A rare case of growth hormone deficiency in a boy with Klinefelter syndrome. Diagnostic and therapeutic challenges: A case report

Introduction: Klinefelter syndrome (KS) is the most common sex chromosome disorder in males, typically associated with tall stature in adolescence, hypergonadotropic hypogonadism, and cognitive or behavioral difficulties. Growth hormone deficiency (GHD) is rare in KS and may mask or alter expected phenotypic features. Patient Presentation: We report a boy of 7 years and 8 months presenting with persistent short stature, selective eating habits, and mild neurodevelopmental delays. Initial evaluation revealed subtle dysmorphic features, cryptorchidism, and delayed bone age. Karyotype analysis confirmed KS (47,XXY). Two consecutive GH stimulation tests demonstrated isolated GHD (peak GH 6.92 ng/mL), and pituitary MRI was normal. The patient was initiated on recombinant human GH therapy, first daily, and later long-acting GH was administered, resulting in sustained catch-up growth over 12 months of follow-up without any adverse effects. Height improved from below the 3rd percentile to the 10th percentile, with favorable changes in growth velocity and IGF-1 levels. Conclusion: This report highlights the importance of considering karyotyping not only in girls but also in boys with persistent, unexplained short stature, as coexisting disorders such as KS and isolated GHD may obscure typical clinical features. Without routine cytogenetic testing, numerical abnormalities of sex chromosomes can remain undiagnosed, delaying appropriate care. Timely diagnosis and multidisciplinary management are essential to optimize growth and long-term outcomes.