Clinical but not histological outcomes in males With 45,X/46,XY mosaicism vary depending on reason for diagnosis

Ljubicic, M. L. et al. (2019) Clinical but not histological outcomes in males With 45,X/46,XY mosaicism vary depending on reason for diagnosis. Journal of Clinical Endocrinology and Metabolism, 104(10), pp. 4366-4381. (doi: 10.1210/jc.2018-02752) (PMID:31127831)

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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.

Item Type:Articles
Additional Information:The I-DSD Registry was supported by Medical Research Council partnership award G1100236 and was initially developed under project grants from the Seventh European Union Framework Program (201444) and the Research Unit of the European Society for Paediatric Endocrinology. Several of the authors participated in this study as part of the COST Action BM1303 DSDnet, supported by COST, under the European Union framework program Horizon 2020. M.L.L. is funded by Copenhagen University Hospital’s Research Foundation (Rigshospitalets Forskningsudvalg; R85- A3105) through a 3-year stipend.
Glasgow Author(s) Enlighten ID:Ahmed, Professor Syed Faisal and Lucas-Herald, Dr Angela
Authors: Ljubicic, M. L., Jørgensen, A., Acerini, C., Andrade, J., Balsamo, A., Bertelloni, S., Cools, M., Cuccaro, R. T., Darendeliler, F., Flück, C. E., Grinspon, R. P., Maciel-Guerra, A., Guran, T., Hannema, S. E., Lucas-Herald, A. K., Hiort, O., Holterhus, P. M., Lichiardopol, C., Looijenga, L. H.J., Ortolano, R., Riedl, S., Ahmed, S. F., and Juul, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Clinical Endocrinology and Metabolism
Publisher:Oxford University Press
ISSN (Online):1945-7197
Published Online:25 April 2019
Copyright Holders:Copyright © 2019 Endocrine Society
First Published:First published in Journal of Clinical Endocrinology and Metabolism 104(10):4366-4381
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190419The International DSD Network (I-DSD)Syed Faisal AhmedMedical Research Council (MRC)G1100236/1Med - Child Health