Endocrine Abstracts (2019) 65 P6 | DOI: 10.1530/endoabs.65.P6

Monitoring metyrapone therapy for Cushing's syndrome using salivary glucocorticoid measurement by liquid chromatography tandem mass spectrometry (LC-MS/MS)

Megan Manson1,2,3, Safwaan Adam1,2,4, Claire Higham1,2,4, Brian Keevil5, Peter Trainer1,2,4 & Phillip Monaghan2,3

1Department of Endocrinology, The Christie NHS Foundation Trust, Manchester, UK; 2Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; 3Christie Pathology Partnership, The Christie NHS Foundation Trust, Manchester, UK; 4Manchester Academic Health Sciences Centre, Manchester, UK; 5Biochemistry Department, Wythenshawe Hospital, Manchester University NHS Trust, Manchester, UK

Introduction: Late-night salivary cortisol assessment is an important element when investigating suspected Cushing’s syndrome (CS). The goal of medical therapy is achieving a mean (of 5 samples during a single day) serum cortisol (serumF) of 150–300 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 LC–MS/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 24–74 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 LC–MS/MS. SalE and SalF were measured by LC–MS/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-LC–MS/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).

Table 1
All measurements (n=220)
SerumF v SalF0.66<0.0001
SerumF v SalE0.77<0.0001
CDC Means (n=44)
SerumF v SalF0.55<0.0001
SerumF v SalE0.72<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-LC–MS/MS. Immunoassay measurements overestimated SerumF when compared to LC–MS/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.

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