Diagnosis of Primary Aldosteronism by Seated Saline Suppression Test-Variability Between Immunoassay and HPLC-MS/MS

Background: In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cutoff 4-hour plasma aldosterone concentration (PAC) measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS is 162 pmol/L. Most diagnostic laboratories, however, use immunoassays to measure PAC. The cutoff for SSST using immunoassay is not known. We hypothesized that the cutoff is different between the assays. Methods: We analyzed 80 of the 87 SSST tests that were performed during our recent study defining the HPLC-MS/MS cutoff. PA was confirmed in 65 by positive fludrocortisone suppression testing (FST) and/or lateralization on adrenal venous sampling and excluded in 15 by negative FST. PAC was measured by a chemiluminescence immunoassay (PAC(IA)) in the SSST samples using the DiaSorin Liaison XL analyzer, and receiver operating characteristics (ROC) analysis was performed to identify the PAC(IA) cutoff. Results: ROC revealed good performance (area under the curve = 0.893; P < .001) of 4-hour postsaline PAC(IA) for diagnosis of PA and an optimal diagnostic cutoff of 171 pmol/L, with sensitivity and specificity of 95.4% and 80.0%, respectively. A higher cutoff of 217 pmol/L improved specificity (86.7%) with lower sensitivity (86.2%). PAC(IA) measurements strongly correlated with PAC measured by HPLC-MS (r = 0.94, P < .001). Conclusions: A higher diagnostic cutoff for SSST should be employed when PAC is measured by immunoassay rather than HPLC-MS/MS. The results suggest that (i) PA can be excluded if 4-hour PAC(IA) is less than 171 pmol/L, and (ii) PA is highly likely if the PAC(IA) is greater than 217 pmol/L by chemiluminescence immunoassay. A gray zone exists between the cutoffs of 171 and 217 pmol/L, likely reflecting a lower specificity of immunoassay.