Prevalence and Risk Factors of Hypothalamic-Pituitary Dysfunction in Infant and Toddler Brain Tumor Survivors

Background: Childhood brain tumor survivors (CBTS) are at risk for hypothalamic-pituitary (HP) dysfunction, mainly caused by radiation exposure or tumor involvement of the HP-region. The risk for HP dysfunction (HPD) may vary between different age groups due to maturation of the brain and differences in oncologic treatment protocols. The aim of this study was to determine the prevalence and risk factors of HPD in infant (IBTS) and toddler brain tumor survivors (TBTS) compared to older childhood brain tumor survivors (OCBTS). Patients and Methods: A retrospective analysis in a nationwide cohort of CBTS was performed. Prevalence and risk factors for HPD were compared between IBTS (aged 0-1 years at diagnosis), TBTS (aged 1-3 years at diagnosis) and OCBTS (aged >3-18 years at diagnosis). Results: In 718 included CBTS, with a median follow-up time of 7.9 years, overall no differences in percentage of HPD were found between the three age groups. Treatment with radiotherapy (RT) (OR 15.41; 95%CI 8.33 to 28.48), suprasellar tumor location (OR 46.62; 95%CI 19.64 to 110.66) and younger age (OR 1.09; 95%CI 1.02 to 1.15) were associated with HP dysfunction. Because IBTS were significantly less often treated with RT, subanalyses were performed for all CBTS not treated with radiation (n=459). In non-irradiated CBTS, IBTS and TBTS were significantly more frequently diagnosed with TSH-, ACTH- and ADH deficiency, compared to ECBTS. IBTS and TBTS showed significantly more weight gain (p<0.0001) and smaller height SDS (p=0.001) during follow-up. Conclusion: Infant and toddler brain tumor survivors seem to be more vulnerable to develop HP dysfunction than when compared to older children. These results emphasize the importance of special infant and toddlers brain tumor treatment protocols and endocrine surveillance in children treated for a brain tumor at young age.