LAUSR

Abstract Background Childhood Brain Tumor Survivors (CBTS) are at increased risk of hypothalamic-pituitary (HP) dysfunction, which may be caused by radiotherapy , be a complication of the tumor itself or due to brain injury. Being overweighted or underweighted (body mass index (BMI) more than 2 SDS or lower than -2 SDS, respectively) at brain tumor diagnosis may reflect early hypothalamic dysfunction and may be a risk factor to develop HP dysfunction during follow-up. This has, to date, not been investigated. The objective of this study was to examine whether BMI at brain tumor diagnosis is associated with the development of HP dysfunction, independent of brain tumor treatment. Methods Children surviving a brain tumor, excluding craniopharyngioma or a pituitary tumor, for minimally two years, in whom BMI at diagnosis of their brain tumor had been recorded were included from a previous cohort study (n=685 of 718). Odds-ratios (OR) for developing HP dysfunction were calculated using multivariable logistic regression, including BMI at diagnosis, gender, age at follow-up, radiotherapy, histology, location of the primary tumor, hydrocephalus and state of disease. Results Of all, 10.8% (n=74) was overweighted and 5.0% (n=34) was underweighted at diagnosis. Median follow-up time was 7.1 years (5.0-9.6). Being overweighted or underweighted at diagnosis was significantly associated with the development of HP dysfunction (anterior or posterior pituitary deficiency or central precocious puberty , OR 2.43, 95% CI 1.46-4.05) and obesity at follow-up (OR 3.75, 95% CI 2.36-5.97).Development of HP dysfunction was also significantly associated with radiotherapy (OR 11.25, 95% CI 6.76-18.72) and location of primary tumor (OR 2.24, 95% CI 1.60-3.13). In children not treated with radiotherapy (n=430), underweight and overweight at brain tumor diagnosis were also both significantly associated with HP dysfunction and precocious puberty (OR 2.91, 95% CI 1.16-7.28 and 3.00 , 95% CI 1.12-8.01, respectively). In this group, other significant risk factors for HP dysfunction included location of primary tumor (OR 8.90, 95% CI 4.11-19.24), hydrocephalus (2.27, 95% CI 1.06-4.88) and state of disease at follow-up (OR 6.38, 95% CI 1.37-29.58). Conclusions Being overweighted or underweighted at brain tumor diagnosis in childhood is associated with the development of anterior pituitary deficiencies, posterior pituitary deficiencies and CPP, independently of given treatment. This suggests that in these children hypothalamic dysfunction may already be present at brain tumor diagnosis. These findings may be used for future studies on hypothalamic dysfunction in CBTS and can be used to develop recommendations on monitoring the development of pituitary disorders in CBTS.