Glucocorticoid receptor polymorphisms influence muscle strength in Cushing's syndrome
Open accessAbstract
CONTEXT: An important clinical feature of Cushing's syndrome (CS) is proximal muscle myopathy caused by glucocorticoid induced protein metabolism. However, interindividual differences cannot be explained solely by the pure extent of hypercortisolemia. OBJECTIVE: To evaluate the effects of glucocorticoid receptor (GR) polymorphisms (BclI, N363S, ER22/23EK and A3669G), which influence peripheral glucocorticoid sensitivity on muscular function in endogenous CS. METHODS: 205 patients with proven endogenous CS (128 central, 77 adrenal) from 3 centers of the German Cushing's Registry and 125 subjects, in whom CS was ruled out, were included. All subjects were assessed for grip strength (via hand grip dynamometer) and performed a chair-rising test (CRT). DNA samples were obtained from peripheral blood leukocytes for GR genotyping. RESULTS: In patients with active CS, normalized handgrip strength of the dominant and nondominant hand was higher in A3669G minor allele than in wildtype carriers (P = .006 and P = .021, respectively). CS patients in remission and ruled-out CS showed no differences in handgrip strength regarding A3669G minor allele and wildtype carriers. Male CS patients harboring the ER22/23EK wildtype presented lower hand grip strength than minor allele carriers (P = .049 dominant hand; P = .027 nondominant hand). The other polymorphisms did not influence handgrip strength. CRT showed no differences regarding GR polymorphisms carrier status. CONCLUSION: Handgrip strength seems to be more susceptible to hypercortisolism in A3669G wildtype than in A3669G minor allele carriers. This might partially explain the inter-individual differences of glucocorticoid-induced myopathy in patients with endogenous CS. ER22/23EK polymorphism seems to exert sex-specific differences.
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Interindividual sensitivity to glucocorticoids is influenced, in part, by polymorphisms in the glucocorticoid receptor gene, which have been associated with altered receptor function and differential metabolic responses to cortisol.
“This variability is influenced, in part, by polymorphisms in the glucocorticoid receptor gene, which have been associated with altered receptor function and differential metabolic responses to cortisol (102-108).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [102]
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- Authors
- Müller, L. M., Kienitz, T., Deutschbein, T., Riester, A., Hahner, S., Burger-Stritt, S., Berr, C. M., Oßwald, A., Braun, L., Rubinstein, G., Reincke, M., & Quinkler, M.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Universitätsklinikum Würzburg (DE)
- LMU Klinikum (DE)
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, Würzburg, Germany
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
- Endocrinology in Charlottenburg, Berlin, Germany
- Corresponding author
- Quinkler, Marcus
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-10-15
- Volume
- 105
- Issue
- 1
- Pages
- 305-313
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2980581643
- Cited by
- 17
- References
- 38
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Else Kröner-Fresenius Stiftung (2012_A103, 2015_A228, CRC/TRR 205)
- Deutsche Forschungsgemeinschaft
- University of Würzburg (Z-2/57)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- Cushing's syndrome, muscle strength, grip strength, glucocorticoid-induced myopathy, ER22/23EK polymorphism, BclI polymorphism, N363S polymorphism, hypercortisolism, sex differences
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Cushing Syndrome, Female, Gene Frequency, Genotype, Germany, Humans, Male, Middle Aged, Muscular Diseases, Polymorphism, Genetic, Receptors, Glucocorticoid, Registries, Sex Characteristics, Hand Strength, Genetic Predisposition to Disease, Muscle Strength, Young Adult
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