title: Longitudinal assessment of adrenal function in the early and prolonged phases of critical illness in septic patients: relations to cytokine levels and outcome.
abstract: BACKGROUND
  Adrenal dysfunction remains a controversial issue in critical care. The long-stay intensive care unit (ICU) population may be at increased risk of adrenal insufficiency.
  
  
  OBJECTIVE
  We aimed to determine whether adrenal dysfunction develops during the course of sepsis.
  
  
  METHODS
  This is a prospective observational longitudinal study.
  
  
  METHODS
  The study was conducted in the ICU of a secondary/tertiary care hospital.
  
  
  METHODS
  We studied 51 consecutive mechanically ventilated patients with sepsis.
  
  
  METHODS
  We measured cortisol, ACTH, cortisol-binding globulin, cytokines, and cortisol 30 minutes after 1 μg ACTH(1-24), upon sepsis diagnosis and every 3 to 4 days, until Day 30 or until recovery or death.
  
  
  METHODS
  We looked for changes in baseline and stimulated cortisol levels and its relationship to ACTH levels, sepsis severity or survival.
  
  
  RESULTS
  Baseline and stimulated cortisol levels did not vary significantly. Septic patients with shock had higher baseline (20 ± 6 vs 17 ± 5 μg/dL, P = .03) and stimulated cortisol levels (26 ± 5 vs 23 ± 6 μg/dL, P = .04), compared with those without shock. On Day 1, ACTH levels could not predict cortisol levels (R(2) = 0.06, P = .08). ACTH levels increased significantly after Day 10 and, at this time point, they related to cortisol levels (R(2) = 0.35, P < .001). Development of septic shock, or resolution from it, was not associated with changes in baseline, stimulated cortisol levels, or the cortisol increment. There was much inpatient variability in the diagnosis of adrenal dysfunction at different time points.
  
  
  CONCLUSIONS
  Total cortisol levels relate both to the severity and outcome of sepsis and remain fairly unchanged during the course of illness. Initially, cortisol levels are largely ACTH independent, whereas ACTH increases and correlates with cortisol levels later on. Adrenal dysfunction does not seem to be a major problem during the prolonged phase of sepsis. Although not significant, the variation in cortisol levels may be such that classification of patients varies, questioning the utility of arbitrary cut-offs to define adrenal dysfunction in septic patients.
authors.affiliation: Department of Endocrinology, Diabetes, and Metabolism (D.A.V., M.T., S.T.), Evangelismos Hospital, 106 76 Athens, Greece; Second Department of Critical Care Medicine (I.D., S.E.O.), National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, 124 62 Athens, Greece; and First Department of Critical Care Medicine (E.D., O.L., A.K.), National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 106 76 Athens, Greece.
authors.forename: Dimitra Argyro
authors.initials: DA
authors.lastname: Vassiliadi
authors.forename: Ioanna
authors.initials: I
authors.lastname: Dimopoulou
authors.forename: Marinella
authors.initials: M
authors.lastname: Tzanela
authors.forename: Evangelia
authors.initials: E
authors.lastname: Douka
authors.forename: Olga
authors.initials: O
authors.lastname: Livaditi
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsagarakis
mesh_terms: D000311:Adrenal Glands / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D016638:Critical Illness; D016207:Cytokines / Q000097:blood*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012121:Respiration, Artificial; D018805:Sepsis / Q000503:physiopathology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D006728:Hormones; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone