167 Leptin, hunger and fat 5 DISCUSSION In this national cohort of children with acute lymphoblastic leukemia, we showed that leptin SDS increased from -0.09 (±2.1) to 1.8 (±1.5) after merely five days of high dose dexamethasone. Fat mass, hunger scores, fatigue and sleep problems increased significantly as well, whereas BMI remained stable. No correlations between delta leptin and delta fat mass, hunger scores, fatigue or sleep problems were found. Our results confirm results from previous studies in ALL patients which also established an increase in leptin during glucocorticoid treatment.8,28-34 However, none of these studies adjusted the leptin values for BMI, sex or age. The current study showed that adjusted leptin values increased considerably after five days of dexamethasone. The feeling of hunger, measured with four different hunger scores, also increased significantly during these days. Under physiological circumstances, an increase in leptin is accompanied by reduced feeling of hunger.12-14 In obese patients, elevated leptin levels also do not exert their usual anorexigenic effect, which may imply leptin resistance.35 The combination of increased leptin levels and feeling of hunger in our cohort, may also suggests a state of acute leptin resistance. However, the interaction between dexamethasone and food intake is regulated through more complex processes than leptin alone.36 Still, since patients with ALL frequently receive high doses glucocorticoids for at least 1,5 year during their treatment, it is possible that the elevated leptin levels may precede certain long-term side effects in survivors, such as obesity.37-39 A study to longitudinally evaluate leptin and other appetite-regulating hormones, in combination with anthropometric measurements, feeling of hunger and caloric intake may be of value to shed more light on possible leptin resistance during treatment. Furthermore, interventions designed to mediate the risk of metabolic adverse events should begin timely, to diminish late toxicities. Even though leptin is mainly produced by adipocytes and is considered as a marker of fat accumulation,33 we did not find a correlation between the rise in leptin SDS and rise in fat mass. This may be due to the fact that bioelectrical impedance analysis tends to underestimate fat mass and is sensitive to changes in fluid balance.40 We measured an average increase of 0.5kg in fat mass in five days, which may also reflect increased fluid retention. Ideally, a dual-energy X-ray absorptiometry (DXA) scan would be used to analyze body composition,41 however, DXA use is limited in children due to logistic issues, the radiation burden and need for sedation in very young children. Besides the most appropriate measurement tool, the question arises whether adipocyte hyperplasia or hypertrophy occurs. Due to the fast increase in fat mass, the latter seems more plausible. Hypertrophic adipocytes seem to secrete less
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