Endocrine Abstracts

Background: Adrenal insufficiency patient (AIP) care is mostly based on symptoms or clinical signs of inadequate glucocorticoid replacement treatment (GRT). Salivary cortisol (F) and cortisone (E) recently emerged as new tools for AIP management, although poorly employed in clinical practice.

Aim: To assess associations between salivary glucocorticoid measures and life quality, anxiety depressive symptoms, sleep quality in AIP.

Method: We enrolled 29 healthy subjects (HS) and 52 AIPs under cortisone acetate (CA, n=27) or hydrocortisone or dual release hydrocortisone (HC, n=25). At observation day, subjects gathered 9 saliva samples at pre-established times from 07:00 (for AIP, immediately before the first GRT dose) to 23:00. Contextually, AIPs completed Addison disease specific quality-of-life questionnaire (AddiQoL-30; subdomains: Fatigue, Symptoms and Emotions), Hospital Anxiety and Depression Scale (HADS; subdomains: Anxiety and Depression) and Pittsburgh Sleep Quality Index (PSQI). E and F were quantified by liquid chromatography-tandem mass spectrometry. Due to GRT oral contamination, we considered F for CA and E for HC. Glucocorticoid exposure was estimated as area under the curve (AUC). F and E rhythms were determined with cosinor analysis. Z-scores (ZS) of F and E values at each time point, AUCs and cosinor parameters were calculated in the overall population including HS and AIPs. Linear and logistic multivariate regression analysis were performed including questionnaire scores as dependent variable and age, disease duration, ongoing GRT scheme duration, GRT equivalent-hydrocortisone dose, GRT type, body mass index, waist circumference and, one at a time, ZS parameters as covariates.

Results: Concerning AddiQoL, ZS-AUC_{07:00→07:30} negatively predicted Emotions (R²=0.125, P=0.040). ZS-AUC_{14:00→16:00} negatively predicted overall score (R²=0.208, P=0.007), Fatigue (R²=0.280, P=0.001) and Emotions (R²=0.12, P=0.045). ZS-AUC_{21:00→23:00} positively predicted Symptoms (R²=0.124, P=0.041). Regarding HADS, ZS-AUC_{14:00→16:00} positively predicted the overall score (R²=0.338, P=0.004) in model with ongoing GRT scheme duration, whereas ZS-AUC_{19:30→21:00} negatively predicted Depression (R²=0.136, P=0.045). About PSQI, ZS-14:00 (R²=0.422, P=0.020) and ZS-amplitude (R²=0.147, P=0.037) positively predicted the overall score, whereas increasing ZS-AUC_{12:30→16:00} predicted abnormal PSQI (OR: 2.382; CI 95%: 1.099-5.164; overall percentage: 69%; P=0.028).

Conclusions: Elevated morning and, to a higher extent, afternoon glucocorticoid exposure predicted poorer life quality, stronger anxiety depressive symptoms, lower sleep quality. Interestingly, reduced evening glucocorticoid exposure predicts worse life quality and anxiety depressive symptoms, possibly indicating the need for greater glucocorticoid coverage at the end of the day. Hence, measurement of salivary cortisol and cortisone maybe useful predictors of physical and psychological wellbeing in AIP and could be employed for GRT management.