Purpose: International guidelines recommend salivary cortisol for the diagnosis of Cushing’s syndrome. Despite mass spectrometry-based assays are considered the analytical gold-standard, there is still the need to define reference intervals and diagnostic accuracy of such methodology. Methods: 100 healthy volunteers and 50 consecutive patients were enrolled to compare LC–MS/MS and electrochemiluminescence assay for the determination of late-night salivary cortisol and cortisone. Moreover, we aimed to determine reference intervals of salivary steroids in a population of healthy individuals and diagnostic accuracy in patients with suspected hypercortisolism and in a population including also healthy individuals. Results: Method comparison highlighted a positive bias (51.8%) of immunoassay over LC–MS/MS. Reference intervals of salivary cortisol (0.17–0.97 µg/L), cortisone (0.84–4.85 µg/L) and ratio (0.08–0.30) were obtained. The most accurate thresholds of salivary cortisol for the diagnosis of hypercortisolism were 1.15 µg/L in the population with suspected hypercortisolism (AUC 1) and 1.30 µg/L in the population including also healthy individuals (AUC 1). Cut-off values of salivary cortisone (7.23 µg/L; Se 92.9%, Sp 97.2%, AUC 0.960 and Se 92.9%, Sp 99.1%, AUC 0.985 in suspected hypercortisolism and in overall population, respectively) and cortisol-to-cortisone ratio (0.20; Se 85.7%, Sp 80.6%, AUC 0.820 and Se 85.7%, Sp 85.5%, AUC 0.855 in suspected hypercortisolism and in overall population, respectively) were accurate and similar in both populations. Conclusion: LC–MS/MS is the most accurate analytical platform for measuring salivary steroids. Obtained reference intervals are coherent with previously published data and diagnostic accuracy for diagnosis of overt hypercortisolism proved highly satisfactory.

Reference ranges of late-night salivary cortisol and cortisone measured by LC–MS/MS and accuracy for the diagnosis of Cushing’s syndrome

Ponzetto F.
Co-first
;
Settanni F.
Co-first
;
Parasiliti-Caprino M.
;
Rumbolo F.;Nonnato A.;Amante E.;Vitali S.;Anfossi L.;Arvat E.;Ghigo E.;Giordano R.;Mengozzi G.
Last
2020

Abstract

Purpose: International guidelines recommend salivary cortisol for the diagnosis of Cushing’s syndrome. Despite mass spectrometry-based assays are considered the analytical gold-standard, there is still the need to define reference intervals and diagnostic accuracy of such methodology. Methods: 100 healthy volunteers and 50 consecutive patients were enrolled to compare LC–MS/MS and electrochemiluminescence assay for the determination of late-night salivary cortisol and cortisone. Moreover, we aimed to determine reference intervals of salivary steroids in a population of healthy individuals and diagnostic accuracy in patients with suspected hypercortisolism and in a population including also healthy individuals. Results: Method comparison highlighted a positive bias (51.8%) of immunoassay over LC–MS/MS. Reference intervals of salivary cortisol (0.17–0.97 µg/L), cortisone (0.84–4.85 µg/L) and ratio (0.08–0.30) were obtained. The most accurate thresholds of salivary cortisol for the diagnosis of hypercortisolism were 1.15 µg/L in the population with suspected hypercortisolism (AUC 1) and 1.30 µg/L in the population including also healthy individuals (AUC 1). Cut-off values of salivary cortisone (7.23 µg/L; Se 92.9%, Sp 97.2%, AUC 0.960 and Se 92.9%, Sp 99.1%, AUC 0.985 in suspected hypercortisolism and in overall population, respectively) and cortisol-to-cortisone ratio (0.20; Se 85.7%, Sp 80.6%, AUC 0.820 and Se 85.7%, Sp 85.5%, AUC 0.855 in suspected hypercortisolism and in overall population, respectively) were accurate and similar in both populations. Conclusion: LC–MS/MS is the most accurate analytical platform for measuring salivary steroids. Obtained reference intervals are coherent with previously published data and diagnostic accuracy for diagnosis of overt hypercortisolism proved highly satisfactory.
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Cortisol; Cortisone; Cushing’s syndrome; Hypercortisolism; LC–MS/MS; Saliva
Ponzetto F.; Settanni F.; Parasiliti-Caprino M.; Rumbolo F.; Nonnato A.; Ricciardo M.; Amante E.; Priolo G.; Vitali S.; Anfossi L.; Arvat E.; Ghigo E.; Giordano R.; Mengozzi G.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1763073
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