{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:02:59Z","timestamp":1788447779054,"version":"build-2803163510"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>17\u03b1-hydroxylase\/17,20-lyase deficiency (17OHD) is a rare autosomal recessive condition. Women who have the complete form of 17OHD typically have a female phenotype, with an absence of secondary sexual characteristics, primary amenorrhea, and hypertension, which is usually detected in adolescence. Generally, 46,XY patients with a partial form of 17OHD have atypical genitalia and intra-abdominal or inguinal testes. The risk of developing malignant testicular tumors or testicular adrenal rest tumors in 21-hydroxylase deficiency congenital adrenal hyperplasia is reported in 46,XY patients. In contrast, these conditions are rarely described in patients with 17OHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to investigate patients with 17OHD who exhibit testicular tumors and spontaneous pubertal development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Results<\/jats:title><jats:p>Two unrelated women with 46,XY karyotype with 17OHD who presented with unexpected spontaneous development of secondary sexual characteristics and testicular tumors were described. Pathogenic allelic variants in <jats:italic>CYP17A1<\/jats:italic> were identified in the compound heterozygous state in both patients. The variants p.Trp406Arg and p.Pro428Leu were identified in the patient with Leydig cell neoplasia plus germ cell neoplasia <jats:italic>in situ<\/jats:italic>, and the p.Arg358Gln and p.Trp406Arg variants were identified in the patient with intratubular seminoma associated with invasive classic seminoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings reinforce the risk of testicular tumor development among 46,XY patients with 17OHD and add data to the discussion of the risk\/benefit ratio of prophylactic gonadectomy in the treatment patients with 46, XY differences in sex development (DSD).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1508792","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T05:24:12Z","timestamp":1744867452000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Estrogen-secreting testicular tumors in 46,XY female patients with 17\u03b1-hydroxylase\/17,20-lyase deficiency: two unusual case reports and a review of the literature"],"prefix":"10.3389","volume":"16","author":[{"given":"Julio Americo Pereira","family":"Batatinha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirian Yumie","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Loch","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ant\u00f4nio Diniz","family":"Faria J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Helena Palma","family":"Sircili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Tibor","family":"Denes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jimena Chafloque","family":"Mesia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura da Silva","family":"Salvanini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Maria Frade","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena Marino","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice Bilharinho","family":"Mendonca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorahia","family":"Domenice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1515\/jpem-2014-0522","article-title":"Gonadal malignancy risk and prophylactic gonadectomy in disorders of sexual development","volume":"28","author":"Abac\u0131","year":"2015","journal-title":"Pediatr Endocrinol Metab. 1o Jan."},{"key":"B2","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1097\/PAP.0000000000000302","article-title":"Testicular tumors: a contemporary update on morphologic, immunohistochemical and molecular features","volume":"28","author":"Al-Obaidy","year":"2021","journal-title":"Adv. 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