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Arginine vasopressin (AVP), which is also known as antidiuretic hormone (ADH), is a neuropeptide that is secreted from the hypothalamus in response to hypovolemia and elevated plasma osmolality. The two primary functions of AVP are water retention and vasoconstriction. Measurement of AVP is helpful in the differential diagnosis of polyuria and water balance disorders.

AVP and copeptin (aka copeptin AVP) are derived from the same pro-hormone and secreted into the circulation in an equimolar ratio. AVP is not stable in plasma, but copeptin is stable for up to 14 days in EDTA plasma. For this reason, copeptin can be used as a surrogate marker of AVP in the assessment of water balance disorders. Both copeptin and AVP are responsive to osmotic stimuli and increase in response to water deprivation. In healthy individuals, water deprivation causes plasma osmolality to rise above approximately 280-290 mOsmol/kg, leading to the release of AVP and copeptin into the circulation.

Measurement of plasma copeptin concentration has been shown to be useful in the workup of patients with polyuria, which can be related to be related to insufficient AVP production (central diabetes insipidus), reduced sensitivity to AVP (nephrogenic diabetes insipidus), or excessive water intake.

Diabetes insipidus (DI) is characterized by the inability to appropriately concentrate urine in response to volume and osmolar stimuli. Central DI is caused by decreased AVP production while nephrogenic DI is due to decreased renal response to AVP.

Diabetes insipidus must be distinguished from primary polydipsia, in which excessive fluid intake leads to decreased plasma osmolality and suppression of AVP synthesis. Primary polydipsia can be caused by an abnormality in the thirst center (dipsogenic polydipsia) or, more commonly, a psychiatric disorder (psychogenic polydipsia).

A baseline copeptin concentration lower than 2.6 pmol/L indicates failure to synthesize AVP and is consistent with central diabetes insipidus.

A baseline copeptin concentration of 21.4 pmol/L or greater indicates overproduction of AVP and is consistent with nephrogenic diabetes insipidus.

In cases where baseline copeptin falls between 2.6 and 21.4 pmol/L, copeptin measurement after water deprivation can discriminate between primary polydipsia and central DI. Copeptin concentration of 4.9 pmol/L or higher indicates primary polydipsia while copeptin <4.9 pmol/L is consistent with complete or partial DI.

An elevated plasma copeptin concentration in a hyponatremic patient may be indicative of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). However copeptin determination alone cannot distinguish SIADH from other hyponatremic disorders.

In patients with heart failure following a myocardial infarction, elevated copeptin concentration is associated with more severe heart failure and a worse prognosis. Copeptin concentrations of 40 pmol/L have been consistent with an increased risk of death or need for cardiac transplantation. The combination of elevated copeptin and hyponatremia was a stronger predictor of heart failure, independent of B-type natriuretic peptide (BNP) and cardiac troponin (cTn) concentrations.

Copeptin concentration can also be increased in patients with sepsis, lower respiratory tract infections, and chronic obstructive pulmonary disease.

Copeptin proAVP is measured using a homogeneous immunofluorescent assay on the BRAHMS Kryptor Compact PLUS.

Reference Values

  • Non-water deprived, non-fasting adults: <13.1 pmol/L
  • Non-water deprived, non-fasting pediatric patients: <14.5 pmol/L
  • Water deprived, fasting adults: <15.2 pmol/L

Specimen is a lavender top tube of blood (EDTA). Copeptin is stable in EDTA plasma for up to 14 days at room temperature.


1. Timper K, Fenske W, Kuhn 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 Jun;100(6):2268-2274. doi: 10.1210/jc.2014-4507

2. Fenske W, Refardt J, Chifu I, et al: A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med. 2018 Aug 2;379(5):428-439. doi: 10.1056/NEJMoa1803760

4. Neuhold S, Huelsmann M, Strunk G, et al: Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease. J Am Coll Cardiol. 2008 Jul 22;52(4):266-272. doi: 10.1016/j.jacc.2008.03.050

6. Morgenthaler NG, Struck J, Alonso C, Bergmann A: Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006 Jan;52(1):112-119. doi: 10.1373/clinchem.2005.060038

 Fenske W, Störk S, Blechschmidt A, Maier SGK, Morgenthaler NG, Allolio B. Copeptin in the differential diagnosis of hyponatremia. J Clin Endocrinol Metab. 2009 Jan;94(1):123-129. PubMed 18984663

 Christ-Crain M, Morgenthaler NG, Fenske W. Copeptin as a biomarker and a diagnostic tool in the evaluation of patients with polyuria-polydipsia and hyponatremia. Best Pract Res Clin Endocrinol Metab. 2016 Mar;30(2):235-247. PubMed 27156761

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