Introduction: Late-night salivary cortisol assessment is an important element when investigating suspected Cushings syndrome (CS). The goal of medical therapy is achieving a mean (of 5 samples during a single day) serum cortisol (serumF) of 150300 nmol/l (Cushing Day Curve [CDC]). Metyrapone is an 11β-hydroxylase inhibitor elevating levels of 11-deoxycortisol causing conventional immunoassay (IA) to overestimate SerumF; a problem obviated by LCMS/MS. We sought to establish if salivary glucocorticoids (salivary cortisol [SalF], cortisone [SalE]) have clinical utility in metyrapone-treated CS patients.
Methods: Seventeen (14 female; age-range 2474 years) patients with CS on metyrapone were studied on 44 occasions: 15 ACTH-dependent (4 ectopic) and 2 ACTH-independent. SerumF with paired SalF and SalE were taken at 5 time-points throughout the day. SerumF was measured by immunoassay (Siemens CentaurXP) and LCMS/MS. SalE and SalF were measured by LCMS/MS.
Results: There was close correlation between SerumF and salivary glucocorticoids both for individual samples and for CDC mean values (Table 1). Bland-Altman analysis comparing SerumF-LCMS/MS to SerumF-IA confirmed a positive bias of 31% for SerumF-IA (95% Cl −3.2 to 64.8%). In patients treated with metyrapone and hydrocortisone, SalF showed spurious elevation due to oral hydrocortisone contamination (up to 50-fold).
|All measurements (n=220)|
|SerumF v SalF||0.66||<0.0001|
|SerumF v SalE||0.77||<0.0001|
|CDC Means (n=44)|
|SerumF v SalF||0.55||<0.0001|
|SerumF v SalE||0.72||<0.0001|
Conclusion: Our observed relationships between salivary and serum glucocorticoids show their utility in metyrapone treatment monitoring. Furthermore, SalE may be a preferred biomarker due to its resistance to oral hydrocortisone contamination and stronger relationship with SerumF-LCMS/MS. Immunoassay measurements overestimated SerumF when compared to LCMS/MS, therefore should be avoided when monitoring metyrapone-treated CS patients. Further work is required to define the salivary glucocorticoid target range for medical therapy.