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Published in: Endocrine 1/2017

01-04-2017 | Review

Cushing’s disease: the burden of illness

Authors: Rosario Pivonello, Maria Cristina De Martino, Monica De Leo, Chiara Simeoli, Annamaria Colao

Published in: Endocrine | Issue 1/2017

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Abstract

Cushing’s syndrome is caused by prolonged exposure to elevated cortisol levels. The most common form of endogenous Cushing’s syndrome is Cushing’s disease, which results from an adrenocorticotropic hormone-secreting pituitary tumour. Cushing’s disease is associated with increased mortality, mostly attributable to cardiovascular complications, and a host of comorbidities such as metabolic and skeletal disorders, infections and neuropsychiatric disturbances. As a consequence, Cushing’s disease substantially impairs health-related quality of life. It is crucial that the condition is diagnosed as early as possible, and that rapid and effective treatment is initiated in order to limit long-term morbidity and mortality. The initial treatment of choice for Cushing’s disease is selective transsphenoidal pituitary surgery; however, the risk of recurrence after initial surgery is high and remains so for many decades after surgery. A particular concern is the growing body of evidence indicating that the negative physical and psychosocial sequelae of chronic hypercortisolism may persist in patients with Cushing’s disease even after long-term surgical ‘cure’. Current treatment options for post-surgical patients with persistent or recurrent Cushing’s disease include second surgery, radiotherapy, bilateral adrenalectomy and medical therapy; however, each approach has its limitations and there is an unmet need for more efficacious treatments. The current review provides an overview of the burden of illness of Cushing’s disease, underscoring the need for prompt diagnosis and effective treatment, as well as highlighting the need for better therapies.
Literature
1.
go back to reference R. Pivonello, M.C. De Martino, M. De Leo, G. Lombardi, A. Colao, Cushing’s syndrome. Endocrinol. Metab Clin. North Am. 37, 135–149 (2008)CrossRefPubMed R. Pivonello, M.C. De Martino, M. De Leo, G. Lombardi, A. Colao, Cushing’s syndrome. Endocrinol. Metab Clin. North Am. 37, 135–149 (2008)CrossRefPubMed
2.
go back to reference J. Newell-Price, X. Bertagna, A.B. Grossman, L.K. Nieman, Cushing’s syndrome. Lancet 367, 1605–1617 (2006)CrossRefPubMed J. Newell-Price, X. Bertagna, A.B. Grossman, L.K. Nieman, Cushing’s syndrome. Lancet 367, 1605–1617 (2006)CrossRefPubMed
4.
go back to reference C. Steffensen, A.M. Bak, K.Z. Rubeck, J.O. Jorgensen, Epidemiology of Cushing’s syndrome. Neuroendocrinology 92(Suppl 1), 1–5 (2010)CrossRefPubMed C. Steffensen, A.M. Bak, K.Z. Rubeck, J.O. Jorgensen, Epidemiology of Cushing’s syndrome. Neuroendocrinology 92(Suppl 1), 1–5 (2010)CrossRefPubMed
5.
go back to reference A. Lacroix, R.A. Feelders, C.A. Stratakis, L.K. Nieman, Cushing’s syndrome. Lancet 386, 913–927 (2015)CrossRefPubMed A. Lacroix, R.A. Feelders, C.A. Stratakis, L.K. Nieman, Cushing’s syndrome. Lancet 386, 913–927 (2015)CrossRefPubMed
6.
go back to reference R. Pivonello, A.M. Isidori, M.C. De Martino et al., Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol. 2016 (in press) R. Pivonello, A.M. Isidori, M.C. De Martino et al., Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol. 2016 (in press)
7.
go back to reference E. Valassi, A. Santos, M. Yaneva et al., The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur. J. Endocrinol. 165, 383–392 (2011)CrossRefPubMed E. Valassi, A. Santos, M. Yaneva et al., The European Registry on Cushing’s syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur. J. Endocrinol. 165, 383–392 (2011)CrossRefPubMed
8.
