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Review Article

Current and Emerging Pharmacological Therapies for Cushing's Disease

Author(s): Efstathios Divaris, Georgios Kostopoulos and Zoe A. Efstathiadou*

Volume 30, Issue 10, 2024

Published on: 28 February, 2024

Page: [757 - 777] Pages: 21

DOI: 10.2174/0113816128290025240216110928

Price: $65

Abstract

Cushing’s Disease (CD), hypercortisolism due to pituitary ACTH secreting neuroendocrine neoplasm, is associated with increased morbidity and, if untreated, mortality in about half of the affected individuals. Consequently, the timely initiation of effective treatment is mandatory. Neurosurgery is the first line and the only potentially curative treatment; however, 30% of patients will have persistent disease post-surgery. Furthermore, a small percentage of those initially controlled will develop hypercortisolism during long-term follow- up. Therefore, patients with persistent or recurrent disease, as well as those considered non-eligible for surgery, will need a second-line therapeutic approach, i.e., pharmacotherapy. Radiation therapy is reserved as a third-line therapeutic option due to its slower onset of action and its unfavorable profile regarding complications. During the past few years, the understanding of molecular mechanisms implicated in the physiology of the hypothalamus-pituitary-adrenal axis has evolved, and new therapeutic targets for CD have emerged. In the present review, currently available treatments, compounds currently tested in ongoing clinical trials, and interesting, potentially new targets emerging from unraveling molecular mechanisms involved in the pathophysiology of Cushing’s disease are discussed.

Keywords: Pituitary, pituitary hormone excess, Cushing’s disease, hypercortisolism, pharmacological therapies, neurosurgery.

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[1]
Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med 2017; 376(15): 1451-9.
[http://dx.doi.org/10.1056/NEJMra1505550] [PMID: 28402781]
[2]
Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing’s disease: A guideline update. Lancet Diabetes Endocrinol 2021; 9(12): 847-75.
[http://dx.doi.org/10.1016/S2213-8587(21)00235-7] [PMID: 34687601]
[3]
Clayton RN, Raskauskiene D, Reulen RC, Jones PW. Mortality and morbidity in Cushing’s disease over 50 years in Stoke-on-Trent, UK: Audit and meta-analysis of literature. J Clin Endocrinol Metab 2011; 96(3): 632-42.
[http://dx.doi.org/10.1210/jc.2010-1942] [PMID: 21193542]
[4]
Gadelha MR, Vieira Neto L. Efficacy of medical treatment in Cushing’s disease: A systematic review. Clin Endocrinol (Oxf) 2014; 80(1): 1-12.
[http://dx.doi.org/10.1111/cen.12345] [PMID: 24118077]
[5]
Bertagna X, Guignat L. Approach to the Cushing’s disease patient with persistent/recurrent hypercortisolism after pituitary surgery. J Clin Endocrinol Metab 2013; 98(4): 1307-18.
[http://dx.doi.org/10.1210/jc.2012-3200] [PMID: 23564942]
[6]
Aghi MK. Management of recurrent and refractory Cushing disease. Nat Clin Pract Endocrinol Metab 2008; 4(10): 560-8.
[http://dx.doi.org/10.1038/ncpendmet0947] [PMID: 18711406]
[7]
Patil CG, Veeravagu A, Prevedello DM, Katznelson L, Vance ML, Laws ER Jr. Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery 2008; 63(2): 266-71.
[http://dx.doi.org/10.1227/01.NEU.0000313117.35824.9F] [PMID: 18797356]
[8]
Rutkowski MJ, Flanigan PM, Aghi MK. Update on the management of recurrent Cushing’s disease. Neurosurg Focus 2015; 38(2): E16.
[http://dx.doi.org/10.3171/2014.11.FOCUS14703] [PMID: 25639318]
[9]
Feelders RA, Newell-Price J, Pivonello R, Nieman LK, Hofland LJ, Lacroix A. Advances in the medical treatment of Cushing’s syndrome. Lancet Diabetes Endocrinol 2019; 7(4): 300-12.
[http://dx.doi.org/10.1016/S2213-8587(18)30155-4] [PMID: 30033041]
[10]
Tritos NA, Biller BMK, Swearingen B. Management of Cushing disease. Nat Rev Endocrinol 2011; 7(5): 279-89.
[http://dx.doi.org/10.1038/nrendo.2011.12] [PMID: 21301487]
[11]
Pivonello R, De Martino MC, Cappabianca P, 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 2009; 94(1): 223-30.
[http://dx.doi.org/10.1210/jc.2008-1533] [PMID: 18957500]
[12]
Ferriere A, Cortet C, Chanson P, et al. Cabergoline for Cushing’s disease: A large retrospective multicenter study. Eur J Endocrinol 2017; 176(3): 305-14.
[http://dx.doi.org/10.1530/EJE-16-0662] [PMID: 28007845]
[13]
Casulari LA, Naves LA, Mello PA, Pereira Neto A, Papadia C. Nelson’s syndrome: Complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment. Horm Res Paediatr 2004; 62(6): 300-5.
[http://dx.doi.org/10.1159/000082235] [PMID: 15557761]
[14]
Woo I, Ehsanipoor RM. Cabergoline therapy for Cushing disease throughout pregnancy. Obstet Gynecol 2013; 122(2): 485-7.
[http://dx.doi.org/10.1097/AOG.0b013e31829e398a] [PMID: 23884269]
[15]
Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno OD, Lacroix A. Cabergoline monotherapy in the long-term treatment of Cushing’s disease. Eur J Endocrinol 2010; 163(5): 709-16.
[http://dx.doi.org/10.1530/EJE-10-0382] [PMID: 20702648]
[16]
Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE. Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 2005; 62(9): 1377-81.
[http://dx.doi.org/10.1001/archneur.62.9.noc50009] [PMID: 16009751]
[17]
Klos KJ, Bower JH, Josephs KA, Matsumoto JY, Ahlskog JE. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2005; 11(6): 381-6.
[http://dx.doi.org/10.1016/j.parkreldis.2005.06.005] [PMID: 16109498]
[18]
Auriemma RS, Pivonello R, Ferreri L, Priscitelli P, Colao A. Cabergoline use for pituitary tumors and valvular disorders. Endocrinol Metab Clin North Am 2015; 44(1): 89-97.
