{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T13:20:50Z","timestamp":1783776050963,"version":"3.55.0"},"reference-count":132,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FOC"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:p>Cushing's disease (CD) is a state of excess glucocorticoid production resulting from an adrenocorticotropic hormone (ACTH)\u2013secreting pituitary adenoma. The gold-standard treatment for CD is transsphenoidal adenomectomy. In the hands of an experienced neurosurgeon, gross-total resection is possible in the majority of ACTH-secreting pituitary adenomas, with early postoperative remission rates ranging from 67% to 95%. In contrast to the strong data in support of resection, the clinical course of postsurgical persistent or recurrent disease remains unclear. There is significant variability in recurrence rates, with reports as high as 36% with a mean time to recurrence of 15\u201350 months. It is therefore important to develop biochemical criteria that define postsurgical remission and that may provide prognosis for long-term recurrence. Despite the use of a number of biochemical assessments, there is debate regarding the accuracy of these tests in predicting recurrence. Here, the authors review the various biochemical criteria and assess their utility in predicting CD recurrence after resection.<\/jats:p>","DOI":"10.3171\/2014.10.focus14682","type":"journal-article","created":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T03:40:53Z","timestamp":1422762053000},"page":"E13","source":"Crossref","is-referenced-by-count":45,"title":["Cushing's disease: predicting long-term remission after surgical treatment"],"prefix":"10.3171","volume":"38","author":[{"given":"Arjun V.","family":"Pendharkar","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Sussman","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen L.","family":"Ho","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie G.","family":"Hayden Gephart","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Katznelson","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"},{"name":"Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1458","article-title":"Recurrences of ACTH-secreting adenomas after pituitary adenomectomy can be accurately predicted by perioperative measurements of plasma ACTH levels","volume":"98","author":"Abdelmannan","year":"2013"},{"key":"b2-focus14682","series-title":"Endocrinol Nutr","first-page":"475","article-title":"[Predictors of long-term remission after transsphenoidal surgery in Cushing's disease]","volume":"60","author":"Abell\u00e1n Galiana","year":"2013"},{"key":"b3-focus14682","series-title":"Acta Neurochir (Wien)","first-page":"471","article-title":"Early post-operative ACTH and cortisol as predictors of remission in Cushing's disease","volume":"149","author":"Acebes","year":"2007"},{"key":"b4-focus14682","series-title":"Neuroendocrinology","first-page":"169","article-title":"Biochemical predictors of outcome of pituitary surgery for Cushing's disease","volume":"91","author":"Alwani","year":"2010"},{"key":"b5-focus14682","series-title":"Pituitary","article-title":"Long-term remission and recurrence rate in a cohort of Cushing's disease: the need for long-term follow-up","author":"Aranda","year":"2014"},{"key":"b6-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"549","article-title":"Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance","volume":"63","author":"Atkinson","year":"2005"},{"key":"b7-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"906","article-title":"The corticotropin-releasing hormone test in the postoperative evaluation of patients with cushing's syndrome","volume":"65","author":"Avgerinos","year":"1987"},{"key":"b8-focus14682","series-title":"J Neurooncol","first-page":"235","article-title":"Detection of recurrent Cushing's disease: proposal for standardized patient monitoring following transsphenoidal surgery","volume":"119","author":"Ayala","year":"2014"},{"key":"b9-focus14682","series-title":"Acta Neurochir (Wien)","first-page":"477","article-title":"Assessment of cure and recurrence after pituitary surgery for Cushing's disease","volume":"143","author":"Barbetta","year":"2001"},{"key":"b10-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"2454","article-title":"Treatment of adrenocorticotropindependent Cushing's syndrome: a consensus 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Metab","first-page":"1897","article-title":"A combined dexamethasone desmopressin test as an early marker of postsurgical recurrence in Cushing's disease","volume":"94","author":"Castinetti","year":"2009"},{"key":"b15-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"617","article-title":"Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome?","volume":"54","author":"Chee","year":"2001"},{"key":"b16-focus14682","series-title":"Eur J Endocrinol","first-page":"227","article-title":"Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing's disease","volume":"143","author":"Colombo","year":"2000"},{"key":"b17-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"309","article-title":"The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery","volume":"53","author":"Courtney","year":"2000"},{"key":"b18-focus14682","series-title":"Ann R Coll Surg Engl","first-page":"180","article-title":"The basophil adenomas of the pituitary