Unmet needs on the current medical management of Cushing's syndrome: results from a Delphi panel of Italian endocrinologists.
Cortisol
Cushing’s disease
Cushing’s syndrome
Rare disease
Steroidogenesis inhibitors
Unmet need
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
03
08
2022
accepted:
02
03
2023
medline:
28
7
2023
pubmed:
20
4
2023
entrez:
19
04
2023
Statut:
ppublish
Résumé
Cushing's syndrome (CS) is a rare clinical condition caused by excessive cortisol secretion from adrenal glands. CS is associated with increased mortality and morbidity; therefore, a prompt diagnosis and an effective therapeutic approach are strongly necessary to improve the patient's clinical management. The first-line treatment for CS is surgery, while medical treatment has historically played a minor role. However, thanks to the availability of novel compounds, the possibility of improving hypercortisolism control using different drug combinations emerged. No absolute recommendations are available to guide the therapeutic choice for patients with CS and, consequently, the awareness of unmet needs in CS management is growing. Although new data from clinical trials are needed to better define the most appropriate management of CS, an expert consensus approach can help define unmet needs and optimize the current CS management and treatment. Twenty-seven endocrinologists from 12 Italian regions, working among the main Italian referral centers for hospital endocrinology where they take care of CS patients, were involved in a consensus process and used the Delphi method to reach an agreement on 24 statements about managing CS patients. In total, 18 statements reached a consensus. Some relevant unmet needs in the management of CS were reported, mainly related to the lack of a pharmacological treatment successful for the majority of patients. While acknowledging the difficulty in achieving complete disease control, a significant change in CS management requires the availability of medical treatment with improved efficacy and safety over available therapeutic options at the time of the current study.
Sections du résumé
BACKGROUND
BACKGROUND
Cushing's syndrome (CS) is a rare clinical condition caused by excessive cortisol secretion from adrenal glands. CS is associated with increased mortality and morbidity; therefore, a prompt diagnosis and an effective therapeutic approach are strongly necessary to improve the patient's clinical management. The first-line treatment for CS is surgery, while medical treatment has historically played a minor role. However, thanks to the availability of novel compounds, the possibility of improving hypercortisolism control using different drug combinations emerged.
PURPOSE
OBJECTIVE
No absolute recommendations are available to guide the therapeutic choice for patients with CS and, consequently, the awareness of unmet needs in CS management is growing. Although new data from clinical trials are needed to better define the most appropriate management of CS, an expert consensus approach can help define unmet needs and optimize the current CS management and treatment.
METHODS
METHODS
Twenty-seven endocrinologists from 12 Italian regions, working among the main Italian referral centers for hospital endocrinology where they take care of CS patients, were involved in a consensus process and used the Delphi method to reach an agreement on 24 statements about managing CS patients.
RESULTS
RESULTS
In total, 18 statements reached a consensus. Some relevant unmet needs in the management of CS were reported, mainly related to the lack of a pharmacological treatment successful for the majority of patients.
CONCLUSION
CONCLUSIONS
While acknowledging the difficulty in achieving complete disease control, a significant change in CS management requires the availability of medical treatment with improved efficacy and safety over available therapeutic options at the time of the current study.
Identifiants
pubmed: 37076758
doi: 10.1007/s40618-023-02058-8
pii: 10.1007/s40618-023-02058-8
pmc: PMC10115381
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1923-1934Informations de copyright
© 2023. The Author(s).
Références
Pivonello R, De Martino MC, De Leo M, Simeoli C, Colao A (2017) Cushing’s disease: the burden of illness. Endocrine 56(1):10–18
pubmed: 27189147
Orphanet Report Series: Rare Diseases Collection. Prevalence and incidence of rare diseases: Bibliographic data. Prevalence, incidence, or number of published cases listed by diseases (in alphabetical order). 2020. https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf . Accessed 1 Jan 2022.
