The relative adrenal insufficiency syndrome revisited: which patients will benefit from low-dose steroids?

Several clinical studies have given rise to optimism about low-dose steroid treatment in patients with sepsis. It reduces time to shock reversal and may even have a positive effect on mortality. The pathophysiology of the relative adrenal insufficiency syndrome has not yet been determined, and the usefulness of basal and stimulated cortisol levels in diagnosing this syndrome is still uncertain. This review will examine recent evidence to elucidate these questions.

Studies performed in more than 1000 patients in intensive care show convincingly that in general serum cortisol levels are increased. Basal or stimulated cortisol levels are at best useful to predict mortality in patients in intensive care, not to decide which patients to treat or when to discontinue treatment. Measuring free cortisol concentrations rather than total cortisol concentrations in critically ill patients may lead to new research strategies to identify the mode of action of low-dose steroid treatment.

It has been shown that low-dose corticosteroid administration to catecholamine-dependent patients in septic shock results in shock reversal. There seems to be a relative shortage of cortisol, because low-dose hydrocortisone administration resulting in cortisol levels as much as four times the already increased levels results in shock reversal. Strong evidence for a positive effect on mortality is still lacking, perhaps because of the relatively low number of patients investigated. A very important topic in interpreting studies is that total (free plus protein-bound) cortisol has been measured. Future studies should also measure free cortisol concentrations, which could add to our knowledge of the pathophysiology and treatment of the relative adrenal insufficiency syndrome. On the basis of current knowledge, there is no evidence to support a treatment strategy based on a random or stimulated cortisol level. At the moment, rapid hemodynamic improvement of catecholamine-dependent patients after the administration of low-dose corticosteroids still seems the best available clue to diagnosis.