Critical Illness Contributes to Adrenal Insufficiency

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Critical illness alters adrenal glands and contributes to adrenal insufficiency in ICU patients.

Adrenal insufficiency in intensive care unit patients may be due to alterations in the adrenal gland effected by critical illness, according to data published in the Journal of Clinical Endocrinology & Metabolism.

This study was also presented as a late-breaker abstract at ICE/ENDO 2014, the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

Adrenal insufficiency is considered to be prevalent during critical illness, although the pathophysiology, diagnostic criteria and optimal therapeutic strategy remain controversial,” wrote Eva Boonen, MD, of the University of Leuven in Belgium, and colleagues.

To further investigate this association, the researchers harvested adrenal glands from 13 long intensive care unit (ICU)-stay patients, 27 short ICU-stay patients and 13 control patients within 24 hours of death.

Hematoxylin and eosin (HE) staining were used to evaluate adrenocortical zonational structure and the amount of adrenal cholesterol-esters was measured using Oil-Red-O (ORO) staining. The researchers also quantified mRNA expression of adrenocorticotropic hormone (ACTH)-regulated steroidogenic enzymes.

Compared with controls, patients exhibited disturbed adrenocortical zonational structure (P<.0001), with only long ICU-stay patients having indistinguishable adrenocortical zones (P=.003), according to study results.

Additionally, compared with controls, long ICU-stay patients’ adrenal glands contained 21% less protein (P-.03) and 9% more fluid (P=.01). However, they generally weighed less for equivalent adrenal surface area. The same results were not observed for short ICU-stay patients.

ORO staining was also 78% less in long ICU-stay patients, as compared with controls and short ICU-stay patients (P=.03). For short ICU-stay patients, ORO staining was similar to controls (P=.31).

Further, in long ICU-stay patients, the researchers observed 58% lower mRNA expression of MC2R, SCARB1, HMGCR, STAR and CYP11A1 (P≤.03) vs. controls. Also in long ICU-stay patients, mRNA expression of MC2R, SCARB1, STAR and CYP11A1 was at least 53% lower, as compared with that of short ICU-stay patients (all P≤.04).

Gene expression in short ICU-stay patients, however, was similar to control patients.

Extended duration of critical illness affects adrenocortical structure and function, which is potentially associated with ACTH deprivation, the researchers concluded.

“Depletion of cholesterol esters and reduced expression of ACTH-regulated genes involved in steroidogenesis may contribute to the risk of adrenal insufficiency in the prolonged phase of critical illness,” they wrote.


  1. Boonen E et al. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2014-2429.