Melmed S, Kaiser UB, Lopes MB, Bertherat J, Syro LV, Raverot G, Reincke M, Johannsson G, Beckers A, Fleseriu M, Giustina A, Wass JAH, Ho KKY (2022) Clinical biology of the pituitary adenoma. Endocr Rev 8:bnac010. https://doi.org/10.1210/endrev/bnac010
Hayes AR, Grossman AB (2018) The ectopic adrenocorticotropic hormone syndrome: rarely easy, always challenging. Endocrinol Metab Clin North Am 47(2):409–425. https://doi.org/10.1016/j.ecl.2018.01.005
pubmed: 29754641
Pivonello R, Ferrigno R, De Martino MC, Simeoli C, Di Paola N, Pivonello C, Barba L, Negri M, De Angelis C, Colao A (2020) Medical treatment of Cushing’s disease: an overview of the current and recent clinical trials. Front Endocrinol (Lausanne) 11:648. https://doi.org/10.3389/fendo.2020.00648
pubmed: 33363514
Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M (2003) Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88(12):5593–5602. https://doi.org/10.1210/jc.2003-030871
pubmed: 14671138
Mazziotti G, Giustina A (2013) Glucocorticoids and the regulation of growth hormone secretion. Nat Rev Endocrinol 9(5):265–276. https://doi.org/10.1038/nrendo.2013.5
pubmed: 23381030
Zilio M, Barbot M, Ceccato F, Camozzi V, Bilora F, Casonato A, Frigo AC, Albiger N, Daidone V, Mazzai L, Mantero F, Scaroni C (2014) Diagnosis and complications of Cushing’s disease: gender-related differences. Clin Endocrinol (Oxf) 80(3):403–410. https://doi.org/10.1111/cen.12299
pubmed: 23889360
Huguet I, Ntali G, Grossman A, Karavitaki N (2015) Cushing’s disease—quality of life, recurrence and long-term morbidity. Eur Endocrinol 11(1):34–38
pubmed: 29632565
pmcid: 5819060
Pivonello R, De Leo M, Cozzolino A, Colao A (2015) The treatment of Cushing’s disease. Endocr Rev 36(4):385–486
pubmed: 26067718
pmcid: 4523083
Mazziotti G, Formenti AM, Adler RA, Bilezikian JP, Grossman A, Sbardella E, Minisola S, Giustina A (2016) Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine 54(3):603–611. https://doi.org/10.1007/s12020-016-1146-8
pubmed: 27766553
Pivonello R, Isidori AM, De Martino MC, Newell-Price J, Biller BM, Colao A (2016) Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol 4(7):611–629. https://doi.org/10.1016/S2213-8587(16)00086-3
pubmed: 27177728
Formenti AM, Maffezzoni F, Doga M, Mazziotti G, Giustina A (2017) Growth hormone deficiency in treated acromegaly and active Cushing’s syndrome. Best Pract Res Clin Endocrinol Metab 31(1):79–90. https://doi.org/10.1016/j.beem.2017.03.002
pubmed: 28477735
Barbot M, Zilio M, Scaroni C (2020) Cushing’s syndrome: overview of clinical presentation, diagnostic tools and complications. Best Pract Res Clin Endocrinol Metab 34(2):101380. https://doi.org/10.1016/j.beem.2020.101380
pubmed: 32165101
Frara S, Allora A, di Filippo L, Formenti AM, Loli P, Polizzi E, Tradati D, Ulivieri FM, Giustina A (2021) Osteopathy in mild adrenal Cushing’s syndrome and Cushing disease. Best Pract Res Clin Endocrinol Metab 35(2):101515. https://doi.org/10.1016/j.beem.2021.101515
pubmed: 33795196
Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR, Boguszewski CL, Bronstein MD, Buchfelder M, Carmichael JD, Casanueva FF, Castinetti F, Chanson P, Findling J, Gadelha M, Geer EB, Giustina A, Grossman A, Gurnell M, Ho K, Ioachimescu AG, Kaiser UB, Karavitaki N, Katznelson L, Kelly DF, Lacroix A, McCormack A, Melmed S, Molitch M, Mortini P, Newell-Price J, Nieman L, Pereira AM, Petersenn S, Pivonello R, Raff H, Reincke M, Salvatori R, Scaroni C, Shimon I, Stratakis CA, Swearingen B, Tabarin A, Takahashi Y, Theodoropoulou M, Tsagarakis S, Valassi E, Varlamov EV, Vila G, Wass J, Webb SM, Zatelli MC, Biller BMK (2021) Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol 9(12):847–875. https://doi.org/10.1016/S2213-8587(21)00235-7
pubmed: 34687601
pmcid: 8743006
Albiger NM, Ceccato F, Zilio M, Barbot M, Occhi G, Rizzati S, Fassina A, Mantero F, Boscaro M, Iacobone M, Scaroni C (2015) An analysis of different therapeutic options in patients with Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia: a single-centre experience. Clin Endocrinol (Oxf) 82(6):808–815. https://doi.org/10.1111/cen.12763
pubmed: 25727927
Störmann S, Schopohl J (2018) New and emerging drug therapies for Cushing’s disease. Expert Opin Pharmacother 19(11):1187–1200
pubmed: 30048162
Casanueva FF, Barkan AL, Buchfelder M, Klibanski A, Laws ER, Loeffler JS, Melmed S, Mortini P, Wass J, Giustina A, Pituitary Society, Expert Group on Pituitary Tumors (2017) Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement. Pituitary 20(5):489–498. https://doi.org/10.1007/s11102-017-0838-2
pubmed: 28884415
pmcid: 5606938
Frara S, Rodriguez-Carnero G, Formenti AM, Martinez-Olmos MA, Giustina A, Casanueva FF (2020) Pituitary tumors centers of excellence. Endocrinol Metab Clin North Am 49(3):553–564. https://doi.org/10.1016/j.ecl.2020.05.010
pubmed: 32741488
Nasa P, Jain R, Juneja D (2021) Delphi methodology in healthcare research: How to decide its appropriateness. World J Methodol 11(4):116–129. https://doi.org/10.5662/wjm.v11.i4.116
pubmed: 34322364
pmcid: 8299905
Ferriere A, Tabarin A (2021) Cushing’s disease. Presse Med 50(4):104091
pubmed: 34718112
Brady Z, Garrahy A, Carthy C, O’Reilly MW, Thompson CJ, Sherlock M, Agha A, Javadpour M (2021) Outcomes of endoscopic transsphenoidal surgery for Cushing’s disease. BMC Endocr Disord 21(1):36. https://doi.org/10.1186/s12902-021-00679-9
pubmed: 33658018
pmcid: 7931517
Ferrante E, Barbot M, Serban AL, Ceccato F, Carosi G, Lizzul L, Sala E, Daniele A, Indirli R, Cuman M, Locatelli M, Manara R, Arosio M, Boscaro M, Mantovani G, Scaroni C (2022) Indication to dynamic and invasive testing in Cushing’s disease according to different neuroradiological findings. J Endocrinol Invest 45(3):629–637. https://doi.org/10.1007/s40618-021-01695-1
pubmed: 34699044
Sarkis P, Rabilloud M, Lifante JC, Siamand A, Jouanneau E, Gay E, Chaffanjon P, Chabre O, Raverot G (2019) Bilateral adrenalectomy in Cushing’s disease: altered long-term quality of life compared to other treatment options. Ann Endocrinol (Paris) 80(1):32–37. https://doi.org/10.1016/j.ando.2018.01.002
pubmed: 30243473
Mancini T, Porcelli T, Giustina A (2010) Treatment of Cushing disease: overview and recent findings. Ther Clin Risk Manag 6:505–516. https://doi.org/10.2147/TCRM.S12952
pubmed: 21063461
pmcid: 2963160
Ceccato F, Zilio M, Barbot M, Albiger N, Antonelli G, Plebani M, Watutantrige-Fernando S, Sabbadin C, Boscaro M, Scaroni C (2018) Metyrapone treatment in Cushing’s syndrome: a real-life study. Endocrine 62(3):701–711. https://doi.org/10.1007/s12020-018-1675-4
pubmed: 30014438
