Conventional glucocorticoids (CGCs) are unable to mimic physiological cortisol rhythm in adrenal insufficiency (AI), resulting in increased metabolic morbidity and impaired quality of life (QoL). Non-physiological cortisol pattern and elevated evening cortisol levels may be responsible for the increased risk of metabolic disorders observed in AI patients under CGCs. Once daily dual-release-hydrocortisone (DR-HC), which better reproduces physiological daily cortisol profile, significantly improves metabolic parameters and QoL in primary AI (PAI) and secondary AI (SAI) patients. The aim of the current study was to evaluate cortisol profile and its impact on metabolism, depression status and QoL in PAI and SAI patients switched from CGCs, including cortisone acetate and immediate-release hydrocortisone, to DR-HC. Fourteen AI patients underwent daily cortisol sampling, at 3 h intervals, at baseline (CGCS treatment) and 12 months after switching to DR-HC. Mean cortisol (24 h, 7-7am) AUC was 15.61% lower with DR-HC than with CGCs. In particular, mean (7am-1pm) and (1-7am) were 15.61% and 2.1% higher whereas mean (1-7pm), (7pm-1am) and (7pm-7am) AUC were 18.8% (P=0.057), 58.39% (P<0.001) and 41.87% (P=0.004) lower with DR-HC than with CGCs, respectively. After 12 months of treatment, DR-HC induced a significant improvement in waist circumference (P=0.002), depression status (P=0.05) and QoL (P=0.05). Moreover, the change (Δ) in cortisol 7pm-1am and 7pm-7am AUC appeared significantly correlated with the change (Δ) in glucose 120 after load (P<0.005), depression score (P<0.05) and QoL score (P<0.05). The change (Δ) in cortisol 7pm-1am AUC appeared also significantly correlated with the change (Δ in fasting insulin (P=0.045) and HOMA index (P=0.045). In conclusion, the switch from CGCs to DR-HC in AI patients induces a significant improvement of waist circumference, depression status and QoL, and a significant decrease of late afternoon, evening and night GC overexposure; this reduction is significantly correlated with the improvement in metabolic profile, depression status and QoL.
20 - 23 May 2017
European Society of Endocrinology