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Management of Cushing's Disease After Failed Surgery - A Review

Published online by Cambridge University Press:  23 July 2018

Nancy McLaughlin
Neuroscience Institute & Brain Tumor Center, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, USA,
Amin B. Kassam
Neuroscience Institute & Brain Tumor Center, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, USA,
Daniel M. Prevedello
Neuroscience Institute & Brain Tumor Center, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, USA,
Daniel F. Kelly*
Neuroscience Institute & Brain Tumor Center, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California, USA,
Brain Tumor Center, John Wayne Cancer Institute at Saint John's Health Center, 2200 Santa Monica Blvd., Santa Monica, California, 90404, USA
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Selective transsphenoidal adenomectomy is generally recommended for initial treatment of Cushing's disease (CD) because it achieves a high (70-85%) rate of remission. However, if initial surgery is not successful, the approach to persistent or recurrent CD is more complex. Because residual or recurrent adenoma is typically found at the site of the original adenoma, repeat transsphenoidal surgery is recommended including selective adenomectomy, hemihypophysectomy or total hypophysectomy. If repeat pituitary surgery does not achieve remission, then possible adjuvant therapies include radiosurgery or stereotactic radiotherapy, bilateral adrenalectomy, and/or medical therapy. In all cases of persistent or recurrent CD, successful treatment requires close collaboration of endocrinologists, radiation oncologists and neurosurgeons.



L'adénomectomie transsphénoïale est généralement recommandée comme traitement initial de la maladie de Cushing (MC) parce que le taux de rémission obtenu est élevé, de l'ordre de 70% à 85%. Cependant, si la chirurgie initiale est un échec, la conduite à tenir en cas de persistance ou de récidive de la MC est plus complexe. Étant donné que, de façon typique, l'adénome résiduel ou récidivant est situé a l'endroit où était situé l'adénome initial, une nouvelle chirurgie transsphénoïale est recommandée, avec adénomectomie sélective, hémihypophysectomie ou hypophysectomie totale. Si une réintervention à l'hypophyse n'entraîne pas de rémission, des traitements adjuvants dont la radiochirurgie ou la radiothérapie stéréotaxique, la surrénalectomie bilatérale et/ou le traitement médical sont des options à considérer. Chez tous les cas de MC persistante ou récidivante, le succès du traitement dépend d'une collaboration étroite entre endocrinologues, radio-oncologues et neurochirurgiens.

Review Article
Copyright © Canadian Neurological Sciences Federation 2011


1. Bertagna, X, Guignat, L, Groussin, L, Bertherat, J. Cushing's disease. Best Pract Res Clin Endocrinol Metab. 2009 Oct;23(5):60723.CrossRefGoogle ScholarPubMed
2. Hammer, GD, Tyrrell, JB, Lamborn, KR, et al. Transsphenoidal microsurgery for Cushing's disease: initial outcome and longterm results. J Clin Endocrinol Metab. 2004 Dec;89(12); 6348-57.Google Scholar
3. Lindholm, J, Juul, S, Jorgensen, JO. et al. Incidence and late prognosis of cushing's syndrome: a population-based study. J Clin Endocrinol Metab. 2001 Jan;86(1): 117-23.Google Scholar
