Hypothalamic-Pituitary Injury after Childhood Cancer and Central Nervous System Tumors: Risk Factors, Course and Consequences

Abstract

The survival rate of childhood cancer is currently estimated at 80%. In up to 60% of childhood cancer survivors, endocrine disorders, such as hypothalamic-pituitary (HP) dysfunction, are reported. To improve screening strategies and allow early treatment of endocrine disorders, we evaluated endocrine data of numerous survivors. We determined the prevalence, latency time, risk factors and associated clinical consequences of HP disorders following childhood cancer. Novel findings include that survivors exposed to low-dose cranial radiotherapy and those with tumor- or treatment related central nervous system injuries, are also at risk for HP disorders. In addition, we observed a higher prevalence of central hypothyroidism than currently reported. Additionally, we were able to describe associations between endocrine disorders and adverse physical (i.e., obesity and impaired bone health), psychological (i.e., impaired quality of life and psychosexual dysfunction) and neurocognitive health outcomes (i.e., lower intelligence and memory scores), which have not been reported as such before. Finally, we focused on the hypothalamus, a region in the brain responsible for homeostasis of the body. Hypothalamic obesity (HO) is a severe form of obesity resulting from damage to the hypothalamus. We propose a new treatment algorithm for HO that combines six domains to serve as targets for treatment and demonstrate that children with HO may benefit from extensive and repetitive dietary counseling, together with intensive coaching. This thesis has increased the knowledge on the development and clinical consequences of HP disorders in childhood cancer survivors with the potential to optimize long-term health outcomes in this vulnerable population.