Glucocorticoid sensitivity in health and disease
Abstract
Glucocorticoids regulate many physiological processes and have an essential role in the systemic response to stress. For example, gene transcription is modulated by the glucocorticoid-glucocorticoid receptor complex via several mechanisms. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Differences in sensitivity to glucocorticoids in healthy individuals are partly genetically determined by functional polymorphisms of the gene that encodes the glucocorticoid receptor. Hereditary syndromes have also been identified that are associated with increased and decreased sensitivity to glucocorticoids. As a result of their anti-inflammatory properties, glucocorticoids are widely used in the treatment of allergic, inflammatory and haematological disorders. The variety in clinical responses to treatment with glucocorticoids reflects the considerable variation in glucocorticoid sensitivity between individuals. In immune-mediated disorders, proinflammatory cytokines can induce localized resistance to glucocorticoids via several mechanisms. Individual differences in how tissues respond to glucocorticoids might also be involved in the predisposition for and pathogenesis of the metabolic syndrome and mood disorders. In this Review, we summarize the mechanisms that influence glucocorticoid sensitivity in health and disease and discuss possible strategies to modulate glucocorticoid responsiveness.
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An ultra-low-dose dexamethasone suppression test showing suppressed morning serum cortisol levels is indicative of increased glucocorticoid sensitivity.
“An ultra-low-dose DST showing suppressed morning serum cortisol levels is also indicative of this rare condition, and functional testing of the glucocorticoid receptor or sequencing of the glucocorticoid receptor gene may be considered in specialized centers (31, 49, 50).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [50]
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Self-citation
- Authors
- Quax, R. A., Manenschijn, L., Koper, J. W., Hazes, J. M., Lamberts, S. W. J., van Rossum, E. F. C., & Feelders, R. A.
- Affiliations
- Erasmus MC (NL)
- Corresponding author
- Feelders, Richard A.
- Venue
- Nature Reviews Endocrinology
- Published
- 2013-10-01
- Volume
- 9
- Issue
- 11
- Pages
- 670-686
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2026370575
- Cited by
- 310
- References
- 24
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 22 · 2023: 16 · 2022: 26 · 2021: 29 · 2020: 27 · 2019: 23 · 2018: 31 · 2017: 36 · 2016: 20 · 2015: 23 · 2014: 22 · 2013: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoid sensitivity, glucocorticoid receptor, glucocorticoid resistance, glucocorticoid therapy, genetic polymorphism, inflammatory cytokines, metabolic syndrome, mood disorders, stress response, transcriptional regulation, treatment response variability
- MeSH terms
- Anti-Inflammatory Agents, Glucocorticoids, Humans, Receptors, Glucocorticoid, Signal Transduction, Cytokines, Genetic Predisposition to Disease
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