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

Abstract

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 (PACIA) in the SSST samples using the DiaSorin Liaison XL analyzer, and receiver operating characteristics (ROC) analysis was performed to identify the PACIA cutoff. Results ROC revealed good performance (area under the curve = 0.893; P < .001) of 4-hour postsaline PACIA 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%). PACIA 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 PACIA is less than 171 pmol/L, and (ii) PA is highly likely if the PACIA 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.

Confirmatory testing of primary aldosteronism with saline infusion test and LC-MS/MS

“…Previous studies reported significant variations between different IAs ( 12 , 14 , 16 ). In our study, IA measurement was on average 31 ng/L higher than LC-MS/MS quantification, and this is well in line with previous reports despite good correlation ( 28 , 42 , 43 ). Even by using highly sensitive and specific IAs like in this study, the lower limit of quantification is significantly higher in IA compared to LC-MS/MS.…”

Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study

“…The study population included all members of LHS who were tested for COVID-19 infection during the study period and who had at least one previous test for plasma 25 (24). According to LHS guidelines, blood was collected from fasting persons and transported on ice to the Center Laboratory for processing within 4 h of collection using DiaSorin Chemiluminescence assay (25)(26)(27)(28). Data of each subject were collected from the LHS computerized database and included age, gender, socioeconomic status (SES), weight, height, body mass index, current smoking status, psychiatric and somatic comorbidities, and hospitalizations as a result of the COVID-19 infection.…”

A GLP-1 Receptor Agonist Inhibits Aldosterone Release in Healthy Volunteers

“…The saline infusion test is widely used for confirming the diagnosis of primary aldosteronism but has important limitations [34]. Recently, a seated version of the test has been established providing comparable testing conditions to our study [35]. Remarkably, exenatide seems to be at least as potent as saline loading to suppress aldosterone in healthy volunteers [35].…”

“…Recently, a seated version of the test has been established providing comparable testing conditions to our study [35]. Remarkably, exenatide seems to be at least as potent as saline loading to suppress aldosterone in healthy volunteers [35]. Further studies are warranted to directly explore the potential of GLP1 RAs in the diagnostic workup of hyperaldosteronism.…”