CONTEXT: 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. DESIGN AND SETTING: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. MAIN OUTCOME MEASURE: 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. CONCLUSION: 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.
CONTEXT: 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 CDpatients. DESIGN AND SETTING: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. MAIN OUTCOME MEASURE: 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. CONCLUSION: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 CDpatients.
Authors: Cédric Fontaine-Sylvestre; Laurent Létourneau-Guillon; Robert A Moumdjian; France Berthelet; André Lacroix Journal: Pituitary Date: 2020-10-19 Impact factor: 4.107
Authors: Lynnette K Nieman; Beverly M K Biller; James W Findling; M Hassan Murad; John Newell-Price; Martin O Savage; Antoine Tabarin Journal: J Clin Endocrinol Metab Date: 2015-07-29 Impact factor: 5.958
Authors: Maria Fleseriu; James W Findling; Christian A Koch; Sven-Martin Schlaffer; Michael Buchfelder; Coleman Gross Journal: J Clin Endocrinol Metab Date: 2014-07-11 Impact factor: 5.958