Endocrinol Metab.  2022 Dec;37(6):938-942. 10.3803/EnM.2022.1535.

Aldosterone Immunoassay-Specific Cutoff Value for Seated Saline Suppression Test for Diagnosing Primary Aldosteronism

• Kwon SY
• Park J
• Park SH
• Cho SH
• Lee YB
• Lee SY
• Kim JH

• KMID: 2537294
• DOI: http://doi.org/10.3803/EnM.2022.1535

Abstract

A seated saline loading test (SLT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is one of the most accepted confirmatory tests of primary aldosteronism. However, LC-MS/MS is time-consuming and is not widely available in diagnostic laboratories compared to immunoassay. With immunoassay, it is unknown whether SLT in the seated position is more accurate than that of the supine position, and a cutoff value of post-seated SLT plasma aldosterone concentration (PAC) must be established in the Korean population. Ninety-eight patients underwent SLT in both positions, and post-SLT PAC was measured by LC-MS/MS and radioimmunoassay. We confirmed primary aldosteronism if post-seated SLT PAC by LC-MS/MS exceeded 5.8 ng/dL. The area under the receiver operating characteristic curve was greater for seated than supine SLT (0.928 vs. 0.834, P=0.003). The optimal cutoff value of post-seated SLT by radioimmunoassay was 6.6 ng/dL (sensitivity 83.3%, specificity 92.2%).

Keyword

Hyperaldosteronism; Aldosterone; Diagnosis; Sitting position; Chromatography, liquid; Tandem mass spectrometry; Radioimmunoassay

Figure

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  Fig. 1. Comparison of receiver operating characteristics curve for the post-seated saline loading test (SLT) plasma aldosterone concentration (PAC; solid line) and the post-supine SLT PAC (dotted line) measured by immunoassay for the diagnosis of primary aldosteronism.

Reference

1. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016; 101:1889–916.

2. Kayser SC, Dekkers T, Groenewoud HJ, van der Wilt GJ, Carel Bakx J, van der Wel MC, et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis. J Clin Endocrinol Metab. 2016; 101:2826–35.

3. Monticone S, Sconfienza E, D’Ascenzo F, Buffolo F, Satoh F, Sechi LA, et al. Renal damage in primary aldosteronism: a systematic review and meta-analysis. J Hypertens. 2020; 38:3–12.

4. Wu X, Yu J, Tian H. Cardiovascular risk in primary aldosteronism: a systematic review and meta-analysis. Medicine (Baltimore). 2019; 98:e15985.

5. Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension. 2007; 50:911–8.

6. Hartmann I, Hruska F, Vaclavik J, Kocianova E, Frysak Z, Nesvadbova M, et al. Hypertension outcomes of adrenalectomy for unilateral primary aldosteronism. Endocrine. 2022; 76:142–50.

7. Stowasser M, Ahmed AH, Cowley D, Wolley M, Guo Z, McWhinney BC, et al. Comparison of seated with recumbent saline suppression testing for the diagnosis of primary aldosteronism. J Clin Endocrinol Metab. 2018; 103:4113–24.

8. Thuzar M, Young K, Ahmed AH, Ward G, Wolley M, Guo Z, et al. Diagnosis of primary aldosteronism by seated saline suppression test-variability between immunoassay and HPLC-MS/MS. J Clin Endocrinol Metab. 2020; 105:dgz150.

9. Burrello J, Monticone S, Buffolo F, Lucchiari M, Tetti M, Rabbia F, et al. Diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in primary aldosteronism. J Hypertens. 2016; 34:920–7.

10. Keevil BG. Novel liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for measuring steroids. Best Pract Res Clin Endocrinol Metab. 2013; 27:663–74.

11. Taylor PJ, Cooper DP, Gordon RD, Stowasser M. Measurement of aldosterone in human plasma by semiautomated HPLC-tandem mass spectrometry. Clin Chem. 2009; 55:1155–62.

12. Guo Z, Poglitsch M, McWhinney BC, Ungerer JP, Ahmed AH, Gordon RD, et al. Aldosterone LC-MS/MS assay-specific threshold values in screening and confirmatory testing for primary aldosteronism. J Clin Endocrinol Metab. 2018; 103:3965–73.

13. Ray JA, Kushnir MM, Palmer J, Sadjadi S, Rockwood AL, Meikle AW. Enhancement of specificity of aldosterone measurement in human serum and plasma using 2D-LC-MS/MS and comparison with commercial immunoassays. J Chromatogr B Analyt Technol Biomed Life Sci. 2014; 970:102–7.

14. Eisenhofer G, Kurlbaum M, Peitzsch M, Constantinescu G, Remde H, Schulze M, et al. The saline infusion test for primary aldosteronism: implications of immunoassay inaccuracy. J Clin Endocrinol Metab. 2022; 107:e2027–36.

15. Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R, et al. Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. J Hypertens. 2015; 33:2500–11.