瑞士巴塞尔大学医院Cornelia Imber团队的一项最新的前瞻性诊断研究，探讨了精氨酸刺激和肽素在尿崩症鉴别诊断中的应用。 2019年8月17日，国际知名学术期刊《柳叶刀》发表了这一成果。

在这项前瞻性诊断研究中，该课题组招募了一个发展队列，52例成人患者中有12例完全性尿崩症，9例不完全性尿崩症，和31例原发性烦渴。20例健康成人和42例儿童为对照组。之后又招募了一个验证队列，46例成人患者中有12例完全性尿崩症，7例不完全性尿崩症，27例原发性烦渴。30例健康成人作为对照组。

所有参与者均接受精氨酸刺激，分别在基线、30、45、60、90和120分钟测量血浆中和肽素浓度。对数据进行综合统计，健康成人对照组精氨酸刺激后和肽素中位浓度从5.2pm增至9.8pm，原发性烦渴患者从3.6pm增至7.9pm，但尿崩症患者增幅很小，仅从2.1pm增至2.5pm。在发展队列中，60分钟和肽素浓度低于3.5pm即可诊断为尿崩症，准确率为94%；而在验证队列中，该准确率降至86%。通过收集两个队列的数据，研究组发现60分钟和肽素浓度低于3.8pm的准确率最佳，可达93%。所有患者均未发生严重不良反应，且耐受良好，尿崩症患者的平均视觉模拟评分（VAS）为3.5分，原发性烦渴患者为3分，健康成人为1分，健康儿童为1分。

精氨酸刺激后测量和肽素是一种诊断尿崩症的新方法，具有准确、简便、新颖、安全等优点，值得临床推广。

据介绍，尿崩症较难鉴别诊断。最可靠的方法是高渗盐水刺激后测量和肽素。然而，该试验基于高钠血症诱导，需要密切监测血浆钠浓度。精氨酸刺激后测量和肽素可提供一种替代性、简单和安全的检测方法。

附：英文原文

Title: Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study

Author: Bettina Winzeler, MD, Nicole Cesana-Nigro, MD, Julie Refardt, MD, Deborah R Vogt, PhD, Cornelia Imber, MD, Benedict Morin, Milica Popovic, MD, Michelle Steinmetz, Clara O Sailer, MD, Gabor Szinnai, MD, Irina Chifu, MD, Prof Martin Fassnacht, MD, Prof Mirjam Christ-Crain, MD

Issue&Volume: Volume 394 Number 10198, 17 August 2019

Summary: 

Background

Differential diagnosis of diabetes insipidus is challenging. The most reliable approach is hypertonic saline-stimulated copeptin measurements. However, this test is based on the induction of hypernatraemia and requires close monitoring of plasma sodium concentrations. Arginine-stimulated copeptin measurements might provide an alternative, simple, and safe test.

Methods

In this prospective diagnostic study, we recruited a development cohort from University Hospital Basel, Basel, Switzerland, and a validation cohort from five centres in Basel, Aarau, Luzern, Bern, and St Gallen, Switzerland, and the University Hospital Würzburg, Würzburg, Germany. For both cohorts, patients were eligible for inclusion if they were aged 18 years or older, were newly referred with polyuria (>50 mL/kg bodyweight per day) or had a known diagnosis of central diabetes insipidus or primary polydipsia. We also recruited a comparator cohort of healthy controls in parallel to each cohort, comprising adults (aged 18 years and older, with normal drinking habits, and no history of polyuria) and children who underwent arginine stimulation to diagnose growth hormone deficiency (children were only included in the comparator cohort to the development cohort as proof of concept). Patients and healthy controls underwent arginine stimulation with measurement of plasma copeptin at baseline and 30, 45, 60, 90, and 120 min. The primary objective in the development cohort was to determine the diagnostic accuracy of plasma copeptin concentrations to discriminate between diabetes insipidus and primary polydipsia, and in the validation cohort was to confirm those results. Adverse effects of the test were monitored in all participants, with tolerability of the test rated using a visual analogue scale (VAS) that ranged from no (0) to maximum (10) discomfort. This trial is registered with ClinicalTrials.gov, number NCT00757276.

Findings

Between May 24, 2013, and Jan 11, 2017, 52 patients were enrolled in the development cohort (12 [23%] with complete diabetes insipidus, nine [17%] with partial diabetes insipidus, and 31 [60%] with primary polydipsia) alongside 20 healthy adults and 42 child controls. Between Oct 24, 2017, and June 27, 2018, 46 patients were enrolled in the validation cohort (12 [26%] with complete diabetes insipidus, seven [15%] with partial diabetes insipidus, and 27 [59%] with primary polydipsia) alongside 30 healthy adult controls (two patients in this cohort were excluded from the main analysis because of early vomiting during the test). In the pooled patient and control datasets, median arginine-stimulated copeptin concentrations increased in healthy adult controls (from 5·2 pM [IQR 3·3–10·9] to a maximum of 9·8 pM [6·4–19·6]) and in participants with primary polydipsia (from 3·6 pM [IQR 2·4–5·7] to a maximum of 7·9 pM [5·1–11·8]), but only minimally in those with diabetes insipidus (2·1 pM [IQR 1·9–2·7] to a maximum of 2·5 pM [1·9–3·1]). In the development cohort, a cutoff of 3·5 pM at 60 min provided the highest diagnostic accuracy of 94% (95% CI 84–98). The accuracy of this cutoff in the validation cohort was 86% (95% CI 73–94). By pooling the data from both cohorts, an optimal accuracy of 93% (95% CI 86–97) was reached at a cutoff of 3·8 pM copeptin at 60 min (sensitivity 93%, 95% CI 86–98; specificity 92%, 95% CI 84–100). The test was safe and well tolerated, with median VAS scores of 3·5 (IQR 2–4) in patients with diabetes insipidus, 3 (2–4) in those with primary polydipsia, 1 (1–3) in healthy adults, and 1 (0–5) in healthy children in the pooled participant dataset.

Interpretation

Arginine-stimulated copeptin measurements are an innovative test for diabetes insipidus with high diagnostic accuracy, and could be a simplified, novel, and safe diagnostic approach to diabetes insipidus in clinical practice.

DOI: https://doi.org/10.1016/S0140-6736(19)31255-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31255-3/fulltext#