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Exp Clin Endocrinol Diabetes 2016; 124(03): 173-177
DOI: 10.1055/s-0035-1569341
Review
© Georg Thieme Verlag KG Stuttgart · New York

Potential Clinical Utility of Copeptin (C-terminal provasopressin) measurements in clinical medicine

K. C. Lewandowski
1   Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland
,
G. Brabant
2   Experimental and Clinical Endocrinology Med Clinic I, University of Luebeck, Germany
› Author Affiliations
Further Information

Publication History

received 17 November 2015
first decision 17 November 2015

accepted 07 December 2015

Publication Date:
23 March 2016 (online)

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Abstract

Copeptin is a 39-amino-acids containing glycosylated peptide derived from the C-terminal part of the arginine vasopressin (AVP) precursor. In the process of proteolysis the AVP precursor is processed to AVP, neurophysin II, and copeptin in equimolar amounts. In contrast to AVP, copeptin remains stable for several days at room temperature in serum or plasma. Hence, copeptin serves as a bona fide biomarker of AVP release. We briefly summarise clinical utility of copeptin in the diagnosis of diabetes insipidus. We also discuss potential applications of copeptin measurements in hyponatraemic states, assessment of an anterior pituitary function, as well as a wide range of several acute and chronic medical conditions, such as myocardial infarction, stroke or diabetes mellitus.

Keywords

Copeptin - AVP - diabetes insipidus - pituitary function - SIADH
 

  • References

  • 1 Mahoney CP, Weinberger E, Bryant C et al. Effects of aging on vasopressin production in a kindred with autosomal dominant neurohypophyseal diabetes insipidus due to the Deltae47 neurophysin mutation. J Clin Endocrinol Metab 2002; 87: 870-876
    CrossrefPubMedGoogle Scholar
  • 2 Morgenthaler NG, Struck J, Jochberger S et al. Copeptin: clinical use of a new biomarker. Trends Endocrinol Metab 2008; 19: 43-49
    CrossrefPubMedGoogle Scholar
  • 3 Barat C, Simpson L, Breslow E. Properties of human vasopressin precursor constructs: inefficient monomer folding in the absence of copeptin a potential contributor to diabetes insipidus. Biochemistry 2004; 43: 8191-8203
    CrossrefPubMedGoogle Scholar
  • 4 Preibisz JJ, Sealey JE, Laragh JH et al. Plasma and platelet vasopressin in essential hypertension and congestive heart failure. Hypertension 1983; 5: I129-I138
    CrossrefPubMedGoogle Scholar
  • 5 Roberston GL, Mahr EA, Athar S et al. Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma. J Clin Invest 1973; 52: 2340-2352
    CrossrefPubMedGoogle Scholar
  • 6 Morgenthaler NG, Struck J, Alonso C et al. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 2006; 52: 112-119
    CrossrefPubMedGoogle Scholar
  • 7 Roussel R, Fezeu L, Marre M et al. Comparison between copeptin and vasopressin in a population from the community and in people with chronic kidney disease. J Clin Endocrinol. Metab 2014; 99: 4656-4663
    CrossrefPubMedGoogle Scholar
  • 8 Winzeler B, Zweifel C, Nigro N et al. Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery. J Clin Endocrinol Metab 2015; 100: 2275-2282
    CrossrefPubMedGoogle Scholar
  • 9 Robertson GL. Diabetes insipidus. Endocrinol Metab Clin North Am 1995; 24: 549-572
    PubMedGoogle Scholar
  • 10 Fenske W, Quinkler M, Lorenz D et al. Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome – revising the direct and indirect water deprivation tests. J Clin Endocrinol Metab 2011; 96: 1506-1515
    CrossrefPubMedGoogle Scholar
  • 11 Baylis PH, Robertson GL. Plasma vasopressin response to hypertonic saline infusion to assess posterior pituitary function. J R Soc Med 1980; 73: 255-260
    PubMedGoogle Scholar
  • 12 Zerbe R, Stropes L, Robertson G. Vasopressin function in the syndrome of inappropriate antidiuresis. Annu Rev Med 1980; 31: 315-327
    CrossrefPubMedGoogle Scholar
  • 13 Robertson GL, Aycinena P, Zerbe RL. Neurogenic disorders of osmoregulation. Am J Med 1982; 72: 339-353
    CrossrefPubMedGoogle Scholar
  • 14 Timper K, Fenske W, Kühn F et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: A prospective multicenter study. J Clin Endocrinol Metab 2015; 100: 2268-2274
    CrossrefPubMedGoogle Scholar
  • 15 Schäffler A, Linner U. Syndrome of inadequate ADH secretion: pitfalls in diagnosis and therapy. Dtsch Med Wochenschr 2015; 150: 343-346
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Fenske W, Störk S, Blechschmidt A et al. Copeptin in the differential diagnosis of hyponatremia. J Clin Endocrinol Metab 2009; 94: 123-129
    CrossrefPubMedGoogle Scholar
  • 17 Wuttke A, Dixit KC, Szinnai G et al. Copeptin as a marker for arginine-vasopressin/antidiuretic hormone secretion in the diagnosis of paraneoplastic syndrome of inappropriate ADH secretion. Endocrine 2013; 44: 744-749
    CrossrefPubMedGoogle Scholar
  • 18 Blanchard A, Steichen O, De Mota N et al. An abnormal apelin/vasopressin balance may contribute to water retention in patients with the syndrome of inappropriate antidiuretic hormone (SIADH) and heart failure. J Clin Endocrinol Metab 2013; 98: 2084-2089
    CrossrefPubMedGoogle Scholar
  • 19 Fenske WK, Christ-Crain M, Hörning A et al. A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis. J Am Soc Nephrol 2014; 25: 2376-2383
    CrossrefPubMedGoogle Scholar
  • 20 Nogueira-Silva L, Blanchard A, Curis E et al. Deciphering the role of vasopressin in primary aldosteronism. J Clin Endocrinol Metab 2015; 100: 3297-3303
    CrossrefPubMedGoogle Scholar
  • 21 Katan M., Morgenthaler N, Widmer I et al. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuroendocrinol Lett 2008; 29: 341-346
    PubMedGoogle Scholar
  • 22 Siegenthaler J, Walti C, Urwyler SA et al. Copeptin concentrations during psychological stress: the PsyCo study. Eur J Endocrinol 2014; 171: 737-742
    CrossrefPubMedGoogle Scholar
  • 23 Urwyler SA, Schuetz P, Sailer C et al. Copeptin as a stress marker prior and after a written examination – the CoEXAM study. Stress 2015; 18: 134-137
    CrossrefPubMedGoogle Scholar
  • 24 Geisel O, Panneck P, Hellweg R et al. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder. Psychiatry Res 2015; 226: 97-102
    CrossrefPubMedGoogle Scholar
  • 25 Grossman AB. Clinical Review. Diagnosis and management of central hypoadrenalism. J Clin Endocrinol Metab 2010; 95: 4855-4863
    CrossrefPubMedGoogle Scholar
  • 26 Katan M, Morgenthaler NG, Dixit KC et al. Anterior and posterior pituitary function testing with simultaneous insulin tolerance test and a novel copeptinassay. J Clin Endocrinol Metab 2007; 92: 2640-2643
    CrossrefPubMedGoogle Scholar
  • 27 Kacheva S, Kolk K, Morgenthaler NG et al. Gender-specific co-activation of arginine vasopressin and the hypothalamic-pituitary-adrenal axis during stress. Clin Endocrinol (Oxf) 2015; 82: 570-576
    CrossrefPubMedGoogle Scholar
  • 28 Seelig E, Biltz S, Keller U et al. Concentrations of the stress hormone copeptin increase upon hypoglycaemia in patients with type 1 diabetes dependent of hypoglycaemia awareness. PLoS One 2013; 8: e72876
    CrossrefPubMedGoogle Scholar
  • 29 Orme SM, Price A, Weetman AP et al. Comparison of the diagnostic utility of the simplified and standard i. m. glucagon stimulation test (IMGST). Clin Endocrinol (Oxf) 1998; 49: 773-778
    CrossrefPubMedGoogle Scholar
  • 30 Gomez JM, Espadero RM, Escobar-Jimenez F et al. Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf) 2002; 56: 329-333
    CrossrefPubMedGoogle Scholar
  • 31 Lewandowski K, Lewinski A, Skowronska-Jozwiak E et al. Copeptin concentrations increase during glucagon stimulation test: possible role of copeptin in assessment of anterior pituitary function. Endocrine Abstracts 2014; 35: P826
    PubMedGoogle Scholar
  • 32 Lewandowski K, Lewinski A, Skowronska-Jozwiak E et al. Copeptin under glucagon stimulation. Endocrine 2015 DOI 10.1007/s12020-015-0783-7
    PubMedGoogle Scholar
  • 33 Tanoue A, Ito S, Honda K et al. The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest 2004; 113: 302-309
    CrossrefPubMedGoogle Scholar
  • 34 Rollin GA, Costenaro F, Gerchman F et al. Evaluation of the DDAVP test in the diagnosis of Cushing’s syndrome. Clin Endocrinol (Oxf) 2015; 82: 793-800
    CrossrefPubMedGoogle Scholar
  • 35 Katan M, Christ-Crain M. The stress hormone copeptin: a new prognostic marker in acute illness. Swiss Med Weekly 2010; 140: w13101
    PubMedGoogle Scholar
  • 36 Müller B, Morgenthaler N, Stoltz D et al. Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections. Eur J Clin Invest 2007; 37: 145-152
    CrossrefPubMedGoogle Scholar
  • 37 Morgenthaler NG, Müller B, Struck J et al. Copeptin, a stable peptide of the arginine vasopressin precursor is elevated in haemorrhagic and septic shock. Shock 2007; 28: 219-226
    CrossrefPubMedGoogle Scholar
  • 38 Katan M, Fluri F, Morgenthaler NG et al. Copeptin: A novel, independent prognostic marker in patients with ischaemic stroke. Ann Neurol 2009; 66: 799-808
    CrossrefPubMedGoogle Scholar
  • 39 Sang G, Du JM, Chen YY et al. Plasma copeptin levels are associated with prognosis of severe acute pancreatitis. Peptides 2014; 51: 4-8
    CrossrefPubMedGoogle Scholar
  • 40 Stöcklin B, Fouzas S, Schillinger P et al. Copeptin as a serum biomarker of febrile seizures. PLoS One 2015; 10: e0124663
    CrossrefPubMedGoogle Scholar
  • 41 Yeung EH, Liu A, Mills JL et al. Increased levels of copeptin before clinical diagnosis of preeclampsia. Hypertension 2014; 64: 1362-1367
    CrossrefPubMedGoogle Scholar
  • 42 Choi KS, Kim HJ, Chun HJ et al. Prognostic role of copeptin after stroke: A systematic review and meta-analysis of observational studies. Scientific Reports 2015; 5: 11665 DOI: 10.1038/srep11665.
    CrossrefPubMedGoogle Scholar
  • 43 Akkoyun DC, Akyuz A, Tulubas F et al. The serum copeptin levels in obstructive sleep apnea patients with prehypertensive. Eur Rev Med Pharmacol Sci 2015; 19: 1721-1728
    PubMedGoogle Scholar
  • 44 Balling L, Gustafsson F. Copeptin as a biomarker in heart failure. 2014; 8: 841-854
    PubMedGoogle Scholar
  • 45 Pozsonyi Z, Föehecz Z, Gombos T et al. Copeptin (C-terminal pro arginine-vasopressin) is an independent long-term prognostic marker in heart failure with reduced ejection fraction. Heart Lung Circ 2015; 24: 359-367
    CrossrefPubMedGoogle Scholar
  • 46 Mueller C. Biomarkers and acute coronary syndromes: an update. Eur Heart J 2014; 35: 552-556
    CrossrefPubMedGoogle Scholar
  • 47 Khan SQ, Dhillon OS, O’Brien RJ et al. C-terminal provasopressin (copeptin) as anovel and prognostic marker in acute myocardial infarction: Leicester acute myocardial infarction peptide (LAMP) study. Circulation 2007; 115: 2103-2110
    CrossrefPubMedGoogle Scholar
  • 48 Gu YL, Voors AA, Zijlstra F et al. Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction. Clin Res Cardiol 2011; 100: 1069-1076
    CrossrefPubMedGoogle Scholar
  • 49 Hupf H, Grimm D, Riegger GAJ et al. Evidence for vasopressin system in rat heart. Circulation Res 1999; 84: 365-370
    CrossrefPubMedGoogle Scholar
  • 50 Reichlin T, Hochholzer W, Stelzig C et al. Incremental value of copeptin for rapid rule out of myocardial infarction. J Am College Cardiol 2009; 54: 60-68
    CrossrefPubMedGoogle Scholar
  • 51 Maisel A, Mueller C, Neath AX et al. Copeptin helps in the early detection of patients with acute myocardial infarction. Primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction). J Am College Cardiol 2013; 62: 150-160
    CrossrefPubMedGoogle Scholar
  • 52 Narayan H, Dhillon OS, Quinn PA et al. C-terminal provasopressin (copeptin) as anovel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide II (LAMP II) study. Clin Sci 2011; 121: 79-89
    CrossrefPubMedGoogle Scholar
  • 53 Lipinski MJ, Escárcega RO, D’Ascenzo F et al. A systematic review and collaborative meta-analysis to determine the incremental value of copeptin for rapid rule out of acute myocardial infarction. Am J Cardiol 2014; 113: 1581-1591
    CrossrefPubMedGoogle Scholar
  • 54 Reinstadler SJ, Klug G, Feistritzer HJ et al. Copeptin testing in acute myocardial infarction: Ready for routine use?. Disease Markers 2015; Article ID 614145 http://dx.doi.org/10.1155/2015/614145
    PubMedGoogle Scholar
  • 55 Zellweger C, Wildi K, Twerenbold R et al. Use of copeptin and high-sensitive cardiac troponin T for diagnosis and prognosis in patients with diabetes mellitus and suspected acute myocardial infarction. Int J Cardiol 2015; 190: 190-197
    CrossrefPubMedGoogle Scholar
  • 56 Enhörning S, Wang TJ, Nilsson PM et al. Plasma copeptin and the risk of diabetes mellitus. Circulation 2010; 121: 2102-2108
    CrossrefPubMedGoogle Scholar
  • 57 Enhörning S, Struck J, Wirfält E et al. Plasma copeptin, A uninifying factor behind the metabolic syndrome. J Clin Endocrinol Metab 2011; 96: E1065-E1072
    CrossrefPubMedGoogle Scholar
  • 58 Hiroyama M, Aoyagi T, Fujjiwara Y et al. Hypermetabolism of fat in V1a vasopressin receptor knockout mice. Mol Endocrinol 2007; 21: 247-258
    CrossrefPubMedGoogle Scholar
  • 59 Filep J, Rosenkranz B. Mechanism of vasopressin-induced platelet aggregation. Thromb Res 1987; 45: 7-15
    PubMedGoogle Scholar
  • 60 Yalta K, Yalta T, Sivri N et al. Copeptin and cardiovascular disease: a review of a novel neurohormone. Int J Cardiol 2013; 167: 1750-1759
    CrossrefPubMedGoogle Scholar
  • 61 Aoyagi T, Birumachi J, Hiroyama M et al. Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. Endocrinology 2007; 148: 2075-2084
    CrossrefPubMedGoogle Scholar
  • 62 Hu W, Ni YJ, Ma L et al. Serum copeptin as a new biomarker in the Elary diagnosis of decline in renal function of type 2 diabetes mellitus patients. Int J. Clin Exp Med 2015; 8: 9730-9736
    PubMedGoogle Scholar
  • 63 Boertien WE, Riphagen IJ, Drion I et al. Copeptin, a surrogate marker for arginine vasopressin is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33). Diabetologia 2013; 56: 1680-1688
    CrossrefPubMedGoogle Scholar
  • 64 Enhörning S, Hedblad B, Nilsson PM et al. Copeptin is an independent predictor of diabetic heart disease and death. Am Heart J 2015; 169: 549-556
    CrossrefPubMedGoogle Scholar
  • 65 Riphagen IJ, Boertien WE, Alkhalaf A et al. Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular and all-cause mortality in patients with type 2 diabeyes (ZODIAC-31). Diabetes Care 2013; 36: 3201-3207
    CrossrefPubMedGoogle Scholar
  • 66 Bar-Shalom D, Poulsen MK, Rasmussen LM et al. Plasma copeptin as a marker of cardiovascular disease in asymptomatic type 2 diabetes patients. Diab Vasc Dis Res 2014; 11: 448-450
    CrossrefPubMedGoogle Scholar
  • 67 Wannamethee SG, Welsh P, Papacosta O et al. Copeptin, insulin resistance, and risk of incident diabetes in older men. J Clin Endocrinol Metab 2015; 100: 3332-3339
    CrossrefPubMedGoogle Scholar
  • 68 Then C, Kowall B, Lechner A et al. Plasma copeptin levels are inversely associated with intima-media-thickness in men: the population-based KORA F4 study. Cardiovascular Diabetol 2013; 12: 168
    PubMedGoogle Scholar
  • 69 Riphagen IJ, Logtenberg SJ, Groenier KH et al. Is the association of serum sodium with mortality in patients with type 2 diabetes explained by copeptin or NT-proBNP? (ZODIAC-46). Atherosclerosis 2015; 242: 179-185
    CrossrefPubMedGoogle Scholar