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

Marie Lindhardt Ljubicic; Anne Jørgensen; Carlo Acerini; Juliana Andrade; Antonio Balsamo; Silvano Bertelloni; Martine Cools; Rieko Tadokoro Cuccaro; Feyza Darendeliler; Christa E Flück; Romina P Grinspon; Andrea Maciel-Guerra; Tulay Guran; Sabine E Hannema; Angela K Lucas-Herald; Olaf Hiort; Paul Martin Holterhus; Corina Lichiardopol; Leendert H J Looijenga; Rita Ortolano; Stefan Riedl; S Faisal Ahmed; Anders Juul

doi:10.1210/jc.2018-02752

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

Marie Lindhardt Ljubicic, Anne Jørgensen, Carlo Acerini, Juliana Andrade, Antonio Balsamo, Silvano Bertelloni, Martine Cools, Rieko Tadokoro Cuccaro, Feyza Darendeliler, Christa E Flück, Romina P Grinspon, Andrea Maciel-Guerra, Tulay Guran, Sabine E Hannema, Angela K Lucas-Herald, Olaf Hiort, Paul Martin Holterhus, Corina Lichiardopol, Leendert H J Looijenga, Rita OrtolanoStefan Riedl, S Faisal Ahmed, Anders Juul

Institut for Klinisk Medicin

10 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	The Journal of clinical endocrinology and metabolism
Vol/bind	104
Udgave nummer	10
Sider (fra-til)	4366-4381
ISSN	0021-972X
DOI	https://doi.org/10.1210/jc.2018-02752
Status	Udgivet - 1 okt. 2019

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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., ... Juul, A. (2019). Clinical but Not Histological Outcomes in Males With 45,X/46,XY Mosaicism Vary Depending on Reason for Diagnosis. The Journal of clinical endocrinology and metabolism, 104(10), 4366-4381. https://doi.org/10.1210/jc.2018-02752

Ljubicic, ML, Jørgensen, A, Acerini, C, Andrade, J, Balsamo, A, Bertelloni, S, Cools, M, Cuccaro, RT, Darendeliler, F, Flück, CE, Grinspon, RP, Maciel-Guerra, A, Guran, T, Hannema, SE, Lucas-Herald, AK, Hiort, O, Holterhus, PM, Lichiardopol, C, Looijenga, LHJ, Ortolano, R, Riedl, S, Ahmed, SF & Juul, A 2019, 'Clinical but Not Histological Outcomes in Males With 45,X/46,XY Mosaicism Vary Depending on Reason for Diagnosis', The Journal of clinical endocrinology and metabolism, bind 104, nr. 10, s. 4366-4381. https://doi.org/10.1210/jc.2018-02752

@article{ed2a1f7ea7304f3882b1054fd1ece0ac,

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

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.",

author = "Ljubicic, {Marie Lindhardt} and Anne J{\o}rgensen and Carlo Acerini and Juliana Andrade and Antonio Balsamo and Silvano Bertelloni and Martine Cools and Cuccaro, {Rieko Tadokoro} and Feyza Darendeliler and Fl{\"u}ck, {Christa E} and Grinspon, {Romina P} and Andrea Maciel-Guerra and Tulay Guran and Hannema, {Sabine E} and Lucas-Herald, {Angela K} and Olaf Hiort and Holterhus, {Paul Martin} and Corina Lichiardopol and Looijenga, {Leendert H J} and Rita Ortolano and Stefan Riedl and Ahmed, {S Faisal} and Anders Juul",

note = "Copyright {\textcopyright} 2019 Endocrine Society.",

year = "2019",

month = oct,

day = "1",

doi = "10.1210/jc.2018-02752",

language = "English",

volume = "104",

pages = "4366--4381",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

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TY - JOUR

T1 - Clinical but Not Histological Outcomes in Males With 45,X/46,XY Mosaicism Vary Depending on Reason for Diagnosis

AU - Ljubicic, Marie Lindhardt

AU - Jørgensen, Anne

AU - Acerini, Carlo

AU - Andrade, Juliana

AU - Balsamo, Antonio

AU - Bertelloni, Silvano

AU - Cools, Martine

AU - Cuccaro, Rieko Tadokoro

AU - Darendeliler, Feyza

AU - Flück, Christa E

AU - Grinspon, Romina P

AU - Maciel-Guerra, Andrea

AU - Guran, Tulay

AU - Hannema, Sabine E

AU - Lucas-Herald, Angela K

AU - Hiort, Olaf

AU - Holterhus, Paul Martin

AU - Lichiardopol, Corina

AU - Looijenga, Leendert H J

AU - Ortolano, Rita

AU - Riedl, Stefan

AU - Ahmed, S Faisal

AU - Juul, Anders

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

U2 - 10.1210/jc.2018-02752

DO - 10.1210/jc.2018-02752

M3 - Journal article

C2 - 31127831

SN - 0021-972X

VL - 104

SP - 4366

EP - 4381

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 10

ER -

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

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