[http://dx.doi.org/10.1016/j.ecl.2014.10.007] [PMID: 25732645]
[19]
de Bruin C, Pereira AM, Feelders RA, et al. Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas. J Clin Endocrinol Metab 2009; 94(4): 1118-24.
[http://dx.doi.org/10.1210/jc.2008-2101] [PMID: 19141584]
[20]
de Bruin C, Feelders RA, Waaijers AM, et al. Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro. J Mol Endocrinol 2009; 42(1): 47-56.
[http://dx.doi.org/10.1677/JME-08-0110] [PMID: 18852217]
[21]
Hofland LJ, van der Hoek J, Feelders R, et al. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol 2005; 152(4): 645-54.
[http://dx.doi.org/10.1530/eje.1.01876] [PMID: 15817922]
[22]
Colao A, Petersenn S, Newell-Price J, et al. A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 2012; 366(10): 914-24.
[http://dx.doi.org/10.1056/NEJMoa1105743] [PMID: 22397653]
[23]
Schopohl J, Gu F, Rubens R, et al. 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 2015; 18(5): 604-12.
[http://dx.doi.org/10.1007/s11102-014-0618-1] [PMID: 25537481]
[24]
Lacroix A, Gu F, Gallardo W, et al. Efficacy and safety of once- monthly pasireotide in Cushing’s disease: A 12 month clinical trial. Lancet Diabetes Endocrinol 2018; 6(1): 17-26.
[http://dx.doi.org/10.1016/S2213-8587(17)30326-1] [PMID: 29032078]
[25]
Albani A, Perez-Rivas LG, Tang S, et al. Improved pasireotide response in USP8 mutant corticotroph tumours in vitro. Endocr Relat Cancer 2022; 29(8): 503-11.
[http://dx.doi.org/10.1530/ERC-22-0088] [PMID: 35686696]
[26]
Colao A, De Block C, Gaztambide MS, Kumar S, Seufert J, Casanueva FF. Managing hyperglycemia in patients with Cushing’s disease treated with pasireotide: Medical expert recommendations. Pituitary 2014; 17(2): 180-6.
[http://dx.doi.org/10.1007/s11102-013-0483-3] [PMID: 23564338]
[27]
Petersenn S, Salgado LR, Schopohl J, et al. Long-term treatment of Cushing’s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial. Endocrine 2017; 57(1): 156-65.
[http://dx.doi.org/10.1007/s12020-017-1316-3] [PMID: 28597198]
[28]
Gadelha M, Gatto F, Wildemberg LE, Fleseriu M. Cushing’s syndrome. Lancet 2023; 402(10418): 2237-52.
[http://dx.doi.org/10.1016/S0140-6736(23)01961-X] [PMID: 37984386]
[29]
McCormack AI, Wass JAH, Grossman AB. Aggressive pituitary tumours: The role of temozolomide and the assessment of MGMT status. Eur J Clin Invest 2011; 41(10): 1133-48.
[http://dx.doi.org/10.1111/j.1365-2362.2011.02520.x] [PMID: 21496012]
[30]
Stupp R, Gander M, Leyvraz S, Newlands E. Current and future developments in the use of temozolomide for the treatment of brain tumours. Lancet Oncol 2001; 2(9): 552-60.
[http://dx.doi.org/10.1016/S1470-2045(01)00489-2] [PMID: 11905710]
[31]
Hirohata T, Asano K, Ogawa Y, et al. DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide: the national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors. J Clin Endocrinol Metab 2013; 98(3): 1130-6.
[http://dx.doi.org/10.1210/jc.2012-2924] [PMID: 23365123]
[32]
Hinojosa-Amaya JM, Cuevas-Ramos D, Fleseriu M. Medical management of Cushing’s syndrome: Current and emerging treatments. Drugs 2019; 79(9): 935-56.
[http://dx.doi.org/10.1007/s40265-019-01128-7] [PMID: 31098899]
[33]
Raverot G, Castinetti F, Jouanneau E, et al. Pituitary carcinomas and aggressive pituitary tumours: Merits and pitfalls of temozolomide treatment. Clin Endocrinol (Oxf) 2012; 76(6): 769-75.
[http://dx.doi.org/10.1111/j.1365-2265.2012.04381.x] [PMID: 22404748]
[34]
McCormack A, Dekkers OM, Petersenn S, et al. Treatment of aggressive pituitary tumours and carcinomas: Results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol 2018; 178(3): 265-76.
[http://dx.doi.org/10.1530/EJE-17-0933] [PMID: 29330228]
[35]
Dillard TH, Gultekin SH, Delashaw JB Jr, Yedinak CG, Neuwelt EA, Fleseriu M. Temozolomide for corticotroph pituitary adenomas refractory to standard therapy. Pituitary 2011; 14(1): 80-91.
[http://dx.doi.org/10.1007/s11102-010-0264-1] [PMID: 20972839]
[36]
Bengtsson D, Schrøder HD, Andersen M, et al. Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide. J Clin Endocrinol Metab 2015; 100(4): 1689-98.
[http://dx.doi.org/10.1210/jc.2014-4350] [PMID: 25646794]
[37]
Zhang D, Heaney AP. Nuclear receptors as regulators of pituitary corticotroph pro-opiomelanocortin transcription. Cells 2020; 9(4): 900.
[http://dx.doi.org/10.3390/cells9040900] [PMID: 32272677]
[38]
Páez-Pereda M, Kovalovsky D, Hopfner U, et al. Retinoic acid prevents experimental Cushing syndrome. J Clin Invest 2001; 108(8): 1123-31.
[http://dx.doi.org/10.1172/JCI11098] [PMID: 11602619]
[39]
Pecori Giraldi F, Ambrogio AG, Andrioli M, et al. Potential role for retinoic acid in patients with Cushing’s disease. J Clin Endocrinol Metab 2012; 97(10): 3577-83.
[http://dx.doi.org/10.1210/jc.2012-2328] [PMID: 22851491]
[40]
Vilar L, Albuquerque JL, Lyra R, et al. The role of isotretinoin therapy for Cushing’s disease: Results of a prospective study. Int J Endocrinol 2016; 2016: 1-9.
