Assessment of tissue cortisol activity.

Area of Science:

• Endocrinology
• Critical Care Medicine
• Biochemistry

Background:

• The diagnosis of relative adrenal insufficiency in severe sepsis remains controversial.
• Current diagnostic methods rely on plasma total cortisol measurements, which may not accurately reflect functional adrenal status.
• A lack of a universally accepted gold standard complicates diagnosis in critically ill patients.

Purpose of the Study:

• To review mechanisms affecting tissue glucocorticoid activity.
• To examine how critical illness modifies these mechanisms.
• To explore alternative diagnostic approaches for adrenal insufficiency in critical illness.

Main Methods:

• Review of existing literature on glucocorticoid metabolism and action.
• Analysis of factors influencing tissue glucocorticoid activity, including free and interstitial cortisol, intracellular generation, and receptor dynamics.
• Discussion of limitations of plasma total cortisol measurements.

Main Results:

• Plasma total cortisol levels do not adequately represent functional glucocorticoid activity at the tissue level.
• Critical illness significantly alters factors governing tissue glucocorticoid activity.
• Free cortisol, interstitial cortisol, intracellular generation, and glucocorticoid-receptor status are key determinants of glucocorticoid action.

Conclusions:

• Assessing tissue-level glucocorticoid activity offers a potentially more accurate index of adrenal function than plasma cortisol measurements.
• Advanced techniques, such as genetic transcriptional surveys, may be necessary to fully understand glucocorticoid insufficiency in critical illness.
• Rethinking diagnostic strategies for adrenal insufficiency in sepsis is warranted.