body","volume":"44","author":"Cushing","year":"1969"},{"key":"b19-focus14682","series-title":"Bull Johns Hopkins Hosp","first-page":"137","article-title":"The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism)","volume":"50","author":"Cushing","year":"1932"},{"key":"b20-focus14682","series-title":"Acta Neurochir (Wien)","first-page":"971","article-title":"Intra- and postoperative plasma ACTH concentrations in patients with Cushing's disease cured by transsphenoidal pituitary surgery","volume":"144","author":"Czirj\u00e1k","year":"2002"},{"key":"b21-focus14682","series-title":"Pituitary","first-page":"183","article-title":"Recurrence of Cushing's disease preceded by the reappearance of ACTH and cortisol responses to desmopressin test","volume":"7","author":"Dall'asta","year":"2004"},{"key":"b22-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"465","article-title":"Evaluation of adrenal function in patients with hypothalamic and pituitary disorders: comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test","volume":"50","author":"Dullaart","year":"1999"},{"key":"b23-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"7","article-title":"Clinical review: Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease","volume":"91","author":"Esposito","year":"2006"},{"key":"b24-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"479","article-title":"Morbidity and mortality in Cushing's disease: an epidemiological approach","volume":"40","author":"Etxabe","year":"1994"},{"key":"b25-focus14682","series-title":"Eur J Endocrinol","first-page":"311","article-title":"The burden of Cushing's disease: clinical and health-related quality of life aspects","volume":"167","author":"Feelders","year":"2012"},{"key":"b26-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"603","article-title":"The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis","volume":"40","author":"Fiad","year":"1994"},{"key":"b27-focus14682","series-title":"Zentralbl Neurochir","first-page":"6","article-title":"The use of postoperative ACTH levels as a marker for successful transsphenoidal microsurgery in Cushing's disease","volume":"64","author":"Flitsch","year":"2003"},{"key":"b28-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"935","article-title":"Hypothalamus-pituitary-adrenal axis evaluation in patients with hypothalamo-pituitary disorders: comparison of different provocative tests","volume":"68","author":"Giordano","year":"2008"},{"key":"b29-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1056","article-title":"Transsphenoidal pituitary surgery for the treatment of Cushing's disease: results in 64 patients and long term follow-up studies","volume":"66","author":"Guilhaume","year":"1988"},{"key":"b30-focus14682","series-title":"Pituitary","first-page":"452","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","volume":"16","author":"Hameed","year":"2013"},{"key":"b31-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"6348","article-title":"Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results","volume":"89","author":"Hammer","year":"2004"},{"key":"b32-focus14682","series-title":"J Clin Endocrinol 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patients","volume":"98","author":"Lambert","year":"2013"},{"key":"b36-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"117","article-title":"Incidence and late prognosis of Cushing's syndrome: a population-based study","volume":"86","author":"Lindholm","year":"2001"},{"key":"b37-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"2057","article-title":"The postoperative basal cortisol and CRH tests for prediction of long-term remission from Cushing's disease after transsphenoidal surgery","volume":"96","author":"Lindsay","year":"2011"},{"key":"b38-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"3322","article-title":"Persistent adrenocorticotropin response to desmopressin in the early postoperative period predicts recurrence of Cushing's disease","volume":"94","author":"Losa","year":"2009"},{"key":"b39-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"61","article-title":"Desmopressin stimulation test before and after 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for remission","volume":"56","author":"Rees","year":"2002"},{"key":"b48-focus14682","series-title":"Pituitary","first-page":"71","article-title":"Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis","volume":"15","author":"Roelfsema","year":"2012"},{"key":"b49-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1131","article-title":"Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease","volume":"89","author":"Rollin","year":"2004"},{"key":"b50-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"117","article-title":"Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing's disease","volume":"69","author":"Romanholi","year":"2008"},{"key":"b51-focus14682","series-title":"Clin Chem","first-page":"1031","article-title":"Dexamethasone-suppressed corticotrophin-releasing hormone-stimulation test does not reliably diagnose or predict recurrence of Cushing disease","volume":"56","author":"Salem","year":"2010"},{"key":"b52-focus14682","series-title":"Endocr Pract","first-page":"1159","article-title":"Utility of adrenocorticotropic hormone in assessing the response to transsphenoidal surgery for Cushing's disease","volume":"20","author":"Salmon","year":"2014"},{"key":"b53-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"4193","article-title":"Diagnosis