title: Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing's disease.
abstract: OBJECTIVE
  Silent corticotroph adenomas (SCAs) are rare pituitary tumours immunoreactive for ACTH, but without clinical evidence of Cushing's disease. We characterized SCAs based on clinical, hormonal and molecular data, and compared the characteristics of these tumours with those of macro (MCA)- and micro (mCA)-ACTH adenomas with Cushing's disease.
  
  
  METHODS
  Fifty ACTH adenomas (14 SCAs, 15 MCAs and 21 mCAs) with complete corresponding clinical, radiological and biochemical data were selected. Histological corticotroph differentiation; immunostaining for ACTH, beta-endorphin and beta-LPH; and mRNA expression levels of TPIT, POMC, GRalpha, prohormone convertase 1/3 (PC1/3) and galectin-3 were compared in 21 representative tumours.
  
  
  RESULTS
  Despite the absence of clinical hypercortisolism in patients with SCA, elevated plasma ACTH levels that were similar to those associated with mCA were observed. The cortisol/ACTH ratio was similar between SCA and MCA groups and lower than that found with mCA (P<0.05). This dissociation could be explained by lower expression of PC1/3 in SCA and MCA than in mCA (P<0.05). After an i.v. dexamethasone suppression test, ACTH levels were significantly higher in patients with MCA than in those with mCA (P<0.05). Cytological and immunocytochemical analyses as well as mRNA expression levels of TPIT, POMC and GRalpha confirmed corticotroph differentiation in both mCAs and MCAs and in half of the SCAs, with a strong correlation between TPIT and POMC mRNA expression levels in SCAs (R(2)=0.72; P<0.01) and in MCAs (R(2)=0.65; P<0.05).
  
  
  CONCLUSIONS
  Despite the absence of hypercortisolism, SCAs exhibit histological, biochemical and molecular corticotroph differentiation. SCA and MCA show hormonal and molecular similarities differentiating them from mCA.
authors.affiliation: INSERM, U842, Lyon F-69372 France. gerald.raverot@chu-lyon.fr
authors.forename: Gérald
authors.initials: G
authors.lastname: Raverot
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jouanneau
authors.forename: Carole
authors.initials: C
authors.lastname: Auger
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: Joël
authors.initials: J
authors.lastname: Lachuer
authors.forename: Michel
authors.initials: M
authors.lastname: Pugeat
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000097:blood* / Q000235:genetics / Q000473:pathology* / Q000652:urine; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D005260:Female; D037502:Galectin 3 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D015592:Immunoradiometric Assay; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000097:blood* / Q000235:genetics / Q000473:pathology* / Q000652:urine; D011333:Pro-Opiomelanocortin / Q000235:genetics; D045664:Proprotein Convertase 1 / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D037502:Galectin 3; D018398:Homeodomain Proteins; D011965:Receptors, Glucocorticoid; D020825:T-Box Domain Proteins; C486589:TBX19 protein, human; C411470:glucocorticoid receptor alpha; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D045664:Proprotein Convertase 1; D006854:Hydrocortisone