CPT: 84588
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Specimen Requirements


Plasma (EDTA)


0.5 mL

Minimum Volume

0.3 mL (Note: This volume does not allow for repeat testing.)


Lavender-top (EDTA) tube


Separate plasma from cells and transfer to a plastic transport tube.

Stability Requirements



Room temperature

14 days


14 days


14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Gross lipemia; gross hemolysis; gross icterus

Test Details


Measurement of copeptin levels in plasma


This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

• Sepsis, severe sepsis, septic shock, lower respiratory tract infections, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases, i.e., chronic heart failure may increase copeptin concentrations.1-3

• Arginine vasopressin (AVP) receptor antagonist therapies and other diseases in which AVP has been shown to play an important pathophysiologic role may also increase copeptin concentration.

• Mixed forms of diabetes insipidus (DI) can exist, and both central and peripheral DI may be incomplete, complicating the interpretation of results.

• Patients with long-standing psychogenic polydipsia may have copeptin levels suggestive of mild nephrogenic DI.

• While an elevated plasma copeptin concentration in a hyponatremic patient can be suggestive of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), copeptin determination alone is not typically sufficient to distinguish SIADH from other hyponatremic disorders.4,5

• Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating anti-animal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.


The ThermoFisher/BRAHMS KRYPTOR® assay employs Time-Resolved Amplified Cryptate Emission Cryptate Emission (TRACE) technology based on a non-radioactive energy transfer between a donor (europium cryptate) and an acceptor (XL665) in a sandwich immunofluorescent format using two mouse monoclonal antibodies.6

Reference Interval

0.0–5.9 pmol/L

Reference interval derived from testing of non-water deprived, non-fasting adults.

Additional Information

Copeptin is a peptide derived from the cleavage of the precursor of arginine vasopressin (AVP).7-10 AVP, also known as antidiuretic hormone (ADH), is a neuropeptide that is secreted from the hypothalamus in response to hypovolemia and elevated plasma osmolality.10-12 AVP has two primary functions: to retain water in the body and to constrict blood vessels.11 The measurement of AVP has been employed in the differential diagnosis of a variety of disorders related to the physiologic response to changes in plasma osmolality and non-osmotic stress.13-15 Unlike AVP, copeptin is a stable molecule and can be readily measured using an automated immunoassay.6 Because copeptin and AVP are produced simultaneously through a common proteolytic process, they are secreted into the circulation in an equimolar ratio.16 Serum copeptin concentrations correlate significantly with AVP levels17 and the levels of the two molecules respond equally to changes in blood volume.9,18

The assessment of circulating AVP levels is challenging because it is released in a pulsatile pattern and is rapidly cleared from plasma. Measurement of AVP is further complicated by the high ex vivo instability of the peptide.13,19 Copeptin levels tend to be relatively constant in plasma and this peptide is much more stable ex vivo, making sample handling more straight forward.9 As a consequence, copeptin can serve as a superior, surrogate marker of physiological AVP release in the assessment of patients with water balance disorders. The correlation of plasma copeptin with plasma osmolality has been shown to be stronger than the correlation of AVP with plasma osmolality,4 in great part due to the complexity and methodological drawbacks of the AVP assay. Copeptin is a stable surrogate marker of AVP and its measurement has proved to be convenient and sensitive diagnostic in a number of clinical applications.13,19

Diabetes insipidus (DI) is a rare disorder of water homeostasis characterized by the excretion of abnormally large volumes of hypotonic urine due to the inability to appropriately concentrate urine in response to volume and osmolar stimuli.7,20 The primary causes for DI are decreased AVP production (central DI) or decreased renal response to AVP (nephrogenic DI), both of which lead to hypotonic polyuria which is usually accompanied by polydipsia. Along with these etiologies, the differential diagnosis of hypotonic polyuria includes primary polydipsia.8 In primary polydipsia, there is no initial compromise in AVP secretion or renal action and instead, excessive fluid intake leads to a drop in plasma osmolality and a suppression of AVP synthesis. Primary polydipsia can be caused by an abnormality in the thirst center (dipsogenic polydipsia) or, more commonly, as the result of one of a number of psychiatric disorders (psychogenic polydipsia).7

Historically, the primary diagnostic test for the evaluation of polyuria-polydipsia syndrome has been the standard water deprivation test.14,21,22 In healthy subjects, water deprivation causes the plasma osmolality to rise, leading to the release of AVP (and copeptin) into the circulation. In this test, insufficient AVP secretion or effect is revealed by insufficient concentration capacity of the kidneys on osmotic stimulation which is achieved by a prolonged period of thirsting and followed by assessment of the response to exogenous AVP administration (Desmopressin). Recent studies aimed at validating the classical water deprivation revealed a diagnostic accuracy of only around 70%, with an even lower diagnostic accuracy in patients with primary polydipsia.21,22 Direct measurement of arginine vasopressin (AVP) upon osmotic stimulation has been proposed as an alternative to measuring 24-hour urine osmolality,23 but this method failed to enter clinical practice in large part due to technical limitations of AVP testing.13,22

The utility of copeptin measurement in assessing polyuria and water balance disorders has been evaluated.14,15,24 A baseline copeptin concentration of 21.4 pmol/L or greater (consistent with pathogenic overproduction of AVP) has been shown to accurately differentiate nephrogenic DI from other causes of polyuria, with a sensitivity and specificity of 100%.14,16 The distinction between central diabetes insipidus and primary polydipsia is not as straightforward because of the considerable overlap in baseline copeptin levels. In particular, distinguishing partial central diabetes insipidus from primary polydipsia is very challenging.22 Two copeptin-based test procedures have been proposed to overcome these difficulties: the hypertonic saline stimulation test21 and the arginine stimulation test.25