4. Atkinson, AB, Kennedy, A, Wiggum, MI, McCanee, DR, Sheridan, B. Long-term remission rates alter pituitary surgery for Cushing's disease: the need for long-term surveillance, Clin Endocrinol (Oxf). 2005 Nov;63(5):549-59.Google Scholar
5. Mancini, T, Kola, B, Mantero, F, Boscaro, M, Arnaldi, G. High cardiovascular risk in patients with Cushing's syndrome according to 1999 WHO/ISH guidelines. Clin Endocrinol (Oxf). 2004 Dec;61(6):76877.CrossRefGoogle ScholarPubMed
6. Ross, EJ, Linch, DC. The clinical response to treatment in adult Cushing's syndrome following remission of hypercortisolaemia. Postgrad Med J. 1985 Mar;61(713):20511.CrossRefGoogle ScholarPubMed
7. Kelly, DF. Transsphenoidal surgery for Cushing's disease: a review of success rates, remission predictors, management of failed surgery, and Nelson's Syndrome. Neurosurg Focus. 2007;23(3):E5.Google Scholar
8. Liu, JK, Fleseriu, M, Delashaw, JB. Jr., Ciric, IS, Couldwell, WT. Treatment options for Cushing disease after unsuccessful transsphenoidal surgery. Neurosurg Focus. 2007:23(3);E8.Google Scholar
9. Dehdashti, AR, Gentilli, F, Current state of the art in the diagnosis and surgical treatment of Cushing disease: early experience with a purely endoscopic endonasal technique. Neurosurg Focus. 2007; 23(3):E9.Google Scholar
10. Esposilo, F, Dusiek, JR, Cohan, P. et al. Clinical review: early morning Cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease. J. Clin Endocrinol Metab. 2006 Jan;91(1):713.CrossRefGoogle Scholar
11. Hofmann, BM, Hlavac, M, Martinez, R, Buchfelder, M, Muller, OA, Fahlhusch, R. Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years. J Neurosurg. 2008 Jan;108(1):918.CrossRefGoogle ScholarPubMed
12. Fomekong, E, Maiter, D, Grandin, C, Raftopoulos, C. Outcome of transsphenoidal surgery for Cushing's disease: a high remission rate in ACTH-secreting macroadenomas. Clin Neurol Neurosurg. 2009 Jun:111 (5):442-9.Google Scholar
13. Shimon, I. Ram, Z, Cohen, ZR. Hadani, M. Transsphenoidal surgery for Cushing's disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery. 2002 Jul:51(1):57-61; discussion-2.Google Scholar
14. Wagenmakers, MA, Netea-Maier, RT, van Lindert, EJ, Timmers, HJ, Grotenhuis, JA, Hermus, AR, Repeated transsphenoidal pituitary surgery (TS) via the endoscopic technique: a good therapeutic option for recurrent or persistent Cushing's disease (CD). Clin Endocrinol (Oxf). 2009 Feb:70(2):274-80.Google Scholar
15. Beauregard, C. Dickstein, G, Lacroix, A. Classic and recent etiologies of Cushing's syndrome: diagnosis and therapy. Treat Endocrinol. 2002:1(2): 79-94.Google Scholar
16. Aghi, MK. Management of recurrent and refractory Cushing disease. Nat Clin Pract Endocrinol Metab. 2008 Oct;4(10): 560-8.Google Scholar
17. Barbetta, L, Dall'Asta, C, Tomei, G, Locatelli, M, Giovanelli, M, Ambrosi, B. Assessment of cure and recurrence after pituitary surgery for Cushing's disease. Acta Neurochir (Wien). 2001; 143(5):477-81; discusston 81-2.Google Scholar
18. Aghi, MK. Petit, J, Chapman, P. et al. Management of recurrent and refractory Cushing's disease with reoperation and/or proton beam radiosurgery. Clin Neurosurg. 2008;55:1414.Google ScholarPubMed
19. Boehicchio, D. Losa, M, Buchfelder, M. Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery: a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab. 1995 Nov;80(11):311420.Google Scholar
