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Licensed Unlicensed Requires Authentication Published by De Gruyter March 14, 2015

Hypothalamic obesity in children: pathophysiology to clinical management

  • Belma Haliloglu and Abdullah Bereket EMAIL logo

Abstract

Hypothalamic obesity (HyOb) is a complex neuroendocrine disorder caused by damage to the hypothalamus, which results in disruption of energy regulation. The key hypothalamic areas of energy regulation are the ARC (arcuate nucleus), the VMH (ventromedial hypothalamus), the PVN (paraventriculer nuclei) and the LHA (lateral hypothalamic area). These pathways can be disrupted mechanically by hypothalamic tumors, neurosurgery, inflammatory disorders, radiotherapy and trauma or functionally as such seen in genetic diseases. Rapid weight gain and severe obesity are the most striking features of HyOb and caused by hyperphagia, reduced basal metabolic rate (BMR) and decreased physical activity. HyOb is usually unresponsive to diet and exercise. Although, GLP-1 and its anologs seem to be a new agent, there is still no curative treatment. Thus, prevention is of prime importance and the clinicians should be alert and vigilant in patients at risk for development of HyOb.


Corresponding author: Abdullah Bereket, Professor of Pediatric Endocrinology, Department of Pediatrics, Marmara University Hospital, Fevzi Çakmak Mahallesi Mimar Sinan Caddesi No: 41 Ustkaynarca-Pendik-Istanbul, Turkey, Phone: +90 216 411 64 18, Fax: +90 216 411 60 49, E-mail:

References

1. Anand BK, Brobeck JR. Localization of a “feeding center” in the hypothalamus of the rat. Proc Soc Exp Biol Med 1951;77:323–4.10.3181/00379727-77-18766Search in Google Scholar PubMed

2. Brobeck JR. Mechanism of the development of obesity in animals with hypothalamic lesions. Physiol Rev 1946;26:541–59.10.1152/physrev.1946.26.4.541Search in Google Scholar PubMed

3. King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav 2006;87:221–44.10.1016/j.physbeh.2005.10.007Search in Google Scholar PubMed

4. Williams KW, Elmquist JK. Lighting up the hypothalamus: coordinated control of feeding behavior. Nat Neurosci 2011;14:277–8.10.1038/nn0311-277Search in Google Scholar PubMed PubMed Central

5. Myers Jr MG, Olson DP. Central nervous system control of metabolism. Nature 2012;491:357–63.10.1038/nature11705Search in Google Scholar PubMed

6. Bereket A, Kiess W, Lustig RH, Muller HL, Goldstone AP, et al. Hypothalamic obesity in children. Obes Rev 2012;13:780–98.10.1111/j.1467-789X.2012.01004.xSearch in Google Scholar PubMed

7. Hochberg I, Hochberg Z. Expanding the definition of hypothalamic obesity. Obes Rev 2010;11:709–21.10.1111/j.1467-789X.2010.00727.xSearch in Google Scholar PubMed

8. Woods SC, Seeley RJ, Porte Jr D, Schwartz MW. Signals that regulate food intake and energy homeostasis. Science 1998;280:1378–83.10.1126/science.280.5368.1378Search in Google Scholar PubMed

9. Wardlaw SL. Hypothalamic proopiomelanocortin processing and the regulation of energy balance. Eur J Pharmacol 2011;6660:213–19.10.1016/j.ejphar.2010.10.107Search in Google Scholar PubMed PubMed Central

10. Pritchard LE, White A. Neuropeptide processing and its impact on melanocortin pathways. Endocrinology 2007;148:4201–07.10.1210/en.2006-1686Search in Google Scholar PubMed

11. Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003;37:649–61.10.1016/S0896-6273(03)00063-1Search in Google Scholar

12. Benoit SC, Clegg DJ, Seeley RJ, Woods SC. Insulin and leptin as adiposity signals. Recent Prog Horm Res 2004;59:267–85.10.1210/rp.59.1.267Search in Google Scholar PubMed

13. Peruzzo B, Pastor FE, Blazquez JL, Schobitz K, Pelaez B, et al. A second look at the barriers of the medial basal hypothalamus. Exp Brain Res 2000;132:10–26.10.1007/s002219900289Search in Google Scholar PubMed

14. Ibrahim N, Bosch MA, Smart JL, Qiu J, Rubinstein M, et al. Hypothalamic proopiomelanocortin neurons are glucose responsive and express KATP channels. Endocrinology 2003;144:1331–40.10.1210/en.2002-221033Search in Google Scholar PubMed

15. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, et al. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 2002;51:271–5.10.2337/diabetes.51.2.271Search in Google Scholar PubMed

16. Cota D, Proulx K, Woods SC, Seeley RJ. The role of leucine in regulating food intake. Science 2006;313:1236–8.10.1126/science.313.5791.1236bSearch in Google Scholar PubMed

17. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 2003;6:736–42.10.1038/nn1073Search in Google Scholar PubMed PubMed Central

18. Maekawa F, Fujiwara K, Toriya M, Maejima Y, Nishio T, et al. Brain-derived neurotrophic factor in VMH as the causal factor for and therapeutic tool to treat visceral adiposity and hyperleptinemia in type 2 diabetic Goto-Kakizaki rats. Front Synaptic Neurosci 2013;5:7.10.3389/fnsyn.2013.00007Search in Google Scholar PubMed PubMed Central

19. Swanson LW, Sanchez-Watts G, Watts AG. Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone. Neurosci Lett 2005;387:80–4.10.1016/j.neulet.2005.06.066Search in Google Scholar PubMed

20. Lustig RH. Hypothalamic obesity: causes, consequences, treatment. Pediatr Endocrinol Rev 2008;6:220–7.Search in Google Scholar

21. Vollenweider L, Tappy L, Owlya R, Jequier E, Nicod P, et al. Insulin induced sympathetic activation and vasodilatation in skeletal muscle. Effects of insulin resistance in lean subjects. Diabetes 1995;44:641–5.10.2337/diab.44.6.641Search in Google Scholar PubMed

22. Collins S, Kuhn CM, Petro AE, Swick AG, Chrunyk BA, et al. Role of leptin in fat regulation. Nature 2000;404:652–60.Search in Google Scholar

23. Lustig RH. Autonomic dysfunction of the β-cell and the pathogenesis of obesity. Rev Endocr Metab Dis 2003;4:23–32.10.1023/A:1021819318484Search in Google Scholar

24. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998;395:763–70.10.1038/27376Search in Google Scholar

25. Guran T, Turan S, Bereket A, Akcay T, Unluguzel G, et al. The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children. Eur J Pediatr 2009;168:1043–8.10.1007/s00431-008-0876-xSearch in Google Scholar

26. Farooqi S. Obesity genes–its all about parents. Cell Metab 2009;9:487–8.10.1016/j.cmet.2009.05.008Search in Google Scholar

27. Maffei M, Fei H, Lee GH, Dani C, Leroy P, et al. Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci USA 1995;92:6957–60.10.1073/pnas.92.15.6957Search in Google Scholar

28. Hustvedt BE, Lovo A. Correlation between hyperinsulinemia and hyperphagia in rats with ventromedial hypothalamic lesions. Acta Physiol Scand 1972;84:29–33.10.1111/j.1748-1716.1972.tb05152.xSearch in Google Scholar

29. Rohner F, Dufour AC, Karakash C, Le Marchand Y, Ruf KB, et al. Immediate effect of lesion of the ventromedial hypothalamic area upon glucose induced insulin secretion in anaesthetized rats. Diabetologia 1977;13:239–42.10.1007/BF01219706Search in Google Scholar

30. Slaunwhite WR 3rd, Goldman JK, Bernardis LL. Sequential changes in glucose metabolism by adipose tissue and liver of rats after destruction of the ventromedial hypothalamic nuclei: effect of three dietary regimens. Metabolism 1972;21:619–31.10.1016/0026-0495(72)90086-8Search in Google Scholar