[http://dx.doi.org/10.1155/2016/8173182] [PMID: 27034666]
[41]
Occhi G, Regazzo D, Albiger NM, et al. Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid in a cellular model of Cushing’s disease mediates the inhibition of cell proliferation and ACTH secretion without a complete corticotroph-to-melanotroph transdifferentiation. Endocrinology 2014; 155(9): 3538-49.
[http://dx.doi.org/10.1210/en.2013-1820] [PMID: 24926820]
[42]
Jordan S, Lidhar K, Korbonits M, Lowe DG, Grossman AB. Cyclin D and cyclin E expression in normal and adenomatous pituitary. Eur J Endocrinol 2000; 143(1): R1-6.
[http://dx.doi.org/10.1530/eje.0.143r001] [PMID: 10870044]
[43]
Roussel-Gervais A, Bilodeau S, Vallette S, et al. Cooperation between cyclin E and p27(Kip1) in pituitary tumorigenesis. Mol Endocrinol 2010; 24(9): 1835-45.
[http://dx.doi.org/10.1210/me.2010-0091] [PMID: 20660298]
[44]
Liu NA, Jiang H, Ben-Shlomo A, et al. Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor. Proc Natl Acad Sci 2011; 108(20): 8414-9.
[http://dx.doi.org/10.1073/pnas.1018091108] [PMID: 21536883]
[45]
Liu NA, Araki T, Cuevas-Ramos D, et al. Cyclin E-mediated human proopiomelanocortin regulation as a therapeutic target for Cushing disease. J Clin Endocrinol Metab 2015; 100(7): 2557-64.
[http://dx.doi.org/10.1210/jc.2015-1606] [PMID: 25942479]
[46]
Liu NA, Ben-Shlomo A, Carmichael JD, et al. Treatment of Cushing disease with pituitary-targeting seliciclib. J Clin Endocrinol Metab 2023; 108(3): 726-35.
[http://dx.doi.org/10.1210/clinem/dgac588] [PMID: 36214832]
[47]
Perez-Rivas LG, Theodoropoulou M, Ferraù F, et al. The gene of the ubiquitin-specific protease 8 is frequently mutated in adenomas causing Cushing’s disease. J Clin Endocrinol Metab 2015; 100(7): E997-E1004.
[http://dx.doi.org/10.1210/jc.2015-1453] [PMID: 25942478]
[48]
Theodoropoulou M, Reincke M, Fassnacht M, Komada M. Decoding the genetic basis of Cushing’s disease: USP8 in the spotlight. Eur J Endocrinol 2015; 173(4): M73-83.
[http://dx.doi.org/10.1530/EJE-15-0320] [PMID: 26012588]
[49]
Reincke M, Sbiera S, Hayakawa A, et al. Mutations in the deubiquitinase gene USP8 cause Cushing’s disease. Nat Genet 2015; 47(1): 31-8.
[http://dx.doi.org/10.1038/ng.3166] [PMID: 25485838]
[50]
Shen Y, Ji C, Jian X, et al. Regulation of the EGFR pathway by HSP90 is involved in the pathogenesis of Cushing’s disease. Front Endocrinol (Lausanne) 2021; 11: 601984.
[http://dx.doi.org/10.3389/fendo.2020.601984] [PMID: 33537004]
[51]
Ma ZY, Song ZJ, Chen JH, et al. Recurrent gain-of-function USP8 mutations in Cushing’s disease. Cell Res 2015; 25(3): 306-17.
[http://dx.doi.org/10.1038/cr.2015.20] [PMID: 25675982]
[52]
Kageyama K, Asari Y, Sugimoto Y, Niioka K, Daimon M. Ubiquitin-specific protease 8 inhibitor suppresses adrenocorticotropic hormone production and corticotroph tumor cell proliferation. Endocr J 2020; 67(2): 177-84.
[http://dx.doi.org/10.1507/endocrj.EJ19-0239] [PMID: 31666445]
[53]
Treppiedi D, Di Muro G, Marra G, et al. USP8 inhibitor RA-9 reduces ACTH release and cell growth in tumor corticotrophs. Endocr Relat Cancer 2021; 28(8): 573-82.
[http://dx.doi.org/10.1530/ERC-21-0093] [PMID: 34086599]
[54]
Duhamel C, Ilie MD, Salle H, et al. Immunotherapy in corticotroph and lactotroph aggressive tumors and carcinomas: Two case reports and a review of the literature. J Pers Med 2020; 10(3): 88.
[http://dx.doi.org/10.3390/jpm10030088] [PMID: 32823651]
[55]
Clark AJ, Forfar R, Hussain M, et al. ACTH antagonists. Front Endocrinol 2016; 7: 101.
[http://dx.doi.org/10.3389/fendo.2016.00101] [PMID: 27547198]
[56]
Crinetics Pharmaceuticals’ Oral ACTH Antagonist, CRN04894, Demonstrates Pharmacologic Proof-of-Concept with Strong Dose-Dependent Cortisol Suppression in Phase 1 Single Ascending Dose Study. 2021. Available from: https://crinetics.com/crn04894-demonstrates-pharmacologic-proof-of-concept/
[57]
A Phase 1b/2a Open-label Multiple-ascending Dose Exploratory Study of CRN04894 in ACTH-dependent Cushing's Syndrome (Cushing's Disease or Ectopic ACTH Syndrome). 2023. Available from: https://www.medifind.com/articles/clinical-trial/439615084
[58]
Feldhaus AL, Anderson K, Dutzar B, et al. ALD1613, a novel long-acting monoclonal antibody to control acth-driven pharmacology. Endocrinology 2016; 158(1): 1-8.
[http://dx.doi.org/10.1210/en.2016-1455]
[59]
Nensey NK, Bodager J, Gehrand AL, Raff H. Effect of novel melanocortin type 2 receptor antagonists on the corticosterone response to ACTH in the neonatal rat adrenal gland in vivo and in vitro. Front Endocrinol 2016; 7: 23.
[http://dx.doi.org/10.3389/fendo.2016.00023] [PMID: 27047449]
[60]
Hu C, Yang J, Qi Z, et al. Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities. MedComm 2022; 3(3): e161.
