The cortisol awakening response is blunted in patients with active Cushing's disease

Abstract

IntroductionCortisol awakening response (CAR) is a rapid increase of cortisol levels within 30–45 min after awakening.ObjectiveThis study evaluates CAR compared with cortisol circadian rhythm in active and in remission Cushing's disease (CD).Materials and methodsWe evaluated healthy controls (HC, n=19), obese (OB, n=10), in remission (n=08), and active CD patients (n=10). Salivary free cortisol (SF) was determined at 0800, 1100, 1700, 2000, and 2300 h on the first day. CAR was obtained the next morning immediately upon awakening and at 15, 30, 45, and 60-min post-wake up.ResultsWe observed differences in SF levels throughout the day in HC, OB, and in remission CD (ANOVA P=0.0001) but not in active CD (P=0.2). We demonstrated SF increment after awakening in HC, OB, and in remission CD (ANOVA P=0.007), with no effect of time on SF in active CD. The relative increment of SF obtained at the peak after awakening (CARi%) in the active CD (67±57%) was lower than in HC (154±107%), OB (240±188%), and in remission CD (186±184%) patients (P=0.009). There was a negative correlation between the SF at awakening and the CARi% in HC (r=−0.8), OB (r=−0.78), and in remission CD (r=−0.74) but not in active CD (r=−0.35; P=0.31).ConclusionThis study originally described a blunted CAR in active CD in contrast to its presence in HC, OB, and in remission CD. This subtle dysfunction of the hypothalamus–pituitary–adrenal axis may represent a distinct and additional physiopathological phenomenon superimposing the dysregulated cortisol circadian rhythm in this disease.