Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin
Abstract
Background In normal plasma free cortisol accounts for less than 6% of the total with 80-90% bound to corticosteroid-binding globulin (CBG) and the remainder associated albumin. However little is known about the distribution of free cortisol in plasma where CBG is inactivated or in congenital CBG deficiency. Methods and results Here we describe ligand binding experiments revealing that while free cortisol in unstressed individuals is less than 6% of total cortisol this rises markedly to 25% when CBG is totally inactivated by heat. Similar elevations of the free cortisol fraction were noted in a patient with a rare genetically determined complete lack of CBG (mean 32% on frequent circadian sampling). Following heat inactivation of CBG or in the congenital absence of CBG, there is a shift in cortisol binding from CBG to albumin. That this shift occurs is further supported by experiments adding [3H]-cortisol to physiological human serum albumin solutions, where 25% of cortisol remained in the free fraction. Conclusion Taken together the data provide strong evidence that when CBG is inactivated or congenitally absent then more than 25% of the total cortisol appears in the free fraction with the remainder associated with albumin. The proportion of free cortisol measured in plasma thus reflects a simple measure of functional corticosteroid-binding globulin.
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Ninety percent of serum cortisol circulates bound to cortisol binding globulin, 5% to generic binding proteins such as albumin and α-1 glycoprotein, and only 5% is unbound or free.
“Ninety percent of serum cortisol circulates bound to cortisol binding globulin, 5% to generic binding proteins, such as albumin and α-1 glycoprotein, and only 5% is unbound or ‘free’ [1].”
From Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone (2018) · cites this paper as [1]
The assessment of absolute bioavailability of oral hydrocortisone is complicated by its saturable binding to cortisol binding globulin (CBG) in the therapeutic range.
“The assessment of bioavailability of oral hydrocortisone is complicated by its saturable binding in the therapeutic range to cortisol binding globulin (CBG).”
From Bioavailability of Oral Hydrocortisone Corrected for Binding Proteins and Measured by LC-MS/MS Using Serum Cortisol and Salivary Cortisone (2018) · cites this paper as [1]
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- Authors
- Lewis, J. G., Bagley, C. J., Elder, P. A., Bachmann, A. W., & Torpy, D. J.
- Affiliations
- Canterbury Health Laboratories (NZ)
- Royal Adelaide Hospital (AU)
- Princess Alexandra Hospital (AU)
- Corresponding author
- Lewis, John G.
- Venue
- Clinica Chimica Acta
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 359
- Issue
- 1-2
- Pages
- 189-194
- ISSN
- 0009-8981 (ISSN-L)
- OpenAlex
- W2032093198
- Cited by
- 214
- References
- 2
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 12 · 2023: 13 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 10 · 2018: 16 · 2017: 9 · 2016: 13 · 2015: 16 · 2014: 12 · 2013: 14 · 2012: 8
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinica Chimica Acta (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- free cortisol, corticosteroid-binding globulin, cortisol binding, serum albumin, ligand binding, diurnal cortisol rhythm
- MeSH terms
- Enzyme-Linked Immunosorbent Assay, Humans, Hydrocortisone, Ligands, Serum Albumin, Transcortin
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