Foetal virilisation caused by overproduction of non-aromatisable 11-oxygenated C19 steroids in maternal adrenal tumour

Keisuke Nagasaki, Kaoru Takase, Chikahiko Numakura, Keiko Homma, Tomonobu Hasegawa, Maki Fukami

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

It is widely believed that adrenal tumours and ovarian luteomas in pregnant women cause virilisation of female foetuses through overproduction of testosterone and/or androstenedione. However, this notion raises a fundamental question as to how these classic androgens pass through the placenta without being converted by aromatase into oestrogens. Here, we report a case of maternal adrenal tumour, in which overproduction of 11-oxygenated C19 steroids (11ox C19s), newly characterised non-aromatisable androgens in humans, caused foetal virilisation. The female proband presented with severely virilised external genitalia at birth. The mother exhibited hirsutism, hyperglycaemia and hypertension and was diagnosed as having adrenal tumour. The mother was subjected to comprehensive steroid measurement. Serum levels of 11ox C19s were markedly elevated. In contrast, testosterone and androstenedione levels remained within the normal range, and levels of most other steroids in the conventional and backdoor androgenic pathways were normal or only mildly elevated. After tumour removal, levels of 11ox C19s were markedly reduced. These results provide the first evidence that 11ox C19s can be synthesised in adrenal adenomas and, due to their non-aromatisable nature, can pass through the placental barrier to cause foetal virilisation. These findings highlight a unique pathogenic property of these newly specified androgens in humans.

Original languageEnglish
Pages (from-to)2609-2612
Number of pages4
JournalHuman Reproduction
Volume35
Issue number11
DOIs
Publication statusPublished - 2020 Nov 1

Keywords

  • 11-oxygenated androgens
  • 46,XX disorders of sex development
  • adrenal tumour
  • foetal virilisation
  • non-aromatisable androgens

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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