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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, . . . [Full Text of this Article]

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