[http://dx.doi.org/10.1002/mco2.161] [PMID: 35928554]
[61]
Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet 2015; 386(9996): 913-27.
[http://dx.doi.org/10.1016/S0140-6736(14)61375-1] [PMID: 26004339]
[62]
Riebold M, Kozany C, Freiburger L, et al. A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease. Nat Med 2015; 21(3): 276-80.
[http://dx.doi.org/10.1038/nm.3776] [PMID: 25665180]
[63]
Sugiyama A, Kageyama K, Murasawa S, Ishigame N, Niioka K, Daimon M. Inhibition of heat shock protein 90 decreases ACTH production and cell proliferation in AtT-20 cells. Pituitary 2015; 18(4): 542-53.
[http://dx.doi.org/10.1007/s11102-014-0607-4] [PMID: 25280813]
[64]
Giraldi PF, Cassarino MF, Sesta A, Lasio G, Losa M. Silibinin, an HSP90 inhibitor, on human ACTH-secreting adenomas. Neuroendocrinology 2023; 113(6): 606-14.
[http://dx.doi.org/10.1159/000529710] [PMID: 36791678]
[65]
Du L, Bergsneider M, Mirsadraei L, et al. Evidence for orphan nuclear receptor TR4 in the etiology of Cushing disease. Proc Natl Acad Sci 2013; 110(21): 8555-60.
[http://dx.doi.org/10.1073/pnas.1306182110] [PMID: 23653479]
[66]
Xia L, Shen D, Zhang Y, et al. Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells. J Cell Mol Med 2021; 25(5): 2404-17.
[http://dx.doi.org/10.1111/jcmm.16074] [PMID: 33491272]
[67]
Fukuoka H, Cooper O, Ben-Shlomo A, et al. EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas. J Clin Invest 2011; 121(12): 4712-21.
[http://dx.doi.org/10.1172/JCI60417] [PMID: 22105169]
[68]
Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16(1): 15-31.
[http://dx.doi.org/10.1517/14728222.2011.648617] [PMID: 22239438]
[69]
Andl CD, Mizushima T, Oyama K, Bowser M, Nakagawa H, Rustgi AK. EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. Am J Physiol Gastrointest Liver Physiol 2004; 287(6): G1227-37.
[http://dx.doi.org/10.1152/ajpgi.00253.2004] [PMID: 15284024]
[70]
Asari Y, Kageyama K, Nakada Y, et al. Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells. OncoTargets Ther 2017; 10: 4329-38.
[http://dx.doi.org/10.2147/OTT.S141345] [PMID: 28919782]
[71]
Xu AW, Ste-Marie L, Kaelin CB, Barsh GS. Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology 2007; 148(1): 72-80.
[http://dx.doi.org/10.1210/en.2006-1119] [PMID: 17023536]
[72]
Sekizaki T, Kameda H, Nakamura A, et al. Neuromedin B receptor as a potential therapeutic target for corticotroph adenomas. Pituitary 2023; 26(5): 597-610.
[http://dx.doi.org/10.1007/s11102-023-01350-3] [PMID: 37642928]
[73]
Hagiwara R, Kageyama K, Iwasaki Y, Niioka K, Daimon M. Effects of tubastatin A on adrenocorticotropic hormone synthesis and proliferation of AtT-20 corticotroph tumor cells. Endocr J 2022; 69(9): 1053-60.
[http://dx.doi.org/10.1507/endocrj.EJ21-0778] [PMID: 35296577]
[74]
Nakada Y, Kageyama K, Sugiyama A, et al. Inhibitory effects of trichostatin A on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT-20 cells. Endocr J 2015; 62(12): 1083-90.
[http://dx.doi.org/10.1507/endocrj.EJ15-0369] [PMID: 26497760]
[75]
Hagiwara R, Kageyama K, Niioka K, Takayasu S, Tasso M, Daimon M. Involvement of histone deacetylase 1/2 in adrenocorticotropic hormone synthesis and proliferation of corticotroph tumor AtT-20 cells. Peptides 2021; 136: 170441.
[http://dx.doi.org/10.1016/j.peptides.2020.170441] [PMID: 33181265]
[76]
Lu J, Chatain GP, Bugarini A, et al. Histone deacetylase inhibitor SAHA is a promising treatment of Cushing disease. J Clin Endocrinol Metab 2017; 102(8): 2825-35.
[http://dx.doi.org/10.1210/jc.2017-00464] [PMID: 28505327]
[77]
Zhang D, Damoiseaux R, Babayan L, et al. Targeting corticotroph HDAC and PI3-kinase in Cushing disease. J Clin Endocrinol Metab 2021; 106(1): e232-46.
[http://dx.doi.org/10.1210/clinem/dgaa699] [PMID: 33000123]
[78]
Luque RM, Ibáñez-Costa A, López-Sánchez LM, et al. A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: Key role of AVPR1b receptor and potential therapeutic implications. J Clin Endocrinol Metab 2013; 98(10): 4160-9.
[http://dx.doi.org/10.1210/jc.2013-1992] [PMID: 23884782]
[79]
Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC, Patel YC. Receptors for dopamine and somatostatin: Formation of hetero-oligomers with enhanced functional activity. Science 2000; 288(5463): 154-7.
[http://dx.doi.org/10.1126/science.288.5463.154] [PMID: 10753124]
[80]
Günther T, Tulipano G, Dournaud P, et al. International union of basic and clinical pharmacology. CV. Somatostatin receptors: Structure, function, ligands, and new nomenclature. Pharmacol Rev 2018; 70(4): 763-835.
[http://dx.doi.org/10.1124/pr.117.015388] [PMID: 30232095]
[81]
Cantone MC, Dicitore A, Vitale G. Somatostatin-dopamine chimeric molecules in neuroendocrine neoplasms. J Clin Med 2021; 10(3): 501.
[http://dx.doi.org/10.3390/jcm10030501] [PMID: 33535394]
[82]
Pivonello R, De Leo M, Cozzolino A, Colao A. The treatment of Cushing’s disease. Endocr Rev 2015; 36(4): 385-486.