go back to reference L.K. Nieman, B.M. Biller, J.W. Findling et al., Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 100, 2807–2831 (2015)CrossRefPubMedPubMedCentral L.K. Nieman, B.M. Biller, J.W. Findling et al., Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 100, 2807–2831 (2015)CrossRefPubMedPubMedCentral
9.
go back to reference J. Newell-Price, P. Trainer, M. Besser, A. Grossman, The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr. Rev. 19, 647–672 (1998)PubMed J. Newell-Price, P. Trainer, M. Besser, A. Grossman, The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr. Rev. 19, 647–672 (1998)PubMed
10.
go back to reference L.K. Nieman, B.M. Biller, J.W. Findling et al., The diagnosis of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 93, 1526–1540 (2008)CrossRefPubMedPubMedCentral L.K. Nieman, B.M. Biller, J.W. Findling et al., The diagnosis of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 93, 1526–1540 (2008)CrossRefPubMedPubMedCentral
11.
go back to reference J. Etxabe, J.A. Vazquez, Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin. Endocrinol. (Oxf) 40, 479–484 (1994)CrossRef J. Etxabe, J.A. Vazquez, Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin. Endocrinol. (Oxf) 40, 479–484 (1994)CrossRef
12.
go back to reference J. Lindholm, S. Juul, J.O. Jorgensen et al., Incidence and late prognosis of Cushing’s syndrome: a population-based study. J. Clin. Endocrinol. Metab. 86, 117–123 (2001)PubMed J. Lindholm, S. Juul, J.O. Jorgensen et al., Incidence and late prognosis of Cushing’s syndrome: a population-based study. J. Clin. Endocrinol. Metab. 86, 117–123 (2001)PubMed
13.
go back to reference D. Graversen, P. Vestergaard, K. Stochholm, C.H. Gravholt, J.O. Jorgensen, Mortality in Cushing’s syndrome: a systematic review and meta-analysis. Eur. J. Intern. Med. 23, 278–282 (2012)CrossRefPubMed D. Graversen, P. Vestergaard, K. Stochholm, C.H. Gravholt, J.O. Jorgensen, Mortality in Cushing’s syndrome: a systematic review and meta-analysis. Eur. J. Intern. Med. 23, 278–282 (2012)CrossRefPubMed
14.
go back to reference G. Ntali, A. Asimakopoulou, T. Siamatras et al., Mortality in Cushing’s syndrome: systematic analysis of a large series with prolonged follow-up. Eur. J. Endocrinol. 169, 715–723 (2013)CrossRefPubMed G. Ntali, A. Asimakopoulou, T. Siamatras et al., Mortality in Cushing’s syndrome: systematic analysis of a large series with prolonged follow-up. Eur. J. Endocrinol. 169, 715–723 (2013)CrossRefPubMed
15.
go back to reference O.M. Dekkers, N.R. Biermasz, A.M. Pereira et al., Mortality in patients treated for Cushing’s disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma. J. Clin. Endocrinol. Metab. 92, 976–981 (2007)CrossRefPubMed O.M. Dekkers, N.R. Biermasz, A.M. Pereira et al., Mortality in patients treated for Cushing’s disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma. J. Clin. Endocrinol. Metab. 92, 976–981 (2007)CrossRefPubMed
16.
go back to reference G.D. Hammer, J.B. Tyrrell, K.R. Lamborn et al., Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J. Clin. Endocrinol. Metab. 89, 6348–6357 (2004)CrossRefPubMed G.D. Hammer, J.B. Tyrrell, K.R. Lamborn et al., Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J. Clin. Endocrinol. Metab. 89, 6348–6357 (2004)CrossRefPubMed
17.
