The protracted effect of o,p'-DDD in Cushing's disease and its impact on adrenal morphogenesis of young human embryo

Abstract

We hereby present a patient with Cushing's disease who became pregnant while being treated with o,p'-DDD and underwent a therapeutic abortion in view of the known embryotoxicity and placental transfer of this drug. Biopsy of adipose tissue in this patient showed it to be the storage site of considerable quantities of o,p'-DDD. Serum levels of o,p'-DDD determined in this patient initially four months after withdrawal of treatment and in another similar case three months after withdrawal were about 20 times higher than those found in untreated patients and reached control values only about 20 months later. Repeated evaluation of plasma and urinary free cortisol failed to reveal any correlation with the serum levels of o,p'-DDD, suggesting that the drug blood values cannot be used as a reliable indicator of the therapeutic effect on the adrenal gland. The histopathological examination of the embryo, aged about 42 days, revealed a dysmorphogenic event in the cortical primordia characterized by pycnotic sympathoblasts. It is suggested that such a toxic effect of o,p'-DDD on the embryonic cortical cells may act indirectly, affecting the viability of the migrating sympathoblasts.