Context: Adrenal insufficiency is considered to be prevalent during critical illness, although the pathophysiology, diagnostic criteria and optimal therapeutic strategy remain controversial.
During critical illness, reduced cortisol breakdown contributes substantially to elevated plasma cortisol and low plasma ACTH concentrations.
Objective: As ACTH has a trophic impact on the adrenal cortex, we hypothesized that with longer duration of critical illness, subnormal ACTH adrenocortical stimulation predisposes to adrenal insufficiency.
Design, Setting and Participants: Adrenal glands were harvested ≤ 24h of death from 13 long ICU-stay patients, 27 short ICU-stay patients and 13 controls. Prior glucocorticoid treatment was excluded.
Main Outcome and Measure(s): Microscopic adrenocortical zonational structure was evaluated by H&E staining. The amount of adrenal cholesterol-esters was determined by Oil-Red-O staining and mRNA expression of ACTH-regulated steroidogenic enzymes was quantified.
Results: The adrenocortical zonational structure was disturbed in patients as compared with controls (P< 0.0001), with indistinguishable adrenocortical zones only present in long ICU-stay patients (P=0.003 vs. controls). Adrenal glands from long ICU-stay patients, but not those of short ICU-stay patients, contained 21% less protein (P=0.03) and 9% more fluid (P=0.01) than those from controls, while they tended to weigh less for comparable adrenal surface area. There was 78% less Oil-Red-O staining in long ICU-stay patients than in controls and in short-stay patients (P=0.03), the latter similar to controls (P=0.31). The mRNA expression of MC2R, SCARB1, HMGCR, STAR and CYP11A1 was at least 58% lower in long ICU-stay patients than in controls (all P≤ 0.03), and of MC2R, SCARB1, STAR and CYP11A1 at least 53% lower than in short ICU-stay patients (all P≤ 0.04), whereas gene expression in short ICU-stay patients was similar to controls.
Conclusion and Relevance: Lipid depletion and reduced ACTH-regulated gene expression in prolonged critical illness suggest that sustained lack of ACTH may contribute to risk of adrenal insufficiency in long-stay ICU patients.
Written by:
Boonen E, Langouche L, Janssens T, Meersseman P, Vervenne H, De Samblanx E, Pironet Z, Van Dijck L, Vander Perre S, Derese I, Van den Berghe G. Are you the author?
Clinical division and laboratory of Intensive Care Medicine, Department Cellular and Mollecular Medicine.
Reference: J Clin Endocrinol Metab. 2014 Jul 25:jc20142429.
doi: 10.1210/jc.2014-2429
PubMed Abstract
PMID: 25062464
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