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

Figures

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  Figure 1.. Agreement between aldosterone concentration by assay type under conditions of oral sodium suppression (A), dietary sodium restriction (B), combined angiotensin II modulation (C), dexamethasone suppression (D), ACTH stimulation (E), and combined ACTH modulation (F). Samples assayed for serum aldosterone concentration by LC-MS/MS (liquid chromatography–tandem mass spectrometry) and immunoassay are shown from overweight normotensive volunteers after oral sodium suppression (red; A and C), sodium restriction (blue; B and C), dexamethasone suppression (green; D and F), and 250 µg ACTH stimulation (orange; E and F). The dashed line represents identity; ie, the same value of aldosterone returned by both assays.

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  Figure 2.. Absolute difference in aldosterone concentration by assay type under conditions of angiotensin II modulation (A) and ACTH modulation (B), ordered from lowest to highest aldosterone concentration. All samples obtained under conditions of oral sodium suppression and dietary sodium restriction to modulate angiotensin II were pooled (A: red, oral sodium suppression; blue; sodium restriction) and all samples obtained under ACTH modulation were pooled (B; green: dexamethasone suppression; orange, ACTH stimulation). Each participant sample is represented, ordered from the lowest to highest aldosterone concentration by immunoassay. The vertical bars represent the absolute difference between immunoassay and LC-MS/MS (liquid chromatography–tandem mass spectrometry), with positive values indicating a higher immunoassay and lower LC-MS/MS result.

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  Figure 3.. Bland–Altman plot demonstrating agreement between immunoassay and LC-MS/MS. The 2 assays yielded an average difference in aldosterone concentration of 7.3 ng/dL higher (solid line; SD 12.0 ng/dL) by immunoassay than using LC-MS/MS, with 95% limits of agreement from –16.2 to 30.8 ng/dL (dashed lines), comparing all 188 samples from n = 48 subjects across 4 experimental conditions.

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  Figure 4.. Percent difference in aldosterone concentration by assay type under conditions of angiotensin II modulation (A) and ACTH modulation (B), ordered from lowest to highest aldosterone concentration. All samples obtained under conditions of oral sodium suppression and dietary sodium restriction to modulate angiotensin II were pooled (A: red, oral sodium suppression; blue; sodium restriction) and all samples obtained under ACTH modulation were pooled (B; green: dexamethasone suppression; orange, ACTH stimulation). Each participant sample is represented, ordered from the lowest to highest aldosterone concentration by immunoassay. The vertical bars represent the percent difference between immunoassay and LC-MS/MS (liquid chromatography–tandem mass spectrometry) as a proportion of the immunoassay aldosterone concentration, with positive values indicating a higher immunoassay and lower LC-MS/MS result.