Cortisol Levels in Shock
In patients with septic shock, cortisol levels are typically markedly elevated, with median values ranging from 44-51 μg/dL (compared to normal 10-20 μg/dL), though the response is highly variable with reported ranges from 15.6 to 400 μg/dL. 1
Expected Cortisol Response in Shock
Typical Elevation Patterns
Baseline cortisol levels in septic shock patients show a median of 50.7 μg/dL (range 15.6-400 μg/dL), representing a 2.5-20 fold increase above normal values of 10-20 μg/dL 1
The cortisol response varies significantly by infection type: Gram-positive infections produce higher cortisol levels (median 83 μg/dL, range 32-400 μg/dL) compared to Gram-negative infections (median 44 μg/dL, range 16-81 μg/dL) 1
Basal cortisol concentrations in septic shock range from 203 to 2,169 nmol/L (approximately 7.4-78.6 μg/dL) in total cortisol, with free cortisol ranging from 17 to 372 nmol/L 2
Dynamic Changes Over Time
Plasma corticotropin (ACTH) levels follow a dynamic pattern during critical illness, with transiently elevated levels followed by subsequent decline over weeks after the initial insult 3
The length of time in shock has a weak negative correlation with cortisol concentrations (p<0.05, rs=0.37), suggesting cortisol levels may decline as shock persists 1
Mean arterial pressure at time of measurement also shows a weak negative correlation with cortisol levels (p<0.05, rs=-0.40) 1
Clinical Significance of Cortisol Levels
Inadequate Cortisol Response (Critical Illness-Related Corticosteroid Insufficiency)
Despite elevated absolute cortisol levels, approximately 61% of septic shock patients demonstrate inadequate cortisol response when using a threshold of <25 μg/dL, and these patients show better hemodynamic response to hydrocortisone therapy 4
Pro-inflammatory cytokines can suppress cortisol response to ACTH or compete with intracellular glucocorticoid function, resulting in CIRCI despite seemingly adequate cortisol levels 3
In pediatric populations, approximately 25% of children with septic shock have absolute adrenal insufficiency, defined as basal cortisol <18 μg/dL and peak ACTH-stimulated cortisol <18 μg/dL 3, 5, 6
Prognostic Value
High basal cortisol levels (≥30 μg/dL) are significantly associated with increased in-hospital mortality, though they do not predict response to corticotropin stimulation 7
Steroid-responsive patients have significantly lower baseline cortisol (14.1 ± 5.2 μg/dL) compared to steroid-nonresponsive patients (33.3 ± 18 μg/dL, p<0.0001) 4
A random cortisol concentration of 23.7 μg/dL represents the most accurate diagnostic threshold for predicting hemodynamic response to glucocorticoid therapy based on receiver operating characteristic curve analysis 4
Key Clinical Pitfalls
Do not assume adequate adrenal function based solely on elevated absolute cortisol levels - the stress response may still be inadequate relative to the severity of illness 3, 4
Cortisol levels show tremendous variability (15.6-400 μg/dL range) and cannot reliably predict mortality or shock reversal on their own 1
The ACTH stimulation test has limited utility in acute management - treatment decisions for septic shock should not be delayed awaiting cortisol testing results 3
Etomidate use for intubation suppresses the hypothalamic-pituitary-adrenal axis and may confound cortisol interpretation 3