of adrenal insufficiency: evaluation of the corticotropin-releasing hormone test and basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease","volume":"88","author":"Schmidt","year":"2003"},{"key":"b54-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1150","article-title":"Corticotropin-releasing hormone stimulation test before and after transsphenoidal selective microadenomectomy in 30 patients with Cushing's disease","volume":"64","author":"Schrell","year":"1987"},{"key":"b55-focus14682","series-title":"J Neurosurg","first-page":"1","article-title":"Serum cortisol response to transsphenoidal surgery for Cushing disease","volume":"95","author":"Simmons","year":"2001"},{"key":"b56-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"2647","article-title":"Risk factors and long-term outcome in pituitary-dependent Cushing's disease","volume":"81","author":"Sonino","year":"1996"},{"key":"b57-focus14682","series-title":"Pituitary","first-page":"312","article-title":"The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing's disease","volume":"14","author":"Srinivasan","year":"2011"},{"key":"b58-focus14682","series-title":"Neurosurgery","first-page":"240","article-title":"Endoscopic transsphenoidal surgery for cushing disease: techniques, outcomes, and predictors of remission","volume":"72","author":"Starke","year":"2013"},{"key":"b59-focus14682","series-title":"Neurosurgery","first-page":"688","article-title":"Utility of the immediate postoperative cortisol concentrations in patients with Cushing's disease","volume":"67","author":"Sughrue","year":"2010"},{"key":"b60-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"73","article-title":"Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment","volume":"38","author":"Trainer","year":"1993"},{"key":"b61-focus14682","series-title":"Handb Clin Neurol","first-page":"221","article-title":"Cushing's disease","volume":"124","author":"Tritos","year":"2014"},{"key":"b62-focus14682","series-title":"Eur J Endocrinol","first-page":"727","article-title":"The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease","volume":"151","author":"Val\u00e9ro","year":"2004"},{"key":"b63-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"145","article-title":"Postoperative metyrapone test in the early assessment of outcome of pituitary surgery for Cushing's disease","volume":"47","author":"van Aken","year":"1997"},{"key":"b64-focus14682","series-title":"Eur J Endocrinol","first-page":"235","article-title":"Early postoperative evaluation in patients with Cushing's disease: usefulness of ovine corticotropin-releasing hormone test in the prediction of recurrence of disease","volume":"130","author":"Vignati","year":"1994"},{"key":"b65-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"25","article-title":"Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease: a single centre audit","volume":"56","author":"Yap","year":"2002"},{"key":"b66-focus14682","series-title":"Int J Endocrinol","first-page":"893781","article-title":"Diagnosis and multimodality management of Cushing's disease: a practical review","volume":"2013","author":"Zada","year":"2013"},{"key":"b1-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1458","article-title":"Recurrences of ACTH-secreting adenomas after pituitary adenomectomy can be accurately predicted by perioperative measurements of plasma ACTH levels","volume":"98","author":"Abdelmannan","year":"2013"},{"key":"b2-focus14682","series-title":"Endocrinol Nutr","first-page":"475","article-title":"[Predictors of long-term remission after transsphenoidal surgery in Cushing's disease]","volume":"60","author":"Abell\u00e1n Galiana","year":"2013"},{"key":"b3-focus14682","series-title":"Acta Neurochir (Wien)","first-page":"471","article-title":"Early post-operative ACTH and cortisol as predictors of remission in Cushing's disease","volume":"149","author":"Acebes","year":"2007"},{"key":"b4-focus14682","series-title":"Neuroendocrinology","first-page":"169","article-title":"Biochemical predictors of outcome of pituitary surgery for Cushing's disease","volume":"91","author":"Alwani","year":"2010"},{"key":"b5-focus14682","series-title":"Pituitary","article-title":"Long-term remission and recurrence rate in a cohort of Cushing's disease: the need for long-term follow-up","author":"Aranda","year":"2014"},{"key":"b6-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"549","article-title":"Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance","volume":"63","author":"Atkinson","year":"2005"},{"key":"b7-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"906","article-title":"The corticotropin-releasing hormone test in the postoperative evaluation of patients with cushing's syndrome","volume":"65","author":"Avgerinos","year":"1987"},{"key":"b8-focus14682","series-title":"J Neurooncol","first-page":"235","article-title":"Detection of recurrent Cushing's disease: proposal for standardized patient monitoring following transsphenoidal surgery","volume":"119","author":"Ayala","year":"2014"},{"key":"b9-focus14682","series-title":"Acta Neurochir (Wien)","first-page":"477","article-title":"Assessment of cure and recurrence after pituitary surgery for Cushing's disease","volume":"143","author":"Barbetta","year":"2001"},{"key":"b10-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"2454","article-title":"Treatment of adrenocorticotropindependent Cushing's syndrome: a consensus statement","volume":"93","author":"Biller","year":"2008"},{"key":"b11-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"63","article-title":"Outcomes of therapy for Cushing's disease due to adrenocorticotropinsecreting pituitary macroadenomas","volume":"83","author":"Blevins","year":"1998"},{"key":"b12-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"3114","article-title":"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","volume":"80","author":"Bochicchio","year":"1995"},{"key":"b13-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"4728","article-title":"Midnight salivary cortisol determination for assessing the outcome of transsphenoidal surgery in Cushing's disease","volume":"93","author":"Carrasco","year":"2008"},{"key":"b14-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1897","article-title":"A combined dexamethasone desmopressin test as an early marker of postsurgical recurrence in Cushing's disease","volume":"94","author":"Castinetti","year":"2009"},{"key":"b15-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"617","article-title":"Transsphenoidal pituitary surgery in Cushing's disease: can we predict outcome?","volume":"54","author":"Chee","year":"2001"},{"key":"b16-focus14682","series-title":"Eur J Endocrinol","first-page":"227","article-title":"Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing's disease","volume":"143","author":"Colombo","year":"2000"},{"key":"b17-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"309","article-title":"The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery","volume":"53","author":"Courtney","year":"2000"},{"key":"b18-focus14682","series-title":"Ann R Coll Surg Engl","first-page":"180","article-title":"The basophil adenomas of the pituitary body","volume":"44","author":"Cushing","year":"1969"},{"key":"b19-focus14682","series-title":"Bull Johns Hopkins Hosp","first-page":"137","article-title":"The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism)","volume":"50","author":"Cushing","year":"1932"},{"key":"b20-focus14682","series-title":"Acta Neurochir (Wien)","first-page":"971","article-title":"Intra- and postoperative plasma ACTH concentrations in patients with Cushing's disease cured by transsphenoidal pituitary surgery","volume":"144","author":"Czirj\u00e1k","year":"2002"},{"key":"b21-focus14682","series-title":"Pituitary","first-page":"183","article-title":"Recurrence of Cushing's disease preceded by the reappearance of ACTH and cortisol responses to desmopressin test","volume":"7","author":"Dall'asta","year":"2004"},{"key":"b22-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"465","article-title":"Evaluation of adrenal function in patients with hypothalamic and pituitary disorders: comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test","volume":"50","author":"Dullaart","year":"1999"},{"key":"b23-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"7","article-title":"Clinical review: Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease","volume":"91","author":"Esposito","year":"2006"},{"key":"b24-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"479","article-title":"Morbidity and mortality in Cushing's disease: an epidemiological approach","volume":"40","author":"Etxabe","year":"1994"},{"key":"b25-focus14682","series-title":"Eur J Endocrinol","first-page":"311","article-title":"The burden of Cushing's disease: clinical and health-related quality of life aspects","volume":"167","author":"Feelders","year":"2012"},{"key":"b26-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"603","article-title":"The overnight single-dose metyrapone test is a simple and reliable index of the hypothalamic-pituitary-adrenal axis","volume":"40","author":"Fiad","year":"1994"},{"key":"b27-focus14682","series-title":"Zentralbl Neurochir","first-page":"6","article-title":"The use of postoperative ACTH levels as a marker for successful transsphenoidal microsurgery in Cushing's disease","volume":"64","author":"Flitsch","year":"2003"},{"key":"b28-focus14682","series-title":"Clin Endocrinol (Oxf)","first-page":"935","article-title":"Hypothalamus-pituitary-adrenal axis evaluation in patients with hypothalamo-pituitary disorders: comparison of different provocative tests","volume":"68","author":"Giordano","year":"2008"},{"key":"b29-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"1056","article-title":"Transsphenoidal pituitary surgery for the treatment of Cushing's disease: results in 64 patients and long term follow-up studies","volume":"66","author":"Guilhaume","year":"1988"},{"key":"b30-focus14682","series-title":"Pituitary","first-page":"452","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","volume":"16","author":"Hameed","year":"2013"},{"key":"b31-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"6348","article-title":"Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results","volume":"89","author":"Hammer","year":"2004"},{"key":"b32-focus14682","series-title":"J Clin Endocrinol Metab","first-page":"440","article-title":"Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study","volume":"84","author":"Invitti","year":"1999"},{"issue":"3","key":"b33-focus14682","series-title":"Neurosurg Focus","first-page":"E5","article-title":"Transsphenoidal 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