Clinical and genetic characteristics of boys with congenital hypogonadotropic hypogonadism: a single-center experience.

CONTEXT: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by deficient secretion or action of gonadotropin-releasing hormone. While its characteristics are well-documented in adults, data from prepubertal patients remain limited. OBJECTIVE: To investigate the clinical, hormonal, and genetic characteristics of CHH in male patients aged < 18 years and assess age-related changes in testicular function. DESIGN: Retrospective analysis of data from patients with CHH. SETTING: Tertiary pediatric endocrine referral center. PATIENTS: Overall, 121 male patients with CHH, aged 0-18 years, were included. MAIN OUTCOME MEASURES: Hormonal profiles, genetic variants, and testicular function indicators across different age groups. RESULTS: All patients had micropenis, and 41.3% had cryptorchidism. The > 14-year group had fewer combined cases of both conditions but more isolated micropenis (p = 0.001). Inhibin B, luteinizing hormone, follicle-stimulating hormone, and post-human chorionic gonadotropin testosterone levels were significantly higher in the ≤ 3-year group (p < 0.05). Leydig and Sertoli cell function declined with age. Inhibin B < 33.895 pg/mL and anti-Müllerian hormone (AMH) < 17.545 ng/mL predicted Leydig cell dysfunction with sensitivities of 78.5% and 85.7% and specificities of 82.3% and 73.8%, respectively. Pathogenic variants were identified in 84.6% of cases, with fibroblast growth factor receptor 1, chromodomain helicase DNA-binding protein 7, and prokineticin receptor 2 being the most frequently impacted. CONCLUSIONS: CHH should be suspected in boys with micropenis and cryptorchidism. AMH and inhibin B are key markers for early detection of Leydig cell dysfunction, with genetic testing being essential for diagnosis.