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Stephen J.LurieMD, PhD, Contributing EditorIndividualAuthor
To the Editor: Dr Annane and colleagues1 found that in patients with septic shock, a high
baseline serum cortisol level (>34 µg/dL), or a maximum increase in
stimulated cortisol concentration of ≤9 µg/dL (following high-dose
cosyntropin testing), or both predicts a higher mortality. We believe that
many of the hypotheses on which this study is based may be incorrect.
The degree of activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal
(HPA) axis is related to the severity of the stressor. In animal models, hypotension
and sepsis are second only to decapitation as the most intense stressors.2 Therefore, serum cortisol levels must be interpreted
in the context of the clinical state. In patients with severe stress (eg,
hypotension, sepsis, trauma, surgery), most studies find random cortisol levels
of greater than 25 µg/dL.3 The change
in cortisol level following cosyntropin stimulation is a measure of adrenal
reserve and not of adrenal function, and therefore must be interpreted in
the context of the baseline cortisol level.
We believe that the study by Annane et al failed to identify those patients
with adrenal insufficiency (AI) who would have benefited from treatment with
corticosteroids. Recent data suggest that systemic inflammatory states such
as sepsis can be associated with reversible AI due to HPA axis suppression
by cytokines and other inflammatory mediators.4
Traditionally, adrenal function has been tested using 250 µg of cosyntropin.
A plasma level of 100 to 300 pg/mL of corticotropin should produce a maximal
cortisol response. However, plasma levels of corticotropin after 250 µg
of cosyntropin are generally greater than 10,000 pg/mL. Thus, 250 µg
of corticotropin is supraphysiologic. We and others prefer to use a more physiologic
dose of 1 µg of corticotropin, which produces a corticotropin level
of approximately 300 pg/mL.5,6
Using the 1-µg dose, we have found that many critically ill patients
in shock with baseline stress cortisol levels of less than 20 µg/dL
who fail to respond to the 1-µg dose can generate cortisol levels of
higher than 20 µg/dL following administration of 250 µg of corticotropin.5 These patients typically improve clinically with
We believe, therefore, that critically ill patients can be stratified
into 3 groups according to their baseline serum cortisol levels. The first
group of patients should have baseline serum cortisol levels of less than
20 µg/dL. This group is likely to have AI and high mortality. Treatment
with corticosteroids may reduce mortality in these patients. Patients with
high baseline cortisol levels (>45 µg/dL) are those with severe stress,
who are likely to have high mortality as a result of overwhelming illness.
Patients whose baseline serum cortisol levels are between 20 µg/dL and
45 µg/dL are likely to have the best prognosis.
Fontanarosa PB, Marik P, Zaloga G. Prognostic Value of Cortisol Response in Septic Shock. JAMA. 2000;284(3):308–309. doi:10.1001/jama.284.3.303
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