{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T03:20:25Z","timestamp":1791602425277,"version":"4.3.4"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drugs"],"published-print":{"date-parts":[[2016,3]]},"DOI":"10.1007\/s40265-016-0539-6","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T10:50:15Z","timestamp":1454323815000},"page":"447-458","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Therapeutic Strategies for the Treatment of Severe Cushing\u2019s Syndrome"],"prefix":"10.1007","volume":"76","author":[{"given":"Krystallenia I.","family":"Alexandraki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley B.","family":"Grossman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,1]]},"reference":[{"key":"539_CR1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/S0140-6736(06)68699-6","volume":"367","author":"J Newell-Price","year":"2006","unstructured":"Newell-Price J, Bertagna X, Grossman AB, et al. Cushing\u2019s syndrome. Lancet. 2006;367:1605\u201317.","journal-title":"Lancet"},{"key":"539_CR2","first-page":"42","volume":"85","author":"NJ Sarlis","year":"2000","unstructured":"Sarlis NJ, Chanock SJ, Nieman LK. Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. J Clin Endocrinol Metab. 2000;85:42\u20137.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1530\/EJE-14-0913","volume":"172","author":"JB Corcuff","year":"2015","unstructured":"Corcuff JB, Young J, Masquefa-Giraud P, et al. Rapid control of severe neoplastic hypercortisolism with metyrapone and ketoconazole. Eur J Endocrinol. 2015;172:473\u20138.","journal-title":"Eur J Endocrinol"},{"key":"539_CR4","doi-asserted-by":"crossref","first-page":"M23","DOI":"10.1530\/EJE-15-0265","volume":"173","author":"M Reincke","year":"2015","unstructured":"Reincke M, Ritzel K, Osswald A, et al. A critical re-appraisal of bilateral adrenalectomy for ACTH-dependent Cushing\u2019s syndrome. Eur J Endocrinol. 2015;173:M23\u201332.","journal-title":"Eur J Endocrinol."},{"key":"539_CR5","first-page":"117","volume":"86","author":"J Lindholm","year":"2001","unstructured":"Lindholm J, Juul S, J\u00f8rgensen JO, et al. Incidence and late prognosis of Cushing\u2019s syndrome: a population-based study. J Clin Endocrinol Metab. 2001;86:117\u201323.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR6","doi-asserted-by":"crossref","first-page":"R143","DOI":"10.1530\/EJE-14-0556","volume":"172","author":"FM Haalen van","year":"2015","unstructured":"van Haalen FM, Broersen LH, Jorgensen JO, et al. Management of endocrine disease: mortality remains increased in Cushing\u2019s disease despite biochemical remission: a systematic review and meta-analysis. Eur J Endocrinol. 2015;172:R143\u20139.","journal-title":"Eur J Endocrinol"},{"key":"539_CR7","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1210\/jc.2015-1818","volume":"100","author":"LK Nieman","year":"2015","unstructured":"Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing\u2019s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:2807\u201331.","journal-title":"J Clin Endocrinol Metab."},{"key":"539_CR8","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1210\/jc.2009-0290","volume":"94","author":"B Zaane Van","year":"2009","unstructured":"Van Zaane B, Nur E, Squizzato A, et al. Hypercoagulable state in Cushing\u2019s syndrome: a systematic review. J Clin Endocrinol Metab. 2009;94:2743\u201350.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR9","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1210\/jc.2011-0536","volume":"96","author":"P Kamenick\u00fd","year":"2011","unstructured":"Kamenick\u00fd P, Droumaguet C, Salenave S, et al. Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent Cushing\u2019s syndrome. J Clin Endocrinol Metab. 2011;96:2796\u2013804.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR10","author":"KI Alexandraki","year":"2014","unstructured":"Alexandraki KI, Grossman AB. Emergency treatment of florid Cushing\u2019s Syndrome in endocrine and metabolic medical emergencies: a clinician\u2019s guide. Endocrine Press. 2014. doi: 10.1210\/EME.9781936704811.ch16 .","journal-title":"Endocrine Press"},{"key":"539_CR11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4614-8684-8_9","volume-title":"Endocrinology and diabetes: a problem oriented approach","author":"KI Alexandraki","year":"2014","unstructured":"Alexandraki KI, Grossman AB. Cushing\u2019s syndrome. In: Bandeira F, Gharib H, Golbert A, Griz L, Faria M, editors. Endocrinology and diabetes: a problem oriented approach. New York: Springer Science\u00a0+\u00a0Business Media; 2014. p. 99\u2013111."