title: Medical combination therapies in Cushing's disease.
abstract: BACKGROUND
  There has been growing interest on medical therapy for the management of Cushing's disease (CD), particularly in cases of persistent or recurrent hypercortisolism. Ketoconazole, an inhibitor of adrenal steroidogenesis, is the most widely used drug, whereas cabergoline and pasireotide are the most promising centrally acting agents. The main purpose of this review article is to highlight the options of medical treatment for CD, with a special emphasis on combination therapies, a topic that has only been addressed by a limited number of studies.
  
  
  CONCLUSIONS
  According to the results of these studies, combination therapies involving medications with additive or synergistic effects on ACTH and cortisol secretion seem quite attractive as they yield higher probability of longterm control of the hypercortisolism at lower doses, a lower incidence of side-effects, and possibly a lower rate of treatment escapes. Currently, ketoconazole, cabergoline, and pasireotide are the best drugs to be prescribed in combination.
authors: Division of Endocrinology, Hospital das Clínicas, Federal University of Pernambuco, Rua Clovis Silveira Barros, 84/1202, Boa Vista, Recife, CEP 50.050-270, Brazil, lvilarf@gmail.com.
authors: Lucio
authors: L
authors: Vilar
authors: Luciana A
authors: LA
authors: Naves
authors: Márcio C
authors: MC
authors: Machado
authors: Marcello D
authors: MD
authors: Bronstein
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000236:Adenoma / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018931:Antineoplastic Agents, Hormonal; D065692:Cytochrome P-450 CYP3A Inhibitors; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid
references: Endocrinol Metab Clin North Am. 1994 Sep;23(3):571-84
references: 7805655
references: Curr Opin Endocrinol Diabetes Obes. 2013 Aug;20(4):330-4
references: 23807605
references: J Clin Endocrinol Metab. 2009 Jan;94(1):223-30
references: 18957500
references: Horm Res. 2004;62(6):300-5
references: 15557761
references: J Clin Endocrinol Metab. 2014 Apr;99(4):1375-83
references: 24423285
references: Pituitary. 2014 Aug;17(4):320-6
references: 23943009
references: N Engl J Med. 2010 May 13;362(19):1846-8
references: 20463350
references: J Endocrinol Invest. 2008 May;31(5):436-44
references: 18560262
references: J Clin Endocrinol Metab. 2004 Jun;89(6):3027-32
references: 15181094
references: Pituitary. 2012 Dec;15 Suppl 1:33-6
references: 22038028
references: J Neurooncol. 2014 May;117(3):407-14
references: 24146187
references: J Clin Endocrinol Metab. 2011 Sep;96(9):2796-804
references: 21752886
references: Nat Rev Endocrinol. 2014 Jul;10 (7):423-35
references: 24821329
references: Exp Clin Endocrinol Diabetes. 2010 Nov;118(10 ):760-3
references: 20496311
references: Pituitary. 2010 Jun;13(2):123-9
references: 19943118
references: Eur J Endocrinol. 2014 Aug;171(2):209-15
references: 24975318
references: Eur J Endocrinol. 2010 Nov;163(5):709-16
references: 20702648
references: Endocr Pract. 2010 Nov-Dec;16(6):968-76
references: 20497937
references: Handb Clin Neurol. 2014;124:317-24
references: 25248596
references: Clin Endocrinol (Oxf). 2014 Jan;80(1):1-12
references: 24118077
references: J Clin Endocrinol Metab. 2008 Feb;93(2):358-62
references: 18056770
references: J Neurooncol. 2013 Aug;114(1):1-11
references: 23673515
references: Pituitary. 2011 Jun;14(2):148-56
references: 21104199
references: Pituitary. 2012 Sep;15(3):330-41
references: 22674211
references: J Clin Endocrinol Metab. 2014 Oct;99(10):3718-27
references: 25013998
references: J Clin Endocrinol Metab. 2012 Oct;97(10):3577-83
references: 22851491
references: Endocrine. 2014 Sep;47(1):9-20
references: 24415169
references: N Engl J Med. 2012 Mar 8;366(10):914-24
references: 22397653
references: Handb Clin Neurol. 2014;124:197-219
references: 25248589
references: Acta Endocrinol (Copenh). 1976 Jun;82(2):330-41
references: 179256
references: Horm Metab Res. 2013 Feb;45(2):109-17
references: 23225246
references: J Clin Res Pediatr Endocrinol. 2013 Sep 10;5(3):194-8
references: 24072089
references: Endocr Pract. 2007 Jul-Aug;13(4):396-402
references: 17669717
references: Eur J Endocrinol. 2012 Aug;167(2):137-43
references: 22577107
references: Neurosurg Clin N Am. 2012 Oct;23(4):639-51
references: 23040749
references: Handb Clin Neurol. 2014;124:221-34
references: 25248590
references: Clin Endocrinol (Oxf). 2005 Nov;63(5):549-59
references: 16268808
references: Discov Med. 2012 Feb;13(69):171-9
references: 22369976
references: J Clin Endocrinol Metab. 2014 May;99(5):1623-30
references: 24471573
references: Indian J Endocrinol Metab. 2013 Mar;17(2):245-8
references: 23776896
references: Pituitary. 2011 Mar;14 (1):80-91
references: 20972839
references: Neurosurgery. 2014 Apr;74(4):E447-55; discussion E455
references: 24226425
references: Science. 2000 Apr 7;288(5463):154-7
references: 10753124
references: Handb Clin Neurol. 2014;124:303-16
references: 25248595
references: J Clin Endocrinol Metab. 1996 Aug;81(8):2885-90
references: 8768846
references: Pituitary. 2014 Apr;17(2):180-6
references: 23564338
references: J Endocrinol. 2014 Nov;223(2):R19-39
references: 25134660
references: Acta Clin Belg. 2002 Jan-Feb;57(1):23-5
references: 12017752
references: Pituitary. 2014 Apr;17(2):109-17
references: 23468128
references: Eur J Endocrinol. 2012 Oct;167(4):473-81
references: 22815335
references: Clin Endocrinol (Oxf). 1991 Aug;35(2):169-78
references: 1657460
references: J Clin Endocrinol Metab. 2009 Nov;94(11):4342-50
references: 19820006
references: Neurosurg Clin N Am. 2012 Oct;23(4):653-68
references: 23040750
references: Endocrine. 2013 Aug;44(1):20-32
references: 23192246
references: J Clin Endocrinol Metab. 2012 Jun;97(6):2039-49
references: 22466348
references: J Mol Endocrinol. 2014 Jun;52(3):R223-40
references: 24647046
references: J Clin Endocrinol Metab. 2013 Feb;98(2):425-38
references: 23345100
references: J Clin Endocrinol Metab. 2008 Jul;93(7):2454-62
references: 18413427
references: F1000Prime Rep. 2014 Mar 03;6:18
references: 24669299
references: Handb Clin Neurol. 2014;124:327-37
references: 25248597
references: Gastroenterology. 1984 Mar;86(3):503-13
references: 6319220