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Foetal exposure to mitotane/Op'DDD: Post-natal study of four children

Abstract : Objective: Mitotane/Op'DDD is used in the treatment of adrenocortical carcinoma and for other causes of hypercortisolism. Mitotane inhibits cortisol secretion and displays adrenolytic and antitumor actions. This compound is a metabolite of the pesticide and endocrine disruptor DDT (dichlorodiphenyltrichloroethane) and is classified among teratogenic compounds worldwide. However, little is known about its effects on human development. Design: The outcome of four children exposed to mitotane during their intrauterine life was examined. Patients: Patients having conceived while taking mitotane, or with detectable mitotane plasma levels, were retrospectively recruited via the French COMETE and FIRENDO networks. Measurements: Mitotane in maternal plasma, adrenocortical hormones in children. Results: Three women treated with mitotane gave birth to four children. During early pregnancy, all patients had detectable mitotane plasma levels (0.9, 2.4 and 6.7 mg/L, respectively). During pregnancy, no foetal malformations were detected. The four exposed newborns presented at birth with apparently normal adrenal function and genitalia. One twin female had a low birthweight. Evaluation at birth and after 3 months, 2 years and 7 years of follow-up showed no significant neurological abnormality. Evaluation of adrenocortical functions showed no cortisol deficiency. Conclusions: Unexpectedly, exposure of these four children to mitotane during foetal life seemed to have no clear teratogenic effect. However, considering the sub-therapeutic mitotane concentrations used here, the small number of cases, and because long-term follow-up is unknown, we strongly advise not to take mitotane during pregnancy and still recommend avoiding pregnancy, at least as long as mitotane plasma levels remain detectable. © 2018 John Wiley & Sons Ltd
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Submitted on : Friday, September 11, 2020 - 11:15:55 AM
Last modification on : Wednesday, November 3, 2021 - 6:04:29 AM

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Dimitra Magkou, Christine Do Cao, Claire Bouvattier, Claire Douillard, Capucine de Marcellus, et al.. Foetal exposure to mitotane/Op'DDD: Post-natal study of four children. Clinical Endocrinology, Wiley, 2018, 89 (6), pp.805-812. ⟨10.1111/cen.13854⟩. ⟨hal-02936360⟩

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