title: Reversible increase in maximal cortisol secretion rate in septic shock.
abstract: OBJECTIVE
  Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects.
  
  
  METHODS
  Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data.
  
  
  METHODS
  Single academic medical center.
  
  
  METHODS
  Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10).
  
  
  METHODS
  I.v. cosyntropin (250 μg).
  
  
  RESULTS
  Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004).
  
  
  CONCLUSIONS
  Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.
authors.affiliation: 1Section of Endocrinology and Metabolism, Medical Service, New Mexico VA Healthcare System, Albuquerque, NM. 2Departments of Medicine and Biochemistry, University of New Mexico School of Medicine, Albuquerque, NM. 3Department of Mathematics and Statistics, Clinical and Translational Science Center, University of New Mexico, Albuquerque, NM. 4Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 5Department of Electrical and Computer Engineering, Florida International University, Miami, FL.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Dorin
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Qualls
authors.forename: David J
authors.initials: DJ
authors.lastname: Torpy
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Schrader
authors.forename: Frank K
authors.initials: FK
authors.lastname: Urban
mesh_terms: D000046:Academic Medical Centers; D000302:Adrenal Cortex / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003366:Cosyntropin / Q000494:pharmacology; D016638:Critical Illness; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000503:physiopathology; D012709:Serum Albumin / Q000032:analysis; D012772:Shock, Septic / Q000503:physiopathology*; D014156:Transcortin / Q000032:analysis
chemical_list: D012709:Serum Albumin; D003366:Cosyntropin; D014156:Transcortin; D006854:Hydrocortisone