Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist.
Level 4 - case-series / case-control
Uncontrolled single-arm before-and-after trial with a pre-study observation baseline
PubMed 10431109 · doi:10.1016/s0022-3476(99)70017-x
What was done
Eight children who developed intractable obesity after treatment for leukemia or brain tumors were treated with octreotide for 6 months. Participants underwent oral glucose tolerance testing (OGTT) with simultaneous insulin measurements before and after treatment. Outcomes, including body weight, body mass index (BMI), recall caloric intake, and metabolic parameters, were compared against a 6-month pre-study observation period.
What was found
Compared with the 6-month pre-study baseline, patients had significant weight loss (+6.0 ± 0.7 kg pre-study vs -4.8 ± 1.8 kg on octreotide; P = .04) and BMI reduction (+2.1 ± 0.3 kg/m² vs -2.0 ± 0.7 kg/m²; P = .0001). Calorie intake by recall decreased (P = .015). Insulin response on OGTT decreased from 281 ± 47 µU/mL to 114 ± 35 µU/mL (P = .04), and biochemical glucose intolerance resolved in 3 of 5 affected patients (present in 5 of 8 at baseline vs 2 of 7 at study completion). Percent weight change correlated with reductions in insulin response (r = 0.72, P = .012) and plasma leptin (r = 0.76, P = .0004).
Why it matters
This study provides evidence that excessive insulin secretion contributes to hypothalamic obesity after pediatric cranial insults and demonstrates that suppressing insulin secretion with somatostatin agonists may reverse rapid weight gain.
Limits
The study is limited by an extremely small sample size (n = 8), an open-label single-arm design without a concurrent control group, incomplete follow-up testing for one subject at study end, reliance on recall for caloric intake, and lack of long-term safety and efficacy data beyond 6 months.
Cited by
- supports In pediatric patients with hypothalamic obesity, administering octreotide suppressed insulin release, resulting in weight loss, spontaneous physical activity, and quality-of-life improvements that correlated directly with the degree of insulin suppression.