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Multicenter Study
. 2025 Oct 1;43(10):1666-1674.
doi: 10.1097/HJH.0000000000004098. Epub 2025 Jul 15.

The saline infusion test with mass spectrometric measurements of aldosterone to confirm primary aldosteronism

Christina Pamporaki  1 , Hanna Remde  2 , Georgiana Constantinescu  1 , Lydia Kürzinger  2 , Carmina Fuss  2 , Sybille Fuld  1 , Mirko Peitzsch  3 , Manuel Schulze  4 , Francesco Alessi  1 , Myron Lee  5 , Jun Yang  6 , Tracy Ann Williams  7 , Denise Brüdgam  7 , Martin Reincke  7 , Sven Gruber  8 , Felix Beuschlein  7   8 , Jacques W M Lenders  9 , Graeme Eisenhofer  1
Affiliations
Multicenter Study

The saline infusion test with mass spectrometric measurements of aldosterone to confirm primary aldosteronism

Christina Pamporaki et al. J Hypertens. .

Abstract

Objective: Confirmation of primary aldosteronism with the saline infusion test requires accurate measurements of plasma aldosterone, which is best achieved by mass spectrometry. Diagnostic performance, appropriate cut-offs and intra-patient variability of the test remain inadequately defined. The objective of this prospective multicenter cohort study was to address these limitations.

Methods: Primary aldosteronism was confirmed and excluded using alternative criteria to confirmatory tests in 138 and 282 respective patients with suspected disease. Those criteria were not satisfied in 89 patients. Diagnostic performance of the saline infusion test and optimal cut-offs were determined from receiver operating characteristic curves. Intra-patient variability was determined in 57 patients.

Results: Analysis of receiver operating characteristic curves indicated an area under the curve of 0.964 and a cut-off of 169 pmol/l for posttest aldosterone concentrations that provided 97% sensitivity and 89% specificity. A cut-off of 255 pmol/l enabled improved specificity of 95% at a sensitivity of 75%. Among the 57 patients in whom the saline infusion test was repeated, 15 (26%) had posttest aldosterone concentrations that were discordant using the 169 pmol/l cut-off. Eighty percent of the discordant results were from a single center. With exclusion of that center, which did not minimize ambulation during saline infusion, the area under the curve increased to 0.985 and an optimal cut-off of 169 pmol/l provided 96% specificity and sensitivity.

Conclusion: The seated saline infusion test with mass spectrometric measurements of aldosterone and the cut-offs documented here provides a useful confirmatory test, although this requires adherence to standard-operating procedures.

Keywords: LC-MS/MS; aldosterone; confirmatory test; diagnosis; diagnostic sensitivity; diagnostic specificity; mass spectrometry; primary aldosteronism; receiver operating characteristic curve; saline suppression test.

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Conflict of interest statement

Scientific support not directly related to this study was provided by DiaSorin Pty Ltd and Australian Medical Research Future Fund (MRFAR000172) to J.Y., the Kurt and Senta Hermann Foundation to S.G., Habilitationsförderung für Frauen der TU Dresden (12/2021–11/2022) to C.P., travel support from the Endocrine Society of Australia to G.E. J. Y Leads the Consumer Engagement Committee of the Primary Aldosteronism Foundation. G.E. consults for Roche Diagnostics. G.E., M.R., F.B., M.S., and C.P. are co-holders of submitted patents (WO-2022171680-A1 and German no. 2383/ 21DE) relevant to this study.

Figures

None
Graphical abstract
FIGURE 1
FIGURE 1
Diagram to illustrate patient flow through the protocol depending on the confirmatory saline infusion tests (SIT) and thereafter according to subtype assessment to confirmation or exclusion of primary aldosteronism (PA) by outcome assessments or use of steroid probability scores (SPS). Flow of patients to the SIT required either or both positive results of the aldosterone:renin ratio or steroid profile-derived probability scores (SP). Other abbreviations: + positive; - negative; ADX, adrenalectomy; IHC, immunohistochemistry; PASO, primary aldosteronism surgical outcome.
FIGURE 2
FIGURE 2
Receiver-operating characteristic curves for use of the SIT vs. the aldosterone:renin ratio to distinguish patients with and without primary aldosteronism. The displayed cut-offs for post-SIT plasma concentrations are those derived from ROC tables to provide Youden-index optimal diagnostic performance (169 pmol/l) vs. optimal specificity and positive predictive value for disease confirmation (242 pmol/l).
FIGURE 3
FIGURE 3
Receiver-operating characteristic curves for the SIT at different participating centers. Displayed data include areas under curves (AUC) with confidence intervals as well as cut-offs indicated as optimal by the Youden index and that offered 95% or higher diagnostic specificity appropriate for a confirmatory test. (a) shows the results for the single center that was characterized by a high proportion of false-positive results, whereas (b) shows the ROC curve for all other centers combined. (c--e) display ROC curves for three of the European centers, whereas (f) includes the ROC curve for the three Australian centers combined and for which numbers of patients were insufficient to assess diagnostic performance for each of those three centers.
FIGURE 4
FIGURE 4
Scatter plots of relationships of plasma concentrations of aldosterone at baseline (a) and for post-SIT samples (b) from the first SIT (x-axes) and second SIT (y-axes) in 50 patients. The dotted vertical and horizontal lines in panel b designate the post-SIT aldosterone cuts-off of 169 pmol/l determined from ROC curve analysis to provide optimal diagnostic performance.
See this image and copyright information in PMC

References

    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; 101:1889–1916. - PubMed
    1. Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zennaro MC, et al. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J Hypertens 2020; 38:1919–1928. - PubMed
    1. Jansen PM, van den Born BJ, Frenkel WJ, de Bruijne EL, Deinum J, Kerstens MN, et al. Test characteristics of the aldosterone-to-renin ratio as a screening test for primary aldosteronism. J Hypertens 2014; 32:115–126. - PubMed
    1. 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; 33:2500–2511. - PubMed
    1. Morimoto R, Ono Y, Tezuka Y, Kudo M, Yamamoto S, Arai T, et al. Rapid screening of primary aldosteronism by a novel chemiluminescent immunoassay. Hypertension 2017; 70:334–341. - PMC - PubMed

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