title: Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment.
abstract: OBJECTIVE
  We tested the hypothesis that in Cushing's disease, ACTH secretion from the normal pituitary surrounding an ACTH-secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post-operative period.
  
  
  METHODS
  A retrospective study of patients undergoing transsphenoidal selective adenomectomy, hemi-hypophysectomy or total hypophysectomy for Cushing's disease at St Bartholomew's Hospital between 1985 and 1990.
  
  
  METHODS
  Forty-eight consecutive patients (33 women, mean age 43, range 7-69 years) undergoing transsphenoidal hypophysectomy for Cushing's disease. Ten patients who underwent a second operation were re-evaluated; the patients were followed for a median time of 40 months after operation (range 15-70).
  
  
  METHODS
  Post-operatively, serum cortisol was measured daily at 0900 h. Serum TSH, T4, prolactin, LH, FSH, testosterone or oestradiol plus plasma and urine osmolality were measured.
  
  
  RESULTS
  After initial surgery, post-operative serum cortisol was undetectable (< 50 nmol/l) in 20 out of 48 patients (42%) and < 300 nmol/l in 32 out of 48 patients (67%). Re-exploration of the pituitary fossa in 10 patients found undetectable cortisol levels in 25 (52%) and levels < 300 nmol/l in 39 (81%) patients. Cushing's syndrome has not recurred, clinically or biochemically, in any patient in whom the post-operative cortisol was < 50 nmol/l. Post-operatively, hypothyroidism was present in 40% of patients and hypogonadism in 53% of men and 30% of premenopausal women. Diabetes insipidus, persisting for at least six months, occurred in 46% of patients.
  
  
  CONCLUSIONS
  Cushing's disease has not recurred in any patient with an undetectable serum cortisol (< 50 nmol/l) post-operatively. Serum cortisol should be regarded as a tumour marker in Cushing's disease and the aim of transsphenoidal hypophysectomy for Cushing's disease should be to render the immediate post-operative serum cortisol undetectable.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
authors.forename: H S
authors.initials: HS
authors.lastname: Lawrie
authors.forename: J
authors.initials: J
authors.lastname: Verhelst
authors.forename: T A
authors.initials: TA
authors.lastname: Howlett
authors.forename: D G
authors.initials: DG
authors.lastname: Lowe
authors.forename: A B
authors.initials: AB
authors.lastname: Grossman
authors.forename: M O
authors.initials: MO
authors.lastname: Savage
authors.forename: F
authors.initials: F
authors.lastname: Afshar
authors.forename: G M
authors.initials: GM
authors.lastname: Besser
mesh_terms: D000236:Adenoma / Q000601:surgery*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D003480:Cushing Syndrome / Q000097:blood / Q000601:surgery*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007016:Hypophysectomy; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000601:surgery*; D011184:Postoperative Period; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D006854:Hydrocortisone