Puglisi S, Perotti P, Barbot M, Cosio P, Scaroni C, Stigliano A, Lardo P, Morelli V, Polledri E, Chiodini I, Reimondo G, Pia A, Terzolo M (2018) Preoperative treatment with metyrapone in patients with cushing’s syndrome due to adrenal adenoma. Endocr Connect 7(11):1227–1235. https://doi.org/10.1530/EC-18-0400
pubmed: 30352400
pmcid: 6215797
Stuijver DJ, van Zaane B, Feelders RA, Debeij J, Cannegieter SC, Hermus AR, van den Berg G, Pereira AM, de Herder WW, Wagenmakers MA, Kerstens MN, Zelissen PM, Fliers E, Schaper N, Drent ML, Dekkers OM, Gerdes VE (2011) Incidence of venous thromboembolism in patients with Cushing’s syndrome: a multicenter cohort study. J Clin Endocrinol Metab 96(11):3525–3532. https://doi.org/10.1210/jc.2011-1661
pubmed: 21880802
Valassi E, Feelders R, Maiter D, Chanson P, Yaneva M, Reincke M, Krsek M, Tóth M, Webb SM, Santos A, Paiva I, Komerdus I, Droste M, Tabarin A, Strasburger CJ, Franz H, Trainer PJ, Newell-Price J, Wass JA, Papakokkinou E, Ragnarsson O, ERCUSYN Study Group (2018) Worse health-related quality of life at long-term follow-up in patients with Cushing’s disease than patients with cortisol producing adenoma. Data from the ERCUSYN. Clin Endocrinol (Oxf) 88(6):787–798. https://doi.org/10.1111/cen.13600
pubmed: 29574994
Barbot M, Daidone V, Zilio M, Albiger N, Mazzai L, Sartori MT, Frigo AC, Scanarini M, Denaro L, Boscaro M, Casonato S, Ceccato F, Scaroni C (2015) Perioperative thromboprophylaxis in Cushing’s disease: what we did and what we are doing? Pituitary 18(4):487–493. https://doi.org/10.1007/s11102-014-0600-y
pubmed: 25239557
Pivonello R, Simeoli C, Di Paola N, Colao A (2022) Cushing’s disease: adrenal steroidogenesis inhibitors. Pituitary 25(5):726–732. https://doi.org/10.1007/s11102-022-01262-8
pubmed: 36036308
pmcid: 9587932
Mondin A, Manara R, Voltan G, Tizianel I, Denaro L, Ferrari M, Barbot M, Scaroni C, Ceccato F (2022) Pasireotide-induced shrinkage in GH and ACTH secreting pituitary adenoma: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 13:935759. https://doi.org/10.3389/fendo.2022.935759
pubmed: 35846311
Puig-Domingo M, Marazuela M, Giustina A (2020) COVID-19 and endocrine diseases. A statement from the European Society of Endocrinology. Endocrine 68(1):2–5. https://doi.org/10.1007/s12020-020-02294-5
pubmed: 32279224
pmcid: 7150529
Giustina A, Marazuela M, Reincke M, Yildiz BO, Puig-Domingo M (2021) One year of the pandemic—how European endocrinologists responded to the crisis: a statement from the European Society of Endocrinology. Eur J Endocrinol 185(2):C1–C7. https://doi.org/10.1530/EJE-21-0397
pubmed: 34132200
pmcid: 9494341
Simões Corrêa Galendi J, Correa Neto ANS, Demetres M, Boguszewski CL, Nogueira VDSN (2021) Effectiveness of medical treatment of cushing’s disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 12:732240. https://doi.org/10.3389/fendo.2021.732240
pubmed: 34603209
Pivonello R, Fleseriu M, Newell-Price J, Bertagna X, Findling J, Shimatsu A, Gu F, Auchus R, Leelawattana R, Lee EJ, Kim JH, Lacroix A, Laplanche A, O’Connell P, Tauchmanova L, Pedroncelli AM, Biller BMK, LINC 3 investigators (2020) Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol 8(9):748–761. https://doi.org/10.1016/S2213-8587(20)30240-0
pubmed: 32730798
Gadelha M, Bex M, Feelders RA, Heaney AP, Auchus RJ, Gilis-Januszewska A, Witek P, Belaya Z, Yu Y, Liao Z, Chen Ku CH, Carvalho D, Roughton M, Wojna J, Pedroncelli AM, Snyder PJ (2022) Randomized trial of osilodrostat for the treatment of Cushing’s disease. J Clin Endocrinol Metab 107(7):e2882–e2895. https://doi.org/10.1210/clinem/dgac178
pubmed: 35325149
pmcid: 9202723
Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA, Bertherat J (2009) Treatment of pituitary-dependent Cushing’s disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab 94(1):115–122. https://doi.org/10.1210/jc.2008-1008
pubmed: 18957506
Colao A, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, Biller BM, Pasireotide B2305 Study Group (2012) A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 366(10):914–924. https://doi.org/10.1056/NEJMoa1105743
pubmed: 22397653
Boscaro M, Bertherat J, Findling J, Fleseriu M, Atkinson AB, Petersenn S, Schopohl J, Snyder P, Hughes G, Trovato A, Hu K, Maldonado M, Biller BM (2014) Extended treatment of Cushing’s disease with pasireotide: results from a 2-year. Phase II study Pituitary 17(4):320–326. https://doi.org/10.1007/s11102-013-0503-3
pubmed: 23943009
Schopohl J, Gu F, Rubens R, Van Gaal L, Bertherat J, Ligueros-Saylan M, Trovato A, Hughes G, Salgado LR, Boscaro M, Pivonello R, Pasireotide B2305 Study Group (2015) Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing’s disease: results from an open-ended, open-label extension trial. Pituitary 18(5):604–612. https://doi.org/10.1007/s11102-014-0618-1
pubmed: 25537481
Petersenn S, Salgado LR, Schopohl J, Portocarrero-Ortiz L, Arnaldi G, Lacroix A, Scaroni C, Ravichandran S, Kandra A, Biller BMK (2017) Long-term treatment of Cushing’s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial. Endocrine 57(1):156–165. https://doi.org/10.1007/s12020-017-1316-3
pubmed: 28597198
pmcid: 5486525
Trementino L, Michetti G, Angeletti A, Marcelli G, Concettoni C, Cardinaletti C, Polenta B, Boscaro M, Arnaldi G (2016) A single-center 10-year experience with pasireotide in Cushing’s disease: Patients’ characteristics and outcome. Horm Metab Res 48(5):290–298. https://doi.org/10.1055/s-0042-101347
pubmed: 27127913
Pivonello R, Arnaldi G, Scaroni C, Giordano C, Cannavò S, Iacuaniello D, Trementino L, Zilio M, Guarnotta V, Albani A, Cozzolino A, Michetti G, Boscaro M, Colao A (2019) The medical treatment with pasireotide in Cushing’s disease: an Italian multicentre experience based on “real-world evidence.” Endocrine 64(3):657–672. https://doi.org/10.1007/s12020-018-1818-7
pubmed: 30968338
pmcid: 6551343
Manetti L, Deutschbein T, Schopohl J, Yuen KCJ, Roughton M, Kriemler-Krahn U, Tauchmanova L, Maamari R, Giordano C (2019) Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing’s disease: interim results from a long-term real-world evidence study. Pituitary 22(5):542–551. https://doi.org/10.1007/s11102-019-00984-6
pubmed: 31440946
pmcid: 6728293
Fleseriu M, Iweha C, Salgado L, Mazzuco TL, Campigotto F, Maamari R, Limumpornpetch P (2019) Safety and efficacy of subcutaneous pasireotide in patients with Cushing’s disease: results from an open-label, multicenter, single-arm, multinational, expanded-access study. Front Endocrinol (Lausanne) 10:436. https://doi.org/10.3389/fendo.2019.00436
pubmed: 31379734
