Objective: Klinefelter syndrome is the most common chromosomal disorder in males, and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal and quantitative ultrasound data in a life-course perspective. Design: Prospective semi-longitudinal study. Methods: We included 155 subjects with 47, XXY karyotype (age range: 7 months - 55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal and testicular ultrasound assessments were performed. Results: Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/FSH ratio thereafter. The Testosterone/LH ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level. Conclusions: The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients.

Testicular dysfunction in 47, XXY boys: when it all begins. A semi-longitudinal study / Pozza, Carlotta; Sesti, Franz; Tenuta, Marta; Spaziani, Matteo; Tarantino, Chiara; Carlomagno, Francesco; Minnetti, Marianna; Pofi, Riccardo; Paparella, Roberto; Lenzi, Andrea; Radicioni, Antonio; Isidori, Andrea M; Tarani, Luigi; Gianfrilli, Daniele. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - (2023), pp. 1-14. [10.1210/clinem/dgad205]

Testicular dysfunction in 47, XXY boys: when it all begins. A semi-longitudinal study

Pozza, Carlotta
;
Sesti, Franz
Co-primo
;
Tenuta, Marta;Spaziani, Matteo;Tarantino, Chiara;Carlomagno, Francesco;Minnetti, Marianna;Pofi, Riccardo;Paparella, Roberto;Lenzi, Andrea;Radicioni, Antonio;Isidori, Andrea M;Tarani, Luigi;Gianfrilli, Daniele
Ultimo
2023

Abstract

Objective: Klinefelter syndrome is the most common chromosomal disorder in males, and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal and quantitative ultrasound data in a life-course perspective. Design: Prospective semi-longitudinal study. Methods: We included 155 subjects with 47, XXY karyotype (age range: 7 months - 55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal and testicular ultrasound assessments were performed. Results: Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/FSH ratio thereafter. The Testosterone/LH ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level. Conclusions: The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients.
2023
bilateral testicular volume; hypogonadism; klinefelter syndrome; puberty; testicular dysfunction; testicular ultrasound
01 Pubblicazione su rivista::01a Articolo in rivista
Testicular dysfunction in 47, XXY boys: when it all begins. A semi-longitudinal study / Pozza, Carlotta; Sesti, Franz; Tenuta, Marta; Spaziani, Matteo; Tarantino, Chiara; Carlomagno, Francesco; Minnetti, Marianna; Pofi, Riccardo; Paparella, Roberto; Lenzi, Andrea; Radicioni, Antonio; Isidori, Andrea M; Tarani, Luigi; Gianfrilli, Daniele. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - (2023), pp. 1-14. [10.1210/clinem/dgad205]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1679340
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