[http://dx.doi.org/10.1210/er.2013-1048] [PMID: 26067718]
[83]
Feelders RA, Hofland LJ, de Herder WW. Medical treatment of Cushing’s syndrome: Adrenal-blocking drugs and ketaconazole. Neuroendocrinology 2010; 92 (Suppl. 1): 111-5.
[http://dx.doi.org/10.1159/000314292] [PMID: 20829630]
[84]
Tritos NA. Adrenally directed medical therapies for Cushing syndrome. J Clin Endocrinol Metab 2021; 106(1): 16-25.
[http://dx.doi.org/10.1210/clinem/dgaa778] [PMID: 33118025]
[85]
Viecceli C, Mattos ACV, Hirakata VN, Garcia SP, Rodrigues TC, Czepielewski MA. Ketoconazole as second-line treatment for Cushing’s disease after transsphenoidal surgery: Systematic review and meta-analysis. Front Endocrinol 2023; 14: 1145775.
[http://dx.doi.org/10.3389/fendo.2023.1145775] [PMID: 37223017]
[86]
Galendi SCJ, Correa Neto ANS, Demetres M, Boguszewski CL, Nogueira VSN. Effectiveness of medical treatment of Cushing’s disease: A systematic review and meta-analysis. Front Endocrinol 2021; 12: 732240.
[http://dx.doi.org/10.3389/fendo.2021.732240] [PMID: 34603209]
[87]
Broersen LHA, Jha M, Biermasz NR, Pereira AM, Dekkers OM. Effectiveness of medical treatment for Cushing’s syndrome: A systematic review and meta-analysis. Pituitary 2018; 21(6): 631-41.
[http://dx.doi.org/10.1007/s11102-018-0897-z] [PMID: 29855779]
[88]
Castinetti F, Guignat L, Giraud P, et al. Ketoconazole in Cushing’s disease: Is it worth a try? J Clin Endocrinol Metab 2014; 99(5): 1623-30.
[http://dx.doi.org/10.1210/jc.2013-3628] [PMID: 24471573]
[89]
Viecceli C, Mattos ACV, Costa MCB, Melo RB, Rodrigues TC, Czepielewski MA. Evaluation of ketoconazole as a treatment for Cushing’s disease in a retrospective cohort. Front Endocrinol 2022; 13: 1017331.
[http://dx.doi.org/10.3389/fendo.2022.1017331] [PMID: 36277689]
[90]
Valassi E, Crespo I, Gich I, Rodríguez J, Webb SM. A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing’s syndrome. Clin Endocrinol 2012; 77(5): 735-42.
[http://dx.doi.org/10.1111/j.1365-2265.2012.04424.x] [PMID: 22533782]
[91]
Young J, Bertherat J, Vantyghem MC, et al. Hepatic safety of ketoconazole in Cushing’s syndrome: Results of a compassionate use programme in France. Eur J Endocrinol 2018; 178(5): 447-58.
[http://dx.doi.org/10.1530/EJE-17-0886] [PMID: 29472378]
[92]
Daniel E, Aylwin S, Mustafa O, et al. Effectiveness of metyrapone in treating Cushing’s syndrome: A retrospective multicenter study in 195 patients. J Clin Endocrinol Metab 2015; 100(11): 4146-54.
[http://dx.doi.org/10.1210/jc.2015-2616] [PMID: 26353009]
[93]
Nieman LK, Boscaro M, Scaroni CM, et al. 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 2021; 5(S1): A515-5.
[http://dx.doi.org/10.1210/jendso/bvab048.1053]
[94]
Caimari F, Valassi E, Garbayo P, et al. Cushing’s syndrome and pregnancy outcomes: A systematic review of published cases. Endocrine 2017; 55(2): 555-63.
[http://dx.doi.org/10.1007/s12020-016-1117-0] [PMID: 27704478]
[95]
Pivonello R, Simeoli C, Di Paola N, Colao A. Cushing’s disease: Adrenal steroidogenesis inhibitors. Pituitary 2022; 25(5): 726-32.
[http://dx.doi.org/10.1007/s11102-022-01262-8] [PMID: 36036308]
[96]
Bertagna X, Pivonello R, Fleseriu M, et al. 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 2014; 99(4): 1375-83.
[http://dx.doi.org/10.1210/jc.2013-2117] [PMID: 24423285]
[97]
Fleseriu M, Pivonello R, Young J, et al. Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing’s disease. Pituitary 2016; 19(2): 138-48.
[http://dx.doi.org/10.1007/s11102-015-0692-z] [PMID: 26542280]
[98]
Pivonello R, Fleseriu M, Newell-Price J, et al. 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 2020; 8(9): 748-61.
[http://dx.doi.org/10.1016/S2213-8587(20)30240-0] [PMID: 32730798]
[99]
Gadelha M, Bex M, Feelders RA, et al. Randomized trial of osilodrostat for the treatment of cushing disease. J Clin Endocrinol Metab 2022; 107(7): e2882-95.
[http://dx.doi.org/10.1210/clinem/dgac178] [PMID: 35325149]
[100]
Fleseriu M, Newell-Price J, Pivonello R, et al. Long-term outcomes of osilodrostat in Cushing’s disease: LINC 3 study extension. Eur J Endocrinol 2022; 187(4): 531-41.
[http://dx.doi.org/10.1530/EJE-22-0317] [PMID: 35980235]
[101]
Gadelha M, Snyder PJ, Witek P, et al. Long-term efficacy and safety of osilodrostat in patients with Cushing’s disease: Results from the LINC 4 study extension. Front Endocrinol 2023; 14: 1236465.
[http://dx.doi.org/10.3389/fendo.2023.1236465] [PMID: 37680892]
[102]
Newell-Price J, Pivonello R, Tabarin A, et al. Use of late-night salivary cortisol to monitor response to medical treatment in Cushing’s disease. Eur J Endocrinol 2020; 182(2): 207-17.
[http://dx.doi.org/10.1530/EJE-19-0695] [PMID: 31804965]
[103]
Fleseriu M, Biller BMK, Bertherat J, et al. Long-term efficacy and safety of osilodrostat in Cushing’s disease: Final results from a Phase II study with an optional extension phase (LINC 2). Pituitary 2022; 25(6): 959-70.
[http://dx.doi.org/10.1007/s11102-022-01280-6] [PMID: 36219274]
[104]
Detomas M, Altieri B, Deutschbein T, Fassnacht M, Dischinger U. Metyrapone versus osilodrostat in the short-term therapy of endogenous Cushing’s syndrome: Results from a single center cohort study. Front Endocrinol 2022; 13: 903545.
[http://dx.doi.org/10.3389/fendo.2022.903545] [PMID: 35769081]
[105]
Bonnet-Serrano F, Poirier J, Vaczlavik A, et al. Differences in the spectrum of steroidogenic enzyme inhibition between Osilodrostat and Metyrapone in ACTH-dependent Cushing syndrome patients. Eur J Endocrinol 2022; 187(2): 315-22.
[http://dx.doi.org/10.1530/EJE-22-0208] [PMID: 35699971]
[106]
Poirier J, Bonnet-Serrano F, Thomeret L, Bouys L, Bertherat J. Prolonged adrenocortical blockade following discontinuation of Osilodrostat. Eur J Endocrinol 2023; 188(6): K29-32.
[http://dx.doi.org/10.1093/ejendo/lvad060] [PMID: 37300549]
[107]
Heleno CT, Hong SPD, Cho HG, Kim MJ, Park Y, Chae YK. Cushing’s syndrome in adenocarcinoma of lung responding to osilodrostat. Case Rep Oncol 2023; 16(1): 130-4.
[http://dx.doi.org/10.1159/000527824] [PMID: 36876215]
[108]
Haissaguerre M, Puerto M, Nunes ML, Tabarin A. Efficacy and tolerance of osilodrostat in patients with severe Cushing’s syndrome due to non-pituitary cancers. Eur J Endocrinol 2020; 183(4): L7-9.
[http://dx.doi.org/10.1530/EJE-20-0557] [PMID: 32688343]
[109]
Dormoy A, Haissaguerre M, Vitellius G, et al. Efficacy and safety of osilodrostat in paraneoplastic cushing syndrome: A real-world multicenter study in France. J Clin Endocrinol Metab 2023; 108(6): 1475-87.
[http://dx.doi.org/10.1210/clinem/dgac691] [PMID: 36470583]
[110]
Creemers SG, Feelders RA, de Jong FH, et al. Levoketoconazole, the 2S,4R enantiomer of ketoconazole, a new steroidogenesis inhibitor for Cushing’s syndrome treatment. J Clin Endocrinol Metab 2021; 106(4): 1618-30.
[http://dx.doi.org/10.1210/clinem/dgaa989] [PMID: 33399817]
[111]
Fleseriu M, Pivonello R, Elenkova A, et al. Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing’s syndrome (SONICS): A phase 3, multicentre, open-label, single-arm trial. Lancet Diabetes Endocrinol 2019; 7(11): 855-65.
[http://dx.doi.org/10.1016/S2213-8587(19)30313-4] [PMID: 31542384]
[112]
Pivonello R, Zacharieva S, Elenkova A, et al. Levoketoconazole in the treatment of patients with endogenous Cushing’s syndrome: A double-blind, placebo-controlled, randomized withdrawal study (LOGICS). Pituitary 2022; 25(6): 911-26.
[http://dx.doi.org/10.1007/s11102-022-01263-7] [PMID: 36085339]
[113]
Fleseriu M, Auchus RJ, Greenman Y, et al. Levoketoconazole treatment in endogenous Cushing’s syndrome: Extended evaluation of clinical, biochemical, and radiologic outcomes. Eur J Endocrinol 2022; 187(6): 859-71.
[http://dx.doi.org/10.1530/EJE-22-0506] [PMID: 36251618]
[114]
Pivonello R, Elenkova A, Fleseriu M, et al. Levoketoconazole in the treatment of patients with Cushing’s syndrome and diabetes mellitus: Results from the SONICS phase 3 study. Front Endocrinol 2021; 12: 595894.
[http://dx.doi.org/10.3389/fendo.2021.595894] [PMID: 33897615]
[115]
Preda VA, Sen J, Karavitaki N, Grossman AB. THERAPY IN ENDOCRINE DISEASE: Etomidate in the management of hypercortisolaemia in Cushing’s syndrome: A review. Eur J Endocrinol 2012; 167(2): 137-43.
[http://dx.doi.org/10.1530/EJE-12-0274] [PMID: 22577107]
[116]
Carroll TB, Peppard WJ, Herrmann DJ, et al. Continuous etomidate infusion for the management of severe Cushing syndrome: Validation of a standard protocol. J Endocr Soc 2019; 3(1): 1-12.
[http://dx.doi.org/10.1210/js.2018-00269] [PMID: 30560224]
[117]
Schulte HM, Benker G, Reinwein D, Sippell WG, Allolio B. Infusion of low dose etomidate: Correction of hypercortisolemia in patients with Cushing’s syndrome and dose-response relationship in normal subjects. J Clin Endocrinol Metab 1990; 70(5): 1426-30.
[http://dx.doi.org/10.1210/jcem-70-5-1426] [PMID: 2159485]
[118]
Łebek-Szatańska A, Nowak KM, Zgliczyński W, Baum E, Żyłka A, Papierska L. Low-dose etomidate for the management of severe hypercortisolaemia in different clinical scenarios: A case series and review of the literature. Ther Adv Endocrinol Metab 2019; 10: 2042018819825541.
[http://dx.doi.org/10.1177/2042018819825541] [PMID: 30800267]
[119]
McGrath M, Ma C, Raines DE. Dimethoxy-etomidate: A nonhypnotic etomidate analog that potently inhibits steroidogenesis. J Pharmacol Exp Ther 2018; 364(2): 229-37.
[http://dx.doi.org/10.1124/jpet.117.245332] [PMID: 29203576]
[120]
Orth DN, Liddle GW. Results of treatment in 108 patients with Cushing’s syndrome. N Engl J Med 1971; 285(5): 243-7.
[http://dx.doi.org/10.1056/NEJM197107292850501] [PMID: 4326256]
[121]
Baudry C, Coste J, Bou Khalil R, et al. Efficiency and tolerance of mitotane in Cushing’s disease in 76 patients from a single center. Eur J Endocrinol 2012; 167(4): 473-81.