go back to reference Z.K. Hassan-Smith, M. Sherlock, R.C. Reulen et al., Outcome of Cushing’s disease following transsphenoidal surgery in a single center over 20 years. J. Clin. Endocrinol. Metab. 97, 1194–1201 (2012)CrossRefPubMed Z.K. Hassan-Smith, M. Sherlock, R.C. Reulen et al., Outcome of Cushing’s disease following transsphenoidal surgery in a single center over 20 years. J. Clin. Endocrinol. Metab. 97, 1194–1201 (2012)CrossRefPubMed
18.
go back to reference R. Pivonello, P. Vitale, L. Mantovani et al., MISSION study. A worldwide epidemiological study on the mortality associated with Cushing’s syndrome performed in nearly 5000 patients. 95th annual meeting of The Endocrine Society. San Francisco, CA, USA, 15–18 Jun abst SAT-LB-07 (2013) R. Pivonello, P. Vitale, L. Mantovani et al., MISSION study. A worldwide epidemiological study on the mortality associated with Cushing’s syndrome performed in nearly 5000 patients. 95th annual meeting of The Endocrine Society. San Francisco, CA, USA, 15–18 Jun abst SAT-LB-07 (2013)
19.
go back to reference J.K. Lambert, L. Goldberg, S. Fayngold et al., Predictors of mortality and long-term outcomes in treated Cushing’s disease: a study of 346 patients. J. Clin. Endocrinol. Metab. 98, 1022–1030 (2013)CrossRefPubMedPubMedCentral J.K. Lambert, L. Goldberg, S. Fayngold et al., Predictors of mortality and long-term outcomes in treated Cushing’s disease: a study of 346 patients. J. Clin. Endocrinol. Metab. 98, 1022–1030 (2013)CrossRefPubMedPubMedCentral
20.
go back to reference H. Prasad, D.A. Ryan, M.F. Celzo, D. Stapleton, Metabolic syndrome: definition and therapeutic implications. Postgrad. Med. 124, 21–30 (2012)CrossRefPubMed H. Prasad, D.A. Ryan, M.F. Celzo, D. Stapleton, Metabolic syndrome: definition and therapeutic implications. Postgrad. Med. 124, 21–30 (2012)CrossRefPubMed
21.
go back to reference R. Pivonello, M. De Leo, P. Vitale et al., Pathophysiology of diabetes mellitus in Cushing’s syndrome. Neuroendocrinology 92(Suppl 1), 77–81 (2010)CrossRefPubMed R. Pivonello, M. De Leo, P. Vitale et al., Pathophysiology of diabetes mellitus in Cushing’s syndrome. Neuroendocrinology 92(Suppl 1), 77–81 (2010)CrossRefPubMed
22.
go back to reference T. Mancini, B. Kola, F. Mantero, M. Boscaro, G. Arnaldi, High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin. Endocrinol. (Oxf) 61, 768–777 (2004)CrossRef T. Mancini, B. Kola, F. Mantero, M. Boscaro, G. Arnaldi, High cardiovascular risk in patients with Cushing’s syndrome according to 1999 WHO/ISH guidelines. Clin. Endocrinol. (Oxf) 61, 768–777 (2004)CrossRef
23.
go back to reference A. Colao, R. Pivonello, S. Spiezia et al., Persistence of increased cardiovascular risk in patients with Cushing’s disease after five years of successful cure. J. Clin. Endocrinol. Metab. 84, 2664–2672 (1999)PubMed A. Colao, R. Pivonello, S. Spiezia et al., Persistence of increased cardiovascular risk in patients with Cushing’s disease after five years of successful cure. J. Clin. Endocrinol. Metab. 84, 2664–2672 (1999)PubMed
24.
go back to reference A. Faggiano, R. Pivonello, S. Spiezia et al., Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission. J. Clin. Endocrinol. Metab. 88, 2527–2533 (2003)CrossRefPubMed A. Faggiano, R. Pivonello, S. Spiezia et al., Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission. J. Clin. Endocrinol. Metab. 88, 2527–2533 (2003)CrossRefPubMed
25.
