Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing’s syndrome

• Published in: European journal of endocrinology Vol. 182; no. 6; pp. 569 - 582
• Main Authors: Bäcklund, Nils, Brattsand, Göran, Israelsson, Marlen, Ragnarsson, Oskar, Burman, Pia, Edén Engström, Britt, Høybye, Charlotte, Berinder, Katarina, Wahlberg, Jeanette, Olsson, Tommy, Dahlqvist, Per
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 2020; Oxford University Press
• Subjects: 80 and over; Accuracy; Adrenocorticotropic hormone; Adult; Aged; Aged, 80 and over; Analytical Chemistry; Analytisk kemi; Area Under Curve; area under the curve; Chemical Sciences; chemistry; Circadian Rhythm; Clinical Study; Cortisol; cortisone; Cortisone - analysis; Cushing syndrome; Cushing Syndrome - diagnosis; Dexamethasone; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Hormones; human; Humans; hydrocortisone; Hydrocortisone - analysis; Kemi; Liquid chromatography; Male; mass screening; Mass Screening - methods; Mass Screening - statistics & numerical data; Mass spectroscopy; Middle Aged; Natural Sciences; Naturvetenskap; Nervous system diseases; Pituitary; procedures; receiver operating characteristic; reference value; Reference Values; ROC Curve; Saliva; Saliva - chemistry; Sensitivity and Specificity; Tandem Mass Spectrometry; time factor; Time Factors; very elderly; Young Adult
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-19-0872

Objective The challenge of diagnosing Cushing’s syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70–99%) and specificity of 96% (91–98%) for cortisol, and a 100% (84–100%) sensitivity and 95% (90–98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75–100%) sensitivity and 96% (92–99%) specificity with cortisol, and 100% (83–100%) sensitivity and 94% (89–97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.