Lynnette K Nieman1. 1. Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Building 10, CRC, 1 East, Rm 1-3140, 10 Center Dr, MSC 1109, Bethesda MD 20892-1109, USA. NiemanL@nih.gov
Abstract
PURPOSE OF REVIEW: Recently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action. RECENT FINDINGS: The dopamine agonist cabergoline and the somatostatin agonist pasireotide target ACTH secretion. Each has low rates of normalization of urine-free cortisol (UFC), about 40% at doses of 1-7 mg weekly and 20% at doses of 600 or 900 μg twice daily, respectively. Cabergoline, an oral agent, has a relatively benign side-effect profile, primarily asthenia. Small trials suggest that combination therapy with ketoconazole increases effectiveness. Pasireotide, a parenteral agent, is associated with types and rates of adverse events similar to those seen with other somatostatin agonists (diarrhea, nausea, cholelithiasis), except for glucose intolerance, which occurs more frequently (∼75%). It may be most effective when UFC is less than two-fold normal. A few case reports suggest that pasireotide or cabergoline may control tumor size and ACTH secretion from macroadenomas. Retinoic acid must be evaluated further. The glucocorticoid antagonist mifepristone ameliorates glucose intolerance but may not normalize other Cushingoid features. SUMMARY: These novel approaches provide options for treatment of patients in whom surgery has failed or is not possible, and those who decline adrenalectomy or radiation therapy.
PURPOSE OF REVIEW: Recently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action. RECENT FINDINGS: The dopamine agonist cabergoline and the somatostatin agonist pasireotide target ACTH secretion. Each has low rates of normalization of urine-free cortisol (UFC), about 40% at doses of 1-7 mg weekly and 20% at doses of 600 or 900 μg twice daily, respectively. Cabergoline, an oral agent, has a relatively benign side-effect profile, primarily asthenia. Small trials suggest that combination therapy with ketoconazole increases effectiveness. Pasireotide, a parenteral agent, is associated with types and rates of adverse events similar to those seen with other somatostatin agonists (diarrhea, nausea, cholelithiasis), except for glucose intolerance, which occurs more frequently (∼75%). It may be most effective when UFC is less than two-fold normal. A few case reports suggest that pasireotide or cabergoline may control tumor size and ACTH secretion from macroadenomas. Retinoic acid must be evaluated further. The glucocorticoid antagonist mifepristone ameliorates glucose intolerance but may not normalize other Cushingoid features. SUMMARY: These novel approaches provide options for treatment of patients in whom surgery has failed or is not possible, and those who decline adrenalectomy or radiation therapy.
Authors: Richard A Feelders; Christiaan de Bruin; Alberto M Pereira; Johannes A Romijn; Romana T Netea-Maier; Ad R Hermus; Pierre M Zelissen; Ramona van Heerebeek; Frank H de Jong; Aart-Jan van der Lely; Wouter W de Herder; Leo J Hofland; Steven W Lamberts Journal: N Engl J Med Date: 2010-05-13 Impact factor: 91.245
Authors: Leo J Hofland; Joost van der Hoek; Richard Feelders; Maarten O van Aken; Peter M van Koetsveld; Marlijn Waaijers; Diana Sprij-Mooij; Christian Bruns; Gisbert Weckbecker; Wouter W de Herder; Albert Beckers; Steven W J Lamberts Journal: Eur J Endocrinol Date: 2005-04 Impact factor: 6.664
Authors: M Páez-Pereda; D Kovalovsky; U Hopfner; M Theodoropoulou; U Pagotto; E Uhl; M Losa; J Stalla; Y Grübler; C Missale; E Arzt; G K Stalla Journal: J Clin Invest Date: 2001-10 Impact factor: 14.808
Authors: Rosario Pivonello; Maria Cristina De Martino; Paolo Cappabianca; Monica De Leo; Antongiulio Faggiano; Gaetano Lombardi; Leo J Hofland; Steven W J Lamberts; Annamaria Colao Journal: J Clin Endocrinol Metab Date: 2008-10-28 Impact factor: 5.958
Authors: L K Nieman; G P Chrousos; C Kellner; I M Spitz; B C Nisula; G B Cutler; G R Merriam; C W Bardin; D L Loriaux Journal: J Clin Endocrinol Metab Date: 1985-09 Impact factor: 5.958
Authors: Luis V Syro; Fabio Rotondo; Michael D Cusimano; Antonio Di Ieva; Eva Horvath; Lina M Restrepo; Min Wong; Donald W Killinger; Harley Smyth; Kalman Kovacs Journal: Pituitary Date: 2015-04 Impact factor: 4.107