20. Hofmann, BM, Fahlbusch, R. Treatment of Cushing's disease: a retrospective clinical study of the latest 100 cases. Front Horm Res. 2006;34:15884.CrossRefGoogle ScholarPubMed
21. Rollin, GA, Ferreira, NP, Junges, M, Gross, JL, Czepielewski, MA. Dynamics of serum Cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease. J Clin Endocrinol Metab. 2004 Mar;89(3):11319.CrossRefGoogle Scholar
22. Simmons, NE, Alden, TD, Thorner, MO, Laws, ER. Jr. Serum Cortisol response to transsphenoidal surgery for Cushing disease. J Neurosurg. 2001 Jul;95(1):18.CrossRefGoogle ScholarPubMed
23. Yap, LB, Turner, HE, Adams, CB, Wass, JA. Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease: a single cenire audit. Clin Endocrinol (Oxf). 2002 Jan;56(1):2531.CrossRefGoogle Scholar
24. McCance, DR, Besser, M, Atkinson, AB. Assessment of cure after transsphenoidal surgery for Cushing's disease. Clin Endocrinol (Oxf). 1996Jan;44(1):l-6.Google Scholar
25. Trainer, PJ, Lawrie, HS, Verhelst, J. et al. Transsphenoidal resection in Cushing's disease: undetectable serum Cortisol as the definition of successful treatment. Clin Endocrinol (Oxf). 1993 Jan;38(1):738.CrossRefGoogle ScholarPubMed
26. Burke, CW, Adams, CB, Esiri, MM, Morris, C, Bevan, JS. Transsphenoidal surgery for Cushing's disease: does what is removed determine the endocrine outcome? Clin Endocrinol (Oxf). 1990 Oct;33(4):525-37.Google Scholar
27. Blevins, LS. Jr., Sanai, N, Kunwar, S, Devin, JK. An approach to the management of patients with residual Cushing's disease. J Neurooncol. 2009 Sep;94(3):3139.CrossRefGoogle ScholarPubMed
28. Dickerman, RD, Oldfield, EH. Basis of persistent and recurrent Cushing disease: an analysis of findings at repeated pituitary surgery. J Neurosurg. 2002 Dec;97(6):13439.CrossRefGoogle ScholarPubMed
29. De Tommasi, C, Vance, ML, Okonkwo, DO, Diallo, A, Laws, ER. Jr. Surgical management of adrenocorticotropic hormone-secreting macroadenomas: outcome and challenges in patients with Cushing's disease or Nelson's syndrome. J Neurosurg. 2005 Nov; 103(5):82530.CrossRefGoogle ScholarPubMed
30. Meij, B, Voorhoul, G, Rijnberk, A. Progress in transsphenoidal hypophyseelomy for treatment of pituitary-dependent hyperadrenocorticism in dogs and cats. Mol Cell Endocrinol. 2002 Nov 29;197(1-2):89-96.Google Scholar
31. Swearingen, B, Biller, BM, Barker, FG, 2nd. et al. Long-term mortality after transsphenoidal surgery for Cushing disease. Ann Intern Med. 1999 May 18;130(10):821-4.Google Scholar
32. Scheithauer, BW, Gaffey, TA, Lloyd, RV, et al. Pathobiology of pituitary adenomas and carcinomas. Neurosurgery. 2006 Aug;59 (2}:341-53; discussion 53.Google Scholar
33. Hague, K, Post, KD, Morgello, S. Absence of peritumoral Crooke's change is associated with recurrence in surgically treated Cushing's disease, Surg Neurol, 2000 Jan;53(1):77-81, Google Scholar
34. Felix, IA, Horvath, E, Kovacs, K. Massive Crooke's hyalinization in corticotroph cell adenomas of the human pituitary. A histological, immunocytological, and electron microscopic study of three cases. Acta Neurochir (Wien). 1981; 58(3-4):235-43.Google Scholar
35. George, DH, Scheithauer, BW, Kovacs, K. et al. Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. Am J Surg Pathol. 2003 Oct;27(10):13306.CrossRefGoogle ScholarPubMed
