Salivary 18-Hydroxycortisol as a Noninvasive Marker for Lateralization in Primary Aldosteronism

Accurate subtyping of primary aldosteronism (PA) is necessary for selecting treatment, but adrenal venous sampling (AVS) is invasive and technically demanding. Plasma and urinary hybrid steroids, including 18-hydroxycortisol (18-OHF) and 18-oxocortisol, have been used to predict PA lateralization; however, whether salivary steroid measurements can provide similar diagnostic information remains unclear.

Six salivary steroids, including 18-OHF, were measured by liquid chromatography-mass spectrometry in 74 patients with confirmed PA who underwent AVS. The ability of salivary steroid markers to predict AVS-confirmed lateralized PA was evaluated using receiver operating characteristic analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI), with the aldosterone-to-renin ratio (ARR) used as the reference model.

Among the salivary steroids evaluated, only 18-OHF was significantly higher in patients with lateralized PA (n=38) than in those with bilateral disease (n=36) (median 0.66 ng/mL vs. 0.25 ng/mL, P<0.001). Salivary 18-OHF showed moderate discrimination for lateralization (area under the curve [AUC], 0.749; 95% confidence interval [CI], 0.633 to 0.866), similar to ARR. Adding salivary 18-OHF to ARR produced only a small increase in AUC, but reclassification analyses showed significant improvement (overall NRI, 0.684; P=0.006; IDI, 0.126; P=0.002), mainly through correct downward reclassification of patients without lateralized disease. Salivary 18-OHF correlated strongly with serum 18-OHF and performed comparably to serum 18-OHF in predicting lateralization.

Salivary 18-OHF may be a noninvasive marker for predicting lateralization in PA. Its addition to ARR improved risk reclassification, particularly by identifying patients less likely to have lateralized disease, and may therefore help refine stepwise diagnostic pathways that determine which patients proceed to AVS.