Background: Primary aldosteronism (PA) is the most common endocrine cause of hypertension associated with high cardiometabolic risk. Identification of PA is important as specific management can reduce the excess risk and potentially lead to cure. We have recently reported that urinary aldosterone excretion measured over 24 hours (24hr-UAE) by LC-MS/MS in the setting of 24-hour urinary sodium (24hr-UNa) ≥190 mmol/24h can confer high sensitivity and specificity to identify PA cases diagnosed by the standard seated saline suppression test (SSST). Most centres however use immunoassay to measure aldosterone, and 24hr-UAE cut-offs in current practice are based on immunoassay measurements.
Aim: To compare the diagnostic performance of 24hr-UAE measured by immunoassay (24hr-UAE-IA) versus LC-MS/MS (24hr-UAE-LCMS) for diagnosing PA.
Methods: We analysed 182 prospectively-collected 24hr-urine samples from 167 patients who had hypertension with elevated aldosterone-renin ratio or had adrenalectomy for unilateral PA, 24hr-UNa measured and SSST performed, at a tertiary centre over 5 years. Patients were off interfering medications and on unrestricted dietary sodium. 24hr-UAE was analysed by LC-MS/MS in 182 samples, and by a concurrent Immunoassay in 121 stored samples. The performance of 24hr-UAE-IA in diagnosing PA was assessed by receiver operating characteristic (ROC) analyses, and compared with 24hr-UAE-LCMS, using SSST as the reference test.
Results: Among patients with 24hr-UNa ≥190 mmol/24h, a 24hr-UAE-IA cut-off of ≥24.5 nmol/24h yielded 92.3% sensitivity with 66.7% specificity. Increasing the cut-off to ≥35.5 nmol/24h improved specificity to 77.8% but reduced sensitivity to 73.0%. In contrast, 24hr-UAE-LCMS cut-off of ≥23.5 nmol/24h in the setting of 24hr-UNa ≥190 mmol/24h achieved 92.1% sensitivity and 82.6% specificity. The correlation between 24hr-UAE-LCMS and 24hr-UAE-IA was modest (r=0.352, P<0.001).
Conclusion: 24hr-UAE analysed by immunoassay offers inferior specificity compared to LC-MS/MS. These findings highlight the limitations of immunoassay-based cut-offs and support the broader use of LC-MS/MS for accurate diagnosis of PA.