36. Nakane, T, Kuwayama, A, Watanabe, M. et al. Long term results of transsphenoidal adenomectomy in patients with Cushing's disease. Neurosurgery. 1987 Aug;21(2):21822.CrossRefGoogle ScholarPubMed
37. Tindall, GT, Herring, CJ, Clark, RV, Adams, DA, Watts, NB. Cushing's disease: results of transsphenoidal microsurgery wiih emphasis on surgical failures. J Neurosurg. 1990 Mar;72(3):3639.CrossRefGoogle Scholar
38. Pereira, AM, van Aken, MO, van Dulken, H. et al. Long-term predictive value of postsurgical cortisol concentrations for cure and risk of recurrence in Cushing's disease. J Clin Endocrinol Metab. 2003 Dec;88(12):585864.CrossRefGoogle ScholarPubMed
39. Knappe, UJ, Ludecke, DK. Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease. Acta Neurochir Suppl. 1996;65:314.Google ScholarPubMed
40. Hofmann, BM, Hlavac, M, Kreutzer, J, Grabenbauer, G, Fahlbusch, R. Surgical treatment of recurrent Cushing's disease. Neurosurgery, 2006 Jun;58(6):1108-18; discussion 18.Google Scholar
41. Tabarin, A, Laurent, F, Catargi, B, et al Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing's disease. Clin Endocrinol (Oxf). 1998 Sep;49(3):293300.CrossRefGoogle Scholar
42. Erickson, D, Erickson, B, Watson, R. et al. 3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing's syndrome. Clin Endocrinol (Oxf). 2010 Jun;72(6): 793-9.Google Scholar
43. Kim, LJ, Lekovic, GP, White, WL, Karis, J. Preliminary Experience with 3-Tesla MRI and Cushing's disease. Skull Base. 2007 Jul; 17(4);273-7.Google Scholar
44. Oldfield, EH, Doppman, JL, Nieman, LK. et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the diffctenlial diagnosis of Cushing's syndrome. N Engl J Med. 1991 Sep 26:325(13):897-905.Google Scholar
45. Locatell, M, Vance, ML, Laws, ER, Clinical review: the strategy of immediate reoperation for transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab. 2005 Sep;90(9):547882.CrossRefGoogle Scholar
46. Ram, Z, Nieman, LK, Cutler, GB. Jr., Chrousos, GP, Doppman, JL, Oldfield, EH. Early repent surgery for persistent Cushing's disease. J Neurosurg. 1994 Jau;80(1):3745.CrossRefGoogle Scholar
47. Patil, CG, Veeravagu, A, Prevedello, DM. Katzuelson, L, Vance, ML, Laws, ER. Jr. Outcomes after repeat transsphenoidal surgery for recurrent Cushing's disease. Neurosurgery. 2008 Aug;63(2):266-70; discussion: 70-1.Google Scholar
48. Fatemi, N, Dusick, JR, de Paiva Neto, MA, Kelly, DF. The endonasal microscopic approach for pituitary adenomas and other parasellar tumors; a 10-year experience. Neurosurgery. 2008 Oct:63(4 Suppl 2):244-56: discussion 256.Google Scholar
49. Dusick, JR, Esposito, F, Mulkasian, D, Kelly, DF. Avoidance of carotid artery injuries in transsphenoidal surgery wiih the Doppler probe and micro-hook blades. Neurosurgery. 2007 Apr; 60(4 Suppl 2):322-8: discussion 328-9.Google Scholar
50. Jagannathan, J, Smith, R, DeVroom, HL. et al. Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease. J Neurosurg. 2009 Sep;111(3):5319.CrossRefGoogle ScholarPubMed
51. Fatemi, N, Dusick, JR, Mattozo, C. et al. Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery. 2008 Oct;63(4):709-18; discussion 718-9.Google Scholar
52. Cavallo, LM, de Divitiis, O, Aydin, S. et al. Extended endoscopic endonasal transsphenoidal approach to the suprasellar area: anatomic considerations--part 1, Neurosurgery. 2007 Sep;6l(3 Suppl):24-33; discussion 34. Google Scholar
