Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness
Purpose To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. Methods A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septi...
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Published in | Intensive care medicine Vol. 37; no. 12; pp. 1986 - 1993 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer-Verlag
01.12.2011
Springer Springer Nature B.V |
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Abstract | Purpose
To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency.
Methods
A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed.
Results
Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (
r
= 0.77–0.79,
P
< 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93–0.97 in sepsis and 0.79–0.85 in non-sepsis (
P
= 0.044 or lower for sepsis vs. non-sepsis).
Conclusions
Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis. |
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AbstractList | To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 [mu]g) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis. Purpose To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. Methods A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 [mu]g) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Results Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). Conclusions Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis. Purpose To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. Methods A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Results Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated ( r = 0.77–0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93–0.97 in sepsis and 0.79–0.85 in non-sepsis ( P = 0.044 or lower for sepsis vs. non-sepsis). Conclusions Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis. To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis. PURPOSETo study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. METHODSA prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. RESULTSAlthough a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). CONCLUSIONSAlthough the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis. To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid insufficiency. A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P < 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis.[PUBLICATION ABSTRACT] |
Audience | Academic |
Author | Dijstelbloem, Hilde M. Heijboer, Annemieke C. de Jong, Margriet F. C. Beishuizen, Albertus Molenaar, Nienke Johan Groeneveld, A. B. Girbes, Armand R. J. |
Author_xml | – sequence: 1 givenname: Nienke surname: Molenaar fullname: Molenaar, Nienke organization: Department of Intensive Care, Vrije Universiteit Medical Center – sequence: 2 givenname: A. B. surname: Johan Groeneveld fullname: Johan Groeneveld, A. B. email: johan.groeneveld@vumc.nl organization: Department of Intensive Care, Vrije Universiteit Medical Center – sequence: 3 givenname: Hilde M. surname: Dijstelbloem fullname: Dijstelbloem, Hilde M. organization: Department of Clinical Chemistry, VU University Medical Center Amsterdam – sequence: 4 givenname: Margriet F. C. surname: de Jong fullname: de Jong, Margriet F. C. organization: Department of Intensive Care, Vrije Universiteit Medical Center – sequence: 5 givenname: Armand R. J. surname: Girbes fullname: Girbes, Armand R. J. organization: Department of Intensive Care, Vrije Universiteit Medical Center – sequence: 6 givenname: Annemieke C. surname: Heijboer fullname: Heijboer, Annemieke C. organization: Department of Clinical Chemistry, VU University Medical Center Amsterdam – sequence: 7 givenname: Albertus surname: Beishuizen fullname: Beishuizen, Albertus organization: Department of Intensive Care, Vrije Universiteit Medical Center |
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Keywords | Sepsis Relative adrenal insufficiency Adrenocorticotropic hormone Corticosteroid-binding globulin Equilibrium dialysis Endocrinopathy Corticosteroid Intensive care Steroid hormone Antiinflammatory agent Hydrocortisone Glucocorticoid Globulin Infection Sepsis syndrome Adrenal insufficiency Adenohypophyseal hormone Adrenal hormone Adrenal gland diseases Comparative study Resuscitation |
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To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid... To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid... Purpose To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid... PURPOSETo study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related corticosteroid... |
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SubjectTerms | ACTH Adrenal Insufficiency - complications Adrenal Insufficiency - diagnosis Adult Aged Aged, 80 and over Albumin Albumins - analysis Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anesthesiology Binding proteins Biological and medical sciences Corticosteroids Critical Care Medicine Critical Illness Emergency and intensive care: metabolism and nutrition disorders. Enteral and parenteral nutrition Emergency Medicine Equilibrium Female Hemodialysis Hormones Humans Hydrocortisone - blood Hydrocortisone - secretion Hypotension Illnesses Intensive Intensive care Intensive care medicine Intensive Care Units Male Medical research Medical sciences Medicine Medicine & Public Health Medicine, Experimental Middle Aged Netherlands Original Pain Medicine Pediatrics Pneumology/Respiratory System Prospective Studies Protein binding Proteins Sepsis Sepsis - etiology Sepsis - physiopathology Steroids Transcortin - analysis |
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Title | Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness |
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