Exp Clin Endocrinol Diabetes 2007; 115 - OR03_6
DOI: 10.1055/s-2007-972220

Copeptin, a stable peptide derived from the AVP precusor, correlates with the severity of traumatic brain injury and predicts the outcome

A Kleindienst 1, C Bock 2, M Buchfelder 1, NG Morgenthaler 3, J Struck 3, G Brabant 4
  • 1University Erlangen-Nuremberg, Dept. of Neurosurgery, Erlangen, Germany
  • 2University Göttingen, Dept. of Neurosurgery, Göttingen, Germany
  • 3BAHMS AG, Biotechnology Centre, Research Dept., Henningsdorf/Berlin, Germany
  • 4Christie Hospital, Dept. of Endocrinology, Manchester, United Kingdom

Purpose: 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, is concomitantly secreted together with mature AVP. Due to a several day lasting ex vivo stability, copeptin can be readily assayed in serum or plasma. In this study we tested the impact of TBI on copeptin release and on 6 months outcome of these patients.

Methods: In 71 consecutive patients admitted for TBI (57 male, 14 female, mean age 53 years) we measured copeptin, a stable derivate of AVP, which has been demonstrated to reflect AVP activity by a sandwich immunoassay. Injury severity was assessed by the Glasgow Coma Score (GCS) and an initial CT. Copeptin and pituitary function were examined on day 0, 3 and 7, and 24 to 36 months post-injury. Recovery was assessed by the Glasgow Outcome Score (GOS).

Results: 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 was normalized at follow-up in all but one patient (4.2±1.7 pmol/l). The data demonstrate a significant correlation of high copeptin levels on day 3 with the GCS (r=-0.661, p<0.001), midline shift on CT (r=0.349, p=0.019), intracerebral hemorrhage (r=0.325, p=0.026), SAPS score (r=0.53, p=0.001), cortisol levels (r=0.437, p<0.001), late somato- (r=0.397, p=0.037) and early thyreotropic (r=0.220, p=0.042) deficiency, as well as with the GOS at 6 months (r=-0.302, p=0.031). Copeptin levels on day 7 were significantly decreased in patients with a skullbase fracture (r=-0.357, p=0.016).

Conclusions: Our data reveal a significant predictive function of copeptin for the severity of TBI. Moreover, since AVP/copeptin serves an important stimulatory function for the anterior pituitary, copeptin levels may also indicate pituitary dysfunction in patients following TBI.