},{"issue":"Suppl 4","key":"539_CR12","doi-asserted-by":"crossref","first-page":"S313","DOI":"10.4103\/2230-8210.86973","volume":"15","author":"Y Singh","year":"2011","unstructured":"Singh Y, Kotwal N, Menon AS. Endocrine hypertension\u2014Cushing\u2019s syndrome. Indian J Endocrinol Metab. 2011;15(Suppl 4):S313\u20136.","journal-title":"Indian J Endocrinol Metab."},{"key":"539_CR13","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1055\/s-2008-1062729","volume":"116","author":"A Arlt","year":"2008","unstructured":"Arlt A, Harbeck B, Anlauf M, et al. Fatal pneumocystis jirovecii pneumonia in a case of ectopic Cushing\u2019s syndrome due to neuroendocrine carcinoma of the kidney. Exp Clin Endocrinol Diabetes. 2008;116:515\u20139.","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"539_CR14","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1210\/jc.2006-2361","volume":"92","author":"M Christ-Crain","year":"2007","unstructured":"Christ-Crain M, Jutla S, Widmer I, et al. Measurement of serum free cortisol shows discordant responsivity to stress and dynamic evaluation. J Clin Endocrinol Metab. 2007;92:1729\u201335.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR15","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S2213-8587(15)00224-7","volume":"3","author":"E Boonen","year":"2015","unstructured":"Boonen E, Bornstein SR, Van den Berghe G. New insights into the controversy of adrenal function during critical illness. Lancet Diabetes Endocrinol. 2015;3:805\u201315.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"539_CR16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1590\/S0004-27302011000500001","volume":"55","author":"RB Moraes","year":"2011","unstructured":"Moraes RB, Czepielewski MA, Friedman G, et al. Diagnosis of adrenal failure in critically ill patients. Arq Bras Endocrinol Metabol. 2011;55:295\u2013302.","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"539_CR17","doi-asserted-by":"crossref","unstructured":"Faucz FR1, Zilbermint M, Lodish MB, et al. Macronodular adrenal hyperplasia due to mutations in an armadillo repeat containing 5 (ARMC5) gene: a clinical and genetic investigation. J Clin Endocrinol Metab. 2014;99:E1113\u20139.","DOI":"10.1210\/jc.2013-4280"},{"key":"539_CR18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1186\/s40064-015-1218-x","volume":"4","author":"N Epperla","year":"2015","unstructured":"Epperla N, McKiernan F. Iatrogenic Cushing syndrome and adrenal insufficiency during concomitant therapy with ritonavir and fluticasone. Springerplus. 2015;4:455.","journal-title":"Springerplus."},{"key":"539_CR19","unstructured":"Pai M, Douketis JD, section editors, Lawrence LK Leung, Jess Mandel, Deputy Editor Geraldine Finlay. Prevention of venous thromboembolic disease in medical patients. Topic 1346 version 40.0. Literature review current through: Mar 2013. This topic last updated: Feb 12, 2013."},{"key":"539_CR20","first-page":"215","volume":"65","author":"JK Oosterhuis","year":"2007","unstructured":"Oosterhuis JK, van den Berg G, Monteban-Kooistra WE, et al. Life-threatening Pneumocystis jiroveci pneumonia following treatment of severe Cushing\u2019s syndrome. Neth J Med. 2007;65:215\u20137.","journal-title":"Neth J Med"},{"key":"539_CR21","first-page":"3542","volume":"83","author":"WM Drake","year":"1998","unstructured":"Drake WM, Perry LA, Hinds CJ, et al. Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing\u2019s syndrome and peritonitis. J Clin Endocrinol Metab. 1998;83:3542\u20134.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR22","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1210\/jc.2011-1661","volume":"96","author":"DJ Stuijver","year":"2011","unstructured":"Stuijver DJ, van Zaane B, Feelders RA, et al. Incidence of venous thromboembolism in patients with Cushing\u2019s syndrome: a multicenter cohort study. J Clin Endocrinol Metab. 2011;96:3525\u201332.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR23","doi-asserted-by":"crossref","first-page":"R205","DOI":"10.1530\/ERC-12-0191","volume":"19","author":"R Pas van der","year":"2012","unstructured":"van der Pas R, de Herder WW, Hofland LJ, et al. New developments in the medical treatment of Cushing\u2019s syndrome. Endocr Relat Cancer. 