Monitoring adrenal insufficiency through salivary steroids: a pilot study.

Various glucocorticoid replacement treatments (GRT) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. Control subjects (CS, n=28) and AI patients receiving hydrocortisone (HC, n=9), cortisone acetate (CA, n=23), dual-release hydrocortisone once (DRHC-od, n=10) and twice a day (DRHC-td, n=6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale and Addison disease specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC, and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaires results predictors were evaluated with multiple regression analysis. Compared to controls, all GRTs resulted in glucocorticoid over-exposure in the morning. HC, CA, and DRHC-td caused over-exposure also in afternoon and evening. Compared to other treatments, CA determined increased Z-score-07:00 (p<0.001), DRHC-td determined increased Z-score-AUC07:00→14:00 (p=0.007) and DRHC-od induced lower Zscore-AUC14:00→23:00 (p=0.015). Z-scores-AUC14:00→16:00 ≥ 0.619 best predicted questionnaire scores. None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.