The aim of this paper was to demonstrate the long-term results following microsurgery in a single surgeon's continuous series of patients with Cushing disease (CD), to assess the influence of changes in surgical procedures, and to compare the results with those of other treatment modalities. In particular, preoperative diagnosis, tumor size, results of histological examination, and complications were considered.
Between 1971 and 2004, 426 patients suffering from newly diagnosed CD underwent primary surgery. Pre-operative measures included clinical examination, endocrinological workup (testing of the hypothalamic-pituitary-adrenal axis, and 2- and 8-mg dexamethasone overnight suppression tests), sellar imaging (polytomography, computed tomography, and magnetic resonance [MR] imaging), and in patients with negative results on imaging studies, inferior petrosal sinus sampling. Follow-up examinations consisting of endocrinological workup, and imaging took place 1 week and 3 months after surgery and then at yearly intervals.
During microsurgery as first treatment, the adenoma finding rate was 86.6%. After selective adenomectomy, the remission rate was 75.9%, and this rate showed no improvement over the years. The best results were achieved in microadenomas confirmed on MR imaging or histopathological investigation. The recurrence rate (15%) and the complication rate (5.9%) declined over the years. If no adenoma was found, exploration of the sella turcica was performed in 45.6%, hypophysectomy in 3.5%, and hemihypophysectomy in 50.9% of these patients, leading to an early remission in 37.9%. In case of persistence or recurrence, further treatment (repeated operation, adrenalectomy, radio-therapy, or medical treatment) was used to control the disease.
Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse.
Bakiri F, , Tatai S, , Aouli R, , Semrouni M, , Derome PJ, & Chitour F, : Treatment of Cushing's disease by transsphenoidal, pituitary microsurgery: prognosis factors and long-term follow-up. J Endocrinol Invest 19:572–580, 1996
Batista DL, , Zhang X, , Gejman R, , Ansell PJ, , Zhou Y, & Johnson SA, : The effect of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 91:4482–4488, 2006
Bax TW, , Marcus DR, , Galloway GQ, , Swanstrom LL, & Sheppard BC: Laparoscopic bilateral adrenalectomy following failed hypophysectomy. Surg Endosc 10:1150–1153, 1996
Blevins LS Jr, , Christy JH, , Khajavi M, & Tindall GT: Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab 83:63–67, 1998
Bochicchio 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 80:3114–3120, 1995
Bonelli FS, , Huston J III, , Carpenter PC, , Erickson D, , Young WF Jr, & Meyer FB: Adrenocorticotropic hormone-dependent Cushing's syndrome: sensitivity and specifity of inferior petrosal sinus sampling. AJNR Am J Neuroradiol 21:690–696, 2000
Brunt LM, , Moley JF, , Doherty GM, , Lairmore TC, , DeBenedetti MK, & Quasebarth MA: Outcome analysis in patients undergoing laparoscopic adrenalectomy for hormonally active adrenal tumors. Surgery 130:629–635, 2001
Buchfelder M, & Fahlbusch R: Neurosurgical treatment of Cushing's disease in children and adolescents. Acta Neurochir Suppl (Wien) 35:101–105, 1985
Cannavò S, , Almoto B, , Dall'asta C, , Corsello S, , Lovicu RM, & DeMenis E, : Long term results of treatment in patients with ACTH-secreting pituitary macroadenomas. Eur J Endocrinol 149:195–200, 2003
Chandler WF, , Schteingart DE, , Lloyd RV, , McKeever PE, & Ibarra-Perrez G: Surgical treatment of Cushing's disease. J Neurosurg 66:204–212, 1987
Chee GH, , Mathias DB, , James RA, & Kendall-Taylor P: Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome?. Clin Endocrinol (Oxf) 54:617–626, 2001
Chen JCT, , Amar AP, , Choi SH, , Singer P, , Couldwell WT, & Weiss MH: Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg 98:967–973, 2003
