Annane et al and Loisa et al identified patients with septic shock who showed relative adrenocortical insufficiency based on a short ACTH stimulation test. These patients benefit from administration of low dose corticosteroids. Annane et al are from multiple hospitals in France while Loisa et al are from Tampere Hospital in Finland.

ACTH stimulation test: 250 µg of tetracosactin administered IV within 24 hours of the diagnosis of severe sepsis.


Specimen sampling: before and at 30 and 60 minutes after ACTH administration.


Criteria for Relative Adrenocortical Insufficiency

Annane et al

Loisa et al

peak cortisol


< 680 nmol/L

rise in serum cortisol level

< 248.5 nmol/L (9 µg/dL)

< 260 nmol/L


peak cortisol level =

= MAX(cortisol 30 minute level, cortisol 60 minute level)


cortisol rise =

= MAX(cortisol 30 minute level, cortisol 60 minute level) – (baseline cortisol level)


Additional findings:

(1) baseline cortisol levels were similar in both adequate and inadequate response groups (Loisa)

(2) plasma ACTH levels tended to be low in patients with an adequate response but within the normal range in patients with an inadequate response (Loisa)


In the study of Loisa et al, patients with relative adrenocortical insufficiency had longer ICU stays and more severe multiple organ failures, but with a marginally higher mortality rate.


In the study of Annane et al, patients showing an inadequate response given low dose corticosteroids (either 50 mg hydrocortisone IV q6h or 50 µg fludrocortisone po qd) showed a significant reduction in risk of death (53% with, 63% on placebo) without increasing adverse events.

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