2012;19:R205\u201323.","journal-title":"Endocr Relat Cancer"},{"key":"539_CR24","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1177\/0956462413480723","volume":"24","author":"JJ Hall","year":"2013","unstructured":"Hall JJ, Hughes CA, Foisy MM, et al. Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient receiving ritonavir-boosted darunavir. Int J STD AIDS. 2013;24:748\u201352.","journal-title":"Int J STD AIDS"},{"key":"539_CR25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.17925\/EE.2008.04.02.74","volume":"4","author":"KI Alexandraki","year":"2009","unstructured":"Alexandraki KI, Grossman AB. Medical therapy for Cushing\u2019s disease: past and future modes of treatment. Eur Endocrinol. 2009;4:74\u201380.","journal-title":"Eur Endocrinol"},{"key":"539_CR26","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1530\/JOE-14-0300","volume":"223","author":"D Cuevas-Ramos","year":"2014","unstructured":"Cuevas-Ramos D, Fleseriu M. Treatment of Cushing\u2019s disease: a mechanistic update. J Endocrinol. 2014;223:R19\u201339.","journal-title":"J Endocrinol"},{"key":"539_CR27","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1136\/bmj.2.6081.215","volume":"2","author":"WJ Jeffcoate","year":"1977","unstructured":"Jeffcoate WJ, Rees LH, Tomlin S, et al. Metyrapone in long-term management of Cushing\u2019s disease. Br J Med. 1977;2:215\u20137.","journal-title":"Br J Med"},{"key":"539_CR28","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/pgmj.62.730.727","volume":"62","author":"J Donckier","year":"1986","unstructured":"Donckier J, Burrin JM, Ramsay ID, et al. Successful control of Cushing\u2019s disease in the elderly with long term metyrapone. Postgrad Med J. 1986;62:727\u201330.","journal-title":"Postgrad Med J"},{"key":"539_CR29","doi-asserted-by":"crossref","first-page":"4146","DOI":"10.1210\/jc.2015-2616","volume":"100","author":"E Daniel","year":"2015","unstructured":"Daniel E, Aylwin S, Mustafa O, et al. Effectiveness of metyrapone in the treatment of Cushing\u2019s Syndrome: a retrospective multicenter study in 195 patients. J Clin Endocrinol Metab. 2015;100:4146\u201354.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1365-2265.1991.tb03517.x","volume":"35","author":"JA Verhelst","year":"1991","unstructured":"Verhelst JA, Trainer PJ, Howlett TA, et al. Short- and long-term responses to metyrapone in the medical management of 91 patients with Cushing\u2019s syndrome. Clin Endocrinol. 1991;35:169\u201378.","journal-title":"Clin Endocrinol"},{"key":"539_CR31","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1258\/acb.2011.011014","volume":"48","author":"PJ Monaghan","year":"2011","unstructured":"Monaghan PJ, Owen LJ, Trainer PJ, et al. Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11\u03b2-hydroxylase inhibitor\u00a0metyrapone. Ann Clin Biochem. 2011;48:441\u20136.","journal-title":"Ann Clin Biochem."},{"key":"539_CR32","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1172\/JCI110903","volume":"71","author":"DS Loose","year":"1983","unstructured":"Loose DS, Kan PB, Hirst MA, et al. Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest. 1983;71:1495\u20139.","journal-title":"J Clin Invest"},{"key":"539_CR33","doi-asserted-by":"crossref","unstructured":"Jimenez Reina L, Leal-Cerro A, Garcia J, et al. In vitro effects of ketoconazole on corticotrope cell morphology and ACTH secretion of two pituitary adenomas removed from patients with Nelson\u2019s syndrome. Acta Endocrinol (Copenh), 1989;121:185\u201390.","DOI":"10.1530\/acta.0.1210185"},{"key":"539_CR34","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1172\/JCI110982","volume":"72","author":"DS Loose","year":"1983","unstructured":"Loose DS, Stover EP, Feldman D. Ketoconazole binds to glucocorticoid receptors and exhibits glucocorticoid antagonist activity in cultured cells. J Clin Invest. 1983;72:404\u20138.","journal-title":"J Clin Invest"},{"key":"539_CR35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1530\/EJE-07-0514","volume":"158","author":"F Castinetti","year":"2008","unstructured":"Castinetti F, Morange I, Jaquet P, et al. Ketoconazole revisited: a preoperative or postoperative treatment in Cushing\u2019s disease. Eur J Endocrinol. 