{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:49:19Z","timestamp":1787899759795,"version":"build-2784847793"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    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,\n                    <jats:italic>CYP21A2<\/jats:italic>\n                    molecular analysis revealed compound heterozygosity for two pathogenic variants (p.I173N, p.R357W), confirming simple virilizing CAH. The patient\u2019s 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 M\u00fcllerian remnants on imaging and the critical issues related to diagnostic communication.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2025.1726368","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:15:55Z","timestamp":1766034955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Challenges of an extremely delayed diagnosis of classic congenital adrenal hyperplasia in a completely virilized 46,XX patient"],"prefix":"10.3389","volume":"16","author":[{"given":"Alice","family":"Casiraghi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Campi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Federici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Cernigliaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soara","family":"Menab\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Persani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1210\/endrev\/bnab016","article-title":"Congenital adrenal hyperplasia \u2013 Current insights in pathophysiology, diagnostics, and management","volume":"43","author":"Claahsen-van der Grinten","year":"2022","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An Endocrine Society clinical practice guideline","volume":"103","author":"Speiser","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2021.101599","article-title":"Genetics of congenital central hypogonadism","volume":"36","author":"Grinspon","year":"2022","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/humu.23351","article-title":"CYP21A2 mutation update: Comprehensive analysis of databases and published genetic variants","volume":"39","author":"Simonetti","year":"2018","journal-title":"Hum Mutat"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1590\/s0004-27302009000600004","article-title":"Search of prostatic tissue in 46,XX congenital adrenal hyperplasia","volume":"53","author":"Paulino","year":"2009","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01994736","article-title":"Beitr\u00e4ge zur Kenntnis des weiblichen Scheinzwittertums","volume":"181","author":"Fibiger","year":"1905","journal-title":"Virchows Arch Pathol Anat Physiol Klin Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1015973","article-title":"Challenges in the treatment of late- identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country","volume":"13","author":"Utari","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-3476(52)80306-3","article-title":"The diagnosis of the adrenogenital syndrome and its treatment with cortisone","volume":"41","author":"Wilkins","year":"1952","journal-title":"J Pediatr"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1951.03670050005002","article-title":"Advisability of surgical reversal of sex in female pseudohermaphroditism","volume":"146","author":"Hinman","year":"1951","journal-title":"JAMA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jpurol.2024.09.030","article-title":"Life with Congenital Adrenal Hyperplasia. Experiences and preferences of women with CAH and parents about disclosure of childhood surgery","volume":"21","author":"Johnston","year":"2025","journal-title":"J Pediatr Urol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1136\/ADC.2006.098319","article-title":"Consensus statement on management of intersex disorders","volume":"91","author":"Hughes","year":"2006","journal-title":"Arch Dis Child"},{"key":"B12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1530\/EJE-12-0454","article-title":"Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia","volume":"167","author":"Bachelot","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-58-2-378","article-title":"Progesterone modulation of pulsatile luteinizing hormone secretion in normal women","volume":"58","author":"Soules","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/MED.0000000000000308","article-title":"Growth and development in children with classic congenital adrenal hyperplasia","volume":"24","author":"Bonfig","year":"2017","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0010-8","article-title":"Caring for individuals with a difference of sex development (DSD): A consensus statement","volume":"14","author":"Cools","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/21642850.2022.2102018","article-title":"'It was Supposed to be a Secret': a study of disclosure and stigma as experienced by adults with differences of sex development","volume":"10","author":"Medi\u00e5","year":"2022","journal-title":"Health Psychol Behav Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1056\/NEJMoa2404655","article-title":"Phase 3 trial of crinecerfont in pediatric congenital adrenal hyperplasia","volume":"391","author":"Sarafoglou","year":"2024","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404656","article-title":"Phase 3 trial of crinecerfont in adult congenital adrenal hyperplasia","volume":"391","author":"Auchus","year":"2024","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00547","article-title":"Glucocorticoid activity of adrenal steroid precursors in untreated patients with congenital adrenal hyperplasia","volume":"104","author":"Engels","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2957","article-title":"Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency","volume":"99","author":"Falhammar","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00281","article-title":"A patient (46,XX) with congenital adrenal hyperplasia and prostate cancer: A case report","volume":"1","author":"Wesselius","year":"2017","journal-title":"J Endocr Soc"},{"key":"B22","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1093\/ajcp\/106.5.660","article-title":"Female pseudohermaphroditism due to congenital adrenal hyperplasia complicated by adenocarcinoma of the prostate and clear cell carcinoma of the endometrium","volume":"106","author":"Winters","year":"1996","journal-title":"Am J Clin Pathol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1007\/s00345-021-03907-y","article-title":"Prostatic metaplasia of the vagina in transmasculine individuals","volume":"40","author":"Xu","year":"2022","journal-title":"World J Urol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1726368\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:15:56Z","timestamp":1766034956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1726368\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":23,"alternative-id":["10.3389\/fendo.2025.1726368"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1726368","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"article-number":"1726368"}}