31. Fan W, Dinulescu DM, Butler AA, Zhou J, Marks DL, et al. The central melanocortin system can directly regulate serum insulin levels. Endocrinology 2000;141:3072–9.10.1210/endo.141.9.7665Search in Google Scholar PubMed

32. Bray GA, Inoue S, Nishizawa Y. Hypothalamic obesity. The autonomic hypothesis and the lateral hypothalamus. Diabetologia 1981;20:366–77.10.1007/BF00254505Search in Google Scholar PubMed

33. Shaikh MG, Grundy R, Kirk J. Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children. Eur J Endocrinol 2008;159:791–7.10.1530/EJE-08-0533Search in Google Scholar

34. Lustig RH, Rose SR, Burghen GA, Velasquez-Mieyer P, Broome DC, et al. Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr 1999;135:162–8.10.1016/S0022-3476(99)70017-XSearch in Google Scholar

35. Simoneau-Roy J, O’Gorman C, Pencharz P, Adeli K, Daneman D, et al. Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma. Clin Endocrinol (Oxf) 2010;72:364–70.10.1111/j.1365-2265.2009.03639.xSearch in Google Scholar

36. Bucher H, Zapf J, Torresani T, Prader A, Froesch ER, et al. Insulin-like growth factors I and II, prolactin, and insulin in 19 growth hormone deficient children with excessive, normal, or decreased longitudinal growth after operation for craniopharyngioma. N Engl J Med 1983;309:1142–6.10.1056/NEJM198311103091902Search in Google Scholar

37. Sakaguchi T, Arase K, Bray GA. Sympathetic activity and food intake of rats with ventromedial hypothalamic lesions. Int J Obes 1988;12:285–91.Search in Google Scholar

38. Penicaud L, Cousin B, Leloup C, Lorsignol A, Casteilla L. The autonomic nervous system, adipose tissue plasticity, and energy balance. Nutrition 2000;16:903–8.10.1016/S0899-9007(00)00427-5Search in Google Scholar

39. Roth CL, Hunneman DH, Gebhardt U, Stoffel-Wagner B, Reinehr T, et al. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res 2007;61:496–501.10.1203/pdr.0b013e3180332cd6Search in Google Scholar PubMed

40. Dun SL, Brailoiu GC, Yang J, Chang JK, Dun NJ. Cocaine and amphetamine-regulated transcript peptide and sympatho-adrenal axis. Peptides 2006;27:1949–55.10.1016/j.peptides.2005.10.027Search in Google Scholar PubMed

41. Wang C, Billington CJ, Levine AS, Kotz CM. Effect of CART in the hypothalamic paraventricular nucleus on feeding and uncoupling protein gene expression. Neuroreport 2000;11:3251–5.10.1097/00001756-200009280-00040Search in Google Scholar PubMed

42. Müller HL, Handwerker G, Wollny B, Faldum A, Sorensen N. Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients. J Clin Endocrinol Metab 2002;87:3993–6.10.1210/jcem.87.8.8751Search in Google Scholar PubMed

43. Wolden-Hanson T, Mitton DR, McCants RI, Yellon SM, Wilkinson CW, et al. Daily melatonin administration to middle aged male rats suppresses body weight, intra abdominal adiposity, and plasma leptin, and insulin independent of food intake and total body fat. Endocrinology 2000;141:487–97.10.1210/endo.141.2.7311Search in Google Scholar PubMed

44. Kassayova M, Markova M, Bojkova B, Adamekova E, Kubartka P, et al. Influence of long-term melatonin administration on basic physiological and metabolic variables of young Wistar Han rats. Biologia 2006;61:313–20.10.2478/s11756-006-0057-1Search in Google Scholar

45. Srinivasan V, YoOhta Y, Espino J, Pariente JA, Rodríguez AB, et al. Metabolic Syndrome, its pathophysiology and the role of melatonin. Recent Pat Endocr Metab Immune Drug Discov 2013;7:11–25.10.2174/187221413804660953Search in Google Scholar

46. Lee M, Korner J. Review of physiology, clinical manifestations, and management of hypothalamic obesity in humans. Pituitary 2009;12:87–95.10.1007/s11102-008-0096-4Search in Google Scholar PubMed

