title: A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing's syndrome.
abstract: OBJECTIVE
  To evaluate the outcome of preoperative therapy with ketoconazole (KTZ) and/or metyrapone (MTP) in previously untreated patients with Cushing's syndrome (CS).
  
  
  METHODS
  Sixty-two patients with CS (85% ACTH dependent), treated with steroidogenesis inhibitors prior to surgery between 1983 and 2010, were retrospectively studied. T(0) and t(1) defined baseline and end of preoperative medical treatment.
  
  
  RESULTS
  Outcomes were based upon clinical and biochemical (normal UFC) control of hypercortisolism at t(1) : group CO (controlled) included 20 patients (32%) with eucortisolism and significant clinical improvement; group NC (not controlled) 30 (48%) with persistent hypercortisolism and no control of symptoms; and group PC (partially controlled) 12 patients (19%) who despite eucortisolism had no real clinical improvement. Median duration of treatment was 4 months (range: 1-30·7), and median cumulative dose of KTZ and MTP was 57 g (range: 3·6-240) and 120 g (range: 7·5-1215). CO patients were treated more with KTZ alone than the other groups (P < 0·05). MTP alone was administered more in PC than in CO patients (P < 0·01). No clinical differences were observed between groups at baseline. Systolic blood pressure at t(1) was higher in PC than in NC patients (P < 0·05). Hypertension persisted more in PC patients than in the other groups (P < 0·05) after a median postsurgery follow-up of 108 months (range: 4-276).
  
  
  CONCLUSIONS
  Preoperative administration of KTZ, MTP or both normalized UFC in 52% of patients with CS, but concomitant clinical improvement did not always follow. Larger, multicentre studies are needed to individualize preoperative medical treatment and improve outcome in patients with CS.
authors.affiliation: Department of Medicine/Endocrinology, Hospital Sant Pau, IIB-Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Universitat Autònoma de Barcelona, Barcelona, Spain. evalassi@santpau.cat
authors.forename: Elena
authors.initials: E
authors.lastname: Valassi
authors.forename: Iris
authors.initials: I
authors.lastname: Crespo
authors.forename: Ignasi
authors.initials: I
authors.lastname: Gich
authors.forename: José
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Susan M
authors.initials: SM
authors.lastname: Webb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000627:therapeutic use*; D002648:Child; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use*; D008297:Male; D008797:Metyrapone / Q000627:therapeutic use*; D008875:Middle Aged; D057234:Preoperative Period; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000963:Antimetabolites; D007654:Ketoconazole; D008797:Metyrapone