Following Brain Trauma, Copeptin, a Stable Peptide Derived from the AVP Precusor, Does Not Reflect Osmoregulation but Correlates with Injury Severity

  • A. KleindienstEmail author
  • G. Brabant
  • N. G. Morgenthaler
  • K. C. Dixit
  • H. Parsch
  • M. Buchfelder
Conference paper
Part of the Acta Neurochirurgica Supplementum book series (NEUROCHIRURGICA, volume 106)


The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, reflects AVP activity.

In 71 TBI patients we measured copeptin in serum by a sandwich immunoassay. Injury severity was assessed by Glasgow Coma Score (GCS) and computed tomography, and recovery by Glasgow Outcome Score (GOS). Neuroendocrine and osmoregulation regulation were examined on day 0, 3 and 7, and 24 months post-injury.

Copeptin was highest on admission (40.0 ± 72.3 pmol/l), stabilized on day 3 and 7 (21.2 ± 18.3 resp. 20.3 ± 17.1 pmol/l), and normalized at follow-up (4.2 ± 1.7 pmol/l). On admission, there was a correlation between serum sodium and urine excretion (p = 0.003), but the correlation got lost on day 3 and 7. Copeptin did not reflect the individual 24 h urine excretion or serum sodium levels indicating an uncoupling of copeptin/AVP release and renal water excretion. High copeptin level on day 3 were correlated with a low GCS (p < 0.001), midline shift (p = 0.019), intracerebral hemorrhage (p = 0.026), SAPS score (p = 0.001), as well as with a low GOS (p = 0.031). Copeptin was significantly decreased following skullbase fracture (p = 0.016).

Our data reveal a loss of hypothalamic osmoregulation following TBI. The measurement of Copeptin/AVP release reveals a significant predictive function for the severity of TBI.


Neuroendocrine function osmoregulation outcome traumatic brain injury 


  1. 1.
    Agha A, Thornton E, O’Kelly P, Tormey W, Phillips J, Thompson CJ (2004) Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab 89:5987–5992PubMedCrossRefGoogle Scholar
  2. 2.
    Dublin AB, Poirier VC (1976) Fracture of the sella turcica. AJR Am J Roentgenol 127:969–972PubMedGoogle Scholar
  3. 3.
    Edwards OM, Clark JD (1986) Post-traumatic hypopituitarism. Six cases and a review of the literature. Medicine (Baltimore) 65:281–290Google Scholar
  4. 4.
    Jennett B (1975) Outcome of severe damage to the central nervous system. Scale, scope and philosophy of the clinical problem. Ciba Found Symp 34:3–21PubMedGoogle Scholar
  5. 5.
    Katan M, Muller B, Christ-Crain M (2008) Copeptin: a new and promising diagnostic and prognostic marker. Crit Care 12:117PubMedCrossRefGoogle Scholar
  6. 6.
    Kaufman HH, Timberlake G, Voelker J, Pait TG (1993) Medical complications of head injury. Med Clin North Am 77:43–60PubMedGoogle Scholar
  7. 7.
    Kojima T, Waga S, Furuno M (1985) Fracture of the sella turcica. Neurosurgery 16:225–229PubMedCrossRefGoogle Scholar
  8. 8.
    Krismer AC, Wenzel V, Stadlbauer KH, Mayr VD, Lienhart HG, Arntz HR, Lindner KH (2004) Vasopressin during cardiopul-monary resuscitation: a progress report. Crit Care Med 32:S432–S435PubMedCrossRefGoogle Scholar
  9. 9.
    Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRefGoogle Scholar
  10. 10.
    Lindner KH, Prengel AW, Pfenninger EG, Lindner IM, Strohmenger HU, Georgieff M, Lurie KG (1995) Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary resuscitation in pigs. Circulation 91:215–221PubMedCrossRefGoogle Scholar
  11. 11.
    Morgenthaler NG, Struck J, Alonso C, Bergmann A (2006) Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 52:112–119PubMedCrossRefGoogle Scholar
  12. 12.
    Nomikos P, Buchfelder M, Honegger J, Fahlbusch R (1997) Head injuries with fractures of the sella turcica. Ann Endocrinol 58(Suppl):1S130PubMedCrossRefGoogle Scholar
  13. 13.
    Ortega FJ, Longridge NS (1975) Fracture of the sella turcica. Injury 6:335–337PubMedCrossRefGoogle Scholar
  14. 14.
    Schneider M, Schneider HJ, Yassouridis A, Saller B, von Rosen F, Stalla GK (2008) Predictors of anterior pituitary insufficiency after traumatic brain injury. Clin Endocrinol (Oxf) 68:206–212Google Scholar
  15. 15.
    Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84PubMedCrossRefGoogle Scholar
  16. 16.
    Vanhorebeek I, Van den Berghe G (2006) The neuroendocrine response to critical illness is a dynamic process. Crit Care Clin 22:1–15PubMedCrossRefGoogle Scholar
  17. 17.
    Young HA, Olin MS, Schmidek HH (1980) Fractures of the sella turcica. Neurosurgery 7:23–29PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2010

Authors and Affiliations

  • A. Kleindienst
    • 1
    Email author
  • G. Brabant
    • 2
  • N. G. Morgenthaler
    • 4
  • K. C. Dixit
    • 2
  • H. Parsch
    • 3
  • M. Buchfelder
    • 1
  1. 1.Department of NeurosurgeryFriedrich-Alexander-University Erlangen-NurembergErlangenGermany
  2. 2.Department of EndocrinologyChristie HospitalManchesterUnited Kingdom
  3. 3.University Erlangen-NurembergCentral LaboratoryErlangenGermany
  4. 4.Research DepartmentB.R.A.H.M.S. AG, Biotechnology CentreHennigsdorfGermany

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