Long-term consequences of Cushing syndrome: a systematic literature review
Abstract
It is held that the condition of endogenous chronic hypersecretion of cortisol (Cushing syndrome, CS), causes several comorbidities, including cardiovascular and metabolic disorders, musculoskeletal alterations, as well as cognitive and mood impairment. Therefore, CS has an adverse impact on the quality of life and life expectancy of affected patients. What remains unclear is whether disease remission may induce a normalization of the associated comorbid conditions. In order to retrieve updated information on this issue, we conducted a systematic search using the Pubmed and Embase databases to identify scientific papers published from January 1, 2000, to December 31, 2022. The initial search identified 1907 potentially eligible records. Papers were screened for eligibility and a total of 79 were included and classified by the main topic (cardiometabolic risk, thromboembolic disease, bone impairment, muscle damage, mood disturbances and quality of life, cognitive impairment, and mortality). Although the limited patient numbers in many studies preclude definitive conclusions, most recent evidence supports the persistence of increased morbidity and mortality even after long-term remission. It is conceivable that the degree of normalization of the associated comorbid conditions depends on individual factors and characteristics of the conditions. These findings highlight the need for early recognition and effective management of patients with CS, which should include active treatment of the related comorbid conditions. In addition, it is important to maintain a surveillance strategy in all patients with CS, even many years after disease remission, and to actively pursue specific treatment of comorbid conditions beyond cortisol normalization.
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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 [28]
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 [28]
Among patients with CS, normalization of cortisol concentrations results in improvements in morbidity, mortality, and quality of life.
“Among patients with CS, normalization of cortisol concentrations results in improvements in morbidity, mortality, and quality of life (28, 35, 109, 110).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [28]
Persistent disruption in cortisol circadian rhythm during remission may play a role in the long-term complications associated with prior glucocorticoid excess.
“This persistent disruption in cortisol circadian rhythm during remission may play a role in the long-term complications associated with prior glucocorticoid excess (28, 113, 114, 116).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [28]
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- Authors
- Puglisi, S., Perini, A. M. E., Botto, C., Oliva, F., & Terzolo, M.
- Affiliations
- Ospedale San Luigi Gonzaga (IT)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Corresponding author
- Terzolo, Massimo
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2023-08-03
- Volume
- 109
- Issue
- 3
- Pages
- e901-e919
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W4385564131
- Cited by
- 53
- References
- 97
- Citations by year
- 2026: 25 · 2025: 17 · 2024: 10 · 2023: 1
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (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, long-term outcomes, comorbidities, remission, cardiovascular risk, thromboembolism, muscle damage, mood disturbance, cognitive impairment, quality of life, mortality, cortisol hypersecretion
- MeSH terms
- Cardiovascular Diseases, Cushing Syndrome, Humans, Hydrocortisone, Metabolic Diseases, Quality of Life, Comorbidity, Cognitive Dysfunction
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