SAT-012 Urinary Aldosterone Assay Using LC-MS/MS Could Improve Primary Aldosteronism Screening

Abstract

Primary aldosteronism (PA) is the first cause of endocrine hypertension accounting for about 6% of all cases of hypertension. According to international guidelines, PA screening is based on plasma aldosterone-to-renin concentration ratio (ARR) computation. Nevertheless, measurement of urine aldosterone excretion may be of interest since it integrates aldosterone secretion over 24 hours. However, available urine aldosterone immuno-assays have poor specificity. In this context, we developed a new aldosterone assay using liquid chromatography and tandem mass spectrometry detection (LC-MS/MS) to recover specifically urine free aldosterone and glucuronide metabolites after 18-hour acid hydrolysis. Our method was validated according to FDA recommendations, and covers the expected range of aldosterone concentrations found in 24-hour urine collection (from 1.10 to 75 nM) with improved specificity. It has a within-run precision below 2% and a maximum between-run precision of 5.6%. The diagnostic performance of the assay was assessed in a cross-sectional retrospective study that included 234 subjects: 63 healthy volunteers (HV), 107 patients with essential hypertension (EH) and 64 PA patients. Final diagnosis was based on routine hormone measurements in accordance with international guidelines. Median (5th to 95th percentile) of 24-hour urine aldosterone excretion was 19.5 (5.2-53.4) nmol/24h in HV, 39.1 (13.3-97.4) nmol/24h in EH and 91.4 (40.6-225.3) nmol/24h in PA subjects. By ROC curve analysis (area 0.864), a cutoff value of aldosterone excretion of 65 nmol/24h yielded a 76.6% sensitivity and 78.5% specificity to discriminate PA from EH patients. 24-hour urinary aldosterone:creatinine ratio was more discriminant than 24-hour aldosterone excretion, with ratios (nmol/mmol) of 1.42 (0.5-3.9) for HV, 3.4 (1.3-7.9) for EH and 6.9 (2.5-30.0) for PA. By ROC curve analysis (area 0.867) a cutoff value of 24-hour urinary aldosterone:creatinine ratio of 5.0 nmol/mmol had 81.3% sensitivity and 81.3% specificity to discriminate PA from EH patients. Finally, 11% of our 64 PA patients showed a urinary aldosterone:creatinine ratio above this suggested cutoff value while ARR was below cut-off value. In conclusion, LC-MS/MS measurement of urinary aldosterone is a specific, sensitive and effective method for the diagnosis of PA.