Endocrine Abstracts

Background: One in 5 million children is affected by adrenocortical carcinoma (ACC) each year. Since prognosis for children older than 4 years is limited, clinicians often choose aggressive treatment with etoposide, doxorubicin, cisplatin (EDP) and mitotane after resection. However, little is known about the impact of EDP-mitotane on development in children. We therefore aimed to provide an overview of side-effects and neurocognitive effects of EDP-mitotane in children.

Method: We searched PubMed for studies listing side-effects or cognitive development in pediatric cases with ACC or Cushing syndrome treated with EDP-mitotane. We have added our own case of a 10-year old girl with ACC treated with EDP-mitotane after irradical resection.

Case: During EDP-mitotane she experienced several side-effects including nausea and hypothyroidism. She developed an impactful, but reversible, decrease in cognitive development measured by a standardized neuropsychological assessment before, during and after mitotane therapy. This decrease was mostly measurable in terms of decreased processing speed and concentration and a significant drop in school performance. Combined with fatigue and insecurity, this caused problems in short-term memory and the need to change her school type.

Review: We found 14 case reports and case series listing side-effects and neurocognitive effects in children treated with EDP-mitotane. The studies listed gastro-intestinal, endocrine and developmental side-effects. Neurocognitive effects included motor- and speech delay, decreased concentration and lower school performance. Especially the gastro-intestinal and neurocognitive side-effects were reversible after mitotane discontinuation.

Conclusion: EDP-mitotane is associated with several side-effects including neurocognitive effects in pediatric cases, all reversible after mitotane discontinuation. This can provide reassurance for clinicians, parents and patients in case mitotane therapy is indicated.