Atila Cihan, Gaisl Odile, Vogt Deborah R, Werlen Laura, Szinnai Gabor, 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.
Eur J Endocrinol. 2022 May 12;187(1):65-74. doi: 10.1530/EJE-22-0033.
The differential diagnosis of diabetes insipidus is challenging. The most reliable approaches are copeptin measurements after hypertonic saline infusion or arginine, which is a known growth hormone secretagogue but has recently also been shown to stimulate the neurohypophysis. Similar to arginine, glucagon stimulates growth hormone release, but its effect on the neurohypophysis is poorly studied.
Double-blind, randomized, placebo-controlled trial including 22 healthy participants, 10 patients with central diabetes insipidus, and 10 patients with primary polydipsia at the University Hospital Basel, Switzerland.
Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test. The primary objective was to determine whether glucagon stimulates copeptin and to explore whether the copeptin response differentiates between diabetes insipidus and primary polydipsia. Copeptin levels were measured at baseline, 30, 60, 90, 120, 150, and 180 min after injection.
In healthy participants, glucagon stimulated copeptin with a median increase of 7.56 (2.38; 28.03) pmol/L, while placebo had no effect (0.10 pmol/L (-0.70; 0.68); P < 0.001). In patients with diabetes insipidus, copeptin showed no relevant increase upon glucagon, with an increase of 0.55 (0.21; 1.65) pmol/L, whereas copeptin was stimulated in patients with primary polydipsia with an increase of 15.70 (5.99; 24.39) pmol/L. Using a copeptin cut-off level of 4.6pmol/L had a sensitivity of 100% (95% CI: 100-100) and a specificity of 90% (95% CI: 70-100) to discriminate between diabetes insipidus and primary polydipsia.
Glucagon stimulates the neurohypophysis, and glucagon-stimulated copeptin has the potential for a safe, novel, and precise test in the differential diagnosis of diabetes insipidus.
尿崩症的鉴别诊断具有挑战性。最可靠的方法是高渗盐水输注或精氨酸后测定 copeptin，精氨酸是一种已知的生长激素促分泌素，但最近也被证明可刺激神经垂体。与精氨酸类似，胰高血糖素可刺激生长激素释放，但其对神经垂体的作用研究较少。
双盲、随机、安慰剂对照试验，纳入了瑞士巴塞尔大学医院的 22 名健康参与者、10 名中枢性尿崩症患者和 10 名原发性烦渴患者。
每位参与者均接受胰高血糖素试验（皮下注射 1 mg 胰高血糖素）和安慰剂试验。主要目的是确定胰高血糖素是否刺激 copeptin，并探讨 copeptin 反应能否区分尿崩症和原发性烦渴。在注射后基线、30、60、90、120、150 和 180 分钟测量 copeptin 水平。
在健康参与者中，胰高血糖素刺激 copeptin，中位数增加 7.56（2.38；28.03）pmol/L，而安慰剂无作用（0.10 pmol/L（-0.70；0.68）；P < 0.001）。在尿崩症患者中，胰高血糖素刺激后 copeptin 无相关增加，增加 0.55（0.21；1.65）pmol/L，而在原发性烦渴患者中 copeptin 受到刺激，增加 15.70（5.99；24.39）pmol/L。使用 4.6 pmol/L 的 copeptin 临界值区分尿崩症和原发性烦渴的敏感性为 100%（95%CI：100 - 100），特异性为 90%（95%CI：70 - 100）。
胰高血糖素刺激神经垂体，胰高血糖素刺激的 copeptin 在尿崩症的鉴别诊断中具有进行安全、新颖且精确检测的潜力。
