Endocrine Abstracts

Background: Evaluation of steroid replacement therapy (SRT) in adrenal insufficiency (AI) is challenging for the lack of reliable parameters. Measurement of salivary cortisol and cortisone emerged as a non-invasive tool for AI management, however poorly investigated.

Aim: To analyse the cortisol and cortisone circadian rhythm in normal controls (NC) and patients with primary AI (PAI) under different SRTs, and to identify useful biomarkers.

Methods: We evaluated 24 NC and 30 PAI under hydrocortisone (HC) (n=8), cortisone acetate (CA) (n=14), and dual-release HC (DRHC) (n=8), with equivalent-HC doses of 13.2 mg/m², 15.8 mg/m², and 14.6 mg/m², respectively. SRT was taken at 07:00 (all patients) and between 13:00-16:00 (mean 15:13, patients under HC and CA). We collected 9 saliva samples throughout a day at 7:00 (before therapy), 7:30, 10:00, 12:30, 14:00, 16:00, 19:30, 21:00, and 23:00 for cortisol and cortisone measurement by liquid-chromatography tandem-mass spectrometry (LC-MS/MS). We performed cosinor analysis, and calculated area under the curves (AUCs) and percentual variation from NC values (V%). Due to oral contamination from drug intake, we evaluated cortisol for patients under CA and cortisone for those under HC and DRHC. Patients with PAI completed the following questionnaires: quality of life (AddiQol-30), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI).

Results: Compared to NC, AUCs between 14:00 and 23:00 were higher in CA (P=0.001) and HC (P<0.001), while similar in DRHC (P=0.12). In the same period, V% was lower under DRHC (-28%) than CA (+128%; P=0.001) and HC (+90%; P=0.001). Cosinor analysis showed comparable mesor, but delayed acrophase (P=0.002 for HC; P=0.026 for DRHC; P=0.027 for CA) and batiphase (P=0.002 for HC; P=0.023 for DRHC; P=0.027 for CA), compared to NC. The number of time points with salivary steroid levels within the range derived from NC was higher in DRHC than CA (P=0.002) and HC (P=0.005). Between 07:00 and 10:00, patients with PAI showed a similar percent increase in salivary steroids among different SRT groups, which was higher than NC (P<0.001 for all comparisons). AddiQol-30, HADS and PSQI were comparable among PAI.

Conclusion: Salivary cortisol and cortisone showed a higher excursion in the morning (all patients) and an increased glucocorticoid exposure in the afternoon/evening (patients under HC and CA), than NC. Although DRHC provides better glucocorticoid exposure than HC and CA, significant differences with NC were observed. Salivary cortisol and cortisone levels and AUC may be useful tools for SRT management in PAI.