title: The cortisol awakening response is blunted in patients with active Cushing's disease.
abstract: BACKGROUND
  Cortisol awakening response (CAR) is a rapid increase of cortisol levels within 30-45 min after awakening.
  
  
  OBJECTIVE
  This study evaluates CAR compared with cortisol circadian rhythm in active and in remission Cushing's disease (CD).
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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).
  
  
  CONCLUSIONS
  This 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.
authors: Department of Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Monte Alegre, Ribeirao Preto, SP, Brazil.
authors: Silvia Liliana Ruiz
authors: SL
authors: Roa
authors: Paula Conde Lamparelli
authors: PC
authors: Elias
authors: Margaret
authors: M
authors: Castro
authors: Ayrton Custodio
authors: AC
authors: Moreira
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry*
chemical_list: D006854:Hydrocortisone