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Cited by 419Pituitary Gland Disorders and TreatmentsAdrenal and Paraganglionic TumorsAdrenal Hormones and Disorders

Multisystem morbidity and mortality in Cushing’s syndrome: a cohort study

Dekkers, Olaf M., Horváth-Puhó, Erzsébet, Jørgensen, Jens Otto L., Cannegieter, Suzanne C., Ehrenstein, Vera, Vandenbroucke, Jan P., Pereira, Alberto M., Sørensen, Henrik Toft·2013·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2012-3582
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Abstract

CONTEXT: Cushing's syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS. OBJECTIVE: We aimed to examine the risks for mortality, cardiovascular disease, fractures, peptic ulcers, and infections in CS patients before and after treatment. DESIGN: Population-based cohort study. SETTING: Source population was the entire population of Denmark (1980 to 2010). Data were obtained from the Danish National Registry of Patients and the Danish Civil Registration System. PATIENTS: Benign CS of adrenal or pituitary origin and a matched population comparison cohort were included. OUTCOME MEASURES: We used Cox regression, and computed hazard ratios (HR) with 95% confidence intervals (95% CI). Morbidity was investigated in the 3 years before diagnosis; morbidity and mortality were assessed during complete follow-up after diagnosis and treatment. RESULTS: Included were 343 CS patients and 34 300 controls. Mortality was twice as high in CS patients (HR 2.3, 95%CI 1.8-2.9) compared with controls. Patients with CS were at increased risk for venous thromboembolism (HR 2.6, 95%CI 1.5-4.7), myocardial infarction (HR 3.7, 95%CI 2.4-5.5), stroke (HR 2.0, 95%CI 1.3-3.2), peptic ulcers (HR 2.0, 95%CI 1.1-3.6), fractures (HR 1.4, 95%CI 1.0-1.9), and infections (HR 4.9, 95%CI 3.7-6.4). This increased multimorbidity risk was present before diagnosis. Mortality and risk of myocardial infarction remained elevated during long-term follow-up. Mortality and risks for acute myocardial infarction, venous thromboembolism, stroke, and infections were similarly increased in adrenal and pituitary CS. CONCLUSIONS: Despite the apparently benign character of the disease, CS is associated with clearly increased mortality and multisystem morbidity, even before diagnosis and treatment.

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  • The loss of cortisol circadian rhythm contributes to multiple complications and ultimately increases morbidity and mortality.

    “The loss of cortisol circadian rhythm contributes to multiple complications and ultimately increases morbidity and mortality (27, 28).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [27]

  • Patients with CS who achieve remission following curative treatment remain at a slightly increased risk of morbidity and mortality compared to patients without CS.

    “Patients with CS who achieve remission following curative treatment remain at a slightly increased risk of morbidity and mortality compared to patients without CS (27, 28, 113-116).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [27]

  • Hypercortisolism is associated with 3.5 to 5 times increased mortality risk compared with the general population.

    “Hypercortisolism is associated with an increase in cardiovascular events (myocardial infarction), cerebrovascular events (stroke), sepsis, and thromboembolism with 3.5 to 5 times increased mortality risk compared with the general population (7-11).”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [8]

  • The risk of myocardial infarction is approximately 4.5 times higher in patients with Cushing syndrome compared with the general population.

    “The risk of myocardial infarction is approximately 4.5 times higher in patients with CS compared with the general population (8, 9).”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [8]

  • Cushing syndrome is associated with a high risk of venous thromboembolic events which can be a presenting symptom.

    “Cushing syndrome is associated with a high risk of venous thromboembolic events which can be a presenting symptom”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [8]

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Authors
Dekkers, O. M., Horváth-Puhó, E., Jørgensen, J. O. L., Cannegieter, S. C., Ehrenstein, V., Vandenbroucke, J. P., Pereira, A. M., & Sørensen, H. T.
Affiliations
  • Leiden University Medical Center (NL)
  • Department of Clinical Epidemiology (E.H.-P., V.E.., H.T.S.), Aarhus DK-8000, Denmark
  • Aarhus University Hospital (DK)
Corresponding author
Dekkers, Olaf M.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2013-06-01
Volume
98
Issue
6
Pages
2277-2284
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2012-3582
OpenAlex
W2093593211
Cited by
419
References
33
Citations by year
2026: 25 · 2025: 31 · 2024: 32 · 2023: 25 · 2022: 55 · 2021: 37 · 2020: 39 · 2019: 37 · 2018: 26 · 2017: 20 · 2016: 29 · 2015: 29 · 2014: 25 · 2013: 9
FWCI
24.12
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • 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
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
Cushing's syndrome, mortality, cardiovascular disease, venous thromboembolism, myocardial infarction, stroke, fracture, peptic ulcer, infection, pituitary Cushing's disease, hypercoagulability, insulin resistance
MeSH terms
Adult, Cushing Syndrome, Female, Heart Failure, Humans, Male, Middle Aged, Morbidity, Myocardial Infarction, Cohort Studies, Proportional Hazards Models, Stroke, Venous Thromboembolism

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