False-positive and false-negative results during screening, confirmatory testing and subtyping for suspected primary aldosteronism: lessons from Prosaldo

Andreea Georgiana Constantinescu; Christina Pamporaki; Francesco Alessi; Jens Passauer; Hanna Remde; Lydia Kuerzinger; CarminaTeresa Fuss; Manuel Schulze; Mirko Peitzsch; Andrea Horvath; Jun Yang; Denise Bruedgam; TracyAnn Williams; Martin Reincke; Sven Gruber; Felix Beuschlein; Jacques Lenders; Graeme Eisenhofer

doi:10.1530/endoabs.99.P16

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Endocrine Abstracts (2024) 99 P16 | DOI: 10.1530/endoabs.99.P16

ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)

False-positive and false-negative results during screening, confirmatory testing and subtyping for suspected primary aldosteronism: lessons from Prosaldo

Andreea Georgiana Constantinescu ¹ , Christina Pamporaki ¹ , Francesco Alessi ¹ , Jens Passauer ¹ , Hanna Remde ² , Lydia Kuerzinger ² , CarminaTeresa Fuss ² , Manuel Schulze ³ , Mirko Peitzsch ⁴ , Andrea Horvath ⁵ , Jun Yang ⁶ , Denise Bruedgam ⁷ , TracyAnn Williams ⁷ , Martin Reincke ⁷ , Sven Gruber ⁸ , Felix Beuschlein ⁸ , Jacques Lenders ⁹ & Graeme Eisenhofer ¹

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¹Carl Gustav University Hospital, Endocrinology and Internal Medicine, Dresden, Germany; ²University Hospital Wurzburg, Endocrinology, Würzburg, Germany; ³Center for Interdisciplinary Digital Sciences, TU Dresden, Department Information Services and High Performance Computing, Dresden, Germany; ⁴Institute for Laboratory Medicine, Dresden, Germany; ⁵Prince of Wales Hospital, Pathology; ⁶Hudson Institute of Medical Research, Center for Endocrinology and Metabolism, Melbourne, Australia; ⁷Ludwig Maximiliam University Hospital Munich, Department of Medicine IV, München, Germany; ⁸University Hospital Zurich, Department of Endocrinology, Zurich, Switzerland; ⁹Radboud University Medical Center, Internal Medicine, Radboud, Netherlands

Background: Diagnostic stratification of patients with suspected primary aldosteronism (PA) is a multistep process reliant on tests that are not infallible. Only through prospective studies can diagnostic accuracy be appropriately assessed.

Methods: The PROSALDO trial enrolled 819 patients between 2019 and 2023 to assess steroid profiles against routine tests for diagnostic stratification. A combination of these tests and outcome assessments, including measurements of aldosterone by mass spectrometry (MS), was used to exclude and confirm PA.

Results: A diagnosis based on routine tests or outcome assessments could not be achieved in 97 patients, leaving 179 and 543 with and without PA. Screening with the aldosterone:renin ratio using a cut-off of 33 pmol/mU that provided 95% sensitivity revealed a false-positive rate (FPR) of 44% (56% specificity). Among 468 patients who underwent a saline infusion test (SIT), that test at a cut-off of 170 pmol/l for immunoassay measurements of aldosterone revealed a FPR of 48%. Even with MS-based measurements of aldosterone, that cut-off was associated with a 9% FPR (91% specificity). This was at a sensitivity of 98% due to three patients with false-negative results for the SIT, all who underwent adrenalectomy. Adrenal venous sampling (AVS) was carried out in 194 patients, including 69 (36%) without evidence of PA in whom subtyping largely reflected the 48% FPR for the SIT by immunoassay measured aldosterone. Among 167 selective AVS procedures, 52 of 62 patients (84%) without evident PA had non-lateralized aldosterone secretion, though 8 showed lateralization to the right and 2 to the left (16% FPR). Among 105 with PA, 78 (74%) showed lateralization; lack of lateralization in some of the other 27 patients may reflect false-negatives. Among 97 patients who underwent adrenalectomy, 87 were confirmed to have PA either by outcome assessments (n=76) or when these remained unavailable (n=11) by positive screening and confirmatory tests by MS. Among the 10 patients in whom PA was not confirmed, there were six in whom confirmatory tests by MS were negative and no outcome confirmation of PA was achieved. There were two others for whom masses in the resected adrenals were not aldosterone-producing adenomas and another two who had an alternative presurgical diagnosis.

Conclusions: The data indicate previously unrecognised inaccuracies in the diagnostic process for identification of patients with PA that in a substantial proportion of patients leads to unnecessary AVS and in some unrequired adrenalectomy. These findings emphasize the need for improved diagnostic strategies.