A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus) (2025)

Atila, C., Winzeler, B., Chifu, I., Fassnacht, M., Refardt, J., & Christ-Crain, M. (2025). A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus). Pituitary, 28(3), Article 53. https://doi.org/10.1007/s11102-025-01523-2

Atila, Cihan ; Winzeler, Bettina ; Chifu, Irina et al. / A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus). In: Pituitary. 2025 ; Vol. 28, No. 3.

@article{346d8a27cfde4ed6844bc6dbdbf588f2,

title = "A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus)",

abstract = "Background:Distinguishing arginine vasopressin (AVP) deficiency (central diabetes insipidus) from primary polydipsia is challenging. While hypertonic saline-stimulated copeptin testing provides the highest diagnostic accuracy, it is often restricted to specialised centres, requiring close monitoring and potentially causing patient discomfort. Initially, arginine-stimulated copeptin was proposed as a simpler alternative, but a head-to-head comparison study found it less precise than hypertonic saline stimulation. However, the same study identified two new high sensitivity and specificity cut-offs for arginine-stimulated copeptin, though these cut-offs have yet to be validated.Methods:This is a secondary post-hoc analysis of the initial prospective multicentre study, including adult patients with confirmed AVP deficiency or primary polydipsia. Participants underwent the arginine stimulation test, with plasma copeptin measured at baseline and 60- and 90min after arginine infusion. The primary objective was to revisit the original study to internally validate the proposed arginine-stimulated copeptin cut-offs of > 5.2pmol/L (high specificity cut-off with > 90% specificity for primary polydipsia) and ≤ 3.0 pmol/L (high specificity cut-off with > 90% specificity for AVP deficiency).Findings:In total, 96 patients were included between May 2013 and June 2018: n = 38 [40%] with AVP deficiency and n = 58 [60%] with primary polydipsia. At 60min after arginine infusion, a copeptin level ≤ 3.0 pmol/L showed a specificity of 95% (95% CI: 0.88-1.00) for AVP deficiency, while a copeptin level > 5.2 pmol/L demonstrated a specificity of 97% (95% CI: 0.92-1.00) for primary polydipsia. The ≤ 3.0 pmol/L cut-off accurately identified 71% (n = 27/38) of patients with AVP deficiency, and the > 5.2 pmol/L cut-off correctly identified 69% (n = 40/58) of patients with primary polydipsia.Interpretation:This analysis validates two new copeptin cut-offs of the arginine stimulation test to distinguish AVP deficiency from primary polydipsia: >5.2 pmol/L for high specificity in diagnosing primary polydipsia and ≤ 3.0 pmol/L for high specificity in diagnosing AVP deficiency. These thresholds might offer a practical initial alternative to hypertonic saline testing.Registration:Clinicaltrials.gov (NCT00757276).",

author = "Cihan Atila and Bettina Winzeler and Irina Chifu and Martin Fassnacht and Julie Refardt and Mirjam Christ-Crain",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = apr,

day = "26",

doi = "10.1007/s11102-025-01523-2",

language = "English",

volume = "28",

journal = "Pituitary",

issn = "1386-341X",

publisher = "Springer",

number = "3",

}

Atila, C, Winzeler, B, Chifu, I, Fassnacht, M, Refardt, J & Christ-Crain, M 2025, 'A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus)', Pituitary, vol. 28, no. 3, 53. https://doi.org/10.1007/s11102-025-01523-2

A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus). / Atila, Cihan; Winzeler, Bettina; Chifu, Irina et al.
In: Pituitary, Vol. 28, No. 3, 53, 26.04.2025.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus)

AU - Atila, Cihan

AU - Winzeler, Bettina

AU - Chifu, Irina

AU - Fassnacht, Martin

AU - Refardt, Julie

AU - Christ-Crain, Mirjam

N1 - Publisher Copyright:© The Author(s) 2025.

PY - 2025/4/26

Y1 - 2025/4/26

N2 - Background:Distinguishing arginine vasopressin (AVP) deficiency (central diabetes insipidus) from primary polydipsia is challenging. While hypertonic saline-stimulated copeptin testing provides the highest diagnostic accuracy, it is often restricted to specialised centres, requiring close monitoring and potentially causing patient discomfort. Initially, arginine-stimulated copeptin was proposed as a simpler alternative, but a head-to-head comparison study found it less precise than hypertonic saline stimulation. However, the same study identified two new high sensitivity and specificity cut-offs for arginine-stimulated copeptin, though these cut-offs have yet to be validated.Methods:This is a secondary post-hoc analysis of the initial prospective multicentre study, including adult patients with confirmed AVP deficiency or primary polydipsia. Participants underwent the arginine stimulation test, with plasma copeptin measured at baseline and 60- and 90min after arginine infusion. The primary objective was to revisit the original study to internally validate the proposed arginine-stimulated copeptin cut-offs of > 5.2pmol/L (high specificity cut-off with > 90% specificity for primary polydipsia) and ≤ 3.0 pmol/L (high specificity cut-off with > 90% specificity for AVP deficiency).Findings:In total, 96 patients were included between May 2013 and June 2018: n = 38 [40%] with AVP deficiency and n = 58 [60%] with primary polydipsia. At 60min after arginine infusion, a copeptin level ≤ 3.0 pmol/L showed a specificity of 95% (95% CI: 0.88-1.00) for AVP deficiency, while a copeptin level > 5.2 pmol/L demonstrated a specificity of 97% (95% CI: 0.92-1.00) for primary polydipsia. The ≤ 3.0 pmol/L cut-off accurately identified 71% (n = 27/38) of patients with AVP deficiency, and the > 5.2 pmol/L cut-off correctly identified 69% (n = 40/58) of patients with primary polydipsia.Interpretation:This analysis validates two new copeptin cut-offs of the arginine stimulation test to distinguish AVP deficiency from primary polydipsia: >5.2 pmol/L for high specificity in diagnosing primary polydipsia and ≤ 3.0 pmol/L for high specificity in diagnosing AVP deficiency. These thresholds might offer a practical initial alternative to hypertonic saline testing.Registration:Clinicaltrials.gov (NCT00757276).

AB - Background:Distinguishing arginine vasopressin (AVP) deficiency (central diabetes insipidus) from primary polydipsia is challenging. While hypertonic saline-stimulated copeptin testing provides the highest diagnostic accuracy, it is often restricted to specialised centres, requiring close monitoring and potentially causing patient discomfort. Initially, arginine-stimulated copeptin was proposed as a simpler alternative, but a head-to-head comparison study found it less precise than hypertonic saline stimulation. However, the same study identified two new high sensitivity and specificity cut-offs for arginine-stimulated copeptin, though these cut-offs have yet to be validated.Methods:This is a secondary post-hoc analysis of the initial prospective multicentre study, including adult patients with confirmed AVP deficiency or primary polydipsia. Participants underwent the arginine stimulation test, with plasma copeptin measured at baseline and 60- and 90min after arginine infusion. The primary objective was to revisit the original study to internally validate the proposed arginine-stimulated copeptin cut-offs of > 5.2pmol/L (high specificity cut-off with > 90% specificity for primary polydipsia) and ≤ 3.0 pmol/L (high specificity cut-off with > 90% specificity for AVP deficiency).Findings:In total, 96 patients were included between May 2013 and June 2018: n = 38 [40%] with AVP deficiency and n = 58 [60%] with primary polydipsia. At 60min after arginine infusion, a copeptin level ≤ 3.0 pmol/L showed a specificity of 95% (95% CI: 0.88-1.00) for AVP deficiency, while a copeptin level > 5.2 pmol/L demonstrated a specificity of 97% (95% CI: 0.92-1.00) for primary polydipsia. The ≤ 3.0 pmol/L cut-off accurately identified 71% (n = 27/38) of patients with AVP deficiency, and the > 5.2 pmol/L cut-off correctly identified 69% (n = 40/58) of patients with primary polydipsia.Interpretation:This analysis validates two new copeptin cut-offs of the arginine stimulation test to distinguish AVP deficiency from primary polydipsia: >5.2 pmol/L for high specificity in diagnosing primary polydipsia and ≤ 3.0 pmol/L for high specificity in diagnosing AVP deficiency. These thresholds might offer a practical initial alternative to hypertonic saline testing.Registration:Clinicaltrials.gov (NCT00757276).

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U2 - 10.1007/s11102-025-01523-2

DO - 10.1007/s11102-025-01523-2

M3 - Article

C2 - 40281371

AN - SCOPUS:105003777043

SN - 1386-341X

VL - 28

JO - Pituitary

JF - Pituitary

IS - 3

M1 - 53

ER -

Atila C, Winzeler B, Chifu I, Fassnacht M, Refardt J, Christ-Crain M. A post-hoc internal validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus). Pituitary. 2025 Apr 26;28(3):53. doi: 10.1007/s11102-025-01523-2