Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome--revisiting the direct and indirect water deprivation tests

J Clin Endocrinol Metab. 2011 May;96(5):1506-15. doi: 10.1210/jc.2010-2345. Epub 2011 Mar 2.


Background: The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia-polyuria syndrome. In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties.

Objective: The aim of the study was to evaluate the utility of copeptin, a surrogate of AVP secretion, in the diagnostic work-up of the polyuria-polydipsia syndrome and to compare its performance with the current diagnostic standard.

Setting and design: In two tertiary referral centers, 20 healthy subjects and 50 patients with polydipsia-polyuria syndrome underwent WDT with measurements of both plasma AVP and copeptin levels. The reference diagnosis was based on clinical information and treatment response.

Results: Twenty-two patients (44%) were diagnosed with primary polydipsia, 17 (34%) with partial central diabetes insipidus (DI), nine (18%) with complete central DI, and two (4%) with nephrogenic DI. The indirect WDT led to a correct diagnosis in 35 of 50 patients (70%). The direct WDT with AVP or copeptin measurement correctly diagnosed 23 patients (46%) or 36 patients (72%), respectively. Baseline copeptin values greater than 20 pmol/liter identified patients with nephrogenic DI, and concentrations below 2.6 pmol/liter indicated complete central DI. The ratio between Δ copeptin (0800 to 1600 h) and serum sodium concentration at 1600 h yielded optimal diagnostic accuracy, allowing us to also discern partial central DI from primary polydipsia (sensitivity 86%, and specificity 100%).

Conclusion: Copeptin holds promise as a diagnostic tool in the polyuria-polydipsia syndrome, improving significantly the diagnostic accuracy of the direct WDT.

Trial registration: NCT01056887.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine Vasopressin / blood
  • Diabetes Insipidus / diagnosis
  • Diagnosis, Differential
  • Female
  • Glycopeptides / blood*
  • Humans
  • Male
  • Osmolar Concentration
  • Polyuria / diagnosis*
  • Radioimmunoassay
  • Reference Values
  • Reproducibility of Results
  • Syndrome
  • Water Deprivation / physiology*


  • Glycopeptides
  • copeptins
  • Arginine Vasopressin

Supplementary concepts

  • Dipsogenic Diabetes Insipidus

Associated data