45,X/46,XY mosaicism is a rare karyotype and patients present with varying phenotypes from Turner females to males. Genital phenotype, gonadal function and histology, and growth are all affected to varying degrees by the karyotype. Information on these long-term outcomes is scarce and larger multicenter studies are needed. Therefore, in collaboration with 17 centers, we performed a study including 59 post-pubertal males that had reached adult height. Centers were identified and invited using the I-DSD Registry and DSDnet network. We found that long-term outcomes such as External Masculinization Score, gonadal function in terms of spontaneous pubertal onset and the need for testosterone substitution, and the frequency of genital surgeries, namely hypospadia repairs and orchidopexies, were significantly affected by whether patients were diagnosed at birth due to genital anomalies or later in life due to reasons such as growth retardation, delayed puberty, lack of virilization in adulthood or infertility. Thus, patients diagnosed at birth had more affected genital phenotypes and poorer gonadal function than patients diagnosed later in life. However, most patients, regardless of reason for referral, entered puberty spontaneously indicative of some Leydig cell function. Moreover, 12% of gonadectomized patients had gonadal neoplasia in situ, highlighting the need for thorough follow-up including ultrasound scans and possibly biopsies in this group of patients. Additionally, growth appeared to be affected in all individuals and many patients were experimentally treated with human growth hormone. This retrospective, non-randomized study failed to find an effect of the treatment on height standard deviation scores. High incidences of renal and cardiac congenital malformations, all reflective of the Turner cell line, were seen regardless of reason for referral. Overall, male patients with 45,X/46,XY mosaicism are affected very differently by their karyotype which is also reflected in the long-term outcomes. Thus, individual management and care is still highly recommended.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology