{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:55:12Z","timestamp":1786445712008,"version":"build-2736575974"},"reference-count":43,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>Cushing's disease is a challenging neuroendocrine disorder. Although resection remains the primary treatment option for most patients, the disease persists if there is residual or recurrent tumor. Stereotactic radiosurgery has been used to treat patients with persistent Cushing's disease after a prior resection. The authors report on the long-term risks and benefits of radiosurgery for Cushing's disease.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective review of a prospectively collected database of radiosurgery patients was undertaken at the University of Virginia. All patients with Cushing's disease treated with Gamma Knife surgery (GKS) were identified. Those without at least 12 months of clinical and radiological follow-up were excluded from this analysis. Rates of endocrine remission, tumor control, and adverse events were assessed. Statistical methods were used to identify favorable and unfavorable prognostic factors.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Ninety-six patients with the required follow-up data were identified. The mean tumor margin dose was 22 Gy. The median follow-up was 48 months (range 12\u2013209.8 months). At the last follow-up, remission of Cushing's disease occurred in 70% of patients. The median time to remission among all patients was 16.6 months (range 1\u2013165.7 months). The median time to remission in those who had temporarily stopped taking ketoconazole at the time of GKS was 12.6 months, whereas it was 21.8 months in those who continued to receive ketoconazole (p &lt; 0.012). Tumor control was achieved in 98% of patients. New loss of pituitary function occurred in 36% of patients. New or worsening cranial neuropathies developed in 5 patients after GKS, with the most common involving cranial nerves II and III.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Gamma Knife surgery offers a high rate of tumor control and a reasonable rate of endocrine remission in patients with Cushing's disease. The cessation of cortisol-lowering medications around the time of GKS appears to result in a more rapid rate of remission. Delayed hypopituitarism and endocrine recurrence develop in a minority of patients and underscore the need for long-term multidisciplinary follow-up.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2013.7.jns13217","type":"journal-article","created":{"date-parts":[[2013,8,9]],"date-time":"2013-08-09T14:01:55Z","timestamp":1376056915000},"page":"1486-1492","source":"Crossref","is-referenced-by-count":93,"title":["Results of Gamma Knife surgery for Cushing's disease"],"prefix":"10.3171","volume":"119","author":[{"given":"Jason P.","family":"Sheehan","sequence":"first","affiliation":[{"name":"Departments of Neurological Surgery and"},{"name":"Radiation Oncology; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Salvetti","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Lee","family":"Vance","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns13217","series-title":"Clin Neurosurg","first-page":"141","article-title":"Management of recurrent and refractory Cushing's disease with reoperation and\/or proton beam radiosurgery","volume":"55","author":"Aghi","year":"2008"},{"key":"b2-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"5593","DOI":"10.1210\/jc.2003-030871","article-title":"Diagnosis and complications of Cushing's syndrome: a consensus statement","volume":"88","author":"Arnaldi","year":"2003"},{"key":"b3-jns13217","series-title":"Eur J Endocrinol","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1530\/EJE-10-0466","article-title":"Nelson's syndrome","volume":"163","author":"Barber","year":"2010"},{"key":"b4-jns13217","series-title":"Eur J Endocrinol","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1530\/EJE-12-0358","article-title":"Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center","volume":"167","author":"Baudry","year":"2012"},{"key":"b5-jns13217","series-title":"Int J Radiat Oncol Biol Phys","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/S0360-3016(99)00159-5","article-title":"The incidence of cerebrovascular accidents in patients with pituitary adenoma","volume":"45","author":"Brada","year":"1999"},{"key":"b6-jns13217","series-title":"BMJ","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1136\/bmj.304.6838.1343","article-title":"Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma","volume":"304","author":"Brada","year":"1992"},{"key":"b7-jns13217","series-title":"Endocrine","article-title":"Mifepristone: is there a place in the treatment of Cushing's disease?","author":"Carmichael","year":"2012"},{"key":"b8-jns13217","series-title":"Eur