Lacroix A, Gu F, Gallardo W, Pivonello R, Yu Y, Witek P, Boscaro M, Salvatori R, Yamada M, Tauchmanova L, Roughton M, Ravichandran S, Petersenn S, Biller BMK, Pasireotide G2304 Study Group (2018) Efficacy and safety of once-monthly pasireotide in Cushing’s disease: a 12 month clinical trial. Lancet Diabetes Endocrinol 6(1):17–26. https://doi.org/10.1016/S2213-8587(17)30326-1
pubmed: 29032078
Fleseriu M, Petersenn S, Biller BMK, Kadioglu P, De Block C, T’Sjoen G, Vantyghem MC, Tauchmanova L, Wojna J, Roughton M, Lacroix A, Newell-Price J (2019) Long-term efficacy and safety of once-monthly pasireotide in Cushing’s disease: a phase III extension study. Clin Endocrinol (Oxf) 91(6):776–785. https://doi.org/10.1111/cen.14081
pubmed: 31465533
Pivonello R, De Martino MC, Cappabianca P, De Leo M, Faggiano A, Lombardi G, Hofland LJ, Lamberts SW, Colao A (2009) 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(1):223–230. https://doi.org/10.1210/jc.2008-1533
pubmed: 18957500
Barbot M, Guarnotta V, Zilio M, Ceccato F, Ciresi A, Daniele A, Pizzolanti G, Campello E, Frigo AC, Giordano C, Scaroni C (2018) Effects of pasireotide treatment on coagulative profile: a prospective study in patients with Cushing’s disease. Endocrine 62(1):207–214. https://doi.org/10.1007/s12020-018-1669-2
pubmed: 29980915
Pivonello R, Pivonello C, Simeoli C, De Martino MC, Colao A (2022) The dopaminergic control of Cushing’s syndrome. J Endocrinol Invest 45(7):1297–1315. https://doi.org/10.1007/s40618-021-01661-x
pubmed: 35460460
pmcid: 9184412
Sonino N, Boscaro M, Paoletta A, Mantero F, Ziliotto D (1991) Ketoconazole treatment in Cushing’s syndrome: experience in 34 patients. Clin Endocrinol (Oxf) 35(4):347–352. https://doi.org/10.1111/j.1365-2265.1991.tb03547.x
pubmed: 1752063
Moncet D, Morando DJ, Pitoia F, Katz SB, Rossi MA, Bruno OD (2007) Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushing’s syndrome. Medicina (B Aires) 67(1):26–31
pubmed: 17408017
Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T (2008) Ketoconazole revisited: a preoperative or postoperative treatment in Cushing’s disease. Eur J Endocrinol 158(1):91–99. https://doi.org/10.1530/EJE-07-0514
pubmed: 18166822
Castinetti F, Guignat L, Giraud P, Muller M, Kamenicky P, Drui D, Caron P, Luca F, Donadille B, Vantyghem MC, Bihan H, Delemer B, Raverot G, Motte E, Philippon M, Morange I, Conte-Devolx B, Quinquis L, Martinie M, Vezzosi D, Le Bras M, Baudry C, Christin-Maitre S, Goichot B, Chanson P, Young J, Chabre O, Tabarin A, Bertherat J, Brue T (2014) Ketoconazole in Cushing’s disease: is it worth a try? J Clin Endocrinol Metab 99(5):1623–1630. https://doi.org/10.1210/jc.2013-3628
pubmed: 24471573
Shirley M (2021) Ketoconazole in Cushing’s syndrome: a profile of its use. Drugs Ther Perspect 37:55–64. https://doi.org/10.1007/s40267-020-00799-7
Jeffcoate WJ, Rees LH, Tomlin S, Jones AE, Edwards CR, Besser GM (1977) Metyrapone in long-term management of Cushing’s disease. Br Med J 2(6081):215–217. https://doi.org/10.1136/bmj.2.6081.215
pubmed: 195666
pmcid: 1631369
Thorén M, Adamson U, Sjöberg HE (1985) Aminoglutethimide and metyrapone in the management of Cushing’s syndrome. Acta Endocrinol (Copenh) 109(4):451–457. https://doi.org/10.1530/acta.0.1090451
pubmed: 3898689
