether hormonal changes of the euthyroid sick syndrome are predictors of poor outcome in sepsis and critical illness. In this prospective study, the prognostic accuracy of thyroid hormone levels in 103 critically ill adult patients on admission and during follow up in a medical intensive care unit (ICU) was assessed and was compared to clinical risk scores, namely, the acute physiology and chronic health evaluation and the simplified acute physiology score. Median T3 levels on admission to the ICU were lower in the 53 septic cases [0.9 nmol/l (IQR 0.6–1.1)] as compared with the 50 patients with a systemic inflammatory response syndrome [1.2 nmol/l (IQR 0.8–1.4), P < 0.001]. The lowest T3 levels were found in patients with severe sepsis [0.8 nmol/l (IQR 0.55–0.95)] and septic shock [0.8 nmol/l (IQR 0.6–1.0)]. There was no difference in T3 and free thyroxin (fT4) levels on admission in non-survivors compared with survivors overall and in subgroups of patients with SIRS and sepsis. During the follow up, fT4 levels decreased significantly in non-survivors, while they increased in survivors [fT4 difference −1.3 (IQR −2.5 to 0.2) vs. 0.8 (IQR −0.85 to 4.1), P = 0.003]. In addition, on the day of death, non-survivors had lower T3 and fT4 levels as compared with survivors (P = 0.04 and P = 0.02). T3 and fT4 levels on admission were not prognostic in this cohort of critically ill patients. A decrease in fT4 levels in the course of disease, however, may point to adverse outcome.

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References

  1. D.C. Angus, R.S. Wax, Epidemiology of sepsis: an update. Crit. Care Med. 29, S109–S116 (2001)

    Article  PubMed  CAS  Google Scholar 

  2. G.S. Martin, D.M. Mannino, S. Eaton, M. Moss, The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med. 348, 1546–1554 (2003)

    Article  PubMed  Google Scholar 

  3. W.A. Knaus, E.A. Draper, D.P. Wagner, J.E. Zimmerman, APACHE II: a severity of disease classification system. Crit. Care Med. 13, 818–829 (1985)

    Article  PubMed  CAS  Google Scholar 

  4. J.R. Le Gall, S. Lemeshow, F. Saulnier, A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270, 2957–2963 (1993)

    Article  PubMed  CAS  Google Scholar 

  5. M. Christ-Crain, N.G. Morgenthaler, J. Struck, S. Harbarth, A. Bergmann, B. Muller, Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit. Care 9, R816–R824 (2005)

    Article  PubMed  Google Scholar 

  6. F. de Groof, K.F. Joosten, J.A. Janssen, E.D. de Kleijn, J.A. Hazelzet, W.C. Hop, P. Uitterlinden, J. van Doorn, A.C. Hokken-Koelega, Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors. J. Clin. Endocrinol. Metab. 87, 3118–3124 (2002)

    Article  PubMed  Google Scholar 

  7. P. Schuetz, M. Christ-Crain, N.G. Morgenthaler, J. Struck, A. Bergmann, B. Muller, Circulating precursor levels of endothelin-1 and adrenomedullin, two endothelium-derived, counteracting substances, in sepsis. Endothelium 14, 345–351 (2007)

    Article  PubMed  CAS  Google Scholar 

  8. M. Christ-Crain, D. Stolz, S. Jutla, O. Couppis, C. Muller, R. Bingisser, P. Schuetz, M. Tamm, R. Edwards, B. Muller, A.B. Grossman, Free and total cortisol levels as predictors of severity and outcome in community-acquired pneumonia. Am. J. Respir. Crit. Care Med. 176, 913–920 (2007)

    Article  PubMed  CAS  Google Scholar 

  9. R. Docter, E.P. Krenning, M. de Jong, G. Hennemann, The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism. Clin. Endocrinol. (Oxf) 39, 499–518 (1993)

    Article  CAS  Google Scholar 

  10. L.J. De Groot, Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J. Clin. Endocrinol. Metab. 84, 151–164 (1999)

    Article  PubMed  Google Scholar 

  11. G. Van den Berghe, F. de Zegher, R. Bouillon, Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J. Clin. Endocrinol. Metab. 83, 1827–1834 (1998)

    Article  PubMed  Google Scholar 

  12. K.F. Joosten, E.D. de Kleijn, M. Westerterp, M. de Hoog, F.C. Eijck, W.C.J. Hop, E.V. Voort, J.A. Hazelzet, A.C. Hokken-Koelega, Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. J. Clin. Endocrinol. Metab. 85, 3746–3753 (2000)

    Article  PubMed  CAS  Google Scholar 

  13. P.M. Rothwell, P.G. Lawler, Prediction of outcome in intensive care patients using endocrine parameters. Crit. Care Med. 23, 78–83 (1995)

