{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:26:13Z","timestamp":1791246373889,"version":"4.1.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Context: Few studies have systematically analyzed the long-term recurrence rates of Cushing\u2019s disease after initial successful transsphenoidal surgery.<\/jats:p>\n                  <jats:p>Setting: This was a retrospective review of patients treated at the University of Virginia Medical Center.<\/jats:p>\n                  <jats:p>Patients: A total of 215 subjects with Cushing\u2019s disease who underwent initial transsphenoidal surgery for resection of a presumed pituitary microadenoma from 1992\u20132006 were included.<\/jats:p>\n                  <jats:p>Main Outcome Measures: Remission and recurrence rates of Cushing\u2019s disease were examined. Recurrence was defined as an elevated 24-h urine free cortisol with clinical symptoms consistent with Cushing\u2019s disease.<\/jats:p>\n                  <jats:p>Results: Of the 215 patients who underwent transsphenoidal surgery for Cushing\u2019s disease, surgical remission was achieved in 184 (85.6%). The mean length of follow-up was 45 months. Actuarial recurrence rates of Cushing\u2019s disease after initially successful transsphenoidal surgery at 1, 2, 3, and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for more than 6 months ultimately had a recurrence of Cushing\u2019s disease. The median time to recurrence was 39 months. Immediate postoperative hypocortisolemia (serum cortisol \u2264 2 \u03bcg\/dl within 72-h surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of more than 2 \u03bcg\/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol less than or equal to 2 \u03bcg\/dl (odds ratio = 2.5; 95% confidence interval 1.12\u20135.52; P = 0.022).<\/jats:p>\n                  <jats:p>Conclusions: A quarter of the patients with Cushing\u2019s disease who achieve surgical remission after transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery.<\/jats:p>","DOI":"10.1210\/jc.2007-2013","type":"journal-article","created":{"date-parts":[[2007,12,4]],"date-time":"2007-12-04T21:52:18Z","timestamp":1196805138000},"page":"358-362","source":"Crossref","is-referenced-by-count":258,"title":["Late Recurrences of Cushing\u2019s Disease after Initial Successful Transsphenoidal Surgery"],"prefix":"10.1210","volume":"93","author":[{"given":"Chirag G.","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Neurosurgery (C.G.P., S.P.L., L.K., E.R.L.), Stanford University School of Medicine, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Prevedello","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery (D.M.P.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivanand P.","family":"Lad","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery (C.G.P., S.P.L., L.K., E.R.L.), Stanford University School of Medicine, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Lee","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Endocrinology (M.L.V., M.O.T.), University of Virginia Health System, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael O.","family":"Thorner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Endocrinology (M.L.V., M.O.T.), University of Virginia Health System, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Katznelson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery (C.G.P., S.P.L., L.K., E.R.L.), Stanford University School of Medicine, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Edward R.","family":"Laws","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery (C.G.P., S.P.L., L.K., E.R.L.), Stanford University School of Medicine, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613291726800_R1","first-page":"137","article-title":"The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism).","volume":"50","author":"Cushing","year":"1932","journal-title":"Bull Johns Hopkins Hosp"},{"key":"2020071613291726800_R2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3171\/jns.2002.97.1.0231","article-title":"Cushing\u2019s case XLV: Minnie G.","volume":"97","author":"Lanzino","year":"2002","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R3","first-page":"117","article-title":"Incidence and late prognosis of Cushing\u2019s syndrome: a population-based study.","volume":"86","author":"Lindholm","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R4","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1210\/jc.2006-2112","article-title":"Mortality in patients treated for Cushing\u2019s disease is increased, compared with patients treated for nonfunctioning pituitary macroadenoma.","volume":"92","author":"Dekkers","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1056\/NEJM199503233321207","article-title":"Cushing\u2019s syndrome.","volume":"332","author":"Orth","year":"1995","journal-title":"N Engl J Med"},{"issue":"(2\u20133 Pt 2)","key":"2020071613291726800_R6","first-page":"294","article-title":"Cushing\u2019s disease resulting from pituitary corticotrophic microadenoma","volume":"48","author":"Laws","year":"2002","journal-title":"Treatment results from transsphenoidal microsurgery and gamma knife radiosurgery. Neurochirurgie"},{"key":"2020071613291726800_R7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0303-7207(02)00281-2","article-title":"The neurosurgical management of Cushing\u2019s disease.","volume":"197","author":"Reitmeyer","year":"2002","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613291726800_R8","doi-asserted-by":"crossref","first-page":"825","DOI":"10.3171\/jns.2005.103.5.0825","article-title":"Surgical management of adrenocorticotropic hormone-secreting macroadenomas: outcome and challenges in patients with Cushing\u2019s disease or Nelson\u2019s syndrome.","volume":"103","author":"De Tommasi","year":"2005","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1530\/eje.0.1300235","article-title":"Early postoperative evaluation in patients with Cushing\u2019s disease: usefulness of ovine corticotropin-releasing hormone test in the prediction of recurrence of disease.","volume":"130","author":"Vignati","year":"1994","journal-title":"Eur J Endocrinol"},{"key":"2020071613291726800_R10","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1210\/jcem-69-6-1122","article-title":"Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing\u2019s disease.","volume":"69","author":"Pieters","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R11","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1046\/j.1365-2265.2002.01511.x","article-title":"Long-term follow-up results of transsphenoidal surgery for Cushing\u2019s disease in a single centre using strict criteria for remission.","volume":"56","author":"Rees","year":"2002","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613291726800_R12","first-page":"33","article-title":"Results