ArticleThe Journal of clinical endocrinology and metabolism2013
How changes in affinity of corticosteroid-binding globulin modulate free cortisol concentration.
Article in The Journal of clinical endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Neuroendocrine signature of ME/CFS: Meta-analytic evidence for bioactive cortisol deficit and exaggerated feedback sensitivity.Molecular psychiatry · 2026Pooled it
- Plasma cortisol-linked gene networks in hepatic and adipose tissues implicate corticosteroid-binding globulin in modulating tissue glucocorticoid action and cardiovascular risk.Frontiers in endocrinology · 2023Pooled it
- A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study.Lipids in health and disease · 2014Trial
- TS3 Asn347 corticosteroid-binding globulin (CBG) glycoform deficiency is associated with mortality in human septic shock.Journal of the Endocrine Society · 2026Article
- Harnessing native corticosteroid-binding globulin to treat life-threatening septic shock.Endocrinology · 2026Article
- Article
- Clinical characteristics of acute adrenal insufficiency in emergency patients: an analysis of data in Lhasa, Xizang Autonomous Region of China.World journal of emergency medicine · 2025Article
- RCL glycosylation of serum corticosteroid-binding globulin: implications in cortisol delivery and septic shock.Glycobiology · 2025Article
- The effect of serum cortisol level on the outcomes of Persistent Inflammation, Immunosuppression and Catabolism Syndrome patients in the intensive care unit.Pakistan journal of medical sciences · 2025Article
- Adrenal crisis-induced cardiogenic shock (ACCS): a comprehensive review.Heart failure reviews · 2025Review
- Steroid Metabolomic Signature in Term and Preterm Infants.Biomolecules · 2024Article
- Critical illness-related corticosteroid insufficiency (CIRCI) - an overview of pathogenesis, clinical presentation and management.Frontiers in endocrinology · 2024Review
- Article
- The Hypothalamus-pituitary-adrenocortical Response to Critical Illness: A Concept in Need of Revision.Endocrine reviews · 2023Article
- High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice.Cardiovascular research · 2023Article
- Potential Biomarkers to Distinguish Type 1 Myocardial Infarction in Troponin-Elevated Diseases.International journal of molecular sciences · 2023Article
- The Added Value of Serum Random Cortisol and Thyroid Function Tests as Mortality Predictors for Critically Ill Patients: A Prospective Cohort Study.Journal of clinical medicine · 2022Article
- Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be.The Journal of clinical endocrinology and metabolism · 2022Review
- Interpretation of Abnormal Dexamethasone Suppression Test is Enhanced With Use of Synchronous Free Cortisol Assessment.The Journal of clinical endocrinology and metabolism · 2022Observational
- Cross-Sectional and Longitudinal Associations Between the Serum G\lobulin Level, and Renal Impairment and All-Cause Deaths in Chinese Patients With Newly Diagnosed Multiple Myeloma.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
contextRecent studies of corticosteroid-binding globulin (CBG) indicate that it does not merely transport cortisol passively but also actively regulates its release in the circulation. We show how CBG binding affinity can vary to give changes in free cortisol concentration in a physiologically relevant range.
objectiveThe objective was to determine how the binding affinity of plasma CBG is affected by glycosylation, changes in body temperature, and the conformational change induced by proteases at sites of inflammation.
designBinding assays were performed over a range of temperatures with plasma and recombinant CBG to determine the contribution of glycosylation. The role of conformational change was assessed by measuring binding affinities of plasma CBG before and after reactive loop cleavage by neutrophil elastase.
main outcome measuresDetermination of binding constants allows calculation of clinically relevant changes in CBG saturation and free cortisol concentrations.
resultsOn reactive loop cleavage at inflammation sites, CBG can continue to act as a buffered source of cortisol, although with a much reduced affinity, to give a potential quadrupling of free cortisol. Predicted increases in systemic free cortisol resulting from elevated body temperatures, previously reported based on affinity measurements using nonglycosylated recombinant CBG, were shown here to be considerably increased using glycosylated plasma CBG, with a doubling for every 2°C rise in body temperature.
conclusionsThe ability of CBG to modulate free cortisol levels in blood must be considered in the understanding and management of disease processes, as illustrated here with predictable changes in inflammation and fever.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.