Long-term quality of life and hypothalamic dysfunction after craniopharyngioma

After diagnosis and management of childhood-onset craniopharyngioma, patients frequently develop a rapid weight gain starting in the first 6-12 months after diagnosis and leading to morbid hypothalamic obesity due to disease- and/or treatment-associated hypothalamic lesions.

A scoping review was performed after search of the MEDLINE/PubMed, Embase, and Web of Science databases for initial identification of articles. The search terms craniopharyngioma, hypothalamic obesity, and quality of life were used.

Hypothalamic obesity should be diagnosed and treated in the context of hypothalamic syndrome. Hypothalamic nuclei are the key-regulators of our body homeostasis. Hypothalamic syndrome includes endocrine deficiencies of hypothalamic-pituitary axes, disruption of circadian rhythm, disturbed hunger-satiety and thirst feelings, temperature dysregulation, and neurocognitive, sleep and psychosocial behavioral problems. Consequently, patients with hypothalamic syndrome develop hypothalamic obesity, chronic fatigue, increased daytime sleepiness and mood disorders resulting in isolation, school drop-out and inability to participate in daily life. Long-term follow-up is frequently impaired by increased risk for metabolic syndrome, cardiovascular health problems, severe impairments of health-related quality of life, and premature mortality. Treatment of hypothalamic syndrome is challenging. Hypothalamic syndrome is not a ,one-size-fits-all- disease, which may not require a ,one-size-fits-all- management. Recently, an algorithm for personalized, risk-specific treatment of hypothalamic syndrome after CP has been published. Dextro-amphetamines and other central stimulating agents (modafinil, methylphenidate) may cause weight loss, especially in children with hyperphagia or decreased resting-energy expenditure. Reports on the use of glucagon-like peptide-1 receptor (GLP-1R) agonists for acquired hypothalamic obesity have been contradictory, with successful reports but also series with limited results. Bariatric surgery is effective. However, non-reversible procedures are controversial due to ethical and legal considerations in minors.

Hypothalamus-sparing treatment strategies and further research on novel therapeutic agents for hypothalamic syndrome are warranted.