    Article  PubMed  CAS  Google Scholar 

  14. R.P. Peeters, P.J. Wouters, H. van Toor, E. Kaptein, T.J. Visser, G. Van den Berghe, Serum 3,3′,5′-triiodothyronine (rT3) and 3,5,3′-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J. Clin. Endocrinol. Metab. 90, 4559–4565 (2005)

    Article  PubMed  CAS  Google Scholar 

  15. K. Plikat, J. Langgartner, R. Buettner, L.C. Bollheimer, U. Woenckhaus, J. Scholmerich, C.E. Wrede, Frequency and outcome of patients with nonthyroidal illness syndrome in a medical intensive care unit. Metabolism 56, 239–244 (2007)

    Article  PubMed  CAS  Google Scholar 

  16. R. Lodha, S. Vivekanandhan, M. Sarthi, S. Arun, S.K. Kabra, Thyroid function in children with sepsis and septic shock. Acta Paediatr. 96, 406–409 (2007)

    Article  PubMed  Google Scholar 

  17. D.C. Ray, G.B. Drummond, E. Wilkinson, G.J. Beckett, Relationship of admission thyroid function tests to outcome in critical illness. Anaesthesia 50, 1022–1025 (1995)

    Article  PubMed  CAS  Google Scholar 

  18. B. Muller, K.L. Becker, H. Schachinger, P.R. Rickenbacher, P.R. Huber, W. Zimmerli, R. Ritz, Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit. Care Med. 28, 977–983 (2000)

    Article  PubMed  CAS  Google Scholar 

  19. P. Schuetz, B. Muller, C. Nusbaumer, M. Wieland, M. Christ-Crain, Circulating levels of GH predict mortality and complement prognostic scores in critically ill medical patients. Eur. J. Endocrinol. 160, 157–163 (2009)

    Article  PubMed  CAS  Google Scholar 

  20. 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit. Care Med. 20:864–874

  21. R.C. Bone, R.A. Balk, F.B. Cerra, R.P. Dellinger, A.M. Fein, W.A. Knaus, R.M. Schein, W.J. Sibbald, Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM consensus conference committee. American college of chest physicians/society of critical care medicine. Chest 101, 1644–1655 (1992)

    Article  PubMed  CAS  Google Scholar 

  22. G.C. Zucchelli, A. Pilo, M.R. Chiesa, S. Masini, Systematic differences between commercial immunoassays for free thyroxine and free triiodothyronine in an external quality assessment program. Clin. Chem. 40, 1956–1961 (1994)

    PubMed  CAS  Google Scholar 

  23. M. den Brinker, B. Dumas, T.J. Visser, W.C. Hop, J.A. Hazelzet, D.A. Festen, A.C. Hokken-Koelega, K.F. Joosten, Thyroid function and outcome in children who survived meningococcal septic shock. Intensive Care Med. 31, 970–976 (2005)

    Article  Google Scholar 

  24. M. den Brinker, K.F. Joosten, T.J. Visser, W.C. Hop, Y.B. de Rijke, J.A. Hazelzet, V.H. Boonstra, A.C. Hokken-Koelega, Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins. J. Clin. Endocrinol. Metab. 90, 5613–5620 (2005)

    Article  Google Scholar 

  25. M.F. Slag, J.E. Morley, M.K. Elson, T.W. Crowson, F.Q. Nuttall, R.B. Shafer, Hypothyroxinemia in critically ill patients as a predictor of high mortality. JAMA 245, 43–45 (1981)

    Article  PubMed  CAS  Google Scholar 

  26. R.P. Peeters, M.H. Kester, P.J. Wouters, E. Kaptein, H. van Toor, T.J. Visser, G. Van den Berghe, Increased thyroxine sulfate levels in critically ill patients as a result of a decreased hepatic type I deiodinase activity. J. Clin. Endocrinol. Metab. 90, 6460–6465 (2005)

    Article  PubMed  CAS  Google Scholar 

  27. G. Van den Berghe, F. de Zegher, R.C. Baxter, J.D. Veldhuis, P. Wouters, M. Schetz, C. Verwaest, E. Van der Vorst, P. Lauwers, R. Bouillon, C.Y. Bowers, Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone secretagogues. J. Clin. Endocrinol. Metab. 83, 309–319 (1998)

    Article  PubMed  Google Scholar 

  28. A. Boelen, J. Kwakkel, D.C. Thijssen-Timmer, A. Alkemade, E. Fliers, W.M. Wiersinga, Simultaneous changes in central and peripheral components of the hypothalamus-pituitary-thyroid axis in lipopolysaccharide-induced acute illness in mice. J. Endocrinol. 182, 315–323 (2004)

