CASE REPORT article
Front. Endocrinol.
Sec. Pediatric Endocrinology
This article is part of the Research TopicUpdate on Differences of Sex Differentiation (DSD)View all 3 articles
Case Report: Challenges of an extremely delayed diagnosis of Classic Congenital Adrenal Hyperplasia in a completely virilized 46,XX patient
Provisionally accepted
- 1Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy, Universita degli Studi di Milano, Milan, Italy
- 2Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
- 3Department of Radiology, Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
- 4Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola, Bologna, Italy
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Classic Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency is typically diagnosed in early life. We report a 46,XX completely virilized 46,XX patient who was diagnosed with classic CAH at the age of 73 years. He was under follow-up for prostate hyperplasia and referred after the finding of giant bilateral adrenal myelolipomas. He presented with hormonal values initially interpreted as suggestive of hypogonadotropic hypogonadism, prompting further biochemical and genetic analysis. Next-generation sequencing identified heterozygous variants in X-linked genes, uncovering a 46,XX difference of sex development (DSD). Then, CYP21A2 molecular analysis revealed compound heterozygosity for two pathogenic variants (p.I173N, p.R357W), confirming simple virilizing CAH. The patient's reticent attitude contributed to the diagnostic delay. However, this unique case reveals the challenges generated by the paraurethral glands hyperplasia - mimicking a prostate due to prolonged untreated hyperandrogenism, as well as the repeated failure to recognize Müllerian remnants on imaging and the critical issues related to diagnostic communication.
Keywords: congenital adrenal hyperplasia, diagnostic delay, 46,XX disorder of sexdevelopment, Adrenal myelolipoma, Skene gland hyperplasia, case report
Received: 16 Oct 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Casiraghi, Campi, Federici, Cernigliaro, Menabò and Persani. 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: Irene Campi
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