ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP199 | DOI: 10.1530/endoabs.63.GP199

LC-MS/MS measurement for urinary aldosterone improves primary aldosteronism screening

Simon Travers1,2, Anne Blanchard3,4,5, Erica Cornu6, Catherine Faucard7, Laurence Baffalie7, Michel Azizi8,9,10, Pascal Houillier5,7,11, Laurence Amar5,6,12 & Stephanie BARON7,9


1Assistance Publique Hôpitaux de Paris (APHP) Georges Pompidou European Hospital, Physiology Department, PARIS, France; 2INSERM UMRS 1185, le Kremlin-Bicêtre, France; 3Assistance Publique Hôpitaux de Paris (APHP) Georges Pompidou European Hospital, Clinical Investigations Center 1418, PARIS, France; 4INSERM UMRS 1138 CNRS ERL 8228, PARIS, France; 5Paris Descartes University, PARIS, France; 6Assistance Publique Hôpitaux de Paris (APHP) Georges Pompidou European Hospital, Hypertension Unit, PARIS, France; 7Assistance Publique Hôpitaux de Paris (APHP) Georges Pompidou European Hospital, Physiology Department, PARIS, France; 8Assistance Publique Hôpitaux de Paris (APHP) Georges Pompidou European Hospital, Clinical Investigations Center 1418, PARIS, France; 9Paris Descartes University, PARIS, France; 10Assistance Publique Hôpitaux de Paris (APHP) Georges Pompidou European Hospital, Hypertension Unit, PARIS, France; 11INSERM UMRS 1138 CNRS ERL 8228, PARIS, France. 12INSERM UMR 970, Paris Cardiovascular Research Center, PARIS, France.


Objective: 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.

Design and method: 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.

Result: 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.

Conclusion: In conclusion, LC-MS/MS measurement of urinary aldosterone is a specific, sensitive and effective method that could improve the screening of PA.

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