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采用质谱法解决矛盾性双侧醛固酮抑制问题。

Resolution of paradoxical bilateral aldosterone suppression with mass spectrometry.

作者信息

Wannachalee Taweesak, Vibhatavata Peeradon, Konzen Sonja, Lee Chaelin, Gherasim Carmen, Shields James J, Turcu Adina F

机构信息

Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, United States.

Division of Endocrinology and Metabolism, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

出版信息

Eur J Endocrinol. 2025 Mar 27;192(4):511-518. doi: 10.1093/ejendo/lvaf079.

DOI:10.1093/ejendo/lvaf079
PMID:40233185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12037276/
Abstract

OBJECTIVE

Adrenal vein sampling (AVS) is the standard-of-care for primary aldosteronism (PA) subtyping. Paradoxical bilateral aldosterone suppression (BAS), defined by lower aldosterone/cortisol ratio in both adrenal veins compared to peripheral circulation, has been reported in AVS studies, but the underlying causes remain poorly understood. We aimed to assess the prevalence of BAS in AVS without and with cosyntropin stimulation based on clinical immunoassays, and to probe the BAS results using liquid chromatography mass spectrometry (LC-MS/MS).

METHODS

We retrospectively assessed the BAS prevalence among patients with confirmed PA who underwent AVS in a referral center between 2015 and 2023. Simultaneous AVS was performed both before and after cosyntropin stimulation. LC-MS/MS quantitation of cortisol and aldosterone was performed in patients with serum available.

RESULTS

Of 402 patients, BAS was observed in 102 (25%): Pre-cosyntropin in 31, post-cosyntropin in 48 (including 10 who did not meet successful catheterization criteria in baseline samples), and both pre- and post- cosyntropin in 23. Paradoxically, AVS indicated lateralized PA in 36% and 43% of patients with BAS based on pre- and post-cosyntropin data, respectively. Using LC-MS/MS, BAS was not present in 42/53 (79%) patients with serum available. Compared to LC-MS/MS, immunoassays overestimated cortisol across the analytical range. In contrast, for aldosterone, immunoassays overestimated low concentrations, but underestimated high concentrations, such as those measured in adrenal veins.

CONCLUSIONS

Apparent BAS derives primarily from artifacts in clinical immunoassays. These data caution against assuming that aldosterone suppression indicates contralateral aldosterone lateralization in cases with partial adrenal vein catheterization failure.

摘要

目的

肾上腺静脉采血(AVS)是原发性醛固酮增多症(PA)亚型分型的标准治疗方法。在AVS研究中,已报道了矛盾性双侧醛固酮抑制(BAS),即与外周循环相比,双侧肾上腺静脉中的醛固酮/皮质醇比值降低,但其潜在原因仍知之甚少。我们旨在基于临床免疫测定评估有无促肾上腺皮质激素刺激时AVS中BAS的患病率,并使用液相色谱质谱联用(LC-MS/MS)对BAS结果进行探究。

方法

我们回顾性评估了2015年至2023年在一家转诊中心接受AVS的确诊PA患者中BAS的患病率。在促肾上腺皮质激素刺激前后均进行同步AVS。对有血清样本的患者进行皮质醇和醛固酮的LC-MS/MS定量分析。

结果

在402例患者中,102例(25%)观察到BAS:促肾上腺皮质激素刺激前31例,刺激后48例(包括10例基线样本未达到成功插管标准的患者),刺激前后均为23例。矛盾的是,根据促肾上腺皮质激素刺激前和刺激后的数据分析,分别有36%和43%的BAS患者AVS显示为单侧PA。使用LC-MS/MS,53例有血清样本的患者中有42例(79%)不存在BAS。与LC-MS/MS相比,免疫测定在整个分析范围内高估了皮质醇。相比之下,对于醛固酮,免疫测定高估了低浓度,但低估了高浓度,如肾上腺静脉中测得的浓度。

结论

明显的BAS主要源于临床免疫测定中的假象。这些数据提醒我们,在部分肾上腺静脉插管失败的病例中,不要假定醛固酮抑制表明对侧醛固酮侧化。

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本文引用的文献

1
Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.单侧选择性肾上腺静脉采血用于识别可手术治愈的原发性醛固酮增多症。
Hypertension. 2023 Oct;80(10):2003-2013. doi: 10.1161/HYPERTENSIONAHA.123.21247. Epub 2023 Jun 15.
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Recalibrating Interpretations of Aldosterone Assays Across the Physiologic Range: Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry Measurements Under Multiple Controlled Conditions.重新校准醛固酮检测在生理范围内的解读:多种控制条件下的免疫分析和液相色谱-串联质谱测量
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High Prevalence of Autonomous Aldosterone Production in Hypertension: How to Identify and Treat It.高血压中自主醛固酮分泌的高发生率:如何识别和治疗。
Curr Hypertens Rep. 2022 May;24(5):123-132. doi: 10.1007/s11906-022-01176-7. Epub 2022 Feb 14.
4
ACTH Stimulation Maximizes the Accuracy of Peripheral Steroid Profiling in Primary Aldosteronism Subtyping.ACTH 刺激可最大程度提高原发性醛固酮增多症亚型分型中外周类固醇谱分析的准确性。
J Clin Endocrinol Metab. 2021 Sep 27;106(10):e3969-e3978. doi: 10.1210/clinem/dgab420.
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"Double-Down" Adrenal Vein Sampling Results in Patients with Apparent Bilateral Aldosterone Suppression: Utility of Repeat Sampling including Super-Selective Sampling.在双侧醛固酮抑制表现明显的患者中,“加倍”肾上腺静脉采样结果:包括超选择性采样在内的重复采样的效用。
J Vasc Interv Radiol. 2021 May;32(5):656-665. doi: 10.1016/j.jvir.2020.12.029. Epub 2021 Mar 27.
6
The 2020 Italian Society of Arterial Hypertension (SIIA) practical guidelines for the management of primary aldosteronism.2020年意大利动脉高血压学会(SIIA)原发性醛固酮增多症管理实用指南。
Int J Cardiol Hypertens. 2020 Apr 15;5:100029. doi: 10.1016/j.ijchy.2020.100029. eCollection 2020 Jun.
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Approach to the Patient with Primary Aldosteronism: Utility and Limitations of Adrenal Vein Sampling.原发性醛固酮增多症患者的处理方法:肾上腺静脉采样的效用和局限性。
J Clin Endocrinol Metab. 2021 Mar 25;106(4):1195-1208. doi: 10.1210/clinem/dgaa952.
8
Confirmatory testing of primary aldosteronism with saline infusion test and LC-MS/MS.用盐水输注试验和 LC-MS/MS 对原发性醛固酮增多症进行确证性检测。
Eur J Endocrinol. 2021 Jan;184(1):167-178. doi: 10.1530/EJE-20-0073.
9
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