title: Copeptin in the differential diagnosis of hyponatremia.
abstract: BACKGROUND
  Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia.
  
  
  METHODS
  In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD).
  
  
  RESULTS
  Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r(2) = 0.62, P < 0.001) or urine osmolality (r(2) = 0.39, P = 0.001) was observed. Plasma copeptin levels were significantly higher in patients with hypo- and hypervolemic hyponatremia compared with SIAD (P < 0.005, respectively) and primary polydipsia (P < 0.001). The copeptin to U-Na ratio differentiated accurately between volume-depleted and normovolemic disorders (area under the receiver-operating characteristic curve 0.88, 95% confidence interval 0.81-0.95; P < 0.001), resulting in a sensitivity and specificity of 85 and 87% if a cutoff value of 30 pmol/mmol was used. The combined information of plasma copeptin less than 3 pmol/liter and urine osmolality less than 200 mOsm/kg ensured primary polydipsia in 100% of suspected patients.
  
  
  CONCLUSIONS
  Copeptin measurement reliably identifies patients with primary polydipsia but has limited utility in the differential diagnosis of other hyponatremic disorders. In contrast, the copeptin to U-Na ratio is superior to the reference standard in discriminating volume-depleted from normovolemic hyponatremic disorders.
authors.affiliation: Endocrinology and Diabetes Unit, Department of Medicine I, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Fenske
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Anne
authors.initials: A
authors.lastname: Blechschmidt
authors.forename: Sebastian G K
authors.initials: SG
authors.lastname: Maier
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
mesh_terms: D000328:Adult; D000368:Aged; D051399:Aquaporin 2 / Q000235:genetics; D001127:Arginine Vasopressin / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D007010:Hyponatremia / Q000175:diagnosis*; D007177:Inappropriate ADH Syndrome / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017483:Receptors, Vasopressin / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C496023:AQP2 protein, human; D051399:Aquaporin 2; D006020:Glycopeptides; D017483:Receptors, Vasopressin; C048197:copeptins; D001127:Arginine Vasopressin