title: Use of the histological pseudocapsule in surgery for Cushing disease: rapid postoperative cortisol decline predicting complete tumor resection.
abstract: OBJECTIVE
  Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18-36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.
  
  
  METHODS
  Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0-2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.
  
  
  RESULTS
  The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).
  
  
  CONCLUSIONS
  Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10-36 hours after surgery despite prolonged and severe hypercortisolism.
authors.affiliation: Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA, USA. sjm9n@virginia.edu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Monteith
authors.forename: Robert M
authors.initials: RM
authors.lastname: Starke
authors.forename: John A
authors.initials: JA
authors.lastname: Jane
authors.forename: Edward H
authors.initials: EH
authors.lastname: Oldfield
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D003907:Dexamethasone; D004724:Endoscopy; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007016:Hypophysectomy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D018365:Neoplasm, Residual / Q000097:blood / Q000473:pathology / Q000601:surgery; D017591:Petrosal Sinus Sampling; D047748:Pituitary ACTH Hypersecretion / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D010902:Pituitary Gland / Q000473:pathology; D010911:Pituitary Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D011184:Postoperative Period; D011446:Prospective Studies; D013101:Sphenoid Sinus / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone