Symbol CT-proAVP OMIM 192340 Locus Chr. 20 p13 | Alt. symbols copeptine UniProt P01185 | |
Copeptin (also known as CT-proAVP) is a 39-amino acid-long peptide derived from a pre-pro-hormone consisting of vasopressin, neurophysin II and copeptin. Arginine vasopressin (AVP), also known as the antidiuretic hormone (ADH), is involved in multiple cardiovascular and renal pathways and functions. However, vasopressin measurements are not commonly used in clinical practice because of the biochemical features of the molecule: its small size and very short half-life make vasopressin testing quite complicated and labor-intensive. On the other hand, copeptin can be immunologically tested with ease and therefore be used as a vasopressin surrogate.
Contents
Synthesis and secretion
Copeptin is a 39-amino acid-long, glycosylated peptide. It is synthesized mainly in the paraventricular neurons of the hypothalamus and in the supraoptical nucleus. During axonal transport, pre-pro-AVP is proteolytically cleaved into vasopressin, neurophysin II and copeptin. These molecules are then stored in secretory granules in the posterior pituitary and released upon osmotic or non-osmotic (hemodynamical; stress-related) stimuli.
Biological role
Once secreted into the bloodstream, there is no known biological role for copeptin. However, when pre-pro-vasopressin is processed during the axonal transport, copeptin may contribute to the 3D folding of vasopressin.
Clinical interest in copeptin testing
The size and half-life of copeptin permit an easier immunological testing, compared to vasopressin, and hence copeptin is proposed as a reliable AVP surrogate. The clinical interest in copeptin testing is closely linked to the pathophysiological pathways in which vasopressin is involved : polydipsia-polyuria syndrome, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH) as well as heart failure and acute coronary syndrome.
Copeptin in blood circulation
The concentration of copeptin in the blood circulation ranges from 1 to 12 pmol/L in healthy individuals. The levels of copeptine are slightly higher in men than in women and are not influenced by age. In response to serum osmolality fluctuations, the kinetics of copeptine are comparable to those of vasopressin. For example, patients with an electrolyte disorders such as diabetes insipidus with very low levels of vasopressin also show very low levels of copeptin in blood plasma. On the other hand, patients suffering from syndrome of inappropriate antidiuretic hormone secretion show both high levels of vasopressin and copeptin.
Copeptin and acute myocardial infarction
Several studies have shown that copeptin is released very early during the onset of an acute myocardial infarction (AMI), raising the question of its potential value in the diagnosis of AMI and particularly in ruling-out AMI. Indeed, copeptin is released much earlier than Troponin making the interpretation of their complementary kinetics a useful tool to rule-out AMI. It has been shown that the combination of a negative result of troponin together with a negative result of copeptin can rule-out AMI at emergency department presentation with a negative predictive value ranging from 95% to 100%. These results have been confirmed in a randomised controlled trial.
Copeptin and cardiogenic shock
High concentrations of vasopressin during a cardiogenic shock have been widely described. It has been shown that the kinetics of copeptin are similar to vasopressin in that context.
Copeptin in heart failure
The prognostic value of vasopressin for prediction of outcome in patients suffering from heart failure has been known since the nineties. Patients presenting with high levels of vasopressin have a worsened outcome. Recently, a similar interest has been demonstrated for copeptin in heart failure.