J Endocrinol","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1530\/eje.1.02323","article-title":"Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's disease","volume":"156","author":"Castinetti","year":"2007"},{"key":"b9-jns13217","series-title":"Clin Endocrinol (Oxf)","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1111\/j.1365-2265.2009.03646.x","article-title":"A change in pituitary magnetic resonance imaging protocol detects ACTH-secreting tumours in patients with previously negative results","volume":"72","author":"Chowdhury","year":"2010"},{"key":"b10-jns13217","series-title":"J Clin Endocrinol Metab","first-page":"3568","article-title":"Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486)","volume":"86","author":"Chu","year":"2001"},{"key":"b11-jns13217","series-title":"Int J Radiat Oncol Biol Phys","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.ijrobp.2004.09.058","article-title":"Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients","volume":"62","author":"Colin","year":"2005"},{"key":"b12-jns13217","series-title":"Acta Endocrinol (Copenh)","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1530\/acta.0.1120310","article-title":"Long-term results of stereotactic radiosurgery to the pituitary gland in Cushing's disease","volume":"112","author":"Degerblad","year":"1986"},{"key":"b13-jns13217","series-title":"Stereotact Funct Neurosurg","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1159\/000083476","article-title":"The efficacy of linear accelerator radiosurgery in the management of patients with Cushing's disease","volume":"82","author":"Devin","year":"2004"},{"key":"b14-jns13217","series-title":"Eur J Cancer","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009"},{"key":"b15-jns13217","series-title":"Clin Endocrinol (Oxf)","first-page":"793","article-title":"3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing's syndrome","volume":"72","author":"Erickson","year":"2010"},{"key":"b16-jns13217","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1056\/NEJM199701163360303","article-title":"The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease","volume":"336","author":"Estrada","year":"1997"},{"key":"b17-jns13217","series-title":"Pituitary","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1007\/s11102-012-0397-5","article-title":"Medical management of Cushing's disease: what is the future?","volume":"15","author":"Fleseriu","year":"2012"},{"key":"b18-jns13217","series-title":"Pituitary","article-title":"Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing's disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience","author":"Hameed","year":"2012"},{"key":"b19-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"6348","DOI":"10.1210\/jc.2003-032180","article-title":"Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results","volume":"89","author":"Hammer","year":"2004"},{"key":"b20-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1210\/jc.2011-2957","article-title":"Outcome of Cushing's disease following transsphenoidal surgery in a single center over 20 years","volume":"97","author":"Hassan-Smith","year":"2012"},{"key":"b21-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"980","DOI":"10.3171\/jns.2007.106.6.980","article-title":"Gamma Knife surgery for Cushing's disease","volume":"106","author":"Jagannathan","year":"2007"},{"key":"b22-jns13217","series-title":"Neurosurgery","first-page":"1262","article-title":"Gamma knife radiosurgery for acromegaly: outcomes after failed transsphenoidal surgery","volume":"62","author":"Jagannathan","year":"2008"},{"key":"b23-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1210\/jcem.85.3.6464","article-title":"Octreotide may act as a radioprotective agent in acromegaly","volume":"85","author":"Landolt","year":"2000"},{"issue":"Suppl 3","key":"b24-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3171\/jns.2000.93.supplement_3.0014","article-title":"Gamma knife radiosurgery for prolactinomas","volume":"93","author":"Landolt","year":"2000"},{"key":"b25-jns13217","series-title":"N Engl J Med","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1056\/NEJM196309192691202","article-title":"The alpha particle or proton beam in radiosurgery of the pituitary gland for Cushing's disease","volume":"269","author":"Linfoot","year":"1963"},{"key":"b26-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1210\/jc.2011-0251","article-title":"Radiation therapy in the management of pituitary adenomas","volume":"96","author":"Loeffler","year":"2011"},{"key":"b27-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1210\/jc.2008-0125","article-title":"The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline","volume":"93","author":"Nieman","year":"2008"},{"issue":"3","key":"b28-jns13217","series-title":"Neurosurg