2008;158:91\u20139.","journal-title":"Eur J Endocrinol"},{"key":"539_CR36","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1001\/archinte.1984.00350170237037","volume":"144","author":"PA Duarte","year":"1984","unstructured":"Duarte PA, Chow CC, Simmons F, et al. Fatal hepatitis associated with ketoconazole therapy. Arch Intern Med. 1984;144:1069\u201370.","journal-title":"Arch Intern Med"},{"key":"539_CR37","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1210\/jc.2013-3628","volume":"99","author":"F Castinetti","year":"2014","unstructured":"Castinetti F, Guignat L, Giraud P, et al. Ketoconazole in Cushing\u2019s disease: is it worth a try? J Clin Endocrinol Metab. 2014;99:1623\u201330.","journal-title":"J Clin Endocrinol Metab."},{"key":"539_CR38","unstructured":"Salvatori R, DelConte A, Geer EB, et al. An open-label study to assess the safety and efficacy of levoketoconazole (COR-003) in the treatment of endogenous Cushing\u2019s syndrome. In: Program of the 97th annual meeting of The Endocrine Society, March 5\u20138, 2015; San Diego, CA. Abstract endocrine reviews. 2015;36:376."},{"key":"539_CR39","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0022-3565(25)22688-X","volume":"240","author":"SW Lamberts","year":"1987","unstructured":"Lamberts SW, Bons EG, Bruining HA, et al. Differential effects of the imidazole derivatives etomidate, ketoconazole and miconazole and of metyrapone on the secretion of cortisol and its precursors by human adrenocortical cells. J Pharmacol Exp Ther. 1987;240:259\u201364.","journal-title":"J Pharmacol Exp Ther"},{"key":"539_CR40","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/S0140-6736(83)90760-2","volume":"2","author":"NO Klausen","year":"1983","unstructured":"Klausen NO, Moelgaard J, Ferguson AH, et al. Negative synacthen test during etomidate infusion. Lancet. 1983;2:848.","journal-title":"Lancet"},{"key":"539_CR41","first-page":"4104","volume":"86","author":"J Krakoff","year":"2001","unstructured":"Krakoff J, Koch CA, Calis KA, et al. Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing\u2019s syndrome. J Clin Endocrinol Metab. 2001;86:4104\u20138.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR42","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1345\/aph.1H365","volume":"41","author":"TN Johnson","year":"2007","unstructured":"Johnson TN, Canada TW. Etomidate use for Cushing\u2019s syndrome caused by an ectopic adrenocorticotropic hormone-producing tumor. Ann Pharmacother. 2007;41:350\u20133.","journal-title":"Ann Pharmacother"},{"key":"539_CR43","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1159\/000088587","volume":"64","author":"JE Greening","year":"2005","unstructured":"Greening JE, Brain CE, Perry LA, et al. Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing\u2019s disease. Horm Res. 2005;64:140\u20133.","journal-title":"Horm Res"},{"key":"539_CR44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1530\/EJE-12-0746","volume":"167","author":"VA Preda","year":"2012","unstructured":"Preda VA, Sen J, Karavitaki N, Ab Grossman, et al. Etomidate in the management or hypercortisolaemia in Cushing\u2019s syndrome: a review. Eur J Endocrinol. 2012;167:137\u201343.","journal-title":"Eur J Endocrinol"},{"key":"539_CR45","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1210\/jcem-70-5-1426","volume":"70","author":"HM Schulte","year":"1990","unstructured":"Schulte HM, Benker G, Reinwein D, et al. Infusion of low dose etomidate: correction of hypercortislemia in patients with Cushing\u2019s syndrome and dose\u2013response relationship in normal subjects. J Clin Endocrinol Metab. 1990;70:1426\u201330.","journal-title":"J Clin Endocrinol Metab"},{"issue":"169","key":"539_CR46","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1530\/EJE-13-0569","volume":"8","author":"G Ntali","year":"2013","unstructured":"Ntali G, Asimakopoulou A, Siamatras T, et al. Mortality in Cushing\u2019s syndrome: systematic analysis of a large series with prolonged follow-up. Eur J Endocrinol. 2013;8(169):715\u201323.","journal-title":"Eur J Endocrinol"},{"key":"539_CR47","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.surg.2013.06.017","volume":"154","author":"LF Morris","year":"2013","unstructured":"Morris LF, Harris RS, Milton DR, et al. Impact and timing of bilateral adrenalectomy for refractory adrenocorticotropic hormone-dependent Cushing\u2019s syndrome. Surgery. 