title: Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center.
abstract: BACKGROUND
  Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first- or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD.
  
  
  OBJECTIVE
  Evaluation of the efficacy and tolerance of mitotane in CD patients.
  
  
  METHODS
  Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center.
  
  
  METHODS
  Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC).
  
  
  RESULTS
  Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5 ± 8.9 mg/l, with a mean daily dose of 2.6 ± 1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P<0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), P=0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery.
  
  
  CONCLUSIONS
  Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.
authors: Department of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France.
authors: Camille
authors: C
authors: Baudry
authors: Joël
authors: J
authors: Coste
authors: Roula
authors: R
authors: Bou Khalil
authors: Stéphane
authors: S
authors: Silvera
authors: Laurence
authors: L
authors: Guignat
authors: Jean
authors: J
authors: Guibourdenche
authors: Halim
authors: H
authors: Abbas
authors: Paul
authors: P
authors: Legmann
authors: Xavier
authors: X
authors: Bertagna
authors: Jérôme
authors: J
authors: Bertherat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D006727:Hormone Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000009:adverse effects* / Q000627:therapeutic use*; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006727:Hormone Antagonists; D008939:Mitotane