ESPE Abstracts

Introduction: Paediatric intracranial germ cell tumours (IC-GCTs) are often accompanied by precocious or delayed puberty, either at diagnosis caused by tumour itself or during follow-up as consequence of treatments.

Aims: We examined the prevalence of pubertal dysfunctions in a cohort of paediatric patients with IC-GCTs at diagnosis and during follow-up.

Methods: We recorded clinical, radiological, histopathological, and hormonal data. Pubertal dysfunctions were diagnosed clinically and confirmed biochemically and classified as: 1) pseudo-precocious puberty (PPP) (gonadotrophin-independent); 2) central precocious puberty (CPP) (gonadotrophin-dependent); 3) hypogonadotrophic hypogonadism (HH).

Results: Twenty-five of 52 patients (56% males) with IC-GCT treated at Royal Marsden Hospital between January 1996 and December 2019 displayed a pubertal disorder (median follow-up 75.7 months, range 0.5-249.9 months). 68% had germinomas, 16% teratomas, 16% mixed GCT. IC-GCTs were suprasellar (64%), pineal (24%) or bifocal (12%). Patients underwent biopsy (72%), surgery (24%), chemotherapy (80%) and radiotherapy (100%). Low gonadotrophin levels were found in 20 cases (10 females, 10 males), along with clinical evidence of either arrested or delayed puberty, at a mean age of 17.5 years for males and 15.1 for females. This condition was already present before tumour diagnosis in 2 patients. One female patient with suprasellar germinoma manifested secondary amenorrhoea, probably due to hypothalamic dysfunction and concomitant polycystic ovarian syndrome; combined oral hormonal replacement therapy was started with benefit. PPP was evident in 3 patients at diagnosis: in one case it reverted spontaneously accordingly with tumour cure and concomitant reduction of HCG levels; one patient subsequently developed CPP and received therapy with an agonist analogue of gonadotropin-releasing hormone for 5 years; one more subject was initially treated with bicalutamide and anastrozole for 14 months and then with triptorelin after he developed CPP. Finally, one subject manifested CPP 3.7 months after the completion of oncologic therapies and received treatment with triptorelin. No cases of hypergonadotrophic hypogonadism due to chemotherapy-related gonadal toxicity were reported in our cohort.

Conclusion: Patients with IC-GCTs are at risk of pubertal dysfunctions, especially suprasellar germinomas. Associated pubertal disorders can be heterogeneous, from HCG-driven PPP to CPP or HH, and may change over time, therefore specialist follow-up is required.