ESPE Abstracts

Background: Klinefelter syndrome (KS) is a genetic disorder consisting in a variable number of additional X chromosomes in a male individual. KS patients can rarely develop peripheral precocious puberty (PPP) caused by extragonadal germ cell cancers (eGCCs) producing hormones with androgenic activity. KS patients are at higher risk for eGCC when compared to the healthy population

Case report: We report the case of M., a 8 years old boy with a genetic diagnosis of KS made at age 2 for delayed speech. M. was born at 40 weeks of gestational age, with no complications during delivery. At age 8 and 6 months he underwent his regular endocrinological assessment to evaluate growth. The auxological parameters were height 140 cm (+0.85 SDS), weight 28.7 kg (+0.67 SDS) and growth velocity 9.2 cm/year (+3.6 SDS). Physical examination showed Tanner stage G2 with testicular volume 5 ml bilaterally. No axillary or pubic hair was found. Basal levels of gonadotropins were suppressed (FSH < 0.3 mIU/Ml, LH < 0.3 mIU/ml) with high level of total testosterone (14 nmol/L). This finding was confirmed by GnRH test. No alteration of adrenal androgens was detected. Germ cell tumor markers assessment showed a high level of hCG (10.4 mUI/ml, nv < 2 mUI/ml) and slightly increased levels of alpha-fetoprotein (12.1 ng/mL, nv < 12 ng/mL). Hand X-ray evaluated according to Greulich & Pyle showed an advanced bone age (10 years + 7 months) compared to a chronological age (8 years +7 months). CT of thorax and abdomen was performed and revealed a triangular shaped formation (24 mm) with inhomogeneous enhancement after contrast medium administration in the thymic region. We decided to start therapy with bicalutamide 25mg daily in order to hamper puberty progression. At age 9 years + 2 months, he underwent total thymectomy. Histological analysis confirmed the diagnosis of mediastinal germ cell tumour of mixed type (according to WHO 2021). After surgery normal germ cell markers were observed. Two months after surgery we stopped bicalutamide therapy and started triptorelin 3.75 mg i.m every 28 days for central precocious puberty diagnosis (FSH 5.0 mIU/mL, LH 3.6 mIU/mL, TT 5nmol/L).

Conclusion: KS patients have an increased risk of several malignancies, especially male breast cancer and extragonadal germ cell tumors, primarily localized in the mediastinum. We suggest to closely monitor patients with KS and provide therm and their parents with adequate information on the risk of malignancy.