Long-term effects of glucocorticoid excess on the brain
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The metabolic and cardiovascular clinical manifestations in patients with Cushing's syndrome (CS) are generally well known. However, recent studies have broadened the perspective of the effects of hypercortisolism, showing that both endogenous and exogenous glucocorticoid excess alter brain functioning on several time scales. Consequently, cognitive deficits and neuropsychological symptoms are highly prevalent during both active CS and CS in remission, as well as during glucocorticoid treatment. In this review, we discuss the effects of endogenous hypercortisolism and exogenously induced glucocorticoid excess on the brain, as well as the prevalence of cognitive and neuropsychological deficits and their course after biochemical remission. Furthermore, we propose possible mechanisms that may underly neuronal changes, based on experimental models and in vitro studies. Finally, we offer recommendations for future studies.
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Both endogenous and exogenous glucocorticoid excess acting on mineralocorticoid and glucocorticoid receptors expressed by neurons in the central nervous system have been shown to directly alter the structure and functioning of the brain.
“Both endogenous and exogenous glucocorticoid excess on MR and GR expressed by neurons in the CNS have been shown directly alter the structure and functioning of the brain (429–431).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [429]
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- Authors
- Dekkers, A. J., Amaya, J. M., van der Meulen, M., Biermasz, N. R., Meijer, O. C., & Pereira, A. M.
- Affiliations
- Leiden University Medical Center (NL)
- Department of Medicine, Division of Endocrinology, Pituitary Center and Center for Endocrine Tumors Leiden University Medical Center Leiden The Netherlands
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Dekkers, Alies J.
- ORCID
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2022-08
- Volume
- 34
- Issue
- 8
- Pages
- e13142-e13142
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- PMC
- PMC9541651
- OpenAlex
- W4224278139
- Cited by
- 56
- References
- 78
- Citations by year
- 2026: 16 · 2025: 8 · 2024: 8 · 2023: 5 · 2022: 18
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroendocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- Cushing's syndrome, glucocorticoid excess, hypercortisolism, cognitive impairment, neuropsychological symptoms, glucocorticoid therapy, remission, neuronal changes
- MeSH terms
- Brain, Cushing Syndrome, Glucocorticoids, Humans
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