Diagnosis of adrenal insufficiency in severe sepsis and septic shock.
BACKGROUND
Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by a more accurate diagnostic standard.


OBJECTIVE
We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin stimulation test, and the prevalence of sepsis-associated adrenal insufficiency.


METHODS
This was an inception cohort study.


RESULTS
In two consecutive septic cohorts (n = 61 and n = 40), in 44 patients without sepsis and in 32 healthy volunteers, we measured (1) serum cortisol before and after cosyntropin stimulation, albumin, and corticosteroid-binding globulin levels, and (2) serum corticotropin, cortisol, and 11beta-deoxycortisol levels before and after an overnight metyrapone stimulation. Adrenal insufficiency was defined by postmetyrapone serum 11beta-deoxycortisol levels below 7 microg/dl. More patients with sepsis (31/61 [59% of original cohort with sepsis] and 24/40 [60% of validation cohort with sepsis]) met criteria for adrenal insufficiency than patients without sepsis (3/44; 7%) (p < 0.001 for both comparisons). Baseline cortisol (< 10 microg/dl), Delta cortisol (< 9 microg/dl), and free cortisol (< 2 microg/dl) had a positive likelihood ratio equal to infinity, 8.46 (95% confidence interval, 1.19-60.25), and 9.50 (95% confidence interval, 1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol of 10 microg/dl or less or Delta cortisol of less than 9 microg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol of 44 microg/dl or greater and Delta cortisol of 16.8 microg/dl or greater.


CONCLUSIONS
In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10 microg/dl or delta cortisol is less than 9 microg/dl, and unlikely when cosyntropin-stimulated cortisol level is 44 microg/dl or greater or Delta cortisol is 16.8 microg/dl or greater.
Annane
Djillali
D
Service de Réanimation, Hôpital Raymond Poincaré (AP-HP), Faculté de Médecine Paris Ile de France Ouest (UVSQ), 104 Boulevard Raymond Poincaré, 92380 Garches, France. djillali.annane@rpc.aphp.fr
Maxime
Virginie
V
Ibrahim
Fidaa
F
Alvarez
Jean Claude
JC
Abe
Emuri
E
Boudou
Philippe
P
D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000209:etiology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D003366:Cosyntropin / Q000494:pharmacology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008797:Metyrapone; D008875:Middle Aged; D018805:Sepsis / Q000097:blood / Q000150:complications*; D012709:Serum Albumin / Q000032:analysis; D012772:Shock, Septic / Q000097:blood / Q000150:complications*; D014156:Transcortin / Q000032:analysis
D012709:Serum Albumin; D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D014156:Transcortin; D006854:Hydrocortisone; D008797:Metyrapone