Atila Cihan, Winzeler Bettina, Chifu Irina, Fassnacht Martin, Refardt Julie, Christ-Crain Mirjam
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Pituitary. 2025 Apr 26;28(3):53. doi: 10.1007/s11102-025-01523-2.
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.
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 90 min 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).
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 min 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.
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.
Clinicaltrials.gov (NCT00757276).
区分精氨酸加压素（AVP）缺乏（中枢性尿崩症）与原发性烦渴具有挑战性。虽然高渗盐水刺激的 copeptin 检测具有最高的诊断准确性，但它通常仅限于专业中心，需要密切监测且可能会给患者带来不适。最初，精氨酸刺激的 copeptin 被提议作为一种更简单的替代方法，但一项直接比较研究发现它不如高渗盐水刺激精确。然而，同一研究确定了精氨酸刺激的 copeptin 的两个新的高灵敏度和特异性临界值，不过这些临界值尚未得到验证。
这是对最初的前瞻性多中心研究的二次事后分析，纳入了确诊为 AVP 缺乏或原发性烦渴的成年患者。参与者接受精氨酸刺激试验，在基线以及精氨酸输注后 60 分钟和 90 分钟测量血浆 copeptin。主要目的是重新审视原始研究，以内部验证提议的精氨酸刺激的 copeptin 临界值：>5.2 pmol/L（原发性烦渴特异性>90%的高特异性临界值）和≤3.0 pmol/L（AVP 缺乏特异性>90%的高特异性临界值）。
2013 年 5 月至 2018 年 6 月期间共纳入 96 例患者：38 例[40%]为 AVP 缺乏，58 例[60%]为原发性烦渴。精氨酸输注后 60 分钟时，copeptin 水平≤3.0 pmol/L 对 AVP 缺乏的特异性为 95%（95%CI：0.88 - 1.00），而 copeptin 水平>5.2 pmol/L 对原发性烦渴的特异性为 97%（95%CI：0.92 - 1.00）。≤3.0 pmol/L 的临界值准确识别出 71%（n = 27/38）的 AVP 缺乏患者，>5.2 pmol/L 的临界值正确识别出 69%（n = 40/58）的原发性烦渴患者。
该分析验证了精氨酸刺激试验中两个新的 copeptin 临界值，以区分 AVP 缺乏与原发性烦渴：>5.2 pmol/L 用于诊断原发性烦渴的高特异性，≤3.0 pmol/L 用于诊断 AVP 缺乏的高特异性。这些阈值可能为高渗盐水检测提供一种实用的初始替代方法。
Clinicaltrials.gov（NCT00757276）
