Validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus)

Michelle Muller; Cihan Atila; Bettina Winzeler; Irina Chifu; Martin Fassnacht; Julie Refardt; Mirjam Christ-Crain

doi:10.1530/endoabs.110.P901

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Endocrine Abstracts (2025) 110 P901 | DOI: 10.1530/endoabs.110.P901

ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)

Validation of arginine-stimulated copeptin cut-offs for diagnosing AVP deficiency (central diabetes insipidus)

Michelle Müller ^1,2 , Cihan Atila ^1,2 , Bettina Winzeler ^1,2 , Irina Chifu ³ , Martin Fassnacht ^3,4 , Julie Refardt ^1,2,5 & Mirjam Christ-Crain ^1,2

Author affiliations

¹University Hospital Basel, Department of Endocrinology, Diabetology and Metabolism, Basel, Switzerland; ²University Hospital Basel, Department of Clinical Research, Basel, Switzerland; ³University Hospital Wuerzburg, Division of Endocrinology and Diabetes, Department of Internal Medicine, Wuerzburg, Germany; ⁴University Hospital Wuerzburg, Central Laboratory, Wuerzburg, Germany; ⁵Erasmus Medical Centre, Rotterdam, Department of Internal Medicine, Section of Endocrinology, Rotterdam, Netherlands.

JOINT708

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 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 90 minutes after infusion. The primary objective was to revisit the original study to validate the proposed arginine-stimulated copeptin cut-offs of >5.2pmol/l (high sensitivity cutoff with >90% sensitivity) and ≤3pmol/l (high specificity cutoff with >90% specificity).

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 60 minutes 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 sensitivity 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 sensitivity 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.