Introduction: Primary brain tumors are the second most common childhood malignancies, with an increasing survival rate over the years. Late effects on puberty and fertility alter survivors quality of life.
Methods: We included 204 patients diagnosed with a primary brain tumor before 18 years, followed in pediatric endocrinology at the University Hospital Necker-Enfants Malades in Paris between January 2010 and December 2015. Data was retrieved from medical records to analyze pubertal timing and the effects of the tumor and its treatments.
Results: The total cohort of 204 patients was studied for early puberty (EP) and gonadal toxicity (GT), and 187 patients (≥13 years (girls) or ≥14 years (boys) were analyzed for hypogonadotropic hypogonadism (HH). Among these 187 patients, only 53 (28.3%) had spontaneous puberty at the same time as their peers, with no significant sex ratio. Of 32 patients with a suprasellar glioma, 19 had EP, with a positive predictive value (PPV): 59.4%, P = 0.001. Risk for EP was lower when radiotherapy dose was high, >40 Gy (n = 2/6, PPV: 33.3%, P = 0.02), and it increased with doses <40 Gy or when the child had not been treated by radiotherapy (n = 17/26, PPV: 65.4%). There was a trend for higher PPV for EP in younger children (diagnosis <5 years), but this was not statistically significant. Thirty out of 43 patients with medulloblastoma treated by high-risk chemotherapy developed GT on average 7.6±3.7 years after the end of treatment (PPV=69.7%, P = 0.001); patients who were not treated by chemotherapy (n = 17) did not develop GT (PPV: 0%, P = 0.001). Children diagnosed <5 years of age had a higher risk of GT after chemotherapy (n = 14/16, PPV=87.5%, P = 0.001). Craniopharyngioma was associated with an increased risk of HH regardless of treatment (n = 39/56, PPV 69.6%, P = 0.001). Growth hormone deficiency (GHD) increased the risk of HH to 79.2%, whereas in absence of GHD, the PPV was 0% (P = 0.001).
Conclusions: The type of tumor, its location and treatment are the main factors that drive the type of pituitary-gonadal axis dysfunction. Craniopharyngioma is associated with a risk of HH, glioma with EP and medulloblastoma (through high-risk chemotherapy) with GT. Awareness of potential secondary effects and their mechanism is essential to assess pubertal status of these patients, to guide parental information, and to decide of an adequate and timely hormone replacement therapy.
22 Sep 2021 - 26 Sep 2021