Dataset Information

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 < .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.

SUBMITTER: Brown JM

PROVIDER: S-EPMC9032635 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Brown Jenifer M JM Auchus Richard J RJ Honzel Brooke B Luther James M JM Yozamp Nicholas N Vaidya Anand A

Journal of the Endocrine Society 20220323 6

<h4>Context</h4>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.<h4>Objective</h4>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 reg ...[more]

PMID: 35475027

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Project description:ObjectiveFor measuring serum 3,3',5'-triiodothyronine (rT3) levels, radioimmunoassay (RIA) has traditionally been used owing to the lack of other reliable methods; however, it has recently become difficult to perform. Meanwhile, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been attracting attention as a novel alternative method in clinical chemistry. To the best of our knowledge, there are no studies to date comparing results of the quantification of human serum rT3 between LC-MS/MS and RIA. We therefore examined the feasibility of LC-MS/MS as a novel alternative method for measuring serum rT3, thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels.MethodsAssay validation was performed by LC-MS/MS using quality control samples of rT3, T4, and T3 at 4 various concentrations which were prepared from reference compounds. Serum samples of 50 outpatients in our department were quantified both by LC-MS/MS and conventional immunoassay for rT3, T4, and T3. Correlation coefficients between the 2 measurement methods were statistically analyzed respectively.ResultsMatrix effects were not observed with our method. Intra-day and inter-day precisions were less than 10.8% and 9.6% for each analyte at each quality control level, respectively. Intra-day and inter-day accuracies were between 96.2% and 110%, and between 98.3% and 108.6%, respectively. The lower limit of quantification was 0.05 ng/mL. Strong correlations were observed between the 2 measurement methods (correlation coefficient, T4: 0.976, p < 0.001; T3: 0.912, p < 0.001; rT3: 0.928, p < 0.001).ConclusionsOur LC-MS/MS system requires no manual cleanup operation, and the process after application of a sample is fully automated; furthermore, it was found to be highly sensitive, and superior in both precision and accuracy. The correlation between the 2 methods over a wide range of concentrations was strong. LC-MS/MS is therefore expected to become a useful tool for clinical diagnosis and research.

Dataset Information

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

Context

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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