Introduction
Hypothalamic obesity (HO) in children may have severe consequences. Lifestyle interventions are often insufficient and no effective drug treatment is available yet. Amphetamines are known for their stimulant effect on resting energy expenditure (REE) and suppressing appetite. Earlier studies have shown positive effect of amphetamines on weight loss in children with acquired HO. We present our experiences with dextroamphetamine treatment in the largest cohort of children with HO.

Methods
A retrospective cohort evaluation was performed of patients with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired, genetic, or congenital HO. Anthropometrics, REE, (hyperphagic) behavior, energy level, and side effects were assessed at start and during treatment.

Results
Nineteen patients with a mean age of 12.3 years ± 4.0 were treated. ΔBMI SDS could be evaluated in 17 patients, mean treatment duration was 26.5 months ± 15.0. Fourteen patients (n=10 with acquired HO, n=3 with genetic HO, n=1 with congenital HO) responded by weight loss or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after mean months 22.4 ± 10.5). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, mean months 29.7 ± 22.6). In the 11 responders of whom REE was measured before and during treatment, mean REE increased with +164 kcal/day (+8.9% of predicted). Thirteen patients (68.4%) reported improvement of hyperphagia, energy level, and/or behavior. Two patients developed hypertension during treatment, which resulted in either adjusting of dosage or stopping of treatment. Twelve children continued treatment at last moment of follow-up.

Conclusion

In addition to supportive lifestyle interventions, dextroamphetamine treatment may lower or stabilize BMI and improve REE in children with acquired, genetic, or congenital HO. Moreover, it has the potential to reduce hyperphagia and improve energy level. In acquired HO, these effects seem to be more pronounced.