53. Kassam, A, Snyderman, CH, Mintz, A, Gardner, P. Carrau, RL. Expanded endonasal approach: the rostrocaudal axis. Part, I. Crista galli to the sella turcica. Neurostiru Focus, 2005 Jul 15:19 (1):E3.Google Scholar
54. Kassam, A, Snyderman, CH, Mintz, A. Gardner, P, Carrau RL Expanded endonasal approach: the rosirocaudal axis. Part, II. Posterior clinoids to the foramen magnum. Neurosurg Focus. 2005 Jul 15:19(1):E4.Google Scholar
55. Kitano, M. Taneda, M, Shimono, T, Nakao, Y. Extended transsphenoidal approach for surgical management of pituitary adenomas invading the cavernous sinus. J Neurosurg. 2008 Jan: 108(1):26-36.Google Scholar
56. Hardy, J. Presidential address: XVII Canadian Congress of Neurological Sciences. Cushing's disease: 50 years later. Can J Neurol Sci. 1982 Nov;9(4):37580.Google ScholarPubMed
57. Weil, RJ, Vortmeycr, AO, Nieman, LK, Devroom, HL, Wanebo, J, Oldfield, EH. Surgical remission of pituitary adenomas confined to the neurohypophysis in Cushing's disease. J Clin Endocrinol Metab. 2006 Jul;91(7):265664.CrossRefGoogle ScholarPubMed
58. Friedman, RB, Oldfield, EH, Nieman, LK, et al. Repeat transsphenoidal surgery for Cushing's disease. J Neurosurg. 1989 Oct;71(4):5207.CrossRefGoogle ScholarPubMed
59. Rudnik, A, Zawadzki, T, Galuszka-Ignasiak, B. et al. Endoscopic transsphenoidal treatment in recurrent and residual pituitary adenomas--first experience. Minim Invasive Neurosurg. 2006 Feb;49(1):10-4,Google Scholar
60. Chee, GH, Mathias, DB, James, RA, Kendall-Taylor, P. Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome? Clin Endocrinol (Oxf). 2001 May;54(5): 617-26.Google Scholar
61. Benveniste, RJ, King, WA, Walsh, J, Lee, JS, Delman, BN, Post, KD, Repeated transsphenoidal surgery to treat recurrent or residual pituitary adenoma. J Neurosurg. 2005 Jun;102(6): 1004-12.Google Scholar
62. Biller, BM, Grossman, AB, Stewart, PM. et al. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2008 Jul;93(7):245462.CrossRefGoogle ScholarPubMed
63. Estrada, J, Boronat, M, Mielgo, M. et al. The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease. N Engl J Med. 1997 Jan 16;336(3): 172-7.Google Scholar
64. Becker, G, Kocher, M, Kortmann, RD. et al. Radiation therapy in the multimodal treatment approach of pituitary adenoma. Strahlenther Onkol. 2002 Apr; 178(4): 173-86.Google Scholar
65. Zierhut, D, Flentje, M, Adolph, J, Erdmann, J, Rnue, F, Wannenmacher, M. External radiotherapy of pituitary adenomas, Iit J Radiat Oncol Biol Phys. 1995 Sep 30;33(2);307-14.Google Scholar
66. Brada, M, Ford, D, Ashley, S. et al. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. BMJ. 1992 May 23;304(6838); 1343-6.Google Scholar
67. Simmons, NE, Laws, ER. Jr. Glioma occurrence after sellar irradiation: case report and review. Neurosurgery. 1998 Jan;42(1): 172-8.Google Scholar
68. Salinger, DJ, Brady, LW, Miyamoto CT Radiation therapy in the treatment of pituitary adenomas. Am J Clin Oncol. 1992 Dec;15 (6):467-73.Google Scholar
69. Constine, LS, Woolf, PD, Cann, D. et al. Hypolhalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med. 1993 Jan l4;328(2):87-94.Google Scholar
70. Colin, P, Delemer, B, Nakib, I, et al. [Unsuccessful surgery of Cushing's disease. Role and efficacy of fraciiouaicd stereotactic radiotherapy]. Neurochirurgie. 2002 May;48(2-3 Pt 2):285-93.Google Scholar
71. Colin, P, Jovenin, N, Delemer, B. et al. Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients. Ini J Radial Oncol Biol Phys. 2005 Jum 1;62(2):333-41.Google Scholar
72. Shechan, JP, Niranjan, A, Seehan, JM. et al. Stereotactic radiosurgery for pituitary adenomas: an tniermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. J Neurosurg. 2005 Apr;102(4);678-91.Google Scholar
73. Sheehan, JM, Vance, ML, Sheehan, JP, Ellegala, DB, Laws, ER. Jr. Radiosurgery for Cushing's disease after failed transsphenoidal surgery. J Neurosurg. 2000 Nov;93(5):73842.CrossRefGoogle ScholarPubMed
74. Jagannathan, J, Sheehan, JP, Pouratian, N, Laws, ER, Steiner, L, Vance, ML. Gamma Knife surgery for Cushing's disease, J Neurosurg. 2007 Jun;106(6):980-7.Google Scholar
75. Castinetti, F, Nagai, M, Dufour, H. et al. Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease. Eur J Endocrinol. 2007 Jan;156(1):918.CrossRefGoogle ScholarPubMed
76. Oyesiku, NM. Stereotactic radiosurgery for Cushing disease; a review, Neurosurg Focus. 2007;23(6):EI4.Google Scholar
77. Kobayashi, T, Kida, Y, Mori, Y. Gamma knife radiosurgery in the treatment of Cushing disease: long-term results. J Neurosurg, 2002 Dec:97 Suppl 5:422-8.Google Scholar
78. Pelit, JH, Biller, BM, Yock, Tl. et al. Proton stereotactic radiotherapy for persistent adrenocorticotropin-producing adenomas, J Clin Endocrinol Metab, 2008 Feb:93(2); 393-9.Google Scholar
79. Lymnn, JT, Phillips, MH, Frankel, KA, Levy, RP, Fabrikant, JI. Radiation physics for particle beam radiosurgery. Neurosurg Clin N Am. 1992 Jan;3(1): 1-8.Google Scholar
80. Miller, JW, Crapo, L. The medical treatment of Cushing's syndrome. Endocr Rev. 1993 Aug;14(4):44358.CrossRefGoogle ScholarPubMed
81. Fleseriu, M, Loriaux, DL, Ludlam, WH. Second-line treatment for Cushing's disease when initial pituitary surgery is unsuccessful. Curr Opin Endocrinol Diabetes Obes. 2007 Aug; l4(4):323-8.Google Scholar
82. O'Riordain, DS, Farley, DR. Young, WF. Jr., Grant, CS, van Heerden, JA. Long-term outcome of bilateral adrenalectomy in patients with Cushing's syndrome. Surgery. 1994 Dec;116(6); 1088-93; discussion 1093-4.Google Scholar
83. Smith, PW, Turza, KC, Carter, CO, Vance, ML, Laws, ER, Hanks, JB. Bilateral adrenalectomy for refractory Cushing disease: a safe and definitive therapy. J Am Coll Surg. 2009 Jun;208(6): 1059-64.Google Scholar
84. Chow, JT, Thompson, GB, Grant, CS, Farley, DR, Richards, ML, Young, WF. Jr. Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience. Clin Endocrinol (Oxf). 2008 Apr;68 (4):5l3-9.Google Scholar
85. Thompson, SK, Hayman, AV, Ludlam, WH, Deveney, CW, Loriaux, DL, Sheppard, BC. Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing's disease: a 10-year experience. Ann Surg. 2007 May;245(5):7904.CrossRefGoogle ScholarPubMed
86. Assie, G, Bahurel, H, Cosie, J. et al. Corticotroph tumor progression after adrenalectomy in Cushing's Disease: a reappraisal of Nelson's Syndrome. J Clin Endocrinol Metab. 2007 Jan;92(1): 172-9.Google Scholar
87. Pereira, MA, Halpern, A, Salgado, LR. et al. A study of patients with Nelson's syndrome. Clin Endocrinol (Oxf). 1998 Oct:49(4): 533-9.Google Scholar
88. Nagesser, SK, van Seters, AP, Kievit, J, et al. Treatment of pituitary dependent Cushing's syndrome: long-term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery. Clin Endocrinol (Oxf). 2000 Apr;52(4):427-35.Google Scholar
89. Invitti, C, Giraldi, FP, de Martin, M, Cavagnini, F. Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endoerinol Metab. 1999 Feb; 84(2):440-8.Google Scholar
90. Favia, G, Boscaro, M, Lumachi, F, D'Amico, DF. Role of bilateral adrenalectomy in Cushing's disease. World J Surg. 1994 Jul-Aug:18(4):462-6.Google Scholar
91. Kemink, SA, Wesseling, P, Pieters, GF, Verhofstad, AA, Hermus, AR, Smals, AG. Progression of a Nelson's adenoma to pituitary carcinoma: a case report and review of the literature. J Endocrinol Invest. 1999 Jan;22(1):705.CrossRefGoogle ScholarPubMed
92. Nagesser, SK, van Seters, AP, Kievit, J, Hermans, J, Krans, HM, van de Velde, CJ. Long-term results of total adrenalectomy for Cushing's disease. World J Surg. 2000 Jan;24(1):10813.CrossRefGoogle ScholarPubMed
93. Kemink, SA, Grotenhuis, JA, De Vries, J, Pieters, GF, Hermus, AR, Smals, AG. Management of Nelson's syndrome: observations in fifteen patients. Clin Endocrinol (Oxf). 2001 Jan;54(1):4552.CrossRefGoogle ScholarPubMed
94. Saeger, W. Surgical pathology of the pituitary in Cushing's disease. Pathol Res Pract. 1991 Jun;187(5):6136.CrossRefGoogle ScholarPubMed
95. Kelly, PA, Samandouras, G, Grossman, AB, Afshar, F, Besser, GM, Jenkins, PJ. Neurosurgical treatment of Nelson's syndrome. J Clin Endocrinol Metab. 2002 Dec;87(12):54659.CrossRefGoogle ScholarPubMed
96. Wislawski, J. Kasperlik-Zaluska, AA, Jeske, W. et al. Results of neurosurgical treatment by a transsphenoidal approach in 10 patients with Nelson's syndrome. J Neurosurg. 1985 Jan:62(1): 68-71.Google Scholar
97. Xing, B, Ren, Z, Su, C, Wang, R, Yang, Y, Hu, Y. Microsurgical treatment of Nelson's syndmme. Chin Med J (Engl). 2002 Aug; 115(8):1150-2.Google Scholar
98. Ganz, JC, Aanderud, S, Mork, SJ, Smievoll, AI. Tumour volume reduction following gamma knife radiosurgery: the relationship between X-ray and histological findings. Acta Neurochir Suppl. 1994;62:3942.CrossRefGoogle ScholarPubMed
99. Jenkins, PJ, Trainer, PJ, Plowman, PN. et al. The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticotropin-dependent Cushing's syndrome. J Clin Endocrinol Metab. 1995 Jan;80(1):16571.Google ScholarPubMed
100. de Bruin, C, Feelders, RA, Lamberts, SW, Hofland, LJ. Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome. Rev Eudocr Metab Disord. 2009 Jun;10 (2):91-102.Google Scholar
101. Batista, DL, Zhang, X, Gejman, R. et al. The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab. 2006 Nov:91(11):4482-8.Google Scholar
102. 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 Apr;152(4):64554.CrossRefGoogle ScholarPubMed
103. Moyes, VJ, Alusi, G, Sabin, HI. et al. Treatment of Nelson's syndrome with temozolomide. Eur J Endocrinol. 2009 Jan; 160(1): 115-9.Google Scholar
104. Ragel, BT, Couldwell, WT. Pituitary carcinoma: a review of the literature. Neurosurg Focus. 2004 Apr 15;16(4):E7.Google Scholar
105. Landman, RE, Horwith, M, Peterson, RE, Khandji, AG, Wardlaw, SL. Long-term survival with ACTH-see re ting carcinoma of the pituitary: a case report and review of the literature. J Clin Endocrinol Metab. 2002 Jul;87(7):30849.CrossRefGoogle Scholar
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Management of Cushing's Disease After Failed Surgery - A Review
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