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

JØRGENSEN, ANNE; BALSAMO, ANTONIO; CUCCARO, RIEKO TADOKORO; GRINSPON, ROMINA P; HANNEMA, SABINE E; HOLTERHUS, PAUL MARTIN; ORTOLANO, RITA; JUUL, ANDERS; LJUBICIC, MARIE LINDHARDT; ANDRADE, JULIANA; COOLS, MARTINE; FLÜCK, CHRISTA E; GURAN, TULAY; HIORT, OLAF; LOOIJENGA, LEENDERT H J; AHMED, S FAISAL; ACERINI, CARLO; BERTELLONI, SILVANO; DARENDELILER, FEYZA; MACIEL-GUERRA, ANDREA; LUCAS-HERALD, ANGELA K; LICHIARDOPOL, CORINA; RIEDL, STEFAN

JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

ENDOCRINE SOC

Año: 2019

0021-972X

AbstractCONTEXT: 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 due to either genital abnormalities at birth or non-genital reasons later in life.DESIGN: A retrospective, multicenter study.SETTING: 16 tertiary centers Patients or other participants: 63 males older than 13 years with 45,X/46,XY mosaicism.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): Health outcomes such as genital phenotype, gonadal function, growth, comorbidities, fertility, and gonadal histology including risk of neoplasia.RESULTS: 35 patients were in the genital group, 28 in the non-genital. 80% of all patients experienced spontaneous pubertal onset, significantly more in the non-genital 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). 27% of patients received recombinant human growth hormone. 44 patients had gonadal histology evaluated. Germ cells were detected in 42%. Neoplasia in situ was found in five patients. 25% had focal spermatogenesis, another 25.0% had arrested spermatogenesis. 14 out of 17 (82%) with semen analyses were azoospermic; three had motile sperm.CONCLUSION: Patients diagnosed due to genital abnormalities have poorer health outcomes than those diagnosed due to non-genital 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 half of patients have germ cells present histologically and up to a quarter have focal spermatogenesis, providing hope for fertility treatment options.