Cushing's syndrome: aftermath of the cure
Open accessAbstract
Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.
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Surgical remission does not eliminate the risk of complications from systemic comorbidities completely.
“Surgical remission does not eliminate the risk of complications from systemic comorbidities completely (12, 13).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [12]
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Self-citationTHERAPY OF ENDOCRINE DISEASE: Treatment of malignant pheochromocytoma and paraganglioma
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“The remission or cure of CS usually reduces but does not completely eliminate these systemic complications. Therefore, a history of CS is associated with a persistent increased cardiovascular risk despite the normalization of cortisol secretion [”
BackgroundSelf-citationApproach to the Patient: Diagnosis of Cushing Syndrome
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“Surgical remission does not eliminate the risk of complications from systemic comorbidities completely (12, 13).”
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“Endogenous hyper-cortisolism can result from ACTH-secreting tumors—either pituitary (Cushing’s Disease, CD) or extra-pituitary (ectopic CS) [33]—or ACTH-independent increase in adrenal production due to bilateral gland hyperplasia or tumoral lesions [34].”
BackgroundTreatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?
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“Hypertension phenotype Hypertension usually occurs early in the course of the disease, equally in both genders, and may persist even after achieving clinical and hormonal remission [96,97].”
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Diagnostic workup of Cushing’s syndrome
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Cushing’s Syndrome Effects on the Thyroid
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“It is well known that glucocorticoid excess exerts an inhibitory action on immune function in humans, as confirmed by the involution of lymphoid tissue and by the increased susceptibility to infections detected in patients with CS [35,38].”
BackgroundClinical characteristics of pain in patients with pituitary adenomas.
Dimopoulou, C., Athanasoulia, A., Hanisch, E., Held, S., Sprenger, T., Toelle, T. R., Roemmler-Zehrer, J., Schopohl, J., Stalla, G., & Sievers, C. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0375 · Cited by 38 · see citing works
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“Dealing with a variety of long-term issues, even after successful surgery, can be very frustrating for both [2–6, 26, 28, 29].”
BackgroundHippocampal and cerebellar atrophy in patients with Cushing's disease.
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“For instance, Pivonello et al. [ 10 ] admit the key role of the surgical approach for these patients, which finally resolves the excessive cortisol secretion.”
BackgroundMilian, M., Honegger, J., Teufel, P., Wolf, A., & Psaras, T. (2013) · Neuroendocrinology · doi:10.1159/000355622 · Cited by 24 · see citing works
Surgical remission of Cushing's syndrome reduces cardiovascular risk
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“results in a rapid improvement of some clinical symptoms in patients with CD, but a significant proportion of comorbidities may persist or even develop after biochemical cure, leading to psychosocial impairment and reduced quality of life (QoL) [4].”
BackgroundDeath in pediatric Cushing syndrome is uncommon but still occurs
Gkourogianni, A., Lodish, M. B., Zilbermint, M. F., Lyssikatos, C., Belyavskaya, E., Keil, M. F., & Stratakis, C. A. (2014) · European Journal of Pediatrics · doi:10.1007/s00431-014-2427-y · Cited by 19 · see citing works
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“Кроме того, независимо от динамики МПК безусловного внимания заслуживают последствия ГКостеопороза — переломы позвонков и связанные с ними деформации скелета, которые сохраняются в течение всей жизни пациента [47].”
Hatipoglu, B. (2012) · Journal of Surgical Oncology · doi:10.1002/jso.23197 · Cited by 18 · see citing works
“It has also been reported that even late in the course after cure of CS, atherosclerosis, hypertension, and diabetes mellitus can occur more frequently than in controls [60].”
BackgroundLocal hyperthermia cleared multifarious viral warts in a patient with Cushing's syndrome
Mu, M.-H., Wang, Y.-N., Huang, Y., Niu, X., Chen, H., Gao, X., & Qi, R. (2019) · Dermatologic Therapy · doi:10.1111/dth.12815 · Cited by 15 · see citing works
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“During a posthypophysectomy follow up in PDH patients, both human and canine, it has been proved that the adverse effects of cortisol persist for a long time (Colao et al., 1999; Meij et al., 2002; Pivonello et al., 2007; Barahona et al., 2009, 2010; Webb et al., 2010).”
BackgroundRamezani, A., Zakeri, A., Mard‐Soltani, M., Mohammadian, A., Hashemi, Z. S., Mohammadpour, H., Jahangiri, A., Khalili, S., & Rasaee, M. J. (2019) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-019-09891-7 · Cited by 12 · see citing works
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“The cure for CD or its remission frequently reduce mortality rates but do not completely eliminate cardiovascular risks, even after the normalization of cortisol (F) secretions (5).”
Current views of the screening and diagnostics of endogenous hypercorticism
Белая, Ж. Е., Рожинская, Л. Я., Mel'nichenko, G. A., & Dedov, I. I. (2012) · Problems of Endocrinology · doi:10.14341/probl201258435-41 · Cited by 10 · see citing works
Quality of life in patients with Cushing's disease: a modern approach
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Self-citationCeccato, F., Terzolo, M., Gatto, F., Cannavò, S., Bianchi, A., Isidori, A. M., Colao, A. A. L., Ferone, D., Aimaretti, G., Giraldi, F. P., et al. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02758-3 · Cited by 10 · see citing works
Self-citationUnmasking sarcoidosis following surgery for Cushing disease
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“Another study even coined the term “Cushing cure syndrome” to highlight the immunologic aftermath of supposed cure.(10) In the study by da Mota overt autoimmune and allergic diseases such as psoriasis, sarcoidosis, Graves’ disease, autoimmune thyroiditis, eczema and asthma were diagnosed in 11 of 66 patients (16.”
BackgroundCognitive decline in Cushing's syndrome: A systematic review
Katragadda, A., Kunadia, J., Kirsch, P., Dorcely, B., Shah, S., Henig, Z., Job, A., Feelders, R., & Agrawal, N. (2024) · Journal of neuroendocrinology · doi:10.1111/jne.13466 · Cited by 6 · see citing works
“4 Neuropsychiatric symptoms and cognitive deficits are prevalent but sometimes overlooked features of CS that adversely impact quality of life.”
Endocrine Disorders that Cause Diabetes
Hanley, N. (2010) · doi:10.1002/9781444324808.ch17 · Cited by 5 · see citing works
Frailty and pituitary surgery: a systematic review
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“These comorbidities do not resolve instantaneously, and may persistent many years after biochemical remission[58–60].”
Kumar, N., Jarial, K., Bhansali, A., Nehra, R., Vyas, S., & Walia, R. (2020) · Indian journal of endocrinology and metabolism · doi:10.4103/ijem.ijem_162_20 · Cited by 4 · see citing works
Pronóstico del paciente tratado de síndrome de Cushing
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“The pathogenesis of brain volume loss induced by high glucocorticoid levels is probably due to multiple factors, including cell death induced by glucocorticoids, interference with neuronal transmission and metabolism processes, and decreased brain water contents.(2) Glucocorticoids may occupy both mineralocorticoid an…”
BackgroundCharacteristics of pain in patients with pituitary adenomas: A cross‐sectional study
Dallel, S., Devoize, L., Tauveron, I., Pereira, B., Clavelou, P., Maqdasy, S., Moisset, X., & Dallel, R. (2021) · European Journal of Pain · doi:10.1002/ejp.1721 · Cited by 3
“, 2009) and peripheral neuropathies due to a high incidence of diabetes mellitus in Cushing’s disease (Pivonello et al., 2007).”
Soares, F. A. C., Matheus, J. P., Carvalho, G. L. C., Neuwald, E. B., Pöppl, Á., Valle, S., & Gonzalez, F. (2016) · Korean Journal of Veterinary Research · doi:10.14405/kjvr.2016.56.3.161 · Cited by 3 · see citing works
“Hypertension, glucose intolerance, dyslipidemia, and visceral obesity represent vascular risk factors in patients with HAC [25, 31].”
BackgroundNumakura, K., Nara, T., Kanda, S., Saito, M., Narita, S., Inoue, T., & Habuchi, T. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00572 · Cited by 3 · see citing works
Pasireotide for the treatment of Cushing's disease
Colao, A., Simeoli, C., de Leo, M., Cozzolino, A., & Pivonello, R. (2013) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2013.807731 · Cited by 2 · see citing works
“Moreover, it has been reported that despite successful cure, a significant number of complications may remain persistent after cure [11,12].”
BackgroundSelf-citationTakiguchi, M. K., Morimoto, S., Watanabe, D., Abe, K., & Ichihara, A. (2022) · Hypertension Research · doi:10.1038/s41440-022-00939-8 · Cited by 1 · see citing works
“Patients with CS present a wide spectrum of clinical manifestations, such as easy bruising, facial plethora, proximal myopathy, striae, buffalo hump, facial fullness, and metabolic complications, such as resistance to hypertension [2], diabetes mellitus, and dyslipidemia [3], which can lead to increased chronic kidney…”
BackgroundAre patients in remission from Cushing's syndrome mentally healthy?
