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

Jenifer M Brown; Richard J Auchus; Brooke Honzel; James M Luther; Nicholas Yozamp; Anand Vaidya

doi:10.1210/jendso/bvac049

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

J Endocr Soc. 2022 Mar 23;6(6):bvac049. doi: 10.1210/jendso/bvac049. eCollection 2022 Jun 1.

Authors

Jenifer M Brown¹, Richard J Auchus^{2

3}, Brooke Honzel⁴, James M Luther⁵, Nicholas Yozamp⁶, Anand Vaidya⁴

Affiliations

¹ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
² Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MA 48105, USA.
³ Endocrinology and Metabolism Section, LTC Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, MA 48105, USA.
⁴ Center for Adrenal Disorders, Division of Diabetes, Endocrinology, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁵ Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁶ Washington University School of Medicine, St. Louis, MO 63110, USA.

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 < .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).

Conclusion: 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.

Keywords: aldosterone; hypertension; primary aldosteronism.

Abstract

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