title: A comprehensive long-term retrospective analysis of silent corticotrophic adenomas vs hormone-negative adenomas.
abstract: BACKGROUND
  Silent corticotrophic adenomas (SCAs) stain adrenocorticotropic hormone (ACTH)+ without causing Cushing disease. SCAs are reportedly more aggressive, but information comes from small series.
  
  
  OBJECTIVE
  To determine whether SCAs behave more aggressively than hormone-negative adenomas (HNAs), and characterize SCA ACTH production alterations.
  
  
  METHODS
  SCAs (n = 75) and HNAs (n = 1726) diagnosed at our institution from 1990 to 2011 were retrospectively reviewed. RT-PCR was used to compare expression of ACTH-producing factors.
  
  
  RESULTS
  SCA patients exhibited comparable sex and age as HNA patients (P = .7-.9). SCAs exhibited comparable size as HNAs (2.2 vs 2.0 cm, P = .2), with cavernous sinus invasion in 30% of SCAs vs 18% of HNAs (P = .03). SCA patients had higher mean preoperative serum ACTH (46 vs 19 ng/L; P = .005; normal = 5-27 ng/L), but comparable serum cortisol (13 vs 12 μg/dL; normal = 4-22 μg/dL; P < .05) as HNA patients. SCAs were gross totally resected 59% of the time, vs 53% for HNAs (P = .8). Kaplan-Meier 3-year progression/recurrence rates were 34% for strongly ACTH-positive Type I SCAs, 10% for weakly ACTH-positive Type II SCAs, and 6% for HNAs (P < .001 SCA vs HNA; P < .001 Type I vs HNA; and P = .08 Type II vs HNA). Expression of ACTH precursor pro-opiomelanocortin was 900-fold elevated in SCAs and 1300-fold elevated in Cushing disease-causing adenomas (CDCAs) vs HNAs (P < .001). Transcription of PC1/3, which cleaves pro-opiomelanocortin into ACTH, was 30-fold higher in CDCAs than SCAs (P = .02).
  
  
  CONCLUSIONS
  In the largest series to date, SCAs exhibited comparable size, but increased cavernous sinus invasion and progression/recurrence vs HNAs. SCAs exhibit deficient pro-opiomelanocortin to ACTH conversion. Close follow-up is warranted for SCAs.
authors.affiliation: Department of Neurosurgery and The California Center for Pituitary Disorders (CCPD), University of California at San Francisco (UCSF), San Francisco, California, USA.
authors.forename: Arman
authors.initials: A
authors.lastname: Jahangiri
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Wagner
authors.forename: Melike
authors.initials: M
authors.lastname: Pekmezci
authors.forename: Anne
authors.initials: A
authors.lastname: Hiniker
authors.forename: Edward F
authors.initials: EF
authors.lastname: Chang
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kunwar
authors.forename: Lewis
authors.initials: L
authors.lastname: Blevins
authors.forename: Manish K
authors.initials: MK
authors.lastname: Aghi
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000097:blood* / Q000453:epidemiology* / Q000628:therapy; D000236:Adenoma / Q000097:blood* / Q000453:epidemiology* / Q000628:therapy; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002648:Child; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000453:epidemiology* / Q000517:prevention & control; D015995:Prevalence; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D012495:San Francisco / Q000453:epidemiology; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone