Aldosterone LC-MS/MS Assay-Specific Threshold Values in Screening and Confirmatory Testing for Primary Aldosteronism

J Clin Endocrinol Metab. 2018 Nov 1;103(11):3965-3973. doi: 10.1210/jc.2018-01041.

Abstract

Context: Current threshold values for primary aldosteronism (PA) diagnostic testing are based on measuring aldosterone (PAC) using immunoassays. Quantification of PAC by liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values.

Objective: To compare aldosterone measurement by radioimmunoassay (RIA) with LC-MS/MS and evaluate performances of proposed LC-MS/MS-specific cutoffs for PA screening and confirmatory testing.

Patients and intervention: Forty-one patients underwent aldosterone/renin ratio (ARR) testing to screen for, and fludrocortisone suppression testing (FST) to confirm or exclude, PA. Renin (DRC) was measured by chemiluminescent immunoassay.

Results: Median serum PACLC-MS/MS was 27.8% lower (P < 0.05) than plasma PACRIA in 164 pairs of FST samples. A positive correlation (Spearman coefficient, 0.894, P < 0.01; Pearson r coefficient, 0.861, P < 0.01) was observed between the two assays. Thirty-seven patients showed consistent FST diagnoses (29 positive, 8 negative), whereas four showed inconsistent FSTs by the two assays. Good agreement (κ coefficient, 0.736; P < 0.01) was observed between the current FST diagnostic PACRIA cutoff of 165 pmol/L and the proposed PACLC-MS/MS cutoff of 133 pmol/L. Among 37 patients with consistent FST results, no differences were observed in sensitivity (89.7% vs 93.1%) or specificity (87.5% vs 87.5%) for PA screening between the current ARR cutoff of 70 pmol/mU (PACRIA/DRC) and the proposed cutoff of 55 pmol/mU (PACLC-MS/MS/DRC).

Conclusions: Adjustment of the current cutoffs for PA diagnostic testing is necessary if PAC is measured by LC-MS/MS. Our preliminary results suggest that the proposed LC-MS/MS cutoffs for ARR and FST perform as well as current RIA cutoffs.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aldosterone / blood*
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, High Pressure Liquid / standards
  • Diagnostic Techniques, Endocrine / standards
  • Female
  • Fludrocortisone / administration & dosage
  • Humans
  • Hyperaldosteronism / blood
  • Hyperaldosteronism / complications
  • Hyperaldosteronism / diagnosis*
  • Hypertension / blood
  • Hypertension / etiology*
  • Male
  • Mass Screening / methods
  • Mass Screening / standards*
  • Middle Aged
  • Prospective Studies
  • Radioimmunoassay / methods
  • Radioimmunoassay / standards
  • Renin / blood
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods
  • Tandem Mass Spectrometry / standards*

Substances

  • Aldosterone
  • Renin
  • Fludrocortisone