Salivary 18-hydroxycortisol as a non-invasive biomarker for subtyping Primary Aldosteronism

초록

Introduction Primary aldosteronism (PA) is the most common cause of secondary hypertension, and accurate subtyping into lateralized or non-lateralized disease is essential for optimal management. Although adrenal venous sampling (AVS) remains the gold standard for lateralization, it is invasive, technically demanding, and not widely available. Steroid profiling using liquid chromatography–tandem mass spectrometry (LC–MS/MS) has emerged as a promising alternative, but the potential role of salivary steroid profiling in PA subtyping has not been systematically evaluated. We aimed to investigate whether salivary steroid measurements, particularly 18-hydroxycortisol (18-OHF), could predict lateralization in patients with PA. Methods This single-center study included 74 patients with confirmed PA who underwent AVS at Seoul National University Hospital between 2017 and 2023. Lateralized PA was defined by a lateralization index ≥4 or confirmed clinical success after adrenalectomy in indeterminate cases. Morning salivary samples were collected and analyzed using LC–MS/MS. Salivary concentrations of cortisol, cortisone, tetrahydrocortisol, 20α-dihydrocortisol, 18-OHF, and dehydroepiandrosterone sulfate were compared between lateralized and non-lateralized PA. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Incremental value beyond conventional biochemical parameters was evaluated using net reclassification improvement (NRI). Correlations between salivary and serum steroid concentrations were also examined. Results Among the 74 patients, 38 had lateralized PA and 36 had non-lateralized PA. Compared with non-lateralized PA, patients with lateralized PA had higher plasma aldosterone (34.9 vs 21.7 ng/dL, P = .021), lower plasma renin activity (0.2 vs 0.5 ng/mL/h, P < .001), and more frequent hypokalemia (71.1% vs 27.8%, P < .001). Among salivary steroids, only 18-OHF differed significantly, with higher levels in LPA (0.66 vs 0.25 ng/mL, P < .001). Salivary 18-OHF predicted lateralization with an area under the ROC curve of 0.756 (95% CI, 0.642-0.870). A cutoff value of 0.29 ng/mL yielded a sensitivity of 78.9% and specificity of 69.4%. When added to a conventional model including plasma aldosterone, renin, and serum potassium, salivary 18-OHF significantly improved classification (category-free NRI 0.52, 95% CI, 0.084-0.929 P = .014). Salivary and serum 18-OHF levels showed a strong correlation (ρ = 0.73, P < .001). Conclusions Salivary 18-OHF is a promising non-invasive biomarker for subtyping PA. It provides clinically meaningful discrimination of lateralized disease and offers incremental diagnostic value beyond conventional biochemical parameters. Salivary steroid profiling may serve as a practical adjunct to current diagnostic strategies and help reduce reliance on invasive AVS. Larger studies are needed to validate its clinical utility.