Marie Lindhardt Ljubicic1,2, Anne Jørgensen1,2, Carlo Acerini3, Juliana Andrade4, Antonio Balsamo5, Silvano Bertelloni6, Martine Cools7, Rieko Tadokoro Cuccaro3, Feyza Darendeliler8, Christa E Flück9, Romina P Grinspon10, Andrea Maciel-Guerra4, Tulay Guran11, Sabine E Hannema12,13, Angela K Lucas-Herald14, Olaf Hiort15, Paul Martin Holterhus16, Corina Lichiardopol17, Leendert H J Looijenga18, Rita Ortolano5, Stefan Riedl19,20, S Faisal Ahmed14, Anders Juul1,2. 1. Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2. International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. Department of Paediatrics, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. 4. Faculty of Medical Sciences, Department of Medical Genetics, State University of Campinas, São Paulo, Brazil. 5. Department of Medical and Surgical Sciences, Pediatric Endocrinology Unit, Centre for Rare Endocrine Conditions, Policlinico S. Orsola-Malpighi University Hospital, Bologna, Italy. 6. Dipartimento Materno-Infantile Azienda Ospedaliero, Universitaria Pisana, Pisa, Italy. 7. Department of Paediatric Endocrinology, University Hospital Ghent, and Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium. 8. Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 9. Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, and Department of BioMedical Research, Bern University Children's Hospital, University of Bern, Bern, Switzerland. 10. Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), National Scientific and Technical Research Council (CONICET) - Fundación de Endocrinología Infantil (FEI) - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 11. Department of Paediatric Endocrinology and Diabetes, School of Medicine, Marmara University, Istanbul, Turkey. 12. Department of Paediatrics, Leiden University Medical Centre, Leiden, Netherlands. 13. Department of Paediatric Endocrinology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, Netherlands. 14. Developmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom. 15. Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, University of Luebeck, Luebeck, Germany. 16. Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Christian-Albrechts-University of Kiel, Kiel, Germany. 17. Department of Endocrinology, University of Medicine and Pharmacy Craiova, University Emergency Hospital, Craiova, Romania. 18. Laboratory for Experimental Patho-Oncology, Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Cancer Institute, Rotterdam, and Princess Maxima Center for Paediatric Oncology, Utrecht, Netherlands. 19. Pediatric Endocrinology, St. Anna Children´s Hospital, Medical University of Vienna, Vienna, Austria. 20. Department of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria.
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.
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.
Authors: A Nordenström; S F Ahmed; E van den Akker; J Blair; M Bonomi; C Brachet; L H A Broersen; H L Claahsen-van der Grinten; A B Dessens; A Gawlik; C H Gravholt; A Juul; C Krausz; T Raivio; A Smyth; P Touraine; D Vitali; O M Dekkers Journal: Eur J Endocrinol Date: 2022-04-21 Impact factor: 6.558
Authors: Marie Lindhardt Ljubicic; Anne Jørgensen; Lise Aksglaede; John Erik Nielsen; Jakob Albrethsen; Anders Juul; Trine Holm Johannsen Journal: Front Endocrinol (Lausanne) Date: 2021-08-10 Impact factor: 5.555
Authors: Bauke Debo; Marlies Van Loocke; Katya De Groote; Els De Leenheer; Martine Cools Journal: Int J Environ Res Public Health Date: 2021-01-21 Impact factor: 3.390