    Article  PubMed  CAS  Google Scholar 

  29. V. Bacci, G.C. Schussler, T.B. Kaplan, The relationship between serum triiodothyronine and thyrotropin during systemic illness. J. Clin. Endocrinol. Metab. 54, 1229–1235 (1982)

    Article  PubMed  CAS  Google Scholar 

  30. P.S. Hamblin, S.A. Dyer, V.S. Mohr, B.A. Le Grand, C.F. Lim, D.V. Tuxen, D.J. Topliss, J.R. Stockigt, Relationship between thyrotropin and thyroxine changes during recovery from severe hypothyroxinemia of critical illness. J. Clin. Endocrinol. Metab. 62, 717–722 (1986)

    Article  PubMed  CAS  Google Scholar 

  31. L.S. Maldonado, G.H. Murata, J.M. Hershman, G.D. Braunstein, Do thyroid function tests independently predict survival in the critically ill? Thyroid 2, 119–123 (1992)

    Article  PubMed  CAS  Google Scholar 

  32. J.M. Stouthard, T. van der Poll, E. Endert, P.J. Bakker, C.H. Veenhof, H.P. Sauerwein, J.A. Romijn, Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. J. Clin. Endocrinol. Metab. 79, 1342–1346 (1994)

    Article  PubMed  CAS  Google Scholar 

  33. A. Boelen, M.C. Platvoet-ter Schiphorst, W.M. Wiersinga, Immunoneutralization of interleukin-1, tumor necrosis factor, interleukin-6 or interferon does not prevent the LPS-induced sick euthyroid syndrome in mice. J. Endocrinol. 153, 115–122 (1997)

    Article  PubMed  CAS  Google Scholar 

  34. T. Schilling, M. Grundling, C.M. Strang, K.U. Moritz, W. Siegmund, T. Hachenberg, Effects of dopexamine, dobutamine or dopamine on prolactin and thyreotropin serum concentrations in high-risk surgical patients. Intensive Care Med. 30, 1127–1133 (2004)

    Article  PubMed  Google Scholar 

  35. G. Van den Berghe, F. de Zegher, Anterior pituitary function during critical illness and dopamine treatment. Crit. Care Med. 24, 1580–1590 (1996)

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  37. E. Bennett-Guerrero, J.L. Jimenez, W.D. White, E.B. D’Amico, B.I. Baldwin, D.A. Schwinn, 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 275, 687–692 (1996)

    Article  PubMed  CAS  Google Scholar 

  38. G.A. Brent, J.M. Hershman, Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. J. Clin. Endocrinol. Metab. 63, 1–8 (1986)

    Article  PubMed  CAS  Google Scholar 

  39. R.A. Becker, G.M. Vaughan, M.G. Ziegler, L.G. Seraile, I.W. Goldfarb, E.H. Mansour, W.F. McManus, B.A. Pruitt Jr., A.D. Mason Jr., Hypermetabolic low triiodothyronine syndrome of burn injury. Crit. Care Med. 10, 870–875 (1982)

    Article  PubMed  CAS  Google Scholar 

  40. J.D. Klemperer, I. Klein, M. Gomez, R.E. Helm, K. Ojamaa, S.J. Thomas, O.W. Isom, K. Krieger, Thyroid hormone treatment after coronary-artery bypass surgery. N. Engl. J. Med. 333, 1522–1527 (1995)

    Article  PubMed  CAS  Google Scholar 

  41. G. Van den Berghe, R.C. Baxter, F. Weekers, P. Wouters, C.Y. Bowers, A. Iranmanesh, J.D. Veldhuis, R. Bouillon, 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. (Oxf) 56, 655–669 (2002)

    Article  Google Scholar 

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Acknowledgments

The authors wish to thank the members of the laboratory of chemical pathology of the University Hospital Basel and the staff of the medical ICU, namely Rudolf Ritz and Hartmut Schächinger, for their support during the study.

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All authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology Diabetes and Clinical Nutrition, University Hospital Basel, Basel, Switzerland

    Stefanie Meyer, Philipp Schuetz, Melanie Wieland & Mirjam Christ-Crain

  2. Department of Chemical Pathology, University Hospital Basel, Basel, Switzerland

    Charly Nusbaumer

  3. Department of Internal Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland

    Beat Mueller

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Correspondence to Beat Mueller.

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Stefanie Meyer and Philipp Schuetz contributed equally to this study.

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Meyer, S., Schuetz, P., Wieland, M. et al. Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis?. Endocr 39, 167–174 (2011). https://doi.org/10.1007/s12020-010-9431-4

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