Focus","first-page":"E7","article-title":"National trends, complications, and outcomes following transsphenoidal surgery for Cushing's disease from 1993 to 2002","volume":"23","author":"Patil","year":"2007"},{"key":"b29-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1210\/jc.2007-2013","article-title":"Late recurrences of Cushing's disease after initial successful transsphenoidal surgery","volume":"93","author":"Patil","year":"2008"},{"key":"b30-jns13217","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1227\/01.NEU.0000313117.35824.9F","article-title":"Outcomes after repeat transsphenoidal surgery for recurrent Cushing's disease","volume":"63","author":"Patil","year":"2008"},{"key":"b31-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1210\/jc.2007-0208","article-title":"Outcomes and management of patients with Cushing's disease without pathological confirmation of tumor resection after transsphenoidal surgery","volume":"92","author":"Pouratian","year":"2007"},{"key":"b32-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"751","DOI":"10.3171\/JNS\/2008\/109\/10\/0751","article-title":"Management of Cushing's disease: outcome in patients with microadenoma detected on pituitary magnetic resonance imaging. Clinical article","volume":"109","author":"Prevedello","year":"2008"},{"key":"b33-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3171\/jns.1994.80.1.0037","article-title":"Early repeat surgery for persistent Cushing's disease","volume":"80","author":"Ram","year":"1994"},{"key":"b34-jns13217","series-title":"Surg Neurol","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/0090-3019(95)80130-9","article-title":"Gamma knife surgery for Cushing's disease","volume":"43","author":"Seo","year":"1995"},{"key":"b35-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"738","DOI":"10.3171\/jns.2000.93.5.0738","article-title":"Radiosurgery for Cushing's disease after failed transsphenoidal surgery","volume":"93","author":"Sheehan","year":"2000"},{"key":"b36-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"678","DOI":"10.3171\/jns.2005.102.4.0678","article-title":"Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium","volume":"102","author":"Sheehan","year":"2005"},{"key":"b37-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3171\/2010.5.JNS091635","article-title":"Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes. Clinical article","volume":"114","author":"Sheehan","year":"2011"},{"key":"b38-jns13217","series-title":"Neurosurg Clin N Am","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.nec.2012.06.011","article-title":"External beam radiation therapy and stereotactic radiosurgery for pituitary adenomas","volume":"23","author":"Sheehan","year":"2012"},{"key":"b39-jns13217","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3171\/jns.2006.104.1.157","article-title":"Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. Technical note","volume":"104","author":"Snell","year":"2006"},{"key":"b40-jns13217","series-title":"Curr Opin Endocrinol Diabetes Obes","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1097\/MED.0b013e32833ab069","article-title":"Radiation therapy and stereotactic radiosurgery for the treatment of Cushing's disease: an evidence-based review","volume":"17","author":"Starke","year":"2010"},{"key":"b41-jns13217","series-title":"Pituitary","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s11102-011-0308-1","article-title":"Excess mortality for patients with residual disease following resection of pituitary adenomas","volume":"14","author":"Sughrue","year":"2011"},{"key":"b42-jns13217","series-title":"J Clin Endocrinol Metab","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1210\/jc.2009-1672","article-title":"Delayed remission after transsphenoidal surgery in patients with Cushing's disease","volume":"95","author":"Valassi","year":"2010"},{"key":"b43-jns13217","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1227\/NEU.0b013e3182846e44","article-title":"Hypopituitarism following stereotactic radiosurgery for pituitary adenomas","volume":"72","author":"Xu","year":"2013"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/119\/6\/article-p1486.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/119\/6\/article-p1486.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/119\/6\/article-p1486.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,14]],"date-time":"2022-08-14T17:08:43Z","timestamp":1660496923000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/119\/6\/article-p1486.xml"}},"subtitle":["Clinical article"],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":43,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2013.7.jns13217","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12]]}}}