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Review article: Biomedical intelligence

Vol. 140 No. 3738 (2010)

The stress hormone copeptin: a new prognostic biomarker in acute illness

  • M Christ-Crain
DOI
https://doi.org/10.4414/smw.2010.13101
Cite this as:
Swiss Med Wkly. 2010;140:w13101
Published
13.09.2010

Abstract

Stress is defined as anything that throws the body out of homeostatic balance; for example an acute illness. Any stressor which activates the hypothalamo-pituitary-adrenal (HPA) axis leads to an increase in concentrations of the adrenal stress hormone, cortisol. One of the major hypothalamic stress hormones, which is stimulated by different stressors, is vasopressin (AVP). However, measurement of circulating AVP levels is challenging because it is released in a pulsatile pattern, it is unstable and is rapidly cleared from plasma. AVP derives from a larger precursor peptide (pre-provasopressin) along with copeptin which is released in an equimolar ratio to AVP and is more stable in the circulation and easy to determine. Copeptin levels were found to closely mirror the production of AVP. We have shown that copeptin more subtly mirrors the individual stress level compared to cortisol. Due to the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness.

The prognostic accuracy of copeptin has been analysed in sepsis, pneumonia, lower respiratory tract infections, stroke and other acute illnesses. Thereby, copeptin was found to accurately mirror disease severity and to discriminate patients with unfavourable outcomes from patients with favourable outcomes. Copeptin improves the prognostic information provided by commonly used clinical scoring instruments. Importantly, interpretation of copeptin levels must always consider the clinical setting. An accurate prognostic assessment has the potential to guide interventions and effectively plan and monitor rehabilitation and, thus optimise the management of individual patients and the allocation of limited health care resources. Future intervention studies must prove the value of copeptin in clinical decision making and in improving the overall medical management of patients with acute illnesses.

