title: Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study.
abstract: BACKGROUND
  The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging.
  
  
  OBJECTIVE
  The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome.
  
  
  METHODS
  This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia.
  
  
  METHODS
  A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response.
  
  
  RESULTS
  Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity.
  
  
  CONCLUSIONS
  This study was limited by incorporation bias from including AVP levels as a diagnostic criterion.
  
  
  CONCLUSIONS
  Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Fenske
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Felix
authors.initials: F
authors.lastname: Kühn
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Nica
authors.initials: N
authors.lastname: Frech
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Birsen
authors.initials: B
authors.lastname: Arici
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Rutishauser
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Kopp
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stettler
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Mira
authors.initials: M
authors.lastname: Katan
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism, Department of Clinical Research (K.T., N.F., M.C.-C.), University Hospital Basel, CH-4031 Basel, Switzerland; Integrated Research and Treatment Center for Adiposity Diseases (W.F.), Leipzig University Medical Center, 04103 Leipzig, Germany; Division of Endocrinology, Diabetes and Clinical Nutrition (F.K., C.S.), University Hospital Bern-Inselspital, CH-3010 Bern, Switzerland; Department of Internal Medicine (B.Ar.), Spital Rheinfelden, CH-4310 Rheinfelden, Switzerland; University Clinic of Internal Medicine (J.R.), Kantonsspital Baselland, CH-4101 Binningen, Switzerland; Division of Endocrinology, Metabolism and Molecular Medicine and Center for Genetic Medicine (P.K.), Northwestern University, Chicago, Illinois 60611; Department of Internal Medicine I, Endocrine and Diabetes Unit (B.Al.), University Hospital Würzburg, 97080 Würzburg, Germany; Division of Endocrinology, Diabetology and Metabolism, Medical University Clinic (B.M.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; and Department of Neurology (M.K.), University Hospital Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000328:Adult; D001127:Arginine Vasopressin / Q000097:blood; D015331:Cohort Studies; D018500:Diabetes Insipidus, Nephrogenic / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D020790:Diabetes Insipidus, Neurogenic / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059606:Polydipsia / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D011141:Polyuria / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013577:Syndrome; D014868:Water Deprivation / Q000502:physiology
chemical_list: D006020:Glycopeptides; C048197:copeptins; D001127:Arginine Vasopressin