TY - JOUR
T1 - Hypothalamic obesity caused by cranial insult in children
T2 - Altered glucose and insulin dynamics and reversal by a somatostatin agonist
AU - Lustig, R. H.
AU - Rose, S. R.
AU - Burghen, G. A.
AU - Velasquez-Mieyer, P.
AU - Broome, D. C.
AU - Smith, K.
AU - Li, H.
AU - Hudson, M. M.
AU - Heideman, R. L.
AU - Kun, L. E.
N1 - Funding Information:
Supported in part by GCRC M01-RR00211, University of Tennessee, Memphis.
PY - 1999
Y1 - 1999
N2 - Objective: Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain. Methods: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simultaneous insulin levels before and after treatment with octreotide for 6 months. Results: In comparison with a 6-month pre-study observation period, patients exhibited weight loss (+6.0 ± 0.7 kg vs -4.8 ± 1.8 kg; P = .04) and decrease in body mass index (+2.1 ± 0.3 kg/m2 vs -2.0 ± 0.7 kg/m2; P = .0001). Recall calorie count decreased during the 6 months of treatment (P = .015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patients initially and in 2 of 7 at study end, whereas insulin response was decreased (281 ± 47 μU/mL vs 114 ± 35 μU/mL; P = .04). Percent weight change 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 insulin secretion. Octreotide administration promoted weight loss, which correlated with reduction in insulin secretion on OGTT and with reduction in leptin levels. Pre-study biochemical glucose tolerance improved in several patients while they were receiving octreotide. These results suggest that normalization of insulin secretion may be an effective therapeutic strategy in this syndrome.
AB - Objective: Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain. Methods: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simultaneous insulin levels before and after treatment with octreotide for 6 months. Results: In comparison with a 6-month pre-study observation period, patients exhibited weight loss (+6.0 ± 0.7 kg vs -4.8 ± 1.8 kg; P = .04) and decrease in body mass index (+2.1 ± 0.3 kg/m2 vs -2.0 ± 0.7 kg/m2; P = .0001). Recall calorie count decreased during the 6 months of treatment (P = .015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patients initially and in 2 of 7 at study end, whereas insulin response was decreased (281 ± 47 μU/mL vs 114 ± 35 μU/mL; P = .04). Percent weight change 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 insulin secretion. Octreotide administration promoted weight loss, which correlated with reduction in insulin secretion on OGTT and with reduction in leptin levels. Pre-study biochemical glucose tolerance improved in several patients while they were receiving octreotide. These results suggest that normalization of insulin secretion may be an effective therapeutic strategy in this syndrome.
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U2 - 10.1016/S0022-3476(99)70017-X
DO - 10.1016/S0022-3476(99)70017-X
M3 - Article
C2 - 10431109
AN - SCOPUS:0033497369
SN - 0022-3476
VL - 135
SP - 162
EP - 168
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 2 I
ER -