Hypothalamic-pituitary dysfunction in children with suprasellar tumors: improving the outcome

Abstract

The main aim of this thesis is to obtain more insight in the risk factors and to evaluate new treatments for hypothalamic-pituitary (HP) dysfunction in children with a suprasellar brain tumor. Improving knowledge on the presence and consequences of HP dysfunction in children with a (suprasellar) brain tumor hopefully improves their outcome and quality of life and may reduce health care costs in the long run.

In part I (HP dysfunction in childhood craniopharyngioma), we focus on identifying risk factors of the treatment for cCP in relation to HP outcome. In part II (The clinical domains of HP dysfunction), we focus on the assessment of HP dysfunction, and on the diagnostics and new treatment options for signs and symptoms within each separate clinical domain (psychosocial disorders, hyperphagia, sleep disturbances, decreased energy expenditure, hyperinsulinemia/insulin resistance, and pituitary dysfunction). In the last part, part III (HP dysfunction in other childhood brain tumor survivors), we aim to describe HP dysfunction in survivors of other childhood brain tumors, excluding craniopharyngioma.

Part Ι. HP dysfunction in childhood craniopharyngioma In chapter 2, we discuss key aspects of the clinical presentation and outcome of cCP, including risk factors, and current available therapeutic agents for hypothalamic dysfunction. Chapter 3 presents a nationwide retrospective review of survivors of cCP diagnosed in the period 2004 - 2021, evaluating the effect of shifting the treatment strategy of cCP on HP outcome.

Part ΙΙ. Signs and symptoms of HP dysfunction assessed per clinical domain In chapter 4, we propose diagnostic criteria for HP dysfunction and a score for the presence of hypothalamic syndrome. Moreover, we evaluated the new score, in two cohorts of cCP and in a cohort of low-grade glioma. In chapter 5, we review the possibility of deep brain stimulation (DBS) as a treatment option for neurobehavioral dysfunction in patients with hypothalamic dysfunction and hypothalamic obesity. Chapter 6 reports on a multicenter retrospective cohort study evaluating dextroamphetamine treatment in children with hypothalamic obesity. In chapter 7, we provide an overview of the etiology of sleep disturbances in children with suprasellar tumors. In addition, we propose a new flowchart to help clinicians diagnose sleep problems in children after treatment for a (supra)sellar brain tumor. Chapter 8 presents a retrospective study of children with suprasellar tumors in whom resting energy consumption was measured. We evaluated the clinical utility of such measurements. Chapter 9 describes a case series of children with acquired hypothalamic obesity who were treated with a GLP-1 receptor agonist, with the aim of improving BMI. Chapter 10 focuses on the safety of GH replacement in cCP. This chapter includes a systematic review and a cohort study. Chapter 11 describes the prevalence and associations with tumor growth of elevated IGF-1 concentrations in a nationwide cohort of LGG in children.

Part III. HP dysfunction in survivors of other childhood brain tumors Chapter 12 reports the on prevalence and risk factors of significant weight gain, overweight and obesity, and their associations with HP dysfunction in a nationwide cohort of CBTS, excluding craniopharyngioma.