Grinspon Romina P, Castro Sebastián, Brunello Franco G, Sansó Gabriela, Ropelato María Gabriela, Rey Rodolfo A
Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, C1425EFD Buenos Aires, Argentina.
Departamento de Química Biológica, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN) CONICET, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
J Endocr Soc. 2021 Sep 2;5(11):bvab145. doi: 10.1210/jendso/bvab145. eCollection 2021 Nov 1.
The diagnosis of male central (or hypogonadotropic) hypogonadism, typically based on low luteinizing hormone (LH) and testosterone levels, is challenging during childhood since both hormones are physiologically low from the sixth month until the onset of puberty. Conversely, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), which show higher circulating levels during infancy and childhood, are not used as biomarkers for the condition. We report the case of a 7-year-old boy with a history of bilateral cryptorchidism who showed repeatedly low FSH and AMH serum levels during prepuberty. Unfortunately, the diagnosis could not be ascertained until he presented with delayed puberty at the age of 14 years. A gonadotropin-releasing hormone (GnRH) test showed impaired LH and FSH response. By then, his growth and bone mineralization were partially impaired. Gene panel sequencing identified a variant in exon 15 of , affecting the tyrosine kinase domain of the receptor, involved in GnRH neuron migration and olfactory bulb morphogenesis. Testosterone replacement was started, which resulted in the development of secondary sexual characteristics and partial improvement of bone mineral density. This case illustrates the difficulty in making the diagnosis of central hypogonadism in boys during childhood based on classical criteria, and how serum FSH and AMH assessment may be helpful if it is suspected before the age of puberty, and confirm it using next-generation sequencing. The possibility of making an early diagnosis of central hypogonadism may be useful for a timely start of hormone replacement therapy, and to avoid delays that could affect growth and bone health as well as psychosocial adjustment.
男性中枢性（或低促性腺激素性）性腺功能减退的诊断通常基于促黄体生成素（LH）和睾酮水平低下，但在儿童期具有挑战性，因为从出生后第六个月到青春期开始，这两种激素的生理水平都较低。相反，在婴儿期和儿童期循环水平较高的促卵泡生成素（FSH）和抗苗勒管激素（AMH），并未用作该病症的生物标志物。我们报告了一名7岁男孩的病例，他有双侧隐睾病史，青春期前血清FSH和AMH水平反复偏低。不幸的是，直到他14岁出现青春期延迟，才得以确诊。促性腺激素释放激素（GnRH）试验显示LH和FSH反应受损。那时，他的生长和骨矿化已部分受损。基因panel测序在[具体基因名称]的第15外显子中发现了一个变体，该变体影响受体的酪氨酸激酶结构域，参与GnRH神经元迁移和嗅球形态发生。开始进行睾酮替代治疗，这导致了第二性征的发育和骨密度的部分改善。该病例说明了基于经典标准在儿童期诊断男孩中枢性性腺功能减退的困难，以及如果在青春期前怀疑该病并使用下一代测序进行确诊，血清FSH和AMH评估可能会有帮助。早期诊断中枢性性腺功能减退的可能性可能有助于及时开始激素替代治疗，并避免可能影响生长、骨骼健康以及心理社会适应的延迟。
