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Horm Metab Res 2013; 45(02): 86-91
DOI: 10.1055/s-0032-1331751
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© Georg Thieme Verlag KG Stuttgart · New York

Androgen Synthesis in Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

C. Kamrath
1   Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany
2   Steroid Research and Mass Spectromity Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany
,
M. F. Hartmann
2   Steroid Research and Mass Spectromity Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany
,
S. A. Wudy
1   Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany
2   Steroid Research and Mass Spectromity Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany
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Further Information

Publication History

received 20 August 2012

accepted 03 December 2012

Publication Date:
23 January 2013 (online)

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Abstract

A hallmark of severe congenital adrenal hyperplasia due to 21-hydroxylase deficiency is pre- and postnatal virilization. The most characteristic biochemical abnormality is the elevation of 17α-hydroxyprogesterone, which is metabolized to the most potent androgen receptor agonist dihydrotestosterone. 17α-Hydroxyprogesterone can be metabolized to dihydrotestosterone via 4-androstenedione through the classical Δ4-pathway or via 17α-hydroxypregnenolone and dehydroepiandrosterone through the classical Δ5-pathway, as well as through an alternative route, called the ‘backdoor pathway’, that bypasses dehydroepiandrosterone, 4-androstenedione, and testosterone as intermediates. This review article will summarize recent advances in the understanding of the activities of androgen synthesis pathways in patients with 21-hydroxylase deficiency obtained by urinary steroid metabolomics based on gas chromatography-mass spectrometry. Compared with healthy controls, the relative activities of the backdoor and Δ4-pathways increase in patients with congenital adrenal hyperplasia during neonatal age and infancy, whereas the activity of the Δ5-pathway remains unchanged. Thereafter, the activity of the Δ5-pathway dominates, whereas a decreasing 5α-reductase activity leads to a diminished role of the backdoor pathway for androgenic steroid production. Beside the backdoor pathway, the Δ4-pathway seems to be responsible for increased androgen generation in patients with 21-hydroxylase deficiency before the onset of adrenarche, whereas the Δ5-pathway might contribute to the increased androgen formation in those patients only after the onset of adrenarche.

Key words

backdoor pathway - 17α-hydroxyallopregnanolone - virilization
 

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