Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies. All cases produced large amounts of androgens of the classic and/or backdoor pathway. Variable expression of steroid enzymes was observed in carcinomas and adenomas. We found no discriminative pattern. This suggests that enhanced androgen production in pediatric ACTs is the result of deregulated steroidogenesis through multiple steroid pathways. Thus future treatments of ACTs targeting androgen overproduction should consider these novel steroid production pathways.

Department of Clinical Research Inselspital Bern University Hospital University of Bern Switzerland; Department of Nephrology and Hypertension Bern University Hospital University of Bern Switzerland

Department of Pediatrics 2 Faculty of Medicine Charles University Prague University Hospital Motol Prague Czech Republic

Institute of Pathology University of Bern Switzerland

Pediatric Endocrinology and Diabetology Department of Pediatrics Switzerland

Pediatric Endocrinology and Diabetology Department of Pediatrics Switzerland; Department of Clinical Research Inselspital Bern University Hospital University of Bern Switzerland

Pediatric Endocrinology and Diabetology Department of Pediatrics Switzerland; Department of Clinical Research Inselspital Bern University Hospital University of Bern Switzerland; Department of Pediatrics 2 Faculty of Medicine Charles University Prague University Hospital Motol Prague Czech Republic

Pediatric Endocrinology and Diabetology Department of Pediatrics Switzerland; Department of Clinical Research Inselspital Bern University Hospital University of Bern Switzerland; Graduate School Bern University of Bern Switzerland

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