go back to reference R.M. Gomez, N.M. Albiger, A.G. Diaz et al., Effect of hypercortisolism control on high blood pressure in Cushing’s syndrome. Medicina (B Aires) 67, 439–444 (2007) R.M. Gomez, N.M. Albiger, A.G. Diaz et al., Effect of hypercortisolism control on high blood pressure in Cushing’s syndrome. Medicina (B Aires) 67, 439–444 (2007)
26.
go back to reference A.L. Espinosa-de-los-Monteros, E. Sosa, N. Martinez, M. Mercado, Persistence of Cushing’s disease symptoms and comorbidities after surgical cure: a long-term, integral evaluation. Endocr. Pract. 19, 252–258 (2013)CrossRefPubMed A.L. Espinosa-de-los-Monteros, E. Sosa, N. Martinez, M. Mercado, Persistence of Cushing’s disease symptoms and comorbidities after surgical cure: a long-term, integral evaluation. Endocr. Pract. 19, 252–258 (2013)CrossRefPubMed
27.
go back to reference G. Kaltsas, P. Makras, Skeletal diseases in Cushing’s syndrome: osteoporosis versus arthropathy. Neuroendocrinology 92(Suppl 1), 60–64 (2010)CrossRefPubMed G. Kaltsas, P. Makras, Skeletal diseases in Cushing’s syndrome: osteoporosis versus arthropathy. Neuroendocrinology 92(Suppl 1), 60–64 (2010)CrossRefPubMed
28.
go back to reference A. Faggiano, R. Pivonello, M. Filippella et al., Spine abnormalities and damage in patients cured from Cushing’s disease. Pituitary 4, 153–161 (2001)CrossRefPubMed A. Faggiano, R. Pivonello, M. Filippella et al., Spine abnormalities and damage in patients cured from Cushing’s disease. Pituitary 4, 153–161 (2001)CrossRefPubMed
29.
go back to reference M.J. Barahona, N. Sucunza, E. Resmini et al., Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing’s syndrome. J. Bone Miner. Res. 24, 1841–1846 (2009)CrossRefPubMed M.J. Barahona, N. Sucunza, E. Resmini et al., Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing’s syndrome. J. Bone Miner. Res. 24, 1841–1846 (2009)CrossRefPubMed
30.
go back to reference C. di Somma, R. Pivonello, S. Loche et al., Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing’s disease: a prospective study. Clin. Endocrinol. (Oxf) 58, 302–308 (2003)CrossRef C. di Somma, R. Pivonello, S. Loche et al., Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing’s disease: a prospective study. Clin. Endocrinol. (Oxf) 58, 302–308 (2003)CrossRef
31.
go back to reference L.A. Cohn, Glucocorticosteroids as immunosuppressive agents. Semin. Vet. Med. Surg. (Small Anim) 12, 150–156 (1997)CrossRef L.A. Cohn, Glucocorticosteroids as immunosuppressive agents. Semin. Vet. Med. Surg. (Small Anim) 12, 150–156 (1997)CrossRef
32.
go back to reference N. Auphan, J.A. DiDonato, C. Rosette, A. Helmberg, M. Karin, Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270, 286–290 (1995)CrossRefPubMed N. Auphan, J.A. DiDonato, C. Rosette, A. Helmberg, M. Karin, Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270, 286–290 (1995)CrossRefPubMed
33.
go back to reference R.I. Scheinman, P.C. Cogswell, A.K. Lofquist, A.S. Baldwin Jr, Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 270, 283–286 (1995)CrossRefPubMed R.I. Scheinman, P.C. Cogswell, A.K. Lofquist, A.S. Baldwin Jr, Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 270, 283–286 (1995)CrossRefPubMed
34.
