258 Chapter 8 Hunger feeling We hypothesized that hydrocortisone addition would diminish dexamethasone-induced feeling of hunger. In contrast, we found that hydrocortisone increased fasting and average hunger scores when compared with placebo. This is in line with a recent randomized, doubleblind study with cross-over design in 16 healthy adult volunteers, which showed an increase in fasting hunger after overnight administration of stress doses hydrocortisone, compared to saline.61 This study showed decreased perfusion in emotion regions of the brain, as well as in reward and executive control regions, supporting the role of hydrocortisone in regulating (increasing) appetite. A study in mice investigated the effect of corticosterone, the natural occurring glucocorticoid in rodents, add-on therapy during dexamethasone treatment to prevent dexamethasone-induced metabolic side effects.62 Conversely, corticosterone aggravated dexamethasone-induced hyperinsulinemia, hyperglycemia, and glucose intolerance.62 Hence, future studies on the treatment of dexamethasone-induced hunger and metabolic side effects should consider other options than hydrocortisone addition , e.g. physical activity interventions, to increase energy expenditure. Health related quality of life All the dexamethasone-induced problems described in this thesis have impact on health related quality of life (HRQoL) during ALL treatment.3,63-65 We did not find a difference between hydrocortisone and placebo in improving HRQoL of the child, as reported by parents. Unfortunately, we did not measure HRQoL during a course without hydrocortisone or placebo addition (i.e. a ‘dexamethasone only’ course), therefore we were not able to ascertain whether a placebo-effect played a role in improving HRQoL. We measured parent-reported HRQoL with the general pediatric quality of life questionnaire, which does not account for treatment-specific problems during dexamethasone treatment. Another questionnaire, the Quality of life Evaluation in patients receiving Steroids (QuESt) tool, examines changes attributable to corticosteroids.66 This tool is a self-report questionnaire for children ≥8 years and even though further validity and reliability testing is still required, it is a promising tool to measure treatment-specific HRQoL in children receiving dexamethasone. Placebo-effect Based on the results of our previous study,5 we considered the design of our current study (randomized, double blind, placebo-controlled, with cross-over), as most optimal to measure differences between hydrocortisone and placebo. However, we did not anticipate that a third, treatment as usual arm, would have been beneficial to irrefutably prove a placebo-effect, which eventually occurred in our cohort. Still, our findings in children with clinically relevant dexamethasone-induced neurobehavioral problems suggest a strong placebo-effect which influences both patient and family. The mechanisms of placebo effects are not extensively
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