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. 2025 Sep 5:dgaf499.
doi: 10.1210/clinem/dgaf499. Online ahead of print.

Clinical Utility of Salivary Steroid Profiling for the Differential Diagnosis of Adrenal Diseases

Kyoung Yeun Jung  1 , Soyeon Park  2 , Chaelin Lee  2 , Eu Jeong Ku  3 , Sihoon Lee  4 , Kyoung-Ah Kim  5 , Sang Wan Kim  6 , Yumie Rhee  7 , Jung Soo Lim  8 , Choon Hee Chung  8   9 , Sung Wan Chun  10 , Soon-Jib Yoo  11 , Ohk-Hyun Ryu  12 , Hochan Cho  13 , A Ram Hong  14 , Hyo-Jeong Kim  1 , Man Ho Choi  2 , Jung Hee Kim  15
Affiliations

Clinical Utility of Salivary Steroid Profiling for the Differential Diagnosis of Adrenal Diseases

Kyoung Yeun Jung et al. J Clin Endocrinol Metab. .

Abstract

Context: Although salivary steroid sampling offers several advantages, the diagnostic potential of salivary steroid metabolites remains largely unexplored.Objective To evaluate the diagnostic utility of salivary steroid profiling in patients with adrenal diseases.

Design: Prospective multicenter study.

Patients: Three hundred thirteen patients with nonfunctioning adrenal adenoma (NF), primary aldosteronism (PA), Cushing's syndrome (CS), and mild autonomous cortisol secretion (MACS).

Methods: Salivary samples for morning and night steroids were collected using standardized protocols. The liquid chromatography-mass spectrometry-based steroid profiling was applied to quantify cortisol, cortisone, tetrahydrocortisone (THE), 20α-dihydrocortisol (20α-DHF), 18-hydroxycortisol (18-OHF), and dehydroepiandrosterone sulfate (DHEA-S).

Main outcome measure: The primary outcome was the diagnostic performance of morning and night salivary steroids.

Results: In the PA group, morning and night salivary levels of 18-OHF were higher compared to other groups (all P<.05). Morning and night salivary levels of cortisone, THE, and 20α-DHF were significantly elevated in the CS group compared to other groups (all P<.05). Only night-time salivary levels of cortisone (P=.040) and 20α-DHF(P=.029) were elevated in the MACS group compared to the NF group. Receiver operating characteristic analyses indicated that morning salivary 18-OHF was moderately specific for PA, whereas night salivary 20α-DHF and cortisone provided robust diagnostic accuracy for CS. Combined night salivary steroids exhibited superior diagnostic performance compared to morning salivary steroids in the CS group (AUC, 0.903 vs. 0.754, P = .007).

Conclusion: Salivary steroid profiling holds promise as a non-invasive tool for the diagnosis of adrenal diseases.

Keywords: Cushing’ syndrome; Mild autonomous cortisol secretion; Non-functioning adrenal adenoma; Primary aldosteronism; Salivary; Steroid profiles.

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