Colao A, , Faggiano A, , Pivonello R, , Giraldi FP, , Cavagnini F, & Lombardi G: Inferior petrosal sinus sampling in the differential diagnosis of Cushing's syndrome: results of an Italian multicenter study. Eur J Endocrinol 144:499–507, 2001
Devoe DJ, , Miller WL, , Conte FA, , Kaplan SL, , Grumbach MM, & Rosenthal SM, : Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab 82:3196–3202, 1997
Dickerman RD, & Oldfield EH: Basis of persistent and recurrent Cushing disease: an analysis of findings and repeated surgery. J Neurosurg 97:1343–1349, 2002
Dyer EH, , Civit T, , Visot A, , Delalande O, & Derome PJ: Transsphenoidal surgery for pituitary adenomas in children. Neurosurgery 34:207–212, 1994
Erem C, , Algun E, , Ozbey N, , Azezli A, , Aral F, & Orhan Y, : Clinical laboratory findings and results of therapy in 55 patients with Cushing's syndrome. J Endocrinol Invest 26:65–72, 2003
Estrada J, , Boronat M, , Mielgo M, , Magallon R, , Millan I, & Diez S, : The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease. N Engl J Med 336:172–177, 1997
Fahlbusch R, , Buchfelder M, & Müller OA: Transsphenoidal surgery for Cushing's disease. J R Soc Med 79:262–269, 1986
Flitsch J, , Knappe UJ, & Lüdecke DK: Direct intraoperative micro-method for hormone measurements of pituitary tissue in Cushing's disease. Surg Neurol 52:585–591, 1999
Flitsch J, , Knappe UJ, & Lüdecke DK: The use of postoperative ACTH levels as a marker for successful transsphenoidal microsurgery in Cushing's disease. Zentralbl Neurochir 64:6–11, 2003
Grabner P, , Hauer-Jensen M, , Jervell J, & Flatmark A: Long-term results of treatment of Cushing's disease by adrenalectomy. Eur J Surg 157:461–464, 1991
Guilhaume B, , Bertagna X, , Thomsen M, , Bricaire C, , Vila-Porcile E, & Olivier L, : Transsphenoidal pituitary surgery for the treatment of Cushing's disease: results in 64 patients and long-term follow-up studies. J Clin Endocrinol Metab 66:1056–1064, 1988
Hofmann BM, & Fahlbusch R: Treatment of Cushing's disease: a retrospective clinical study of the latest 100 cases. Front Horm Res 34:158–184, 2006
Hofmann BM, , Hlavac M, , Kreutzer J, , Grabenbauer G, & Fahlbusch R: Surgical treatment of recurrent Cushing's disease. Neurosurgery 58:1108–1118, 2006
Howlett TA, , Plowman PN, , Wass JA, , Rees LH, , Jones AE, & Besser GM: Megavoltage pituitary irradiation in the management of Cushing's disease and Nelson's syndrome: long-term follow-up. Clin Endocrinol (Oxf) 31:309–323, 1989
Hoybye C, , Grenback E, , Rahn T, , Degerblad M, , Thorén M, & Hulting AL: Adrenocorticotropic hormone-producing pituitary tumors: 12- to 22-year follow-up after treatment with stereotactic radiosurgery. Neurosurgery 49:284–292, 2001
Hoybye C, , Grenback E, , Thorén M, , Hulting AL, , Lundblad L, & von Holst H, : Transsphenoidal surgery in Cushing's disease: 10 years of experience in 34 consecutive cases. J Neurosurg 100:634–638, 2004
Inoue HK, , Kohga H, , Hirato M, , Sasaki T, , Ishihara J, & Shibazaki T, : Pituitary adenomas treated by microsurgery with or without gamma knife surgery: experience in 122 cases. Stereotact Funct Neurosurg 72:1 Suppl 125–131, 1999
Izawa M, , Hayashi M, , Nakaya K, , Satoh H, , Ochiai T, & Hori T, : Gamma knife radiosurgery for pituitary adenomas. J Neurosurg 93:3 Suppl 19–22, 2000
Jennings AS, , Liddle GW, & Orth DN: Results of treating childhood Cushing's disease with pituitary irradiation. N Engl J Med 297:957–962, 1977
Joshi SM, , Hewitt RJD, , Storr HL, , Rezajooi K, , Ellamushi H, & Grossman AB, : Cushing's disease in children and adolescents: 20 years of experience in a single neurosurgical center. Neurosurgery 57:281–285, 2005
Kaltsas GA, , Giannulis MG, , Newell-Price JDC, , Dacie JE, , Thakkar C, & Afshar F, : A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing's disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 84:487–492, 1999
Kim SH, , Huh R, , Chang JW, , Park YG, & Chung SS: Gamma knife radiosurgery for functioning pituitary adenomas. Stereotact Funct Neurosurg 72:1 Suppl 101–110, 1999