References

  1. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007;87(3):873–904.
  2. Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Annu Rev Physiol. 2005;67:259–84.
  3. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992;267(9):1244–52.
  4. Volpi S, Rabadan-Diehl C, Aguilera G. Vasopressinergic regulation of the hypothalamic pituitary adrenal axis and stress adaptation. Stress. 2004;7(2):75–83.
  5. Aguilera G, Subburaju S, Young S, Chen J. The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress. Prog Brain Res. 2008;170:29–39.
  6. Tanoue A, Ito S, Honda K, Oshikawa S, Kitagawa Y, Koshimizu TA, et al. The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest. 2004;113(2):302–9.
  7. Joels M, Baram TZ. The neuro-symphony of stress. Nat Rev Neurosci. 2009;10(6):459–66.
  8. Petraglia F, Genazzani AD, Aguzzoli L, Gallinelli A, de Vita D, Caruso A, et al. Pulsatile fluctuations of plasma-gonadotropin-releasing hormone and corticotropin-releasing factor levels in healthy pregnant women. Acta Obstet Gynecol Scand. 1994;73 (4):284–9.
  9. Evans MJ, Livesey JH, Ellis MJ, Yandle TG. Effect of anticoagulants and storage temperatures on stability of plasma and serum hormones. Clin Biochem. 2001;34 (2):107–12.
  10. Latendresse G, Ruiz RJ. Bioassay research methodology: measuring CRH in pregnancy. Biol Res Nurs. 2008;10 (1):54–62.
  11. Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005;26(12):2500–4.
  12. Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005;26(12):2500–4.
  13. Donald RA, Perry EG, Wittert GA, Chapman M, Livesey JH, Ellis MJ, et al. The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy. Clin Endocrinol. (Oxf) 1993;38(6):609–15.
  14. Udelsman R, Norton JA, Jelenich SE, Goldstein DS, Linehan WM, Loriaux DL, et al. Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. J Clin Endocrinol Metab. 1987;64(5):986–94.
  15. Widmer IE, Puder JJ, Konig C, Pargger H, Zerkowski HR, Girard J, et al. Cortisol response in relation to the severity of stress and illness. J Clin Endocrinol Metab. 2005;90(8):4579–86.
  16. Katan M, Morgenthaler N, Widmer I, Puder JJ, Konig C, Muller B, et al. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuro Endocrinol Lett. 2008;29(3):341–6.
  17. Sapolsky RM, Pulsinelli WA. Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications. Science. 1985;229(4720):1397–400.
  18. Morse JK, Davis JN. Regulation of ischemic hippocampal damage in the gerbil: adrenalectomy alters the rate of CA1 cell disappearance. Exp Neurol. 1990;110(1):86–92.
  19. Smith-Swintosky VL, Pettigrew LC, Sapolsky RM, Phares C, Craddock SD, Brooke SM, et al. Metyrapone, an inhibitor of glucocorticoid production, reduces brain injury induced by focal and global ischemia and seizures. J Cereb Blood Flow Metab. 1996;16(4):585–98.
  20. Morgenthaler NG, Muller B, Struck J, Bergmann A, Redl H, Christ-Crain M. Copeptin, a Stable Peptide of the Arginine Vasopressin Precursor, Is Elevated in Hemorrhagic and Septic Shock. Shock 2007.
  21. Lindner KH, Strohmenger HU, Ensinger H, Hetzel WD, Ahnefeld FW, Georgieff M. Stress hormone response during and after cardiopulmonary resuscitation. Anesthesiology. 1992;77(4):662–8.
  22. Muller B, Morgenthaler N, Stolz D, Schuetz P, Muller C, Bingisser R, et al. Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections. Eur J Clin Invest. 2007;37(2):145–52.
  23. Stolz D, Christ-Crain M, Morgenthaler NG, Leuppi J, Miedinger D, Bingisser R, et al. Copeptin, C-reactive protein, and procalcitonin as prognostic biomarkers in acute exacerbation of COPD. Chest. 2007;131 (4):1058–67.
  24. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999;341(8):577–85.
  25. Stoiser B, Mortl D, Hulsmann M, Berger R, Struck J, Morgenthaler NG, et al. Copeptin, a fragment of the vasopressin precursor, as a novel predictor of outcome in heart failure. Eur J Clin Invest. 2006;36(11):771–8.
  26. Gegenhuber A, Struck J, Dieplinger B, Poelz W, Pacher R, Morgenthaler NG, et al. Comparative evaluation of B-type natriuretic peptide, mid-regional pro-A-type natriuretic peptide, mid-regional pro-adrenomedullin, and Copeptin to predict 1-year mortality in patients with acute destabilized heart failure. J Card Fail. 2007;13(1):42–9.
  27. Khan SQ, Dhillon OS, O’Brien RJ, Struck J, Quinn PA, Morgenthaler NG, et al. C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study. Circulation. 2007;115(16):2103–10.
  28. Tang WH, Francis GS, Morrow DA, Newby LK, Cannon CP, Jesse RL, et al. National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: Clinical utilization of cardiac biomarker testing in heart failure. Circulation. 2007;116 (5):e99–109.
  29. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, et al. Heart disease and stroke statistics – 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119 (3):e21–181.
  30. Cooper R, Cutler J, Desvigne-Nickens P, Fortmann SP, Friedman L, Havlik R, et al. Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: findings of the national conference on cardiovascular disease prevention. Circulation. 2000;102(25):3137–47.
  31. Counsell C, Dennis M, McDowall M. Predicting functional outcome in acute stroke: comparison of a simple six variable model with other predictive systems and informal clinical prediction. J Neurol Neurosurg Psychiatry. 2004;75(3):401–5.
  32. Whiteley W, Chong WL, Sengupta A, Sandercock P. Blood markers for the prognosis of ischemic stroke: a systematic review. Stroke. 2009;40 (5):e380–9.
  33. Fassbender K, Schmidt R, Mossner R, Daffertshofer M, Hennerici M. Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome. Stroke. 1994;25 (6):1105–8.
  34. Johansson A, Olsson T, Carlberg B, Karlsson K, Fagerlund M. Hypercortisolism after stroke--partly cytokine-mediated? J Neurol Sci. 1997;147(1):43–7.
  35. Slowik A, Turaj W, Pankiewicz J, Dziedzic T, Szermer P, Szczudlik A. Hypercortisolemia in acute stroke is related to the inflammatory response. J Neurol Sci. 2002;196(1–2):27–32.
  36. Johansson A, Ahren B, Nasman B, Carlstrom K, Olsson T. Cortisol axis abnormalities early after stroke – relationships to cytokines and leptin. J Intern Med. 2000;247(2):179–87.
  37. Sapolsky RM. Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion. Stress. 1996;1(1):1–19.
  38. Joynt RJ, Feibel JH, Sladek CM. Antidiuretic hormone levels in stroke patients. Ann Neurol. 1981;9(2):182–4.
  39. Barreca T, Gandolfo C, Corsini G, Del Sette M, Cataldi A, Rolandi E, et al. Evaluation of the secretory pattern of plasma arginine vasopressin in stroke patients. Cerebrovasc Dis. 2001;11(2):113–8.
  40. Katan M, Fluri F, Morgenthaler NG, Schuetz P, Zweifel C, Bingisser R, et al. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann Neurol. 2009;66(6):799–808.
  41. de Kruif MD, Lemaire LC, Giebelen IA, Struck J, Morgenthaler NG, Papassotiriou J, et al. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med. 2008;34(3):518–22.
  42. Bhandari SS, Loke I, Davies JE, Squire IB, Struck J, Ng LL. Gender and renal function influence plasma levels of copeptin in healthy individuals. Clin Sci. (Lond) 2009;116(3):257–63.
  43. Christ-Crain M, Muller B. Procalcitonin in bacterial infections – hype, hope, more or less? Swiss Med Wkly. 2005;135(31-32):451–60.
  44. Marshall JC. Biomarkers of Sepsis. Curr Infect Dis Rep. 2006;8(5):351–7.
  45. G. M. De Marchis, M. Katan, A. Weck, H. P. Mattle, C. Breckenfeld, Ph. Schütz, Ch. Foerch, et al. Validation of Copeptin as prognostic marker in ischemic stroke. Abstract; Meeting of the European Neurological Society 2010.