The objective of this project is to examine the trajectories of height, weight, and body mass index (BMI) in individuals in the CBTN with pathological diagnoses of craniopharyngioma. Our overarching research goal is to develop a risk prediction model for the development of hypothalamic obesity related to craniopharyngioma that will inform the design and testing of individualized prevention strategies. Individuals who have undergone treatment for craniopharyngiomas in childhood experience lasting metabolic sequelae, most notably hypothalamic obesity. Hypothalamic obesity and related comorbidities including diabetes mellitus, fatty liver disease, and psychiatric disorders, adversely both impact health and quality of life. Dr. McCormack is a pediatric endocrinologist who cares for patients with hypothalamic obesity in clinic, is the PI of a clinical trial for a novel hormonal therapy for hypothalamic obesity supported by a Doris Duke Clinical Scientist Development Award. Consistent with other interventional studies, initial findings from this trial highlight that hypothalamic obesity, once entrenched, is very challenging to treat. It would be far preferable to prevent hypothalamic obesity than to treat it. Critical barriers to the development of strategies to prevent hypothalamic obesity include the lack of rigorous, prospectively collected natural history data about the development of this condition, and a limited understanding of associated risk factors.
What are the goals of this project?
We propose to examine the trajectory of height, weight, and body mass index (BMI) in individuals in the CBTN with pathological diagnoses of craniopharyngioma. We will measure the following outcomes: height, weight, and BMI Z-scores (relative to age- and sex-based CDC 2000 reference values) at diagnosis, and over the available follow up intervals. We will examine the prevalence of obesity (BMI greater than or equal to 95%ile for age and sex) at each of the follow up time points, stratified by sex, age, and obesity status at diagnosis. We will describe the distribution of change in height, weight, and BMI Z-scores over each of these time intervals.
What is the impact of this project?
These results will be informative to clinicians who care for children with craniopharyngioma. In addition, these initial data will form the basis for a future collaborative funding proposal to perform a more detailed hypothalamic obesity risk assessment including curated clinical factors (e.g., tumor characteristics and treatment, pituitary hormone replacement, use of weight loss medications); there are pediatric endocrinologists with a clinical focus in hypothalamic obesity at many of the CBTN sites who have expressed interest in this work.
Why the CBTN request is important to this project?
For this project, we can leverage the rich genetic data available in the CBTN to examine how background risk for obesity (polygenic risk score, based on genetic variants known to impact BMI) influences BMI trajectory in children with craniopharyngioma.
The Children's Brain Tumor Network contributed to this project by providing access to the CBTN clinical data and the Pediatric Brain Tumor Atlas.
Childhood craniopharyngiomas are rare tumors usually found near the pituitary gland (a pea-sized organ at the bottom of the brain that controls other glands) and the hypothalamus (a small cone-shaped organ connected to the pituitary gland by nerves).Craniopharyngiomas are usually part soli