Boguszewski, C. L. (2013) · Clinical Endocrinology · doi:10.1111/cen.12278 · Cited by 1 · see citing works
Khodakova, I. V., Arapova, S., Sukhanova, G., Chirkova, L., & Rozhinskaia, L. (2010) · Problems of Endocrinology · doi:10.14341/probl201056434-38 · Cited by 1 · see citing works
“По данным литературы, синдром гиперкортицизма ассоциирован с 4-кратным увеличением частоты развития тромбоэмболии легочной артерии (ТЭЛА), тромбозов глубоких вен и смертностью от них по сравнению с аналогичными показателями в общей популяции [6, 9].”
Male Osteoporosis: Gender Differences in Pathophysiology, Clinical Aspects, Diagnosis and Treatment
Jannini, E., Foresta, C., Lenzi, A., Maggi, M., Ferlin, A., & Migliaccio, S. (2020) · Trends in Andrology and Sexual Medicine · doi:10.1007/978-3-319-96376-1 · Cited by 1
Osteoporosis: May Doping Cause It?
Menafra, D., Minetto, M. A., Salzano, C., de Angelis, C., & Pivonello, R. (2020) · Trends in andrology and sexual medicine · doi:10.1007/978-3-319-96376-1_15
Self-citationPosttreatment Management of Cushing’s Disease
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“[16] Biochemically, 57.14% had hypokalaemia with metabolic alkalosis, which distinguishes ectopic from pituitary ACTH sources, given the high levels of ACTH and cortisol from ectopic tumours.”
InfluentialThe Cardiovascular Risk in Cushing’s Syndrome
Dobrescu, M., Păun, D., Grigorie, D., Ghemigian, A., & Poiană, C. (2019) · Internal Medicine · doi:10.2478/inmed-2019-0058
“Mortality in CS is increased: untreated patients have a 5-year survival rate estimated at 50% ; some studies (1, 2, 3, 4)”
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The clinical characteristics of pain in patients with pituitary adenomas
Dimopoulou, C., Athanasoulia, A., Hanisch, E., Held, S., Toelle, T., Sprenger, T., Zieglgänsberger, W., Pfister, H., Roemmler, J., Schopohl, J., et al. (2013) · Endocrine Abstracts · doi:10.1530/endoabs.32.p858
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Progress in Subclinical Cushing’s Syndrome
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Hypertension in Cushing’s Syndrome
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“It has been documented that the resolution of depression, anxiety disorders, psychosis and some neurocognitive disorders does not correlate with normalization of cortisol levels [11].”
BackgroundLong-Term Effects of Prior Cushing’s Syndrome
Aulinas, A., Valassi, E., Resmini, E., Vives, A. S., Crespo, I., Barahona, M. J., & Webb, S. M. (2016) · Springer eBooks · doi:10.1007/978-3-319-45950-9_11
Psychosocial Aspects of Cushing’s Disease
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“Adding to psychological and cognitive impairments (as outlined above), long-standing hypercortisolism may be associated with underlying organic pathological processes [57, 58].”
- Authors
- Pivonello, R., De Martino, M. C., De Leo, M., Tauchmanovà, L., Faggiano, A., Lombardi, G., & Colao, A.
- Affiliations
- University of Naples Federico II (IT)
- ’Federico II’ University of Naples, Italy
- Venue
- Arquivos Brasileiros de Endocrinologia & Metabologia
- Publisher
- FapUNIFESP (SciELO)
- Published
- 2007-11
- Volume
- 51
- Issue
- 8
- Pages
- 1381-1391
- ISSN
- 0004-2730 (ISSN-L)
- OpenAlex
- W2170677825
- Cited by
- 85
- References
- 85
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 10 · 2013: 8 · 2012: 8
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Arquivos Brasileiros de Endocrinologia & Metabologia (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- 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, hypercortisolism, pituitary-dependent Cushing's syndrome, pituitary tumor resection, metabolic syndrome, insulin resistance, cardiovascular risk, osteoporosis, bisphosphonates, cognitive decline, autoimmune thyroid disease, quality of life
- MeSH terms
- Autoimmune Diseases, Bone Diseases, Cardiovascular Diseases, Cushing Syndrome, Humans, Hydrocortisone, Kidney Diseases, Remission Induction, Treatment Outcome, Metabolic Syndrome
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