Clinical but Not Histological Outcomes in Males With 45,X/46,XY Mosaicism Vary Depending on Reason for Diagnosis

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 10; pp. 4366 - 4381
• Main Authors: Ljubicic, Marie Lindhardt, Jørgensen, Anne, Acerini, Carlo, Andrade, Juliana, Balsamo, Antonio, Bertelloni, Silvano, Cools, Martine, Cuccaro, Rieko Tadokoro, Darendeliler, Feyza, Flück, Christa E, Grinspon, Romina P, Maciel-Guerra, Andrea, Guran, Tulay, Hannema, Sabine E, Lucas-Herald, Angela K, Hiort, Olaf, Holterhus, Paul Martin, Lichiardopol, Corina, Looijenga, Leendert H J, Ortolano, Rita, Riedl, Stefan, Ahmed, S Faisal, Juul, Anders
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.10.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: Adolescent; Adult; Biopsy, Needle; Cohort Studies; Comorbidity; Fertility; Genitalia, Male - abnormalities; Germ cells; Gonadal Dysgenesis, 46,XY - epidemiology; Gonadal Dysgenesis, 46,XY - genetics; Gonads - pathology; Health aspects; Histology; Humans; Immunohistochemistry; Karyotyping; Male; Males; Mosaicism; Patients; Phenotype; Phenotypes; Quality of Life; Registries; Retrospective Studies; Semen Analysis - methods; Sex Characteristics; Sex Chromosome Aberrations; Spermatogenesis; Spermatogenesis - genetics; Turner Syndrome - epidemiology; Turner Syndrome - genetics; Young Adult; Denmark; Netherlands
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-02752

Abstract Context Larger studies on outcomes in males with 45,X/46,XY mosaicism are rare. Objective To compare health outcomes in males with 45,X/46,XY diagnosed as a result of either genital abnormalities at birth or nongenital reasons later in life. Design A retrospective, multicenter study. Setting Sixteen tertiary centers. Patients or Other Participants Sixty-three males older than 13 years with 45,X/46,XY mosaicism. Main Outcome Measures Health outcomes, such as genital phenotype, gonadal function, growth, comorbidities, fertility, and gonadal histology, including risk of neoplasia. Results Thirty-five patients were in the genital group and 28 in the nongenital. Eighty percent of all patients experienced spontaneous pubertal onset, significantly more in the nongenital group (P = 0.023). Patients were significantly shorter in the genital group with median adult heights of 156.7 cm and 164.5 cm, respectively (P = 0.016). Twenty-seven percent of patients received recombinant human GH. Forty-four patients had gonadal histology evaluated. Germ cells were detected in 42%. Neoplasia in situ was found in five patients. Twenty-five percent had focal spermatogenesis, and another 25.0% had arrested spermatogenesis. Fourteen out of 17 (82%) with semen analyses were azoospermic; three had motile sperm. Conclusion Patients diagnosed as a result of genital abnormalities have poorer health outcomes than those diagnosed as a result of nongenital reasons. Most patients, however, have relatively good endocrine gonadal function, but most are also short statured. Patients have a risk of gonadal neoplasia, and most are azoospermic, but almost one-half of patients has germ cells present histologically and up to one-quarter has focal spermatogenesis, providing hope for fertility treatment options. Clinical health outcomes in males with 45,X/46,XY mosaicism vary depending on reason for diagnosis. However, pre-neoplasia and ongoing spermatogenesis are both relatively common in all patients.