Decrease in salivary cortisol levels after glucocorticoid dose reduction in patients with adrenal insufficiency: A prospective proof‐of‐concept study

摘要

Summary Background and aim Patients with adrenal insufficiency ( AI ) require lifelong glucocorticoid ( GC ) replacement therapy. Cortisol measurement in saliva is increasingly being used: we assessed salivary cortisol rhythm in outpatients with AI , to provide new insights regarding the management of GC treatment. Materials and methods Nineteen AI outpatients collected six saliva samples from awakening (F a , before taking the morning GC therapy), during the day (F 1.5?h , F 6?h before the afternoon GC dose, F 8.5?h , F 12?h ) until bedtime (F b ). We measured daily cortisol exposure by calculating the area under the curve (AUC Fa→Fb ). Saliva samples were collected at baseline and one year after GG dose reduction (by at least 5?mg of hydrocortisone). Results Hydrocortisone equivalents decreased from median 25?mg/d (baseline, interquartile range IQR 20‐27.5) to 15?mg/d ( IQR 15‐20, P ??.01). As expected, we observed a reduction in both daily cortisol exposure (AUC Fa→Fb 23?982?nmol·h/L, IQR 12?635‐45?369, to 14?689?nmol·h/L, IQR 7168‐25?378, P ??.001) and salivary cortisol levels at F 6?h (24.8?nmol/L, IQR 20.1‐35.7, to 21?nmol/L, IQR 8.7‐29.2, P ??.05) and F b (8.7?nmol/L, IQR 3.4‐20.2, to 3.7?nmol/L, IQR 3.0‐5.8, P ??.05). None of the patients developed signs or symptoms consistent with AI after GC reduction. Median diastolic blood pressure ( DPB ) values fell from baseline to the end of follow‐up (87.5?mm Hg, IQR 80‐90, to 80?mm Hg, IQR 80‐85, P ??.05). The AUC Fa→Fb of patients at baseline was above the reference value (90th percentile of controls) in 12 patients (60%); after the dosage reduction, 30% of patients normalized their daily cortisol exposure (AUC Fa→Fb ). Conclusions The reduction in GC treatment in patients with AI resulted in better control of daily cortisol rhythm, measured with salivary cortisol, and in an improvement of DPB . Further studies are needed to ascertain if salivary cortisol could be used as a biomarker to manage GC replacement therapy.