Validation of the Fujirebio Lumipulse G1200 aldosterone assay for measurements during adrenal venous sampling for primary hyperaldosteronism

Primary aldosteronism (PA) is a group of disorders in which aldosterone production is inappropriately high for sodium status, relatively autonomous of the major regulators of secretion and non-suppressible by sodium loading [1]. PA is commonly caused by an adrenal adenoma, unior bi-lateral hyperplasia or in rare cases by adrenal carcinoma or familial hyperaldosteronism like glucocorticoid-remediable aldosteronism. PA results in hypertension, cardiovascular damage, sodium retention, suppression of plasma renin and increased potassium excretion [2]. Case detection of PA is performed by determining the aldosterone-renin ratio, and if divergent from normal followed by a confirmatory test (e.g. saline infusion) and ultimately CT-scan and/or adrenal venous sampling [1, 3]. Adrenal vein sampling (AVS) is used to determine whether patients suffer from primary hyperaldosteronism caused by a unilateral aldosteroneproducing adenoma or bilateral adrenal hyperplasia. The ratio between aldosterone and cortisol is used to determine whether there is lateralization and/or suppression of the adrenal glands [4]. A unilateral adenoma can be treated with laparoscopic adrenalectomy. In case of bilateral hyperplasia or when the patient is unable or unwilling to undergo surgery, it is recommended for the patient to undergo medical treatment including a mineralocorticoid receptor antagonist like spironolactone [1]. Therefore, it is adamant to assess whether aldosterone is produced uni-, or bi-lateral. Here, we describe a novel fully automated two-step immunoassay EIA (Fujirebio Lumipulse G System [Fujirebio, Inc., Tokyo, Japan]). This cartridge based automated immunoassay has a time-to-first result of 28 min, and in contrast to LC-MS/MS can be implemented in all routine laboratories. The Lumipulse G Aldosterone assay was also traceable to LC-MS/MS. Imprecision of the Fujirebio Lumipulse was CV 2.1% (mean 147 pM), CV 1.8% (mean 609 pM) and CV 2.4% (mean 2,285 pM), in 25 separate runs in two months. The same controls were used for both assays (pooled serum in the lower, middle and higher range stored at −20 °C). The Lumipulse method was compared to a LC-MS/MS method developed in the Erasmus Medical Centre (Waters Xevo-TQ-S, Waters Corporation, Inc., Milford, USA). The LC-MS/MS method was calibrated using a commercially available reference standard (Aldosterone Cerillant No. A-096). Trueness of the method was assessed by external proficiency testing (SKML, The Netherlands). Proficiency was within limits set by the distributor for a reviewed period of one complete year both in terms of bias and imprecision. During this period, mean bias was 1.7% when compared to the LC-MS/MS consensus (n=9 participants). For Lumipulse, no peers were available in any scheme due to the recent introduction of the assay. The LC-MS/MS method was based on denaturation of the sample followed by Solid Phase Extraction (OASISMAX μElution 96 well plate). The eluate was injected on the reversed phase UPLC column (Acquity UPLC BEH Phenyl column, 1.7 μM, 2.1 mm × 50 mm) using a gradient of deionized water and methanol in 4 min. Aldosterone was *Corresponding author: Febe C. Vermue, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, E-mail: febevermue@gmail.com Sjoerd A. A. van den Berg, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands Clin Chem Lab Med 2021; aop