[http://dx.doi.org/10.1530/EJE-12-0358] [PMID: 22815335]
[122]
LaPensee CR, Mann JE, Rainey WE, Crudo V, Hunt SW III, Hammer GD. ATR-101, a selective and potent inhibitor of Acyl-CoA acyltransferase 1, induces apoptosis in h295r adrenocortical cells and in the adrenal cortex of dogs. Endocrinology 2016; 157(5): 1775-88.
[http://dx.doi.org/10.1210/en.2015-2052] [PMID: 26986192]
[123]
Smith DC, Kroiss M, Kebebew E, et al. A phase 1 study of nevanimibe HCl, a novel adrenal-specific sterol O-acyltransferase 1 (SOAT1) inhibitor, in adrenocortical carcinoma. Invest New Drugs 2020; 38(5): 1421-9.
[http://dx.doi.org/10.1007/s10637-020-00899-1] [PMID: 31984451]
[124]
El-Maouche D, Merke DP, Vogiatzi MG, et al. A phase 2, multicenter study of nevanimibe for the treatment of congenital adrenal hyperplasia. J Clin Endocrinol Metab 2020; 105(8): 2771-8.
[http://dx.doi.org/10.1210/clinem/dgaa381] [PMID: 32589738]
[125]
Burris-Hiday SD, Scott EE. Steroidogenic cytochrome P450 17A1 structure and function. Mol Cell Endocrinol 2021; 528: 111261.
[http://dx.doi.org/10.1016/j.mce.2021.111261] [PMID: 33781841]
[126]
Fiorentini C, Fragni M, Perego P, et al. Antisecretive and antitumor activity of abiraterone acetate in human adrenocortical cancer: A preclinical study. J Clin Endocrinol Metab 2016; 101(12): 4594-602.
[http://dx.doi.org/10.1210/jc.2016-2414] [PMID: 27626976]
[127]
Auchus RJ, Buschur EO, Chang AY, et al. Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency. J Clin Endocrinol Metab 2014; 99(8): 2763-70.
[http://dx.doi.org/10.1210/jc.2014-1258] [PMID: 24780050]
[128]
Chacko R, Abdel-Razeq NH, Abu Rous F, Loutfi R. Abiraterone acetate for treatment of ectopic Cushing syndrome caused by ACTH-producing neuroendocrine tumor: A case report. J Gastrointest Oncol 2022; 13(5): 2626-32.
[http://dx.doi.org/10.21037/jgo-22-376] [PMID: 36388644]
[129]
Wu N, Katz DA, An G. Population target-mediated pharmacokinetic/pharmacodynamic modeling to evaluate SPI-62 exposure and hepatic 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibition in healthy adults. Clin Pharmacokinet 2023; 62(9): 1275-88.
[http://dx.doi.org/10.1007/s40262-023-01278-8] [PMID: 37452998]
[130]
Brown DR, East HE, Eilerman BS, et al. Clinical management of patients with Cushing syndrome treated with mifepristone: Consensus recommendations. Clin Diabetes Endocrinol 2020; 6(1): 18.
[http://dx.doi.org/10.1186/s40842-020-00105-4] [PMID: 33292727]
[131]
Fleseriu M, Biller BMK, Findling JW, et al. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J Clin Endocrinol Metab 2012; 97(6): 2039-49.
[http://dx.doi.org/10.1210/jc.2011-3350] [PMID: 22466348]
[132]
Pivonello R, Ferrigno R, De Martino MC, et al. Medical treatment of Cushing’s disease: An overview of the current and recent clinical trials. Front Endocrinol 2020; 11: 648.
[http://dx.doi.org/10.3389/fendo.2020.00648] [PMID: 33363514]
[133]
Fein HG, Vaughan TB III, Kushner H, Cram D, Nguyen D. 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 2015; 15(1): 63.
[http://dx.doi.org/10.1186/s12902-015-0059-5] [PMID: 26507877]
[134]
Ault TA, Braxton DR, Watson RA, Marcus AO, Fong TL. Mifepristone induced liver injury in a patient with Cushing syndrome: A case report and review of the literature. J Med Case Reports 2023; 17(1): 33.
[http://dx.doi.org/10.1186/s13256-022-03696-x] [PMID: 36732814]
[135]
Castinetti F, Fassnacht M, Johanssen S, et al. Merits and pitfalls of mifepristone in Cushing’s syndrome. Eur J Endocrinol 2009; 160(6): 1003-10.
[http://dx.doi.org/10.1530/EJE-09-0098] [PMID: 19289534]
[136]
Guarda FJ, Findling J, Yuen KCJ, Fleseriu M, Nachtigall LB. Mifepristone increases thyroid hormone requirements in patients with central hypothyroidism: A multicenter study. J Endocr Soc 2019; 3(9): 1707-14.
[http://dx.doi.org/10.1210/js.2019-00188] [PMID: 31528830]
[137]
Pivonello R, Munster PN, Terzolo M, et al. Glucocorticoid receptor antagonism upregulates somatostatin receptor subtype 2 expression in acth-producing neuroendocrine tumors: New insight based on the selective glucocorticoid receptor modulator relacorilant. Front Endocrinol 2022; 12: 793262.
[http://dx.doi.org/10.3389/fendo.2021.793262] [PMID: 35058882]
[138]
Molitch ME. Glucocorticoid receptor blockers. Pituitary 2022; 25(5): 733-6.
[http://dx.doi.org/10.1007/s11102-022-01227-x] [PMID: 35507245]
[139]
Pivonello R, Bancos I, Feelders RA, et al. Relacorilant, a selective glucocorticoid receptor modulator, induces clinical improvements in patients with Cushing syndrome: Results from a prospective, open-label phase 2 study. Front Endocrinol 2021; 12: 662865.
[http://dx.doi.org/10.3389/fendo.2021.662865] [PMID: 34335465]
[140]
Donegan DM, Pivonello R, Stigliano A, et al. Relacorilant, a selective glucocorticoid receptor modulator in development for the treatment of patients with Cushing syndrome, does not cause prolongation of the cardiac QT interval. Endocr Pract 2024; 30(1): 11-8.
