Disrupted ACTH and Cortisol Response to Osmotic and Non-Osmotic Stress in Patients with AVP-Deficiency.

IF 5.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

European Journal of Endocrinology Pub Date : 2025-06-11 DOI:10.1093/ejendo/lvaf119

Andi Nikaj, Cihan Atila, Irina Chifu, Emanuele Ferrante, Zoran Erlic, Juliana B Drummond, Rita Indirli, Roosmarijn Drexhage, Andrew S Powlson, Mark Gurnell, Beatriz Santana Soares Rocha, Johannes Hofland, Felix Beuschlein, Martin Fassnacht, Bettina Winzeler, Julie Refardt, Mirjam Christ-Crain

{"title":"Disrupted ACTH and Cortisol Response to Osmotic and Non-Osmotic Stress in Patients with AVP-Deficiency.","authors":"Andi Nikaj, Cihan Atila, Irina Chifu, Emanuele Ferrante, Zoran Erlic, Juliana B Drummond, Rita Indirli, Roosmarijn Drexhage, Andrew S Powlson, Mark Gurnell, Beatriz Santana Soares Rocha, Johannes Hofland, Felix Beuschlein, Martin Fassnacht, Bettina Winzeler, Julie Refardt, Mirjam Christ-Crain","doi":"10.1093/ejendo/lvaf119","DOIUrl":null,"url":null,"abstract":"Objective: 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 (CRH)-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 HPA axis response between patients with AVP-Deficiency and primary polydipsia (PP).Design: Secondary sub-analysis of a prospective diagnostic study conducted at seven tertiary centers that utilised hypertonic saline and arginine infusion for diagnostic evaluation of patients with hypotonic polyuria-polydipsia syndrome.Methods: ACTH and cortisol levels were measured at baseline and 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.Results: 20 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 ACTH (7.0 ng/L [95% CI 0.8-13.3], P=0.04) and cortisol (106 nmol/L [95% CI 24-188], P=0.02). Upon hypertonic saline, the changes in plasma ACTH (0.3 ng/l [95% CI -10.0 to 11.0]) and cortisol (78 nmol/l [95% CI -32 to 188]) were similar. However, upon arginine infusion, ACTH (9.2 ng/L [95% CI 1.8-17]) and cortisol (141 nmol/L [95% CI 40-242]) increases were significantly greater in patients with AVP-Deficiency.Conclusion: 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.","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ejendo/lvaf119","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: 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 (CRH)-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 HPA axis response between patients with AVP-Deficiency and primary polydipsia (PP).

Design: Secondary sub-analysis of a prospective diagnostic study conducted at seven tertiary centers that utilised hypertonic saline and arginine infusion for diagnostic evaluation of patients with hypotonic polyuria-polydipsia syndrome.

Methods: ACTH and cortisol levels were measured at baseline and 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.

Results: 20 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 ACTH (7.0 ng/L [95% CI 0.8-13.3], P=0.04) and cortisol (106 nmol/L [95% CI 24-188], P=0.02). Upon hypertonic saline, the changes in plasma ACTH (0.3 ng/l [95% CI -10.0 to 11.0]) and cortisol (78 nmol/l [95% CI -32 to 188]) were similar. However, upon arginine infusion, ACTH (9.2 ng/L [95% CI 1.8-17]) and cortisol (141 nmol/L [95% CI 40-242]) increases were significantly greater in patients with AVP-Deficiency.

Conclusion: 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.

查看原文本刊更多论文

avp缺乏症患者对渗透和非渗透应激的ACTH和皮质醇反应中断。

目的：精氨酸加压素（AVP）由下丘脑合成，储存于垂体后叶，调节渗透平衡和应激反应。应激时，AVP促进促肾上腺皮质激素释放激素（CRH）刺激促肾上腺皮质激素（ACTH）的分泌，皮质醇和AVP提供负反馈调节。AVP产生的中断可能会损害这种反馈，导致持续的皮质醇升高。本研究旨在探讨高渗盐水（渗透应激）和精氨酸输注（非渗透应激）对avp缺乏症和原发性渴饮（PP）患者HPA轴反应的影响。设计：对在7个三级中心进行的前瞻性诊断研究进行二级亚分析，该研究使用高渗生理盐水和精氨酸输注对低渗多尿-烦渴综合征患者进行诊断评估。方法：在刺激试验和各组的基线和预期峰值时测量ACTH和皮质醇水平。采用混合线性效应模型（不以刺激类型为变量）比较各组之间的激素反应，然后采用特定刺激测试的线性回归模型来评估两种测试之间的差异。结果：avp缺乏症患者20例，PP患者10例。在合并分析中，avp缺乏症患者ACTH （7.0 ng/L [95% CI 0.8 ~ 13.3]， P=0.04）和皮质醇（106 nmol/L [95% CI 24 ~ 188]， P=0.02）显著升高。高渗生理盐水治疗后，血浆ACTH （0.3 ng/l [95% CI -10.0 ~ 11.0]）和皮质醇（78 nmol/l [95% CI -32 ~ 188]）的变化相似。然而，在精氨酸输注后，avp缺乏症患者ACTH （9.2 ng/L [95% CI 1.8-17]）和皮质醇（141 nmol/L [95% CI 40-242]）升高明显更大。结论：avp缺乏患者ACTH和皮质醇对应激的反应模式发生改变，表明HPA轴调节受损。这种变化主要是由非渗透胁迫引起的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Endocrinology 医学-内分泌学与代谢

CiteScore

9.80

自引率

3.40%

发文量

354

审稿时长

1 months

期刊介绍： European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.