Recalibrating Interpretations of Aldosterone Assays Across the Physiologic Range: Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry Measurements Under Multiple Controlled Conditions.
Recalibrating Interpretations of Aldosterone Assays Across the Physiologic Range: Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry Measurements Under Multiple Controlled Conditions.
复制标题
DOI：
10.1210/jendso/bvac049
复制
发表时间：
2022-06-01
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
--
作者：
临床医生诊断原发性醛固酮增多症时，往往依赖于较老的免疫测定法得出的醛固酮阈值。液相色谱-串联质谱仪(LC-MS/MS)越来越广泛，据报道可以得到较低浓度的醛固酮。考虑到对醛固酮水平的错误解释对健康的影响，我们通过评估血管紧张素II和促肾上腺皮质激素(ACTH)的不同调节，比较了使用LC-MS/MS和免疫分析在整个醛固酮生理学范围内的测量结果。通过免疫分析和LC-MS/MS对血压正常的受试者在4种情况下(n = 188)的醛固酮产生进行前瞻性表征：口服钠抑制和限制(评估血管紧张素II介导的醛固酮产生)和地塞米松抑制和促肾上腺皮质激素刺激(评估促肾上腺皮质激素介导的醛固酮产生)。LC-MS/MS法与免疫法测定血清醛固酮浓度的相关性为0.69(P <； .001)，组内相关系数为0.76；95%可信区间为0.52-0.87。LC-MS/MS法测定的醛固酮低于免疫法(中位数10.5[3.8，21.9]vs19.6[9.5，28.0]ng/dL；P <； .001)，平均相差37.2%。最显著的差异是在临床鉴别范围内，免疫测定法为9.9(7.1，13.8)ng/dL，LC-MS/MS为5.5(1.4，8.9)ng/dL(P <； .001)。在口服钠抑制后，免疫测定法的醛固酮/肾素比率增加了4倍(27.2vs6.4[3.519.1]ng/dL每ng/mL/小时；P <； .001)。在整个生理范围内，LC-MS/MS测定的醛固酮显著低于免疫测定法，特别是当醛固酮水平低于20 ng/dL时。这些发现强调了通过LC-MS/MS测量醛固酮时重新校准诊断解释的必要性，并为分析不同的潜在生物原因提供了洞察力。
Clinicians frequently rely on aldosterone thresholds derived from older immunoassays to diagnose primary aldosteronism. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is increasingly widespread and reported to yield lower aldosterone concentrations. Given the health impact of incorrect interpretations of aldosterone levels, we compared measurements using LC-MS/MS and immunoassay across the full range of aldosterone physiology by evaluating distinct regulation by angiotensin II and adrenocorticotropin (ACTH). Normotensive volunteers underwent prospective characterization of aldosterone production by immunoassay and LC-MS/MS during 4 conditions (n = 188): oral sodium suppression and restriction (to assess angiotensin II–mediated aldosterone production) and dexamethasone suppression and cosyntropin stimulation (to assess ACTH-mediated aldosterone production). Serum aldosterone concentrations by LC-MS/MS and immunoassay had a correlation of 0.69 (P < .001), with good agreement (intraclass correlation 0.76; 95% CI 0.52-0.87). Aldosterone was lower by LC-MS/MS than immunoassay (median 10.5 [3.8, 21.9] vs 19.6 [9.5, 28.0] ng/dL; P < .001), with an average difference of 37.2%. The most notable discrepancy was in the clinically discriminatory range <20 ng/dL: 9.9 (7.1, 13.8) ng/dL using immunoassay corresponded to 5.5 (1.4, 8.9) ng/dL by LC-MS/MS (P < .001). Following oral sodium suppression, the aldosterone-to-renin ratio was 4-fold higher using immunoassay (27.2 [19.7, 62.4] vs 6.4 [3.5, 19.1] ng/dL per ng/mL/hour; P < .001). Aldosterone measurements are substantially lower by LC-MS/MS than immunoassay across the full physiologic range, especially when aldosterone levels were less than 20 ng/dL. These findings highlight the need to recalibrate diagnostic interpretations when measuring aldosterone via LC-MS/MS and provide insights into potential biologic causes of assay differences.