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

• Published in: Clinical endocrinology (Oxford) 2018-12, Vol.89 (6), p.805-812
• Main Authors: Magkou, Dimitra, Do Cao, Christine, Bouvattier, Claire, Douillard, Claire, de Marcellus, Capucine, Cazabat, Laure, Gérard, Maxime, Raffin‐Sanson, Marie‐Laure, Young, Jacques
• Format: Article
• Language: English
• Subjects: Adrenal glands; Adult; adverse effects; Birth weight; Child, Preschool; Children; DDT; Dichlorodiphenyldichloroethane; Female; Fetus; foetus; Genitalia; Humans; Infant; Infant, Newborn; Life Sciences; Mitotane; Neonates; Neuroendocrine tumors; Patients; Pesticides; Plasma levels; Pregnancy; Prenatal exposure; Retrospective Studies; Secretion; Teratogenicity; Young Adult
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.13854

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.