go back to reference M.S. Lionakis, D.P. Kontoyiannis, Glucocorticoids and invasive fungal infections. Lancet 362, 1828–1838 (2003)CrossRefPubMed M.S. Lionakis, D.P. Kontoyiannis, Glucocorticoids and invasive fungal infections. Lancet 362, 1828–1838 (2003)CrossRefPubMed
35.
go back to reference G.G. Fareau, R. Vassilopoulou-Sellin, Hypercortisolemia and infection. Infect. Dis. Clin. North Am. 21, 639–657 (2007)CrossRefPubMed G.G. Fareau, R. Vassilopoulou-Sellin, Hypercortisolemia and infection. Infect. Dis. Clin. North Am. 21, 639–657 (2007)CrossRefPubMed
36.
go back to reference N.J. Sarlis, S.J. Chanock, L.K. Nieman, Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. J. Clin. Endocrinol. Metab. 85, 42–47 (2000)PubMed N.J. Sarlis, S.J. Chanock, L.K. Nieman, Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. J. Clin. Endocrinol. Metab. 85, 42–47 (2000)PubMed
37.
go back to reference R.C. Bakker, P.R. Gallas, J.A. Romijn, W.M. Wiersinga, Cushing’s syndrome complicated by multiple opportunistic infections. J. Endocrinol. Invest. 21, 329–333 (1998)CrossRefPubMed R.C. Bakker, P.R. Gallas, J.A. Romijn, W.M. Wiersinga, Cushing’s syndrome complicated by multiple opportunistic infections. J. Endocrinol. Invest. 21, 329–333 (1998)CrossRefPubMed
39.
go back to reference N. Sonino, G.A. Fava, A.R. Raffi, M. Boscaro, F. Fallo, Clinical correlates of major depression in Cushing’s disease. Psychopathology 31, 302–306 (1998)CrossRefPubMed N. Sonino, G.A. Fava, A.R. Raffi, M. Boscaro, F. Fallo, Clinical correlates of major depression in Cushing’s disease. Psychopathology 31, 302–306 (1998)CrossRefPubMed
40.
go back to reference J. Tiemensma, N.R. Biermasz, H.A. Middelkoop et al., Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing’s disease. J. Clin. Endocrinol. Metab. 95, E129–E141 (2010)CrossRefPubMed J. Tiemensma, N.R. Biermasz, H.A. Middelkoop et al., Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing’s disease. J. Clin. Endocrinol. Metab. 95, E129–E141 (2010)CrossRefPubMed
41.
go back to reference C. Dimopoulou, M. Ising, H. Pfister et al., Increased prevalence of anxiety-associated personality traits in patients with Cushing’s disease: a cross-sectional study. Neuroendocrinology 97, 139–145 (2013)CrossRefPubMed C. Dimopoulou, M. Ising, H. Pfister et al., Increased prevalence of anxiety-associated personality traits in patients with Cushing’s disease: a cross-sectional study. Neuroendocrinology 97, 139–145 (2013)CrossRefPubMed
42.
go back to reference A.A. Kasperlik-Zaluska, J. Slowinska-Srzednicka, W. Zgliczynski, A woman who gained weight and became schizophrenic. Lancet 361, 705 (2003)CrossRefPubMed A.A. Kasperlik-Zaluska, J. Slowinska-Srzednicka, W. Zgliczynski, A woman who gained weight and became schizophrenic. Lancet 361, 705 (2003)CrossRefPubMed
43.
go back to reference E. Singer, S. Strohm, U. Gobel et al., Cushing’s disease, hypertension, and other sequels. Hypertension 52, 1001–1005 (2008)CrossRefPubMed E. Singer, S. Strohm, U. Gobel et al., Cushing’s disease, hypertension, and other sequels. Hypertension 52, 1001–1005 (2008)CrossRefPubMed
44.
go back to reference M.N. Starkman, B. Giordani, S.S. Gebarski et al., Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s disease. Biol. Psychiatry 46, 1595–1602 (1999)CrossRefPubMed M.N. Starkman, B. Giordani, S.S. Gebarski et al., Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s disease. Biol. Psychiatry 46, 1595–1602 (1999)CrossRefPubMed
45.