[http://dx.doi.org/10.1016/j.eprac.2023.09.011] [PMID: 37805100]
[141]
Vilar L, Naves LA, Azevedo MF, et al. Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing’s disease. Pituitary 2010; 13(2): 123-9.
[http://dx.doi.org/10.1007/s11102-009-0209-8] [PMID: 19943118]
[142]
Barbot M, Albiger N, Ceccato F, et al. Combination therapy for Cushing’s disease: Effectiveness of two schedules of treatment. Should we start with cabergoline or ketoconazole? Pituitary 2014; 17(2): 109-17.
[http://dx.doi.org/10.1007/s11102-013-0475-3] [PMID: 23468128]
[143]
Kamenický P, Droumaguet C, Salenave S, et al. Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 2011; 96(9): 2796-804.
[http://dx.doi.org/10.1210/jc.2011-0536] [PMID: 21752886]
[144]
Pivonello R, Kadioglu P, Bex M, Devia DG, Boguszewski C, Yavuz DG. Pasireotide alone or in combination with cabergoline effectively controls urinary free cortisol levels: Results from a prospective study in patients with Cushing’s disease (CAPACITY). Endocr Abstr 2017. 49: Bioscientifica.
[http://dx.doi.org/10.1530/endoabs.49.GP187]
[145]
Feelders RA, de Bruin C, Pereira AM, et al. Pasireotide alone or with cabergoline and ketoconazole in Cushing’s disease. N Engl J Med 2010; 362(19): 1846-8.
[http://dx.doi.org/10.1056/NEJMc1000094] [PMID: 20463350]
[146]
Amodru V, Brue T, Castinetti F. Synergistic cortisol suppression by ketoconazole–osilodrostat combination therapy. Endocrinol Diabetes Metab Case Rep 2021; 2021: 21-0071.
[http://dx.doi.org/10.1530/EDM-21-0071] [PMID: 34877930]
[147]
Bogusławska A, Kluczyński Ł, Godlewska M, Rzepka E, Hubalewska-Dydejczyk A, Gilis-Januszewska A. Multimodal treatment including temozolomide (TMZ) and pasireotide for aggressive, giant silent corticotroph PiTNET in a young patient. Endocr Abstr 2022. 81: Bioscientifica.
[http://dx.doi.org/10.1530/endoabs.81.P693]
[148]
Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T. Ketoconazole revisited: A preoperative or postoperative treatment in Cushing’s disease. Eur J Endocrinol 2008; 158(1): 91-9.
[http://dx.doi.org/10.1530/EJE-07-0514] [PMID: 18166822]
[149]
Ghervan C, Nemes C, Valea A, Silaghi A, Georgescu CE, Ghervan L. Ketoconazole treatment in Cushing’s syndrome: Results of a tertiary referral center in Romania. Acta Endocrinol 2015; 11(1): 46-54.
[http://dx.doi.org/10.4183/aeb.2015.46]
[150]
Invitti C, Giraldi PF, de Martin M, Cavagnini F. Diagnosis and management of Cushing’s syndrome: Results of an Italian multicentre study. J Clin Endocrinol Metab 1999; 84(2): 440-8.
[http://dx.doi.org/10.1210/jc.84.2.440] [PMID: 10022398]
[151]
Luisetto G, Zangari M, Camozzi V, Boscaro M, Sonino N, Fallo F. Recovery of bone mineral density after surgical cure, but not by ketoconazole treatment, in Cushing’s syndrome. Osteoporos Int 2001; 12(11): 956-60.
[http://dx.doi.org/10.1007/s001980170025] [PMID: 11804023]
[152]
Moncet D, Morando DJ, Pitoia F, et al. Ketoconazole therapy: An efficacious alternative to achieve eucortisolism in patients with Cushing's syndrome. Medicina 2007; 67(1): 26-31.
[153]
Sonino N, Boscaro M, Paoletta A, Mantero F, Zillotto D. Ketoconazole treatment in Cushing’s syndrome: Experience in 34 patients. Clin Endocrinol 1991; 35(4): 347-52.
[http://dx.doi.org/10.1111/j.1365-2265.1991.tb03547.x] [PMID: 1752063]
[154]
van den Bosch OFC, Stades AME, Zelissen PMJ. Increased long-term remission after adequate medical cortisol suppression therapy as presurgical treatment in Cushing’s disease. Clin Endocrinol 2014; 80(2): 184-90.
[http://dx.doi.org/10.1111/cen.12286] [PMID: 23841642]
[155]
Ceccato F, Zilio M, Barbot M, et al. Metyrapone treatment in Cushing’s syndrome: A real-life study. Endocrine 2018; 62(3): 701-11.
[http://dx.doi.org/10.1007/s12020-018-1675-4] [PMID: 30014438]
[156]
Verhelst JA, Trainer PJ, Howlett TA, et al. Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing’s syndrome. Clin Endocrinol 1991; 35(2): 169-78.
[http://dx.doi.org/10.1111/j.1365-2265.1991.tb03517.x] [PMID: 1657460]
[157]
Thorén M, Adamson U, Sjöberg HE. Aminoglutethimide and metyrapone in the management of Cushing’s syndrome. Eur J Endocrinol 1985; 109(4): 451-7.
[http://dx.doi.org/10.1530/acta.0.1090451] [PMID: 3898689]
[158]
Jeffcoate WJ, Rees LH, Tomlin S, Jones AE, Edwards CR, Besser GM. Metyrapone in long-term management of Cushing’s disease. BMJ 1977; 2(6081): 215-7.
[http://dx.doi.org/10.1136/bmj.2.6081.215] [PMID: 195666]
[159]
Schteingart D, Tsao HS, Taylor CI, McKenzie A, Victoria R, Therrien BA. Sustained remission of Cushing’s disease with mitotane and pituitary irradiation. Ann Intern Med 1980; 92(5): 613-9.
[http://dx.doi.org/10.7326/0003-4819-92-5-613] [PMID: 6247946]
[160]
Luton JP, Mahoudeau JA, Bouchard P, et al. Treatment of Cushing’s disease by o,p′DDD. N Engl J Med 1979; 300(9): 459-64.
[http://dx.doi.org/10.1056/NEJM197903013000903] [PMID: 215912]

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