ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Adrenal Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1658362
This article is part of the Research TopicThe Systemic and Metabolic effects of 17-Beta EstradiolView all 3 articles
Bilateral Breast Nodules as an Unusual Manifestation of 17α-Hydroxylase/17,20-Lyase Deficiency
Provisionally accepted
- Shenzhen Nanshan People's Hospital, Shenzhen, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: 17α-hydroxylase/17,20-lyase deficiency (17-OHD) typically presents with sexual infantilism, hypertension, and hypokalemia. However, phenotypic variability, particularly breast development, may obscure diagnosis. This study aims to characterize an atypical presentation of 17-OHD with preserved breast development and breast nodules, and to evaluate clinical and hormonal features associated with breast development through a systematic literature review. Methods: A 38-year-old woman with bilateral breast nodules and ductal ectasia was diagnosed with 17-OHD, confirmed by CYP17A1 variants. A literature review of 17-OHD cases with near-complete breast development (Tanner stage 4–5) was conducted to analyze clinical, hormonal, and genotypic features. Results: The patient exhibited classic signs of 17-OHD including hypertension, hypokalemia, adrenal hyperplasia, and hypogonadism, but also presented with atypical bilateral breast nodules and mammary duct ectasia. Hormone therapy resulted in clinical improvement and regression of the breast findings. Literature analysis of 43 patients with breast development showed that patients with 46,XX were diagnosed later than 46,XY (29.5 ± 11.5 vs. 19.8 ± 6.9 years, P = 0.0095). Estradiol was more often subnormal in 46,XX, while both groups showed progesterone excess and androgen deficiency. Pubic hair development differed by karyotype (P = 0.027), which was more advanced in the 46,XY group. Genetic data revealed that breast development was associated with non-null CYP17A1 variants, and most variants clustered in exons 5–8, with exon 8 as a hotspot. Conclusion: This case broadens the phenotypic spectrum of 17-OHD, highlighting that preserved breast development and benign breast lesions may delay diagnosis. Literature review suggests partial loss-of-function variants contribute to this phenotype. Greater awareness is essential to prevent misdiagnosis and unnecessary interventions.
Keywords: 17α-hydroxylase/17,20-lyase deficiency, Breast nodules, Mammary duct ectasia, CYP17A1, breast development
Received: 02 Jul 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Zhang, Huang, Li, Gui, Fan and YANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: JING YANG, yangjing9803@hotmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.