Recalibrating Interpretations of Aldosterone Assays Across the Physiologic Range: Immunoassay and Liquid Chromatography–Tandem Mass Spectrometry Measurements Under Multiple Controlled Conditions

Abstract Context 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. Objective 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). Methods 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). Results Serum aldosterone concentrations by LC-MS/MS and immunoassay had a correlation of 0.69 (P