47. Tiosano D, Eisentein I, Militianu D, Chrousos GP, Hochberg Z. 11 Beta-hydroxysteroid dehydrogenase activity in hypothalamic obesity. J Clin Endocrinol Metab 2003;88:379–84.10.1210/jc.2002-020511Search in Google Scholar PubMed

48. Friedberg M, Zoumakis E, Hiroi N, Bader T, Chrousos GP, et al. Modulation of 11 beta-hydroxysteroid dehydrogenase type 1 in mature human subcutaneous adipocytes by hypothalamic messengers. J Clin Endocrinol Metab 2003;88:385–93.10.1210/jc.2002-020510Search in Google Scholar PubMed

49. Müller HL. Craniopharyngioma. Endocr Rev 2014;35:513–43.10.1210/er.2013-1115Search in Google Scholar PubMed

50. Ahmet A, Blaser S, Stephens D, Guger S, Rutkas JT, et al. Weight gain in craniopharyngioma–a model for hypothalamic obesity. J Pediatr Endocrinol Metab 2006;19:121–7.10.1515/JPEM.2006.19.2.121Search in Google Scholar

51. Lek N, Prentice P, Williams RM, Ong KK, Burke GA, et al. Risk factors for obesity in childhood survivors of suprasellar brain tumours: a retrospective study. Acta Paediatr 2010;99:1522–6.10.1111/j.1651-2227.2010.01867.xSearch in Google Scholar PubMed

52. Müller HL, Bueb K, Bartels U, Roth C, Harz K, et al. Obesity after childhood craniopharyngioma–German multicenter study on pre-operative risk factors and quality of life. Klin Padiatr 2001;213:244–9.10.1055/s-2001-16855Search in Google Scholar PubMed

53. Müller HL, Emser A, Faldum A, Bruhnken G, Etavard-Gorris N, et al. Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 2004;89:3298–305.10.1210/jc.2003-031751Search in Google Scholar PubMed

54. Lustig RH, Post SM, Srivannaboon K, Rose SR, Danish RK, et al. Risk factors for the development of obesity in children surviving brain tumors. J Clin Endocrinol Metab 2003;88:611–16.10.1210/jc.2002-021180Search in Google Scholar PubMed

55. Gautier A, Godbout A, Grosheny C, Tejedor I, Coudert M, et al. Markers of recurrence and long-term morbidity in craniopharygioma: a systematic analysis of 171 patients. J Clin Endocrinol Metab 2012;97:1258–67.10.1210/jc.2011-2817Search in Google Scholar PubMed

56. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903–8.10.1038/43185Search in Google Scholar PubMed

57. Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398–401.10.1038/32911Search in Google Scholar PubMed

58. Martinelli CE, Keogh JM, Greenfield JR, Henning E, van der Klaauw AA, et al. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab 2011;96:181–8.10.1210/jc.2010-1369Search in Google Scholar PubMed

59. Krude H, Biebermann H, Luck W, Horn R, Brabant G, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998;19:155–7.10.1038/509Search in Google Scholar PubMed

60. del Giudice EM, Santoro N, Cirillo G, D’Urso L, Di Toro R, et al. Mutational screening of the CART gene in obese children: identifying a mutation (Leu34Phe) associated with reduced resting energy expenditure and cosegregating with obesity pheno- type in a large family. Diabetes 2001;50:2157–60.10.2337/diabetes.50.9.2157Search in Google Scholar PubMed

61. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997;16:303–6.10.1038/ng0797-303Search in Google Scholar PubMed

62. Yeo GS, Connie Hung CC, Rochford J, Keogh J, Gray J, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 2004;7:1187–9.10.1038/nn1336Search in Google Scholar PubMed

63. Rodríguez-López R, Pérez JM, Balsera AM, Rodríguez GG, Moreno TH, et al. The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome. Gene 2013;516:285–90.10.1016/j.gene.2012.11.073Search in Google Scholar PubMed