go back to reference N.E. Simmons, H.M. Do, M.H. Lipper, E.R. Laws Jr, Cerebral atrophy in Cushing’s disease. Surg. Neurol. 53, 72–76 (2000)CrossRefPubMed N.E. Simmons, H.M. Do, M.H. Lipper, E.R. Laws Jr, Cerebral atrophy in Cushing’s disease. Surg. Neurol. 53, 72–76 (2000)CrossRefPubMed
46.
go back to reference I. Bourdeau, C. Bard, B. Noel et al., Loss of brain volume in endogenous Cushing’s syndrome and its reversibility after correction of hypercortisolism. J. Clin. Endocrinol. Metab. 87, 1949–1954 (2002)PubMed I. Bourdeau, C. Bard, B. Noel et al., Loss of brain volume in endogenous Cushing’s syndrome and its reversibility after correction of hypercortisolism. J. Clin. Endocrinol. Metab. 87, 1949–1954 (2002)PubMed
47.
go back to reference C.D. Andela, S.J. van der Werff, J.N. Pannekoek et al., Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing’s disease: a case-control study. Eur. J. Endocrinol. 169, 811–819 (2013)CrossRefPubMed C.D. Andela, S.J. van der Werff, J.N. Pannekoek et al., Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing’s disease: a case-control study. Eur. J. Endocrinol. 169, 811–819 (2013)CrossRefPubMed
48.
go back to reference H. Forget, A. Lacroix, H. Cohen, Persistent cognitive impairment following surgical treatment of Cushing’s syndrome. Psychoneuroendocrinology 27, 367–383 (2002)CrossRefPubMed H. Forget, A. Lacroix, H. Cohen, Persistent cognitive impairment following surgical treatment of Cushing’s syndrome. Psychoneuroendocrinology 27, 367–383 (2002)CrossRefPubMed
49.
go back to reference D.P. Merke, J.N. Giedd, M.F. Keil et al., Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J. Clin. Endocrinol. Metab. 90, 2531–2536 (2005)CrossRefPubMed D.P. Merke, J.N. Giedd, M.F. Keil et al., Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J. Clin. Endocrinol. Metab. 90, 2531–2536 (2005)CrossRefPubMed
50.
go back to reference J. Tiemensma, N.E. Kokshoorn, N.R. Biermasz et al., Subtle cognitive impairments in patients with long-term cure of Cushing’s disease. J. Clin. Endocrinol. Metab. 95, 2699–2714 (2010)CrossRefPubMed J. Tiemensma, N.E. Kokshoorn, N.R. Biermasz et al., Subtle cognitive impairments in patients with long-term cure of Cushing’s disease. J. Clin. Endocrinol. Metab. 95, 2699–2714 (2010)CrossRefPubMed
51.
go back to reference O. Ragnarsson, P. Berglund, D.N. Eder, G. Johannsson, Long-term cognitive impairments and attentional deficits in patients with Cushing’s disease and cortisol-producing adrenal adenoma in remission. J. Clin. Endocrinol. Metab. 97, E1640–E1648 (2012)CrossRefPubMed O. Ragnarsson, P. Berglund, D.N. Eder, G. Johannsson, Long-term cognitive impairments and attentional deficits in patients with Cushing’s disease and cortisol-producing adrenal adenoma in remission. J. Clin. Endocrinol. Metab. 97, E1640–E1648 (2012)CrossRefPubMed
52.
go back to reference L. Pikkarainen, T. Sane, A. Reunanen, The survival and well-being of patients treated for Cushing’s syndrome. J. Intern. Med. 245, 463–468 (1999)CrossRefPubMed L. Pikkarainen, T. Sane, A. Reunanen, The survival and well-being of patients treated for Cushing’s syndrome. J. Intern. Med. 245, 463–468 (1999)CrossRefPubMed
53.
go back to reference M.D. Johnson, C.J. Woodburn, M.L. Vance, Quality of life in patients with a pituitary adenoma. Pituitary 6, 81–87 (2003)CrossRefPubMed M.D. Johnson, C.J. Woodburn, M.L. Vance, Quality of life in patients with a pituitary adenoma. Pituitary 6, 81–87 (2003)CrossRefPubMed
54.
go back to reference S.M. Webb, X. Badia, M.J. Barahona et al., Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire. Eur. J. Endocrinol. 158, 623–630 (2008)CrossRefPubMed S.M. Webb, X. Badia, M.J. Barahona et al., Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire. Eur. J. Endocrinol. 158, 623–630 (2008)CrossRefPubMed
55.
go back to reference M.O. van Aken, A.M. Pereira, N.R. Biermasz et al., Quality of life in patients after long-term biochemical cure of Cushing’s disease. J. Clin. Endocrinol. Metab. 90, 3279–3286 (2005)CrossRefPubMed M.O. van Aken, A.M. Pereira, N.R. Biermasz et al., Quality of life in patients after long-term biochemical cure of Cushing’s disease. J. Clin. Endocrinol. Metab. 90, 3279–3286 (2005)CrossRefPubMed
56.
go back to reference J.R. Lindsay, T. Nansel, S. Baid, J. Gumowski, L.K. Nieman, Long-term impaired quality of life in Cushing’s syndrome despite initial improvement after surgical remission. J. Clin. Endocrinol. Metab. 91, 447–453 (2006)CrossRefPubMed J.R. Lindsay, T. Nansel, S. Baid, J. Gumowski, L.K. Nieman, Long-term impaired quality of life in Cushing’s syndrome despite initial improvement after surgical remission. J. Clin. Endocrinol. Metab. 91, 447–453 (2006)CrossRefPubMed
57.
go back to reference R. Pivonello, M.C. De Martino, M. De Leo et al., Cushing’s syndrome: aftermath of the cure. Arq. Bras. Endocrinol. Metabol. 51, 1381–1391 (2007)CrossRefPubMed R. Pivonello, M.C. De Martino, M. De Leo et al., Cushing’s syndrome: aftermath of the cure. Arq. Bras. Endocrinol. Metabol. 51, 1381–1391 (2007)CrossRefPubMed
58.
go back to reference J.T. Chow, G.B. Thompson, C.S. Grant et al., Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing’s syndrome: a review of the Mayo Clinic experience. Clin. Endocrinol. (Oxf) 68, 513–519 (2008)CrossRef J.T. Chow, G.B. Thompson, C.S. Grant et al., Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing’s syndrome: a review of the Mayo Clinic experience. Clin. Endocrinol. (Oxf) 68, 513–519 (2008)CrossRef
61.
go back to reference E. Daniel, J.D. Newell-Price, Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing’s syndrome. Eur. J. Endocrinol. 172, R263–R280 (2015)CrossRefPubMed E. Daniel, J.D. Newell-Price, Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing’s syndrome. Eur. J. Endocrinol. 172, R263–R280 (2015)CrossRefPubMed
62.
go back to reference M. Fleseriu, R. Pivonello, J. Young et al., Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing’s disease. Pituitary 19, 138–148 (2016)CrossRefPubMed M. Fleseriu, R. Pivonello, J. Young et al., Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing’s disease. Pituitary 19, 138–148 (2016)CrossRefPubMed
64.
go back to reference H.G. Fein, T.B. Vaughan III, H. Kushner, D. Cram, D. Nguyen, Sustained weight loss in patients treated with mifepristone for Cushing’s syndrome: a follow-up analysis of the SEISMIC study and long-term extension. BMC. Endocr. Disord. 15, 63 (2015)CrossRefPubMedPubMedCentral H.G. Fein, T.B. Vaughan III, H. Kushner, D. Cram, D. Nguyen, Sustained weight loss in patients treated with mifepristone for Cushing’s syndrome: a follow-up analysis of the SEISMIC study and long-term extension. BMC. Endocr. Disord. 15, 63 (2015)CrossRefPubMedPubMedCentral
65.
