Department of Endocrinology and Nutrition, Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne Billancourt, France.
Department of Endocrinology Centre Hospitalier, Universitaire de Lille, Lille, France.
Clin Endocrinol (Oxf). 2018 Dec;89(6):805-812. doi: 10.1111/cen.13854. Epub 2018 Oct 16.
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.
The outcome of four children exposed to mitotane during their intrauterine life was examined.
Patients having conceived while taking mitotane, or with detectable mitotane plasma levels, were retrospectively recruited via the French COMETE and FIRENDO networks.
Mitotane in maternal plasma, adrenocortical hormones in children.
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.
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.
米托坦/Op'DDD 用于治疗肾上腺皮质癌和其他皮质醇增多症的原因。米托坦抑制皮质醇的分泌，并显示出肾上腺溶解和抗肿瘤作用。这种化合物是杀虫剂和内分泌干扰物滴滴涕（二氯二苯基三氯乙烷）的代谢物，被列为世界范围内的致畸化合物。然而，人们对它对人类发育的影响知之甚少。
研究了四名在宫内生活中接触米托坦的儿童的结局。
通过法国 COMETE 和 FIRENDO 网络，回顾性招募了服用米托坦或检测到米托坦血浆水平的患者。
母亲血浆中的米托坦、儿童的肾上腺皮质激素。
三名接受米托坦治疗的女性生育了四名儿童。在妊娠早期，所有患者均检测到米托坦的血浆水平（分别为 0.9、2.4 和 6.7mg/L）。在妊娠期间，未发现胎儿畸形。四名暴露的新生儿出生时肾上腺功能和生殖器似乎正常。一名双胞胎女性出生体重低。出生时和 3 个月、2 年和 7 年随访后的评估均未发现明显的神经异常。评估肾上腺皮质功能未发现皮质醇缺乏。
出乎意料的是，这些儿童在胎儿期接触米托坦似乎没有明显的致畸作用。然而，考虑到这里使用的治疗浓度较低，病例数较少，而且长期随访情况未知，我们强烈建议不要在怀孕期间服用米托坦，并仍建议避免怀孕，至少在米托坦血浆水平仍可检测到的情况下如此。