Verhelst JA, Trainer PJ, Howlett TA, Perry L, Rees LH, Grossman AB, Wass JA, Besser GM (1991) Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing’s syndrome. Clin Endocrinol (Oxf) 35(2):169–178. https://doi.org/10.1111/j.1365-2265.1991.tb03517.x
pubmed: 1657460
Valassi E, Crespo I, Gich I, Rodríguez J, Webb SM (2012) A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing’s syndrome. Clin Endocrinol (Oxf) 77(5):735–742. https://doi.org/10.1111/j.1365-2265.2012.04424.x
pubmed: 22533782
Daniel E, Aylwin S, Mustafa O, Ball S, Munir A, Boelaert K, Chortis V, Cuthbertson DJ, Daousi C, Rajeev SP, Davis J, Cheer K, Drake W, Gunganah K, Grossman A, Gurnell M, Powlson AS, Karavitaki N, Huguet I, Kearney T, Mohit K, Meeran K, Hill N, Rees A, Lansdown AJ, Trainer PJ, Minder AE, Newell-Price J (2015) Effectiveness of metyrapone in treating Cushing’s syndrome: a retrospective multicenter study in 195 patients. J Clin Endocrinol Metab 100(11):4146–4154. https://doi.org/10.1210/jc.2015-2616
pubmed: 26353009
Nieman LK, Boscaro M et al (2021) Metyrapone treatment in endogenous cushing’s syndrome: results at week 12 from PROMPT, a Prospective International Multicenter, Open-Label, Phase III/IV Study. J Endocr Soc 5(Suppl 1):A515. https://doi.org/10.1210/jendso/bvab048.1053
Patil CG, Veeravagu A, Prevedello DM, Katznelson L, Vance ML, Laws ER Jr (2008) Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery 63:266–270
pubmed: 18797356
Hinojosa-Amaya JM, Cuevas-Ramos D, Fleseriu M (2019) Medical management of Cushing’s syndrome: current and emerging treatments. Drugs 79:935–956
pubmed: 31098899
Carroll TB, Peppard WJ, Herrmann DJ, Javorsky BR, Wang TS, Patel H, Zarnecki K, Findling JW (2018) Continuous etomidate infusion for the management of severe Cushing syndrome: Validation of a standard protocol. J Endocr Soc 3(1):1–12. https://doi.org/10.1210/js.2018-00269
pubmed: 30560224
pmcid: 6291660
Bertagna X, Pivonello R, Fleseriu M, Zhang Y, Robinson P, Taylor A, Watson CE, Maldonado M, Hamrahian AH, Boscaro M, Biller BM (2014) LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing’s disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab 99(4):1375–1383. https://doi.org/10.1210/jc.2013-2117
pubmed: 24423285
Fleseriu M, Pivonello R, Young J, Hamrahian AH, Molitch ME, Shimizu C, Tanaka T, Shimatsu A, White T, Hilliard A, Tian C, Sauter N, Biller BM, Bertagna X (2016) Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, phase II study in Cushing’s disease. Pituitary 19(2):138–148. https://doi.org/10.1007/s11102-015-0692-z
pubmed: 26542280
Gadelha M, Bex M, Feelders RA, Heaney AP, Auchus RJ, Gilis-Januszewska A, Witek P, Belaya Z, Yu Y, Liao Z, Ku CHC, Carvalho D, Roughton M, Wojna J, Pedroncelli AM, Snyder PJ (2022) Randomized trial of osilodrostat for the treatment of Cushing disease. J Clin Endocrinol Metab 107(7):e2882–e2895. https://doi.org/10.1210/clinem/dgac178
pubmed: 35325149
pmcid: 9202723
Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C, SEISMIC Study Investigators (2012) Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J Clin Endocrinol Metab 97(6):2039–2049. https://doi.org/10.1210/jc.2011-3350
pubmed: 22466348
DeGueme AM, King EE, Mirfakhraee S (2015) Medical treatment of Cushing’s disease with mifepristone: a clinical case series. Endocrine Rev. https://doi.org/10.1093/edrv/36.supp.1