2013;154:1174\u201383.","journal-title":"Surgery"},{"key":"539_CR48","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1590\/S0004-27302012000500008","volume":"56","author":"M Farage","year":"2012","unstructured":"Farage M, Costa MA, Godoy-Matos AF. A rare case of Cushing syndrome by cyclic ectopic-ACTH. Arq Bras Endocrinol Metabol. 2012;56:324\u201330.","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"539_CR49","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1210\/endo-62-3-326","volume":"62","author":"C Cueto","year":"1958","unstructured":"Cueto C, Brown JHU. Biological studies on an adrenocorticolytic agent and the isolation of the active components. Endocrinology. 1958;62:326\u201333.","journal-title":"Endocrinology"},{"key":"539_CR50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1365-2265.2011.04214.x","volume":"75","author":"M Kroiss","year":"2011","unstructured":"Kroiss M, Quinkler M, Lutz WK, et al. Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma. Clin Endocrinol (Oxf). 2011;75:585\u201391.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"539_CR51","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1365-2265.2009.03631.x","volume":"72","author":"KI Alexandraki","year":"2010","unstructured":"Alexandraki KI, Kaltsas GA, le Roux CW, et al. Assessment of serum-free cortisol levels in patients with adrenocortical carcinoma treated with mitotane: a pilot study. Clin Endocrinol (Oxf). 2010;72:305\u201311.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"539_CR52","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1210\/jcem-63-3-639","volume":"63","author":"X Bertagna","year":"1986","unstructured":"Bertagna X, Bertagna C, Laudat MH, et al. Pituitary-adrenal response to the antiglucocorticoid action of RU 486 in Cushing\u2019s syndrome. J Clin Endocrinol Metab. 1986;63:639\u201343.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR53","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1210\/jc.2011-3350","volume":"97","author":"M Fleseriu","year":"2012","unstructured":"Fleseriu M, Biller BM, Findling JW, et al. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing\u2019s syndrome. J Clin Endocrinol Metab. 2012;97:2039\u201349.","journal-title":"J Clin Endocrinol Metab."},{"key":"539_CR54","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1210\/jc.2011-1264","volume":"97","author":"C Bruin de","year":"2012","unstructured":"de Bruin C, Hofland LJ, Nieman LK, et al. Mifepristone effects on tumor somatostatin receptor expression in two patients with Cushing\u2019s syndrome due to ectopic adrenocorticotropin secretion. J Clin Endocrinol Metab. 2012;97:455\u201362.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR55","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1530\/EJE-09-0098","volume":"160","author":"F Castinetti","year":"2009","unstructured":"Castinetti F, Fassnacht M, Johanssen S, et al. Merits and pitfalls of mifepristone in Cushing\u2019s syndrome. Eur J Endocrinol. 2009;160:1003\u201310.","journal-title":"Eur J Endocrinol"},{"key":"539_CR56","first-page":"3568","volume":"86","author":"JW Chu","year":"2001","unstructured":"Chu JW, Matthias DF, Belanoff J, et al. Successful long-term treatment of refractory Cushing\u2019s disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001;86:3568\u201373.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR57","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1210\/jc.2014-1843","volume":"99","author":"M Fleseriu","year":"2014","unstructured":"Fleseriu M, Findling JW, Koch CA, et al. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing\u2019s disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone. J Clin Endocrinol Metab. 2014;99:3718\u201327.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR58","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1161\/CIRCULATIONAHA.111.029892","volume":"124","author":"DA Calhoun","year":"2011","unstructured":"Calhoun DA, White WB, Krum H, et al. Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial. Circulation. 2011;124:1945\u201355.","journal-title":"Circulation"},{"key":"539_CR59","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1210\/jc.2013-2117","volume":"99","author":"X Bertagna","year":"2014","unstructured":"Bertagna X, Pivonello R, Fleseriu M, et al. LCI699, a potent 11\u03b2-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing\u2019s disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014;99:1375\u201383.