64. Holder JL Jr, Butte NF, Zinn AR. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet 2000;9:101–8.10.1093/hmg/9.1.101Search in Google Scholar PubMed

65. Doche ME, Bochukova EG, Su HW, Pearce LR, Keogh JM, et al. Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest 2012;122:4732–6.10.1172/JCI62696Search in Google Scholar PubMed PubMed Central

66. Pearce LR, Atanassova N, Banton MC, Bottomley B, van der Klaauw AA, et al. KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. Cell 2013;155:765–77.10.1016/j.cell.2013.09.058Search in Google Scholar PubMed PubMed Central

67. Borman AD, Pearce LR, Mackay DS, Nagel-Wolfrum K, Davidson AE, et al. A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity. Hum Mutat 2014;35:289–93.10.1002/humu.22482Search in Google Scholar PubMed PubMed Central

68. Prada PO, Quaresma PG, Caricilli AM, Santos AC, Guadagnini D, et al. Tub has a key role in insulin and leptin signaling and action in vivo in hypothalamic nuclei. Diabetes 2013;62:137–48.10.2337/db11-1388Search in Google Scholar PubMed PubMed Central

69. Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab 2008;93:4183–97.10.1210/jc.2008-0649Search in Google Scholar PubMed

70. Seo S, Guo DF, Bugge K, Morgan DA, Rahmouni K, et al. Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling. Hum Mol Genet 2009;18:1323–31.10.1093/hmg/ddp031Search in Google Scholar PubMed PubMed Central

71. Patwari PP, Wolfe LF. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: review and update. Curr Opin Pediatr 2014;26:487–92.10.1097/MOP.0000000000000118Search in Google Scholar PubMed

72. Farooqi IS. Monogenic human obesity. Front Horm Res 2008;36:1–11.10.1159/000115333Search in Google Scholar PubMed

73. Hinney A, Volckmar AL, Antel J. Genes and the hypothalamic control of metabolism in humans. Best Pract Res Clin Endocrinol Metab 2014;28:635–47.10.1016/j.beem.2014.04.007Search in Google Scholar PubMed

74. Goldstone AP. Prader-Willi syndrome: advances in its genetics, pathophysiology and treatment. Trends Endocrinol Metab 2004;15:12–20.10.1016/j.tem.2003.11.003Search in Google Scholar PubMed

75. Swaab DF, Purba JS, Hofman MA. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J Clin Endocrinol Metab 1995;80:573–9.Search in Google Scholar

76. Kweh FA, Miller JL, Sulsona CR, Wasserfall C, Atkinson M, et al. Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia. Am J Med Genet A 2015:167A:69–79.10.1002/ajmg.a.36810Search in Google Scholar PubMed PubMed Central

77. Goldstone AP, Patterson M, Kalingag N, Ghatei MA, Brynes AE, et al. Fasting and post-prandial hyperghrelinemia in Prader-Willi syndrome is partially explained by hypoinsulinemia, and is not due to peptide YY 3-36 deficiency or seen in hypothalamic obesity due to craniopharyngioma. J Clin Endocrinol Metab 2005;90:2681–90.10.1210/jc.2003-032209Search in Google Scholar PubMed

78. Kanumakala S, Greaves R, Pedreira C, Donath S, Warne G, et al. Fasting ghrelin levels are not elevated in children with hypothalamic obesity. J Clin Endocrinol Metab 2005;90: 2691–5.10.1210/jc.2004-2175Search in Google Scholar PubMed

79. Dhondt K, Verloo P, Verhelst H, Van Coster R, Overeem S. Hypocretin-1 deficiency in a girl with ROHHAD syndrome. Pediatrics 2013;132:e788–92.10.1542/peds.2012-3225Search in Google Scholar PubMed

80. Okonska M, Birkholz D, Korpal-Szczyrska M, Adamkiewicz-Drozynska E, Alska A, et al. The evaluation of the influence of growth hormone therapy on growing process and metabolic functions in patients after treatment of craniopharyngioma. Pediatr Endocrinol Diabetes Metab 2010;16:19–24.Search in Google Scholar

