Nikaj Andi, Atila Cihan, Chifu Irina, Ferrante Emanuele, Erlic Zoran, Drummond Juliana B, Indirli Rita, Drexhage Roosmarijn, Powlson Andrew S, Gurnell Mark, Soares Beatriz S, Hofland Johannes, Beuschlein Felix, Fassnacht Martin, Winzeler Bettina, Refardt Julie, Christ-Crain Mirjam
Departments of Endocrinology, Diabetology and Metabolism University Hospital Basel, 4031 Basel, Switzerland.
Department of Clinical Research, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
Eur J Endocrinol. 2025 Jun 30;193(1):1-9. doi: 10.1093/ejendo/lvaf119.
Arginine vasopressin (AVP), synthesized in the hypothalamus and stored in the posterior pituitary, regulates osmotic balance and stress responses. During stress, AVP enhances corticotropin-releasing hormone-stimulated adrenocorticotropic hormone (ACTH) secretion, with cortisol and AVP providing negative feedback regulation. Disruption in AVP production might impair this feedback, leading to sustained cortisol elevations. The current analysis aims to investigate the effect of hypertonic saline (osmotic stress) and arginine infusion (non-osmotic stress) on the hypothalamic-pituitary-adrenal (HPA) axis response between patients with AVP-Deficiency and primary polydipsia (PP).
Secondary sub-analysis of a prospective diagnostic study conducted at seven tertiary centers that utilized hypertonic saline and arginine infusion for diagnostic evaluation of patients with hypotonic polyuria-polydipsia syndrome.
ACTH and cortisol levels were measured at baseline and the expected peak for both stimulation tests and groups. A pooled linear mixed-effects model (without stimulation type as a variable) was used to compare hormone responses between groups, followed by stimulation test-specific linear regression models to assess differences between both tests.
Twenty patients with AVP-Deficiency and 10 patients with PP were included. In the pooled analysis, patients with AVP-Deficiency showed a significantly greater increase in plasma ACTH [7.0 ng/L (95% CI, 0.8-13.3), P = .04] and plasma cortisol [106 nmol/L (95% CI, 24-188), P = .02] compared to patients with PP. Upon hypertonic saline, the changes in plasma ACTH [0.3 ng/L (95% CI, -10.0 to 11.0)] and plasma cortisol [78 nmol/L (95% CI, -32 to 188)] were similar. However, upon arginine infusion, plasma ACTH [9.2 ng/L (95% CI, 1.8-17)] and plasma cortisol [141 nmol/L (95% CI, 40-242)] increases were significantly greater in patients with AVP-Deficiency.
An altered ACTH and cortisol response pattern to stress in patients with AVP-Deficiency was observed, indicating impaired regulation of the HPA axis. This alteration was primarily driven by differences observed for non-osmotic stress.
精氨酸加压素（AVP）在下丘脑合成并储存于垂体后叶，调节渗透压平衡和应激反应。在应激期间，AVP增强促肾上腺皮质激素释放激素刺激的促肾上腺皮质激素（ACTH）分泌，皮质醇和AVP提供负反馈调节。AVP产生的破坏可能会损害这种反馈，导致皮质醇持续升高。当前分析旨在研究高渗盐水（渗透压应激）和精氨酸输注（非渗透压应激）对AVP缺乏症患者和原发性烦渴（PP）患者下丘脑-垂体-肾上腺（HPA）轴反应的影响。
对在七个三级中心进行的一项前瞻性诊断研究的二次亚分析，该研究利用高渗盐水和精氨酸输注对低渗性多尿-烦渴综合征患者进行诊断评估。
在基线以及两种刺激试验和两组的预期峰值时测量ACTH和皮质醇水平。使用汇总线性混合效应模型（不将刺激类型作为变量）比较两组之间的激素反应，然后使用特定于刺激试验的线性回归模型评估两种试验之间的差异。
纳入20例AVP缺乏症患者和10例PP患者。在汇总分析中，与PP患者相比，AVP缺乏症患者的血浆ACTH[7.0 ng/L（95%CI，0.8 - 13.3），P = 0.04]和血浆皮质醇[106 nmol/L（95%CI，24 - 188），P = 0.02]显著升高。高渗盐水输注后，血浆ACTH[0.3 ng/L（95%CI，-10.0至11.0）]和血浆皮质醇[78 nmol/L（95%CI，-32至188）]的变化相似。然而，精氨酸输注后，AVP缺乏症患者的血浆ACTH[9.2 ng/L（95%CI，1.8 - 17）]和血浆皮质醇[141 nmol/L（95%CI，40 - 242）]升高显著更大。
观察到AVP缺乏症患者对压力的ACTH和皮质醇反应模式改变，表示HPA轴调节受损。这种改变主要由非渗透压应激观察到的差异驱动。
