title: Surgical outcomes in patients with Cushing's disease: the Cleveland clinic experience.
abstract: BACKGROUND
  Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging.
  
  
  OBJECTIVE
  To report surgical outcomes and predictors of remission in a specialist center for patients with CD.
  
  
  METHODS
  Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated.
  
  
  RESULTS
  One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%).
  
  
  CONCLUSIONS
  A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA. pcjohnston@doctors.org.uk.|Regional Center for Endocrinology and Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, UK. pcjohnston@doctors.org.uk.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Johnston
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Kennedy
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA.|Department of Endocrinology, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hamrahian
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA.
authors.forename: Zahrae
authors.initials: Z
authors.lastname: Sandouk
authors.affiliation: Department of Biostatistics, Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: Bena
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA.
authors.forename: Betul
authors.initials: B
authors.lastname: Hatipoglu
authors.affiliation: Department of Neurosurgery, the Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.|National Clinical Enterprise, Catholic Health Initiatives, Englewood, CO, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Weil
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003480:Cushing Syndrome / Q000601:surgery; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D047748:Pituitary ACTH Hypersecretion / Q000601:surgery*; D010911:Pituitary Neoplasms / Q000601:surgery; D011446:Prospective Studies; D013101:Sphenoid Sinus / Q000601:surgery; D016896:Treatment Outcome; D055815:Young Adult
keywords: Cushing’s syndrome; Remission; Single center experience; Transsphenoidal surgery