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The hypothalamic pituitary adrenal axis in sepsis
Andrea Polito1, Jérôme Aboab, Djillali Annane
1Hospital Raymond Poincaré (AP-HP), University of Versailles SQY, 104 Boulevard Raymond Poincaré, Garches 92380.
Novartis Foundation Symposium
|March 27, 2007
Summary
Early 20th-century observations highlighted adrenal glands in infection defense. Renewed interest in low-dose corticosteroid therapy for septic shock emerges due to established links with adrenal insufficiency and inflammation-induced resistance.
Area of Science:
- Endocrinology
- Infectious Diseases
- Critical Care Medicine
Background:
- Adrenal gland apoplexy in meningococcemia identified early role in infection defense.
- Cortisone discovery revealed diverse physiological roles in stress response.
- Corticosteroids introduced for severe infections in the 1940s.
Purpose of the Study:
- To review the critical role of the hypothalamic-pituitary-adrenal axis in host stress response.
- To explore the historical and recent perspectives on corticosteroid use in severe infections.
Main Methods:
- Historical review of clinical observations and therapeutic interventions.
- Analysis of randomized controlled trials regarding glucocorticoid efficacy.
- Examination of recent findings linking septic shock to adrenal insufficiency and glucocorticoid receptor resistance.
Main Results:
- Early high-dose glucocorticoid trials for sepsis/ARDS yielded negative results, casting doubt on their benefit.
- Recent research establishes a connection between septic shock, adrenal insufficiency, and inflammation-induced glucocorticoid receptor resistance.
- These findings have prompted a resurgence of interest in low-dose, long-term corticosteroid replacement therapy.
Conclusions:
- The hypothalamic-pituitary-adrenal axis is central to the host's response to stress.
- Evidence suggests a nuanced role for corticosteroids in managing severe infections, shifting towards lower doses and longer durations.
- Further investigation into corticosteroid replacement therapy for septic shock is warranted.
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