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Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study
Open accessAbstract
CONTEXT: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. OBJECTIVE: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. DESIGN, PATIENTS, AND METHODS: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. RESULTS: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. CONCLUSION: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
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“These challenges often lead to delayed diagnosis, contributing to increased morbidity and mortality (48-50, 53).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [53]
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Nakabayashi, H., Akiyama, M., Yodokawa, T., Itoh, W., Taguchi, A., Takeda, K., Yamamoto, N., Morishige, T., Ikeda, E., & Ohta, Y. (2025) · Cureus · doi:10.7759/cureus.77459
Johannsson, G., Ragnarsson, O., & Skoglund, T. (2024) · Clinical Endocrinology · doi:10.1111/cen.15170
“It is influenced by the pituitary tumour phenotype and its behaviour, the presence of hypopituitarism, but also other related comorbidities such as cardiovascular disorders, hypertension and diabetes mellitus [4 – 7].”
Self-citationAdenomas hipofisarios y adenomas funcionantes
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“It is typical for patients to report symptoms for up to three years before Cushing syndrome is diagnosed because many of the symptoms are ambiguous(12).”
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Metadata
- Authors
- Ragnarsson, O., Olsson, D. S., Papakokkinou, E., Chantzichristos, D., Dahlqvist, P., Segerstedt, E., Olsson, T., Petersson, M., Berinder, K., Bensing, S., Höybye, C., Edén-Engström, B., Burman, P., Bonelli, L., Follin, C., Petranek, D., Erfurth, E. M., Wahlberg, J., Ekman, B., Åkerman, A.-K., Schwarcz, E., Bryngelsson, I.-L., & Johannsson, G.
- Affiliations
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Sahlgrenska University Hospital (SE)
- Umeå University (SE)
- Karolinska University Hospital (SE)
- Department of Medical Sciences; Endocrinology, Diabetes and Metabolism, Uppsala University Hospital, Uppsala, Sweden
- Skåne University Hospital (SE)
- Linköping University (SE)
- Örebro University (SE)
- Örebro University Hospital (SE)
- ORCID
- Ragnarsson, Oskar
- Olsson, Daniel S
- Papakokkinou, Eleni
- Chantzichristos, Dimitrios
- Dahlqvist, Per
- Olsson, Tommy
- Petersson, Maria
- Berinder, Katarina
- Bensing, Sophie
- Höybye, Charlotte
- Burman, Pia
- Bonelli, Lorenza
- Follin, Cecilia
- Erfurth, Eva Marie
- Wahlberg, Jeanette
- Ekman, Bertil
- Åkerman, Anna-Karin
- Schwarcz, Erik
- Bryngelsson, Ing-Liss
- Johannsson, Gudmundur
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-02-01
- Volume
- 104
- Issue
- 6
- Pages
- 2375-2384
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2914799087
- Cited by
- 134
- References
- 36
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 14 · 2023: 18 · 2022: 29 · 2021: 18 · 2020: 14 · 2019: 7
- FWCI
- 13.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Göteborgs Läkaresällskap
- Västra Götalandsregionen
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Keywords
- Cushing's disease, mortality, remission, cardiovascular disease, suicide, infection, bilateral adrenalectomy, glucocorticoid replacement therapy, growth hormone replacement therapy, hormone replacement therapy, mortality risk factors, active surveillance
- MeSH terms
- Adult, Cardiovascular Diseases, Female, Humans, Male, Middle Aged, Retrospective Studies, Proportional Hazards Models, Hormone Replacement Therapy, Pituitary ACTH Hypersecretion
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