Reduced Cortisol Metabolism during Critical Illness

Eva Boonen; Hilke Vervenne; Philippe Meersseman; Ruth Andrew; Leen Mortier; Peter E. Declercq; Yoo-Mee Vanwijngaerden; Isabel Spriet; Pieter J. Wouters; Sarah Vander Perre; Lies Langouche; Ilse Vanhorebeek; Brian R. Walker; Greet Van den Berghe

doi:10.1056/NEJMoa1214969

Reduced Cortisol Metabolism during Critical Illness

Eva Boonen, Hilke Vervenne, Philippe Meersseman, Ruth Andrew, Leen Mortier, Peter E. Declercq, Yoo-Mee Vanwijngaerden, Isabel Spriet, Pieter J. Wouters, Sarah Vander Perre, Lies Langouche, Ilse Vanhorebeek, Brian R. Walker, Greet Van den Berghe^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND

Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.

METHODS

In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes.

RESULTS

Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P

CONCLUSIONS

During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.)

Original language	English
Pages (from-to)	1477-1488
Number of pages	12
Journal	New England Journal of Medicine
Volume	368
Issue number	16
DOIs	https://doi.org/10.1056/NEJMoa1214969
Publication status	Published - 18 Apr 2013

Keywords / Materials (for Non-textual outputs)

BILE-ACIDS
HUMANS
ADRENOCORTICOTROPIN
BETA-HYDROXYSTEROID DEHYDROGENASE
ADRENAL AXIS
SEPTIC SHOCK
11-BETA-HYDROXYSTEROID DEHYDROGENASE
ADIPOSE-TISSUE
IN-VIVO
APPARENT MINERALOCORTICOID EXCESS

Access to Document

10.1056/NEJMoa1214969

Reduced Cortisol Metabolism during Critical Illness
Reprinted with permission.
Final published version, 832 KB

http://www.nejm.org/doi/full/10.1056/NEJMoa1214969

Cite this

Boonen, E., Vervenne, H., Meersseman, P., Andrew, R., Mortier, L., Declercq, P. E., Vanwijngaerden, Y.-M., Spriet, I., Wouters, P. J., Vander Perre, S., Langouche, L., Vanhorebeek, I., Walker, B. R., & Van den Berghe, G. (2013). Reduced Cortisol Metabolism during Critical Illness. New England Journal of Medicine, 368(16), 1477-1488. https://doi.org/10.1056/NEJMoa1214969

@article{893b0f26d9e84d15b370794924ed6372,

title = "Reduced Cortisol Metabolism during Critical Illness",

abstract = "BACKGROUNDCritical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.METHODSIn a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes.RESULTSTotal and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (PCONCLUSIONSDuring critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.)",

keywords = "BILE-ACIDS, HUMANS, ADRENOCORTICOTROPIN, BETA-HYDROXYSTEROID DEHYDROGENASE, ADRENAL AXIS, SEPTIC SHOCK, 11-BETA-HYDROXYSTEROID DEHYDROGENASE, ADIPOSE-TISSUE, IN-VIVO, APPARENT MINERALOCORTICOID EXCESS",

author = "Eva Boonen and Hilke Vervenne and Philippe Meersseman and Ruth Andrew and Leen Mortier and Declercq, {Peter E.} and Yoo-Mee Vanwijngaerden and Isabel Spriet and Wouters, {Pieter J.} and {Vander Perre}, Sarah and Lies Langouche and Ilse Vanhorebeek and Walker, {Brian R.} and {Van den Berghe}, Greet",

year = "2013",

month = apr,

day = "18",

doi = "10.1056/NEJMoa1214969",

language = "English",

volume = "368",

pages = "1477--1488",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "MASSACHUSETTS MEDICAL SOC",

number = "16",

}

TY - JOUR

T1 - Reduced Cortisol Metabolism during Critical Illness

AU - Boonen, Eva

AU - Vervenne, Hilke

AU - Meersseman, Philippe

AU - Andrew, Ruth

AU - Mortier, Leen

AU - Declercq, Peter E.

AU - Vanwijngaerden, Yoo-Mee

AU - Spriet, Isabel

AU - Wouters, Pieter J.

AU - Vander Perre, Sarah

AU - Langouche, Lies

AU - Vanhorebeek, Ilse

AU - Walker, Brian R.

AU - Van den Berghe, Greet

PY - 2013/4/18

Y1 - 2013/4/18

N2 - BACKGROUNDCritical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.METHODSIn a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes.RESULTSTotal and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (PCONCLUSIONSDuring critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.)

AB - BACKGROUNDCritical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism.METHODSIn a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes.RESULTSTotal and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (PCONCLUSIONSDuring critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.)

KW - BILE-ACIDS

KW - HUMANS

KW - ADRENOCORTICOTROPIN

KW - BETA-HYDROXYSTEROID DEHYDROGENASE

KW - ADRENAL AXIS

KW - SEPTIC SHOCK

KW - 11-BETA-HYDROXYSTEROID DEHYDROGENASE

KW - ADIPOSE-TISSUE

KW - IN-VIVO

KW - APPARENT MINERALOCORTICOID EXCESS

U2 - 10.1056/NEJMoa1214969

DO - 10.1056/NEJMoa1214969

M3 - Article

SN - 0028-4793

VL - 368

SP - 1477

EP - 1488

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 16

ER -

Reduced Cortisol Metabolism during Critical Illness

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Cite this