Cited by 726Adrenal Hormones and DisordersStress Responses and CortisolClinical Laboratory Practices and Quality Control

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Measurements of Serum Free Cortisol in Critically Ill Patients

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Hamrahian, Amir H., Oseni, Tawakalitu S., Arafah, Baha M.·2004·New England Journal of Medicine

DOI 10.1056/nejmoa020266

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Abstract

BACKGROUND: Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone. We investigated the effect of decreased amounts of cortisol-binding proteins on serum total and free cortisol concentrations during critical illness, when glucocorticoid secretion is maximally stimulated. METHODS: Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter). RESULTS: Base-line and cosyntropin-stimulated serum total cortisol concentrations were lower in the patients with hypoproteinemia than in those with near-normal serum albumin concentrations (P<0.001). However, the mean (+/-SD) base-line serum free cortisol concentrations were similar in the two groups of patients (5.1+/-4.1 and 5.2+/-3.5 microg per deciliter [140.7+/-113.1 and 143.5+/-96.6 nmol per liter]) and were several times higher than the values in controls (0.6+/-0.3 microg per deciliter [16.6+/-8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated serum total cortisol concentrations were subnormal (18.5 microg per deciliter [510.4 nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia. In all 66 patients, including these 14 who had hypoproteinemia, the base-line and cosyntropin-stimulated serum free cortisol concentrations were high-normal or elevated. CONCLUSIONS: During critical illness, glucocorticoid secretion markedly increases, but the increase is not discernible when only the serum total cortisol concentration is measured. In this study, nearly 40 percent of critically ill patients with hypoproteinemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. Measuring serum free cortisol concentrations in critically ill patients with hypoproteinemia may help prevent the unnecessary use of glucocorticoid therapy.

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Background
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Background
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“Additionally, because more than 90% of circulating cortisol in human serum is bound to proteins (corticosteroid binding protein and albumin), either the baseline cortisol level or the Δmax value may be influenced by serum protein levels, and alterations in the binding proteins could affect the measured concentration o…”
BackgroundResult

Authors: Hamrahian, A. H., Oseni, T. S., & Arafah, B. M.
Affiliations: University Hospitals of Cleveland (US)
ORCID: Hamrahian, Amir H.
Arafah, Baha M.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2004-04-15
Volume: 350
Issue: 16
Pages: 1629-1638
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa020266
OpenAlex: W2125017989
Cited by: 726
References: 40
Citations by year: 2026: 8 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 17 · 2021: 18 · 2020: 17 · 2019: 22 · 2018: 14 · 2017: 28 · 2016: 28 · 2015: 37 · 2014: 41 · 2013: 26 · 2012: 34
FWCI: 40.09
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Center for Research Resources (M01RR000080)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Health Professions › Medical Laboratory Technology › Clinical Laboratory Practices and Quality Control
Keywords: free cortisol, cortisol-binding protein, hypoproteinemia, critically ill patients, ACTH stimulation test, glucocorticoid secretion, adrenal function, serum albumin, hypercortisolism, adrenal insufficiency, aldosterone, critically ill children, critically ill adults, critically ill neonates, critically ill infants
MeSH terms: Adrenal Insufficiency, Adrenocorticotropic Hormone, Aged, Aldosterone, Cosyntropin, Humans, Hydrocortisone, Hypoproteinemia, Middle Aged, Pituitary-Adrenal System, Regression Analysis, Critical Illness, APACHE, Hypoalbuminemia

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Measurements of Serum Free Cortisol in Critically Ill Patients

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