go back to reference M. Fleseriu, B.M. Biller, J.W. Findling et al., Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J. Clin. Endocrinol. Metab. 97, 2039–2049 (2012)CrossRefPubMed M. Fleseriu, B.M. Biller, J.W. Findling et al., Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J. Clin. Endocrinol. Metab. 97, 2039–2049 (2012)CrossRefPubMed
66.
go back to reference N.A. Tritos, B.M.K. Biller, Advances in medical therapies for Cushing’s syndrome. Discov. Med. 13, 171–179 (2012)PubMed N.A. Tritos, B.M.K. Biller, Advances in medical therapies for Cushing’s syndrome. Discov. Med. 13, 171–179 (2012)PubMed
69.
go back to reference A. Colao, S. Petersenn, J. Newell-Price et al., A 12-month phase 3 study of pasireotide in Cushing’s disease. N. Engl. J. Med. 366, 914–924 (2012)CrossRefPubMed A. Colao, S. Petersenn, J. Newell-Price et al., A 12-month phase 3 study of pasireotide in Cushing’s disease. N. Engl. J. Med. 366, 914–924 (2012)CrossRefPubMed
70.
go back to reference R. Pivonello, S. Petersenn, J. Newell-Price et al., Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing’s disease: results from a Phase III study. Clin. Endocrinol. (Oxf) 81, 408–417 (2014)CrossRef R. Pivonello, S. Petersenn, J. Newell-Price et al., Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing’s disease: results from a Phase III study. Clin. Endocrinol. (Oxf) 81, 408–417 (2014)CrossRef
71.
go back to reference A.R. Lila, R.A. Gopal, S.V. Acharya et al., Efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy. Endocr. Pract. 16, 968–976 (2010)CrossRefPubMed A.R. Lila, R.A. Gopal, S.V. Acharya et al., Efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy. Endocr. Pract. 16, 968–976 (2010)CrossRefPubMed
72.
go back to reference R. Pivonello, M.C. De Martino, P. Cappabianca et al., The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J. Clin. Endocrinol. Metab. 94, 223–230 (2009)CrossRefPubMed R. Pivonello, M.C. De Martino, P. Cappabianca et al., The medical treatment of Cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J. Clin. Endocrinol. Metab. 94, 223–230 (2009)CrossRefPubMed
73.
go back to reference R.A. Feelders, C. de Bruin, A.M. Pereira et al., Pasireotide alone or with cabergoline and ketoconazole in Cushing’s disease. N. Engl. J. Med. 362, 1846–1848 (2010)CrossRefPubMed R.A. Feelders, C. de Bruin, A.M. Pereira et al., Pasireotide alone or with cabergoline and ketoconazole in Cushing’s disease. N. Engl. J. Med. 362, 1846–1848 (2010)CrossRefPubMed
74.
go back to reference R.A. Feelders, S.J. Pulgar, A. Kempel, A.M. Pereira, The burden of Cushing’s disease: clinical and health-related quality of life aspects. Eur. J. Endocrinol. 167, 311–326 (2012)CrossRefPubMed R.A. Feelders, S.J. Pulgar, A. Kempel, A.M. Pereira, The burden of Cushing’s disease: clinical and health-related quality of life aspects. Eur. J. Endocrinol. 167, 311–326 (2012)CrossRefPubMed
Metadata
Title
Cushing’s disease: the burden of illness
Authors
Rosario Pivonello
Maria Cristina De Martino
Monica De Leo
Chiara Simeoli
Annamaria Colao
Publication date
01-04-2017
Publisher
Springer US
Published in
Endocrine / Issue 1/2017
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-016-0984-8

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