ESPE Abstracts

Background: It is well known that endocrine comorbidities occur frequently in children with cancer, especially in those with a brain tumor. In those children, increased intracranial pressure or hydrocephalus may lead to central precocious puberty. Furthermore, chemotherapy, especially alkylating agents, increases the risk for gonadal insufficiency. In this case series we describe 3 young girls with a brain tumor, who develop premature gonadotrophic activation, but without estrogen production as result of simultaneous premature ovarian insufficiency.

Cases: Girl A was known with a supratentorial embryonal tumor with midline shift at age 1 year. She was treated with neurosurgery followed by chemotherapy. At relapse, second neurosurgery, proton radiotherapy involving 0.05 Gy to pituitary and metronomic chemotherapy were given with a cyclophosphamide equivalent dose (CED) of 45,6 g/m2. At age 3.7 years during relapse therapy she presented with impaired longitudinal growth, no thelarche and no bone age advancement (-0.1 years). Biochemical evaluation showed LH 3.8 IU/L, FSH 34 IU/L, estradiol <40 pmol/L and AMH <0.03 µg/L. Girl B was known with increased intracranial pressure at age 2, due to a large supratentorial primitive neuro-ectodermal tumor with mass effect. After surgery she was treated with chemotherapy (CED of 75,8 g/m2) and focal proton radiotherapy. At age 7.8 years she presented with normal longitudinal growth, no thelarche and delayed bone age (-0.8 years). Biochemical evaluation revealed LH of 1.7 IU/L, FSH 34 IU/L, estradiol <40 pmol/L, AMH <0.03 µg/L. Girl C had been diagnosed with an atypical teratoid rhabdoid tumor at age 10 months leading to hydrocephalus. After surgery she received alkylating chemotherapy (CED of 53,2 g/m2). At age 5.8 years, she showed impaired longitudinal growth, no thelarche and delayed bone age (-0.7 years). Biochemically, a LH of 7.6 IU/L, FSH of 64 IU/L, estradiol <40 pmol/L and AMH <0.03 µg/L were found. None of the girls had been treated with GnRH analogues. In all, during follow-up of at least 7 months, LH and FSH remained increased with no signs of thelarche or measurable estradiol.

Discussion: This case series illustrates that young girls with a history of brain tumor have an increased risk to develop premature gonadotrophic activation with simultaneous gonadal insufficiency. Although these findings do not require clinical intervention, the early diagnosis of gonadal insufficiency enables timely counselling of the children and their parents in terms of pubertal induction and future fertility.