Sick adrenal or sick euadrenal?

The role of glucocorticoid supplementation in septic shock remains contentious. In septic shock, the driver for steroid therapy is the premise that there is relative adrenal insufficiency (based on reduced plasma cortisol and blunted cortisol response to corticotropin). The uncertainty arises from the inability of current tests to clearly identify patients who are truly corticosteroid "deficient" at a cellular level, and hence require supplemental glucocorticoid administration. We hypothesise that plasma measurements (total plasma cortisol level and the response to corticotropin) do not consistently reflect the functional adrenal response to stress. Published evidence indicates that there are cellular adaptations in stress, such as pre-receptor upregulation of cortisol, altered receptor density and gene transcription changes, none of which are reflected by plasma cortisol level. This leads us to postulate that the lack of a clearly defined plasma response in severe stress and the presence of an adequate response at the cellular level suggest it is a "sick euadrenal state", analogous to the sick euthyroid state, and not a sick adrenal indicating adrenal insufficiency.