Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate.
BACKGROUND
This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11β-hydroxylase into account.


METHODS
This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI. The patients underwent a 250-μg ACTH test (n = 67). ACTH, adrenal steroids, substrates, and precursors (modified tandem mass spectrometry) also were measured. Clinical characteristics including use of etomidate to facilitate intubation (n = 14 within 72 hours of ACTH testing) were recorded.


RESULTS
At the time of ACTH testing, patients had septic (n = 43) or nonseptic critical illness (n = 24). Baseline cortisol directly related to sepsis and endogenous ACTH, independent of etomidate use. Etomidate was associated with a lower baseline cortisol and cortisol/11β-deoxycortisol ratio as well as higher 11β-deoxycortisol, reflecting greater 11β-hydroxylase inhibition in nonsepsis than in sepsis. Cortisol increases < 250 mM in exogenous ACTH were associated with relatively low baseline (HDL-) cholesterol, and high endogenous ACTH with low cortisol/ACTH ratio, independent of etomidate. Although cortisol increases with exogenous ACTH, levels were lower in sepsis than in nonsepsis patients, and etomidate was associated with diminished increases in cortisol with exogenous ACTH, so that its use increased, albeit nonsignificantly, low cortisol increases to exogenous ACTH from 38% to 57%, in both conditions.


CONCLUSIONS
A single dose of etomidate may attenuate stimulated more than basal cortisol synthesis. However, it may only partly contribute, particularly in the stressed sepsis patient, to the adrenal dysfunction of CIRCI, in addition to substrate deficiency.
Nienke
N
Molenaar
Ronald M
RM
Bijkerk
Albertus
A
Beishuizen
Christel M
CM
Hempen
Margriet F C
MF
de Jong
Istvan
I
Vermes
Gertjan
G
van der Sluijs Veer
Armand R J
AR
Girbes
A B Johan
AB
Groeneveld
D000309:Adrenal Insufficiency / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000368:Aged; D016638:Critical Illness; D005045:Etomidate / Q000008:administration & dosage*; D005260:Female; D006785:Hospitals, University; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007362:Intensive Care Units; D008297:Male; D009426:Netherlands; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood*
D006993:Hypnotics and Sedatives; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D005045:Etomidate