Endocrine Abstracts (2011) 26 OC1.4

Results of 1,Ortho-1,para'-dichloro-diphenyl-dichloroethane (O,p'DDD) treatment in 76 patients with Cushing's disease

C Baudry1,2, J Coste2, R Bou Khalil1, L Guignat1, H Abbas3, J Guibourdenche4, S Silvera5, X Bertagna1,6 & J Bertherat1,6


1Centre de Référence des Maladies Rares de la Surrénale et Service d’Endocrinologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Faculté de Médecine, Université Paris Descartes, Paris, France; 2Unité de Biostatistique et Epidemiologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Faculté de Médecine, Université Paris Descartes, Paris, France; 3Service de Toxicologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; 4Service d’ Hormonologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; 5Service de Radiologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; 6Institut National de la Santé et de la Recherche Médicale Unité 567, Paris, France.


Introduction: Alternative to transsphenoidal pituitary surgery (TSS) may be required in Cushing’s disease (CD), as first or second line treatment. 1,ortho-1,para′-dichloro-diphenyl-dichloroethane (o,p′DDD) has a potent anticortisolic action. Its place in CD treatment is not well defined. The aim of this study was to further evaluate the efficacy and tolerance of o,p′DDD in CD.

Patients and methods: Seventy-six patients treated with o,p′DDD out of a single center cohort of 219 patients with CD diagnosed between 1993 and 2009 were retrospectively studied. Remission was defined as normalization of 24-h urinary cortisol (24 h-UC). Remission, recurrence and time-to-event were estimated by the Kaplan–Meier method, and potential predictors analyzed using Cox’s proportional hazards regression models.

Results: Remission was achieved in 48 (72%) patients, with a median time of 6.7 months (5.2–8.2, 95% confidence limits). Plasma o,p′DDD (mean±S.D.) at the time of remission was 10.5 μg/ml ±8.9, with a mean daily dose of 2.6±1.1 g. A negative linear relationship was observed between plasma o,p′DDD and 24 h-UC (P<0.0001). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). Recurrence after drug cessation occurred in 71% of patients, with a median time of 13.2 months (5.0–67.9, 95% confidence limits). Only high ACTH plasma level at the time of treatment discontinuation was statistically associated with a lower recurrence probability (HR 0.57 (0.32–1.00), P=0.05). A pituitary adenoma became visible during o,p′DDD treatment in 12 patients (25%) with initial negative pituitary imaging allowing subsequent TSS.

Conclusion: O,p′DDD is useful at different steps of CD management, either as first line when pituitary adenoma is not visible or because of the severity of hypercortisolism, or as a second line after TSS failure or recurrence, with most often easily manageable side effects. Monitoring of plasma o,p′DDD allows dosage adaptation to optimize hormonal control together with drug tolerance.

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