Knappe UJ, & Lüdecke DK: Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease. Acta Neurochir Suppl 65:31–34, 1996
Knappe UJ, & Lüdecke DK: Transnasal microsurgery in children and adolescents with Cushing's disease. Neurosurgery 39:484–493, 1996
Lefournier V, , Martinie M, , Vasdev A, , Bessou P, , Passagia JG, & Labat-Moleur F, : Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing's disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage. J Clin Endocrinol Metab 88:196–203, 2003
Leinung MC, , Kane LA, , Scheithauer BW, , Carpenter PC, , Laws ER Jr, & Zimmermann D: Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood. J Clin Endocrinol Metab 80:2475–2479, 1995
Liddle GW: Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 20:1539–1560, 1960
Lim YL, , Leem W, , Kim TS, , Rhee BA, & Kim GK: Four years' experiences in the treatment of pituitary adenomas with gamma knife radiosurgery. Stereotact Funct Neurosurg 70:1 Suppl 95–109, 1998
Littley MD, , Shalet SM, , Beardwell CG, , Ahmed SR, & Sutton ML: Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease. Clin Endocrinol (Oxf) 33:445–455, 1990
Liu C, , Lo JC, , Dowd CF, , Wilson CB, , Kunwar S, & Aron DC, : Cavernous and inferior petrosal sinus sampling in the evaluation of ACTH-dependent Cushing's syndrome. Clin Endocrinol (Oxf) 61:478–486, 2004
Mampalam TJ, , Tyrrell JB, & Wilson CB: Transsphenoidal microsurgery for Cushing's disease. A report of 216 cases. Ann Intern Med 109:487–493, 1988
Martinez R, , Bravo G, , Burzaco J, & Rey G: Pituitary tumors and gamma knife surgery. Clinical experience with more than two years of follow-up. Stereotact Funct Neurosurg 70:Suppl 1 110–118, 1998
McCance DR, , Russell CFJ, , Kennedy TL, , Hadden DR, , Kennedy L, & Atkinson AB: Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease. Clin Endocrinol (Oxf) 39:315–321, 1993
Morange-Ramos I, , Regis J, , Dufour H, , Andrieu JM, , Grisoli F, & Jaquet P, : Short-term endocrinological results after gamma knife surgery of pituitary adenomas. Stereotact Funct Neurosurg 70:1 Suppl 127–138, 1998
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 24:108–113, 2000
Nagesser SK, , van Seters AP, , Kievit J, , Hermans J, , van Dulken H, & Krans HM, : 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) 52:427–435, 2000
Nakane T, , Kuwayama A, , Watanabe M, , Takahashi T, , Kato T, & Ichihara K, : Long term results of transsphenoidal adenomectomy in patients with Cushing's disease. Neurosurgery 21:218–222, 1987
Nomikos P, , Buchfelder M, & Fahlbusch R: Current management of prolactinomas. J Neurooncol 54:139–150, 2001
Nomikos P, , Buchfelder M, & Fahlbusch R: The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical “cure”. Eur J Endocrinol 152:379–387, 2005
Nomikos P, , Fahlbusch R, & Buchfelder M: Recent developments in transsphenoidal surgery of pituitary tumors. Hormones (Athens, Greece) 3:85–91, 2004
O'Riordain DS, , Farley DR, , Young WF Jr, , Grant CS, & van Herden JA: Long-term outcome of bilateral adrenalectomy in patients with Cushing's syndrome. Surgery 116:1088–1094, 1994
Oldfield EH, , Chrousos GP, , Schulte HM, , Schaaf M, , McKeever PE, & Krudy AG, : Preoperative lateralization of ACTH-secreting pituitary microadenomas by bilateral and simultaneous inferior petrosal venous sinus sampling. N Engl J Med 312:100–103, 1985
Pan L, , Zhang N, , Wang B, & Xu W: Pituitary adenomas: the effect of gamma knife radiosurgery on tumor growth and endocrinopathies. Stereotact Funct Neurosurg 70:1 Suppl 119–126, 1998
Pollock BE, & Young WF Jr: Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy. Int J Radiat Oncol Biol Phys 54:839–841, 2002
Rahn T, , Thorén M, , Hall K, & Backlund EO: Stereotactic radiosurgery in Cushing's syndrome: acute radiation effects. Surg Neurol 14:85–92, 1980
Ram Z, , Nieman LK, , Cutler GB Jr, , Chrousos GP, , Doppman JL, & Oldfield EH: Early repeat surgery for persistent Cushing's disease. J Neurosurg 80:37–45, 1994
Ross WM, , Evered DC, , Hunter P, , Benaim M, , Cook D, & Hall R: Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy of the pituitary. Clin Radiol 30:149–153, 1979
Saeger W, & Lüdecke DK: Pituitary hyperplasia. Definition, light and electron microscopical structures and significance in surgical specimens. Virchows Arch A Pathol Anat Histopathol 399:277–287, 1983
Savage MO, , Lienhardt A, , Lebrethon MC, , Johnston LB, , Huebner A, & Grossman AB, : Cushing's disease in childhood: presentation, investigation, treatment and long-term outcome. Horm Res 55:1 Suppl 24–30, 2001
Semple PL, & Laws ER Jr: Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing's disease. J Neurosurg 91:175–179, 1999
Semple PL, , Vance ML, , Findling J, & Laws ER Jr: Transsphenoidal surgery for Cushing's disease: outcome in patients with a normal magnetic resonance imaging scan. Neurosurgery 46:553–559, 2000
Sheehan JM, , Lopes MB, , Sheehan JP, , Ellegala DB, , Webb KM, & Laws ER Jr: Results of transsphenoidal surgery for Cushing's disease in patients with no histologically confirmed tumor. Neurosurgery 47:33–39, 2000
Sheehan JM, , Vance ML, , Sheehan JP, , Ellegala DB, & Laws ER Jr: Radiosurgery for Cushing's disease after failed transsphenoidal surgery. J Neurosurg 93:738–742, 2000
Shimon I, , Ram Z, , Cohen ZR, & Hadani M: Transsphenoidal surgery for Cushing's disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery 51:57–62, 2002
Sonino N, , Zielezny M, , Fava GA, , Fallo F, & Boscaro M: Risk factors and long-term outcome in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab 81:2647–2652, 1996
Stévenaert A, , Perrin G, , Martin D, & Beckers A: [Cushing's disease and corticotrophic adenoma: results of pituitary microsurgery.]. Neurochirurgie 48:234–265, 2002. (Fr)
Storr HL, , Plowman PN, , Caroll PV, , Francois I, , Krassas GE, & Afsahr F, : Clinical and endocrine responses to pituitary radio-therapy in pediatric Cushing's disease: an effective second-line treatment. J Clin Endocrinol Metab 88:34–37, 2003
Tagliaferri M, , Berselli ME, & Loli P: Transsphenoidal microsurgery for Cushing's disease. Acta Endocrinol (Copenh) 113:5–11, 1986
Tindall GT, , Herring CJ, , Clark RV, , Adams DA, & Watts NB: Cushing's disease: results of transsphenoidal microsurgery with emphasis on surgical failures. J Neurosurg 72:363–369, 1990
Trainer PJ, , Lawrie HS, , Verhelst J, , Howlett TA, , Lowe DG, & Grossman AB, : Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf) 38:73–78, 1993
Trecan GV, , Laudat MH, , Thomopoulos P, , Luton JP, & Bricaire H: Urinary free corticoids: an evaluation of their usefulness in the diagnosis of Cushing's syndrome. Acta Endocrinol (Copenh) 103:110–115, 1983
Tyrrell JB, , Findling JW, , Aaron DC, , Fitzgerald PA, & Forsham PH: An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing's syndrome. Ann Intern Med 104:180–186, 1986
Vicente A, , Estrada J, , de la Cuerda C, , Astigarra B, , Marazuela M, & Blanco C, : Results of external pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease. Acta Endocrinol (Copenh) 125:470–474, 1991
Vladyka V, , Liscak R, , Simonova G, , Chytka T, , Novotny J Jr, & Vymaza J, : Radiosurgical treatment of hypophyseal adenomas with gamma knife: results in a group of 163 patients during a 5-year period. Cas Lek Cesk 139:757–766, 2000
Walz MK, , Peitgen K, , Hoermann R, , Giebler RM, , Mann K, & Eigler FW: Posterior retroperitoneoscopy as a new minimally invasive approach for adrenalectomy: results of 30 adrenalectomies in 27 patients. World J Surg 20:769–774, 1996
Weber A, , Trainer PJ, , Grossman AB, , Afsahr F, , Medbak S, & Perry LA, : Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing's syndrome. Clin Endocrinol (Oxf) 43:19–28, 1995
Yoon SC, , Suh TS, , Jang HS, , Chung SM, , Kim YS, & Ryu MR, : Clinical results of 24 pituitary macroadenomas with LINAC-based stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 41:849–853, 1998
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