Katan and coworkers found that the measurement of copeptin after insulin induced hypoglycemia could be used to assess posterior pituitary function in patients after pituitary surgery.3 They found that a significant induction of copeptin levels was seen in patients with normal posterior pituitary function, but copeptin levels remained low in patients with postsurgical DI.3 This same group went on to demonstrate, in a prospective multicenter study, that a copeptin concentration of less 2.5 pmol/L after trans- sphenoidal surgery (without the need for induction of hypoglycemia) had a predictive value of 81% for central DI, with a specificity of 97%.25


1. Katan M, Fluri F, Morgenthaler NG, et al. Copeptin: a novel, independent prognostic marker in patients with ischemic stroke. Ann Neurol. 2009 Dec;66(6):799-808. Erratum in Ann Neurol. 2010 Feb;67(2):277-281.20035506
2. Reichlin T, Hochholzer W, Stelzig C, et al. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009 Jun 30;54(1):60-68.19555842
3. Katan M, Christ-Crain M. The stress hormone copeptin: a new prognostic biomarker in acute illness. Swiss Med Wkly. 2010 Sep 24;140:w13101.20872295
4. 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):123-129.18984663
5. Baldrighi M, Castello LM, Bartoli E. Copeptin in hyponatremia: is there a role for this biomarker in the diagnostic workup? Endocrine. 2018 Jun;60(3):384-385.29497972
6. BRAHMS Copeptin proAVP Kryptor [package insert]. ThermoFisher Scientific, Ver. R01 September 2015.
7. Christ-Crain M, Fenske W. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis. Nat Rev Endocrinol. 2016 Mar;12(3):168-176.26794439
8. 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):235-247.27156761
9. Morgenthaler NG, Müller B, Struck J, Bergmann A, Redl H, Christ-Crain M. Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock. Shock. 2007 Aug;28(2):219-226.17515850
10. Balanescu S, Kopp P, Gaskill MB, Morgenthaler NG, Schindler C, Rutishauser J. Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and hyperosmolar States. J Clin Endocrinol Metab. 2011 Apr;96(4):1046-1052.21289257
11. Bankir L, Bichet DG, Morgenthaler NG. Vasopressin: physiology, assessment and osmosensation. J Intern Med. 2017 Oct;282(4):284-297.28649750
12. Szinnai G, Morgenthaler NG, Berneis K, et al. Changes in plasma copeptin, the c-terminal portion of arginine vasopressin during water deprivation and excess in healthy subjects. J Clin Endocrinol Metab. 2007 Oct;92(10):3973-3978.17635944
13. Christ-Crain M. Diabetes Insipidus: New Concepts for Diagnosis. Neuroendocrinology. 2020;110(9-10):859-867.31986514
14. Timper K, Fenske W, Kühn 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):2268-2274.25768671
15. Rosen CJ, Ingelfinger JR. A Reliable Diagnostic Test for Hypotonic Polyuria. N Engl J Med. 2018 Aug;379(5):483-484.30067935
16. Fenske WK, Schnyder I, Koch G, et al. Release and Decay Kinetics of Copeptin vs AVP in Response to Osmotic Alterations in Healthy Volunteers. J Clin Endocrinol Metab. 2018 Feb 1;103(2):505-513.29267966
17. Jochberger S, Zitt M, Luckner G, et al. Postoperative vasopressin and copeptin levels in noncardiac surgery patients: a prospective controlled trial. Shock. 2009 Feb;31(2):132-138.18650776
18. 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):112-119.16269513
19. Refardt J. Diagnosis and differential diagnosis of diabetes insipidus: Update. Best Pract Res ClinEndocrinol Metab. 2020 Sep;34(5):101398. Epub 2020 Feb 28.32387127
20. Garrahy A, Moran C, Thompson CJ. Diagnosis and management of central diabetes insipidus in adults. Clin Endocrinol (Oxf). 2019 Jan;90(1):23-30.30269342
21. Fenske W, Refardt J, Chifu I, et al. A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus. N Engl J Med. 2018 Aug;379(5):428-439.30067922
22. Fenske W, Quinkler M, Lorenz D, et al. 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):1506-1515.21367924
23. Zerbe RL, Robertson GL. A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med. 1981 Dec 24;305(26):1539-1546.7311993
24. Katan M, Morgenthaler NG, Dixit KCS, et al. Anterior and posterior pituitary function testing with simultaneous insulin tolerance test and a novel copeptin assay. J Clin Endocrinol Metab. 2007 Jul;92(7):2640-2643.17426098
25. Winzeler B, Cesana-Nigro N, Refardt J, et al. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet. 2019 Aug 17;394(10198):587-595.31303316


Christ-Crain M, Bichet DG, Fenske WK, et al. Diabetes insipidus. Nat Rev Dis Primers. 2019 Aug 8;5(1):54.31395885
Christ-Crain M, Refardt J, Winzeler B. Approach to the Patient: "Utility of the Copeptin Assay." J Clin Endocrinol Metab. 2022 May 17;107(6):1727-1738.35137148
Refardt J, Atila C, Chifu I, et al. Arginine or Hypertonic Saline-Stimulated Copeptin to Diagnose AVP Deficiency. N Engl J Med. 2023 Nov 16;389(20):1877-1887.37966286


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
010505 Copeptin 78987-5 010506 Copeptin pmol/L 78987-5

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