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

R. H. Lustig, S. R. Rose, G. A. Burghen, P. Velasquez-Mieyer, D. C. Broome, K. Smith, H. Li, M. M. Hudson, R. L. Heideman, L. E. Kun

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131 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)162-168
Number of pages7
JournalJournal of Pediatrics
Volume135
Issue number2 I
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Lustig, R. H., Rose, S. R., Burghen, G. A., Velasquez-Mieyer, P., Broome, D. C., Smith, K., Li, H., Hudson, M. M., Heideman, R. L., & Kun, L. E. (1999). Hypothalamic obesity caused by cranial insult in children: Altered glucose and insulin dynamics and reversal by a somatostatin agonist. Journal of Pediatrics, 135(2 I), 162-168. https://doi.org/10.1016/S0022-3476(99)70017-X