Production of 11-ketotestosterone in childhood adrenal tumors with virilization or peripheral precocious puberty: Dominant expression of 11β-hydroxysteroid dehydrogenase type 2.

11-Oxygenated androgens are important components of the androgen pool in humans. Among them, 11-ketotestosterone (11-KT), a potent 11-oxygenated androgen primarily produced in peripheral tissues outside the adrenal glands, has garnered research interest for its crucial role in several diseases associated with androgen excess. This study aimed to investigate the biosynthesis of 11-oxygenated androgens, particularly 11-KT, in childhood adrenocortical tumors (ACTs) presenting with symptoms of androgen excess. This retrospective study included three patients, aged 6 months, 2 years, and 12 years, presenting with symptoms of androgen excess due to childhood ACTs. Multiple androgen metabolites were simultaneously measured using pre- or postoperative serum samples, tumors, and tumor-attached adrenal glands obtained from patients using liquid chromatography-tandem mass spectrometry. The expression of genes involved in androgen synthesis was analyzed using DNA microarray analysis. Serum androgen levels were elevated prior to tumor removal and decreased to within or near reference ranges after tumor removal. Notably, serum 11-KT levels were markedly elevated compared to reference ranges, similar to testosterone (T), and 11-KT was abundant within the tumor tissues. Unique gene expression patterns were observed across the three cases of childhood ACTs, including marked HSD11B2, attenuated HSD11B1, and elevated HSD17B3 expression levels, which are involved in 11-KT biosynthesis. This study confirms the direct production of 11-KT in childhood ACTs; gene expression patterns observed in these cases favored 11-KT biosynthesis, providing insight into their potential role in androgen excess.