ESPE2022 Free Communications Pituitary, Neuroendocrinology and Puberty (6 abstracts)
Background: Endocrine deficiencies, including impairment of the hypothalamic-pituitary-gonadal axis (HPGA), are found in the majority of survivors of medulloblastoma, due to high-dose craniospinal irradiation and gonadotoxic chemotherapy. Data regarding HPGA function in survivors of medulloblastoma is limited to small groups of patients and focusses mainly on female survivors. Furthermore, few studies investigated specific risk factors such as treatment protocol, age at diagnosis, and time elapsed from treatment.
Methods: A retrospective study comprising all patients diagnosed with medulloblastoma between 1987-2021 and followed at The Late Effects Endocrine Clinic at Sheba Medical Centre. Clinical markers of HPGA function included onset and progression of puberty, regularity of menstrual cycles, and fertility outcomes in both male and females. Biochemical parameters included levels of LH, FSH, estradiol, testosterone, and anti-Mullerian hormone. Patients still undergoing treatment, and those that had died within 2 years of diagnosis or had not completed 2 years of follow-up after completion of treatment were excluded.
Results: Sixty-two patients were included in the analysis (41 male). There was a significant (P<0.01) difference in prevalence of HPGA dysfunction between males and females. Among female patients, 16/21 (76%) showed clinical or biochemical evidence of HPGA dysfunction. Furthermore, biochemical evidence of diminished ovarian reserve was seen in all prepubertal girls (n=4). Among the male cohort, 14/41 (34%) showed clinical or biochemical evidence of HPGA dysfunction: eleven had high FSH levels suggesting primary testicular failure, and 3 had hypogonadotrophic hypogonadism (HH); twelve patients were prepubertal with age-appropriate LH and FSH levels. Two female patients achieved successful pregnancies following fertility treatment, and two male patients achieved spontaneous conception, resulting in 7 live births. Treatment by “High risk” protocol was associated with HPGA dysfunction in males (P=0.02) but not in females. There was no association between HPGA dysfunction and other endocrine deficiencies, age at diagnosis or length of follow up.
Conclusions: Damage to the pituitary-gonadal axis is common after treatment for childhood medulloblastoma. This is seen more in females, likely due to damage to the ovaries from spinal radiotherapy. In males, both primary testicular failure and HH were observed. The association between HPGA dysfunction and “High risk” treatment protocol is likely due to the higher dose of irradiation to the posterior fossa, resulting in HH. These data may assist in counselling patients and their families with regards to risk to future fertility and need for fertility preservation.
15 Sep 2022 - 17 Sep 2022