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR60","doi-asserted-by":"crossref","first-page":"R263","DOI":"10.1530\/EJE-14-1014","volume":"172","author":"E Daniel","year":"2015","unstructured":"Daniel E, Newell-Price JD. Therapy of endocrine disease: steroidogenesis enzyme inhibitors in Cushing\u2019s syndrome. Eur J Endocrinol. 2015;172:R263\u201380.","journal-title":"Eur J Endocrinol"},{"key":"539_CR61","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1530\/eje.1.02120","volume":"154","author":"M Riedl","year":"2006","unstructured":"Riedl M, Maier C, Zettinig G, et al. Long term control of hypercortisolism with fluconazole: case report and in vitro studies. Eur J Endocrinol. 2006;154:519\u201324.","journal-title":"Eur J Endocrinol"},{"key":"539_CR62","first-page":"150027","volume":"2015","author":"V Schwetz","year":"2015","unstructured":"Schwetz V, Aberer F, Stiegler C, et al. Fluconazole and acetazolamide in the treatment of ectopic Cushing\u2019s syndrome with severe metabolic alkalosis. Endocrinol Diabetes Metab Case Rep. 2015;2015:150027.","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"539_CR63","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1006\/frne.1999.0183","volume":"20","author":"YC Patel","year":"1999","unstructured":"Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol. 1999;20:157\u201398.","journal-title":"Front Neuroendocrinol"},{"key":"539_CR64","first-page":"1386","volume":"80","author":"GM Miller","year":"1995","unstructured":"Miller GM, Alexander JM, Bikkal HA, et al. Somatostatin receptor subtype gene expression in pituitary adenomas. J Clin Endocrinol Metab. 1995;80:1386\u201392.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR65","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1210\/endo-110-4-1147","volume":"110","author":"A Schonbrunn","year":"1982","unstructured":"Schonbrunn A. Glucocorticoids down-regulate somatostatin receptors on pituitary cells in culture. Endocrinology. 1982;110:1147\u201354.","journal-title":"Endocrinology"},{"key":"539_CR66","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1530\/eje.0.1300125","volume":"130","author":"GK Stalla","year":"1994","unstructured":"Stalla GK, Brockmeier SJ, Renner U, et al. Octreotide exerts different effects in vivo and in vitro in Cushing\u2019s disease. Eur J Endocrinol. 1994;130:125\u201331.","journal-title":"Eur J Endocrinol"},{"key":"539_CR67","doi-asserted-by":"crossref","first-page":"E1880","DOI":"10.1210\/jc.2013-1987","volume":"98","author":"R Pas van der","year":"2013","unstructured":"van der Pas R, Feelders RA, Gatto F, et al. Preoperative normalization of cortisol levels in Cushing\u2019s disease after medical treatment: consequences for somatostatin and dopamine receptor subtype expression and in vitro response to somatostatin analogs and dopamine agonists. J Clin Endocrinol Metab. 2013;98:E1880\u201390.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR68","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1159\/000072798","volume":"78","author":"S Park","year":"2003","unstructured":"Park S, Kamegai J, Kineman RD. Role of glucocorticoids in the regulation of pituitary somatostatin receptor subtype (sst1-sst5) mRNA levels: evidence for direct and somatostatin-mediated effects. Neuroendocrinology. 2003;78:163\u201375.","journal-title":"Neuroendocrinology"},{"key":"539_CR69","doi-asserted-by":"crossref","first-page":"E278","DOI":"10.1152\/ajpendo.00004.2005","volume":"289","author":"J Hoek van der","year":"2005","unstructured":"van der Hoek J, Waaijers M, van Koetsveld PM, et al. Distinct functional properties of native somatostatin receptor subtype 5 compared with subtype 2 in the regulation of ACTH release by corticotroph tumor cells. Am J Physiol Endocrinol Metab. 2005;289:E278\u201387.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"539_CR70","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1210\/jc.2008-1008","volume":"94","author":"M Boscaro","year":"2009","unstructured":"Boscaro M, Ludlam WH, Atkinson B, et al. Treatment of pituitary-dependent Cushing\u2019s disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab. 2009;94:115\u201322.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR71","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1056\/NEJMoa1105743","volume":"366","author":"A Colao","year":"2012","unstructured":"Colao A, Petersenn S, Newell-Price J, et al. A 12-month phase 3 study of pasireotide in Cushing\u2019s disease. N Engl J Med. 2012;366:914\u201324.","journal-title":"N Engl J Med"},{"key":"539_CR72","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s12020-015-0557-2","volume":"50","author":"C Simeoli","year":"2015","unstructured":"Simeoli C, Auriemma RS, Tortora F, et al. The treatment with pasireotide in Cushing\u2019s disease: effects of long-term treatment on tumor mass in the experience of a single center. Endocrine. 2015;50:725\u201340.","journal-title":"Endocrine"},{"key":"539_CR73","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s11154-008-9082-4","volume":"10","author":"C Bruin de","year":"2009","unstructured":"de Bruin C, Feelders RA, Lamberts SW, et al. Somatostatin and dopamine receptors as targets for medical treatment of Cushing\u2019s syndrome. Rev Endocr Metab Disord. 2009;10:91\u2013102.","journal-title":"Rev Endocr Metab Disord"},{"key":"539_CR74","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1056\/NEJMc1000094","volume":"362","author":"RA Feelders","year":"2010","unstructured":"Feelders RA, de Bruin C, Pereira AM, et al. Pasireotide alone or with cabergoline and ketoconazole in Cushing\u2019s disease. N Engl J Med. 2010;362:1846\u20138.","journal-title":"N Engl J Med"},{"key":"539_CR75","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/S0021-9258(17)38065-1","volume":"253","author":"MG Caron","year":"1978","unstructured":"Caron MG, Beaulieu M, Raymond V, et al. Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release. J Biol Chem. 1978;253:2244\u201353.","journal-title":"J Biol Chem"},{"key":"539_CR76","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1385\/ENDO:14:3:329","volume":"14","author":"L Stefaneanu","year":"2001","unstructured":"Stefaneanu L, Kovacs K, Horvath E, et al. Dopamine D2 receptor gene expression in human adenohypophysial adenomas. Endocrine. 2001;14:329\u201336.","journal-title":"Endocrine"},{"key":"539_CR77","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1210\/jc.2003-030837","volume":"89","author":"R Pivonello","year":"2004","unstructured":"Pivonello R, Ferone D, de Herder WW, et al. Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metab. 2004;89:2452\u201362.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR78","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1210\/jcem-50-2-387","volume":"50","author":"MJ Cronin","year":"1980","unstructured":"Cronin MJ, Cheung CY, Wilson CB, et al. [3H]Spiperone binding to human anterior pituitaries and pituitary adenomas secreting prolactin, growth hormone, and adrenocorticotropic hormone. J Clin Endocrinol Metab. 1980;50:387\u201391.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR79","first-page":"1931","volume":"37","author":"W Pirker","year":"1996","unstructured":"Pirker W, Riedl M, Luger A, et al. Dopamine D2 receptor imaging in pituitary adenomas using iodine-123-epidepride and SPECT. J Nucl Med. 1996;37:1931\u20137.","journal-title":"J Nucl Med"},{"key":"539_CR80","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1210\/jc.2008-1533","volume":"94","author":"R Pivonello","year":"2009","unstructured":"Pivonello R, De Martino MC, Cappabianca P, et al. The medical treatment of Cushing\u2019s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab. 2009;94:223\u201330.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR81","doi-asserted-by":"crossref","first-page":"968","DOI":"10.4158\/EP10031.OR","volume":"16","author":"AR Lila","year":"2010","unstructured":"Lila AR, Gopal RA, Acharya SV, et al. 2010 efficacy of cabergoline in uncured (persistent or recurrent) Cushing disease after pituitary surgical treatment with or without radiotherapy. Endocr Pract. 2010;16:968\u201376.","journal-title":"Endocr Pract"},{"key":"539_CR82","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1530\/EJE-10-0382","volume":"163","author":"A Godbout","year":"2010","unstructured":"Godbout A, Manavela M, Danilowicz K, et al. Cabergoline monotherapy in the long-term treatment of Cushing\u2019s disease. Eur J Endocrinol. 2010;163:709\u201316.","journal-title":"Eur J Endocrinol"},{"key":"539_CR83","doi-asserted-by":"crossref","unstructured":"Zanettini R, Antonini A, Gatto G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson\u2019s disease. N Engl J Med. 2007;356:39\u201346.","DOI":"10.1056\/NEJMoa054830"},{"key":"539_CR84","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1056\/NEJMoa062222","volume":"356","author":"R Schade","year":"2007","unstructured":"Schade R, Andersohn F, Suissa S, et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007;356:29\u201338.","journal-title":"N Engl J Med"},{"key":"539_CR85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1365-2265.2011.04326.x","volume":"77","author":"V Delgado","year":"2012","unstructured":"Delgado V, Biermasz NR, van Thiel SW, et al. Changes in heart valve structure and function in patients treated with dopamine agonists for prolactinomas, a 2-year follow-up study. Clin Endocrinol (Oxf). 2012;77:99\u2013105.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"539_CR86","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1210\/jc.2006-0728","volume":"92","author":"R Pivonello","year":"2007","unstructured":"Pivonello R, Ferone D, de Herder WW, et al. Dopamine receptor expression and function in corticotroph ectopic tumors. J Clin Endocrinol Metab. 2007;92:65\u20139.","journal-title":"J Clin Endocrinol Metab"},{"key":"539_CR87","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11102-013-0475-3","volume":"17","author":"M Barbot","year":"2014","unstructured":"Barbot M, Albiger N, Ceccato F, et al. Combination therapy for Cushing\u2019s disease: effectiveness of two schedules of treatment: should we start with cabergoline or ketoconazole? Pituitary. 2014;17:109\u201317.","journal-title":"Pituitary"},{"key":"539_CR88","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1111\/j.1365-2362.2011.02520.x","volume":"41","author":"AI McCormack","year":"2011","unstructured":"McCormack AI, Wass JA, Grossman AB. Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status. Eur J Clin Invest. 2011;41:1133\u201348.","journal-title":"Eur J Clin Invest"},{"key":"539_CR89","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s11102-010-0264-1","volume":"14","author":"TH Dillard","year":"2011","unstructured":"Dillard TH, Gultekin SH, Delashaw JB Jr, et al. Temozolomide for corticotroph pituitary adenomas refractory to standard therapy. Pituitary. 2011;14:80\u201391.","journal-title":"Pituitary"},{"key":"539_CR90","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1100\/tsw.2010.210","volume":"10","author":"L Curt\u00f2","year":"2010","unstructured":"Curt\u00f2 L, Torre ML, Ferra\u00f9 F, et al. Temozolomide-induced shrinkage of a pituitary carcinoma causing Cushing\u2019s disease\u2014report of a case and literature review. ScientificWorldJournal. 2010;10:2132\u20138.","journal-title":"ScientificWorldJournal."},{"issue":"EP75","key":"539_CR91","first-page":"4","volume":"37","author":"K Alexandraki","year":"2015","unstructured":"Alexandraki K, Boutzios G, Nikolopoulos G, et al. Optic neuropathy following radiotherapy for Cushing\u2019s disease followed by the diagnosis of pituitary carcinoma. Endocrine Abstracts. 2015;37(EP75):4.","journal-title":"Endocrine Abstracts"},{"key":"539_CR92","doi-asserted-by":"crossref","first-page":"E862","DOI":"10.1210\/jc.2013-4359","volume":"99","author":"SM Corsello","year":"2014","unstructured":"Corsello SM, Senes P, Iezzi R, Rufini, et al. Cushing\u2019s syndrome due to a bronchial ACTH-secreting carcinoid successfully treated with radiofrequency ablation (RFA). J Clin Endocrinol Metab. 2014;99:E862\u20135.","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Drugs"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40265-016-0539-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40265-016-0539-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40265-016-0539-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T08:18:48Z","timestamp":1748765928000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40265-016-0539-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,1]]},"references-count":92,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["539"],"URL":"https:\/\/doi.org\/10.1007\/s40265-016-0539-6","relation":{},"ISSN":["0012-6667","1179-1950"],"issn-type":[{"value":"0012-6667","type":"print"},{"value":"1179-1950","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,1]]}}}