Hypothalamic obesity caused by cranial insult in children: Altered glucoseand insulin dynamics and reversal by a somatostatin agonist

Objective: Hypothalamic obesity is a rare sequela of cranial insult, for wh ich pathogenesis and treatment remain obscure. In rodents ventromedial hypo thalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin r esistance. Reduction of insulin secretion in humans may attenuate weight ga in. Methods: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simul taneous insulin levels before and after treatment with octreotide for 6 mon ths. Results: In comparison with a 6-month pre-study observation period, patient s exhibited weight loss (+6.0 +/- 0.7 kg vs -4.8 +/- 1.8 kg; P = .04) and d ecrease in body mass index (+2.1 +/- 0.3 kg/m(2) vs -2.0 +/- 0.7 kg/m(2); P =.0001). Recall calorie count decreased during the 6 months of treatment ( P =.015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patie nts initially and in 2 of 7 at study end, whereas insulin response was decr eased (281 +/- 47 mu U/mL vs 114 +/- 35 mu U/mL; P = .04). Percent weight c hange correlated with changes in insulin response (r = 0.72, P = .012) and changes in plasma leptin r = 0.76, P = .0004). Conclusions: Patients with hypothalamic obesity demonstrate excessive insul in secretion. Octreotide administration promoted weight loss, which correla ted with reduction in insulin secretion on OGTT and with reduction in lepti n levels. Pre-study biochemical glucose tolerance improved in several patie nts while they were receiving octreotide. These results suggest that normal ization of insulin secretion may be an effective therapeutic strategy in th is syndrome.