Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness

• Published in: Intensive care medicine Vol. 37; no. 12; pp. 1986 - 1993
• Main Authors: Molenaar, Nienke, Johan Groeneveld, A. B., Dijstelbloem, Hilde M., de Jong, Margriet F. C., Girbes, Armand R. J., Heijboer, Annemieke C., Beishuizen, Albertus
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2011; Springer; Springer Nature B.V
• Subjects: 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; Netherlands; 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
• DOI: 10.1007/s00134-011-2342-x
• ISSN: 0342-4642

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.