Unit:
Κατεύθυνση Μοριακή και Εφαρμοσμένη ΦυσιολογίαLibrary of the School of Health Sciences
Author:
Stamogiannos Georgios
Supervisors info:
Δημοπούλου Ιωάννα, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Φιλίππου Αναστάσιος, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Κουτσιλιέρης Μιχαήλ, Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Φλοιοεπινεφριδιακή ανεπάρκεια σχετιζόμενη με την κρίσιμη νόσο
Translated title:
Critical illness related corticosteroid insufficiency
Summary:
INTRODUCTION: Adrenal cortex is part of the hypothalamus – pituitary – adrenal (HPA) axis, activation of which is one of the most important components of body’s response to various stress stimuli. It’s functional integrity is essential for homeostasis and survival. Critical illness related corticosteroid insufficiency refers to inadequate activation of HPA axis to match severity of patient’s critical illness and is associated with poor prognosis. HPA axis dysregulation, impaired cortisol metabolism and tissue resistance to corticosteroids are responsible for development of CIRCI. Tissue resistance can be due to reduced GR expression, impaired ligand affinity or altered intteractions with DNA regions and various transcription factors. Lately, research has focused on the main splicing variant of GR, the GR-β, and the role it might play in resistance development.
STUDY DESIGN: A prospective observational study conducted in a university affiliated multidisciplinary intensive care unit. 32 critically ill adults not receiving corticosteroid included. Blood samples for GR measurement were collected within 48 hours after admission and twice weekly thereafter for up to two weeks.
RESULTS: During critical illness the mRNA levels of both GR isoforms significantly reduced. This however occurred in different time points. GR-α reduced 4-fold four days after admission (p < 0.0001) and remained low during the 2 week period (p <0.001). GR-β on the other hand remained stable four days after admission but reduced thereafter. More specifically it reduced 3-fold one week aftter admission (p < 0.01) and remained low two weeks after admission (p < 0.001).
DISCUSSION: According our study GR-α and GR-β mRNA expression during critical illness is highly variable among different patients and within same patients at different time points. Both GR-α and GR-β finally reduced during critical illness, result which was statistically significant. In addition, GR-β remained stable four days after admission before decreasing. The highly variable GR expression could at least partially explain the differential responsiveness to corticosteroid administration.
Main subject category:
Health Sciences
Keywords:
Corticosteroid insufficiency, Critical illness, GR isoforms, Septic shock