of transsphenoidal surgery for Cushing\u2019s disease in patients with no histologically confirmed tumor.","volume":"47","author":"Sheehan","year":"2000","journal-title":"Neurosurgery"},{"key":"2020071613291726800_R13","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3171\/jns.2003.98.5.0967","article-title":"Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test.","volume":"98","author":"Chen","year":"2003","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3171\/jns.1983.59.2.0195","article-title":"Transsphenoidal microsurgical management of Cushing\u2019s disease. Report of 100 cases.","volume":"59","author":"Boggan","year":"1983","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R15","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3171\/jns.1987.66.2.0204","article-title":"Surgical treatment of Cushing\u2019s disease.","volume":"66","author":"Chandler","year":"1987","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3171\/jns.1994.80.1.0037","article-title":"Early repeat surgery for persistent Cushing\u2019s disease.","volume":"80","author":"Ram","year":"1994","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R17","first-page":"2475","article-title":"Long term follow-up of transsphenoidal surgery for the treatment of Cushing\u2019s disease in childhood.","volume":"80","author":"Leinung","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R18","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1210\/jc.2007-0208","article-title":"Outcomes and management of patients with Cushing\u2019s disease without pathological confirmation of tumor resection after transsphenoidal surgery.","volume":"92","author":"Pouratian","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R19","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.1210\/jc.2003-030871","article-title":"Diagnosis and complications of Cushing\u2019s syndrome: a consensus statement.","volume":"88","author":"Arnaldi","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R20","first-page":"3114","article-title":"Factors influencing the immediate and late outcome of Cushing\u2019s disease treated by transsphenoidal surgery: a retrospective study by the European Cushing\u2019s Disease Survey Group.","volume":"80","author":"Bochicchio","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R21","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.ecl.2005.01.007","article-title":"Pituitary surgery and postoperative management in Cushing\u2019s disease.","volume":"34","author":"Utz","year":"2005","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2020071613291726800_R22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s007010170077","article-title":"Assessment of cure and recurrence after pituitary surgery for Cushing\u2019s disease.","volume":"143","author":"Barbetta","year":"2001","journal-title":"Acta Neurochir (Wien)"},{"key":"2020071613291726800_R23","first-page":"2647","article-title":"Risk factors and long-term outcome in pituitary-dependent Cushing\u2019s disease.","volume":"81","author":"Sonino","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R24","doi-asserted-by":"crossref","first-page":"6348","DOI":"10.1210\/jc.2003-032180","article-title":"Transsphenoidal microsurgery for Cushing\u2019s disease: initial outcome and long-term results.","volume":"89","author":"Hammer","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R25","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1210\/jc.2004-2436","article-title":"Clinical review: the strategy of immediate reoperation for transsphenoidal surgery for Cushing\u2019s disease.","volume":"90","author":"Locatelli","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R26","first-page":"1135","article-title":"Pituitary adenomas in childhood and adolescence.","volume":"79","author":"Kane","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R27","first-page":"413","article-title":"Single-center experience with pediatric Cushing\u2019s disease.","volume":"103","author":"Kanter","year":"2005","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R28","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1210\/jcem-50-2-348","article-title":"Cushing\u2019s disease: management by transsphenoidal pituitary microsurgery.","volume":"50","author":"Bigos","year":"1980","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R29","first-page":"24","article-title":"Transsphenoidal removal of pituitary microadenoma in Cushing\u2019s disease.","volume":"53","author":"Salassa","year":"1978","journal-title":"Mayo Clin Proc"},{"key":"2020071613291726800_R30","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1530\/acta.0.1230423","article-title":"A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing\u2019s disease: prediction of outcome.","volume":"123","author":"Arnott","year":"1990","journal-title":"Acta Endocrinol (Copenh)"},{"key":"2020071613291726800_R31","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1365-2265.2005.02380.x","article-title":"Long-term remission rates after pituitary surgery for Cushing\u2019s disease: the need for long-term surveillance.","volume":"63","author":"Atkinson","year":"2005","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071613291726800_R32","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3171\/jns.2003.98.5.0948","article-title":"Cushing disease.","volume":"98","author":"Oldfield","year":"2003","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R33","first-page":"440","article-title":"Diagnosis and management of Cushing\u2019s syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.","volume":"84","author":"Invitti","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613291726800_R34","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3171\/jns.1998.89.3.0353","article-title":"Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly.","volume":"89","author":"Freda","year":"1998","journal-title":"J Neurosurg"},{"key":"2020071613291726800_R35","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1210\/jcem.86.9.7819","article-title":"Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria.","volume":"86","author":"Kreutzer","year":"2001","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/2\/358\/10418064\/jcem0358.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/2\/358\/10418064\/jcem0358.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T19:56:06Z","timestamp":1594929366000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/93\/2\/358\/2597991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,1]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,2,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2007-2013","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,1]]}}}