81. Geffner M, Lundberg M, Koltowska-Häggström M, Abs R, Verhelst J, et al. Changes in height, weight, and body mass index in children with craniopharyngioma after three years of growth hormone therapy: analysis of KIGS (Pfizer International Growth Database). J Clin Endocrinol Metab 2004;89:5435–40.10.1210/jc.2004-0667Search in Google Scholar PubMed

82. Srinivasan S, Ogle GD, Garnett SP, Briody JN, Lee JW, et al. Features of the metabolic syndrome after childhood craniopharyngioma. J Clin Endocrinol Metab 2004;89:81–6.10.1210/jc.2003-030442Search in Google Scholar PubMed

83. Hoffmann A, Postma FP, Sterkenburg AS, Gebhardt U, Müller HL. Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma. J Pediatr Endocrinol Metab 2015;28:35–43.10.1515/jpem-2014-0415Search in Google Scholar PubMed

84. Holmer H, Pozarek G, Wirfält E, Popovic V, Ekman B, et al. Reduced energy expenditure and impaired feeding-related signals but not high energy intake reinforces hypothalamic obesity in adults with childhood onset craniopharyngioma. J Clin Endocrinol Metab 2010;95:5395–402.10.1210/jc.2010-0993Search in Google Scholar PubMed

85. Shaikh MG, Grundy RG, Kirk JMV. Reductions in basal metabolic rate and physical activity contribute to hypothalamic obesity. J Clin Endocrinol Metab 2008;93:2588–93.10.1210/jc.2007-2672Search in Google Scholar PubMed

86. Müller HL, Handwerker G, Gebhardt U, Faldum A, Emser A, et al. Melatonin treatment in obese patients with childhood craniopharyngioma and increased daytime sleepiness. Cancer Causes Control 2006;17:583–9.10.1007/s10552-005-9012-7Search in Google Scholar

87. O’Gorman CS, Simoneau-Roy J, Pencharz P, MacFarlane J, MacLusky I, et al. Sleep- disordered breathing is increased in obese adolescents with craniopharyngioma compared with obese controls. J Clin Endocrinol Metab 2010;95:2211–18.10.1210/jc.2009-2003Search in Google Scholar

88. Rosen G, Brand SR. Sleep in children with cancer: case review of 70 children evaluated in a comprehensive pediatric sleep center. Support Care Cancer 2011;19:985–94.10.1007/s00520-010-0921-ySearch in Google Scholar

89. Manni R, Politini L, Nobili L, Ferrillo F, Livieri C, et al. Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features and underlying factors. Clin Neurophysiol 2001;112:800–5.10.1016/S1388-2457(01)00483-7Search in Google Scholar

90. Müller HL, Müller-Stover S, Gebhardt U, Kolb R, Sörensen N, et al. Secondary narcolepsy may be a causative factor of increased daytime sleepiness in obese childhood craniopharyngioma patients. J Pediatr Endocrinol Metab 2006;19:423–9.10.1055/s-2006-954715Search in Google Scholar

91. Mason PW, Krawiecki N, Meacham LR. The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma. Arch Pediatr Adolesc Med 2002;156:887–92.10.1001/archpedi.156.9.887Search in Google Scholar PubMed

92. Rakhshani N, Jeffery AS, Schulte F, Barrera M, Atenafu EG, et al. Evaluation of a comprehensive care clinic model for children with brain tumor and risk for hypothalamic obesity. Obesity 2010;18:1768–74.10.1038/oby.2009.491Search in Google Scholar PubMed

93. Ismail D, O’Connell MA, Zacharin MR. Dexamphetamine use for management of obesity and hypersomnolence following hypothalamic injury. J Pediatr Endocrinol Metab 2006;19: 129–34.10.1515/JPEM.2006.19.2.129Search in Google Scholar PubMed

94. Greenway FL, Bray GA. Treatment of hypothalamic obesity with caffeine and ephedrine. Endocr Pract 2008;14:697–703.10.4158/EP.14.6.697Search in Google Scholar PubMed

95. Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2003;88:2586–92.10.1210/jc.2002-030003Search