title: Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: 'The Co-MED Study'.
abstract: OBJECTIVE
  Hyponatraemia is common and its differential diagnosis is challenging. Commonly used diagnostic algorithms have limited diagnostic accuracy. Copeptin, the c-terminal portion of the precursor peptide of arginine vasopressin might help in the differential diagnosis of hyponatraemia.
  
  
  METHODS
  Prospective multicentre observational study.
  
  
  METHODS
  A total of 298 patients admitted with profound hypoosmolar hyponatraemia (Na < 125 mmol/l) were evaluated. Three experts uninvolved in the patients' care determined the aetiology of hyponatraemia after standardized diagnostic evaluation.
  
  
  RESULTS
  Hyponatraemia differential diagnoses were as follows: syndrome of inappropriate antidiuresis (SIAD), 106 patients (35·6%); 'diuretic-induced', 72 (24·2%); 'hypovolaemic', 59 (19·8%); 'hypervolaemic', 33 (11·1%); primary polydipsia (PP), 24 (8·1%); and cortisol deficiency, 4 (1·3%). Copeptin levels <3·9 pmol/l identified patients with PP with high specificity (91%). Further, copeptin levels >84 pmol/l were highly predictive for hypovolaemic hyponatraemia (specificity: 90%). Urinary sodium levels and copeptin/urinary sodium ratio in patients with SIAD were higher and lower as compared to other hyponatraemia aetiologies (P < 0·0001). However, the specificity to identify SIAD was moderate for both parameters (31% and 61%). Fractional uric acid excretion (FEUA) and fractional urea excretion (FEurea) were higher in patients with SIAD compared to other hyponatraemia aetiologies (both P < 0·0001). FEureavalues >55% and FEUAvalues >12% had a specificity of 96% and 77% to detect patients with SIAD. These results remained similar after excluding patients taking diuretics.
  
  
  CONCLUSIONS
  Overall, there is only limited diagnostic utility of copeptin in the differential diagnosis of profound hyponatraemia. Very low copeptin levels are seen in patients with PP and highest copeptin levels in hypovolaemic hyponatraemia. To discriminate between SIAD and other hyponatraemia aetiologies, FEureaand FEUAlevels are valuable irrespective of diuretics use.
authors.affiliation: Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nigro
authors.affiliation: Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Winzeler
authors.affiliation: Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Suter-Widmer
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Medical University Clinic and Divisions of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.affiliation: Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Birsen
authors.initials: B
authors.lastname: Arici
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Medical University Clinic and Divisions of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Bally
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Medical University Clinic and Divisions of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Claudine A
authors.initials: CA
authors.lastname: Blum
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Emergency Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Nickel
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Emergency Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Bingisser
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Nephrology, Dialysis & Transplantation, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bock
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Huber
authors.affiliation: Department of Clinical Research, University Hospital Basel, Basel, Switzerland.|Medical University Clinic and Divisions of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.affiliation: Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.|Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D006020:Glycopeptides / Q000032:analysis*; D006760:Hospitalization; D006801:Humans; D006854:Hydrocortisone / Q000172:deficiency; D007010:Hyponatremia / Q000175:diagnosis*; D007177:Inappropriate ADH Syndrome / Q000175:diagnosis; D008875:Middle Aged; D059607:Polydipsia, Psychogenic / Q000175:diagnosis; D011446:Prospective Studies; D014508:Urea / Q000032:analysis; D014527:Uric Acid / Q000032:analysis
chemical_list: D006020:Glycopeptides; C048197:copeptins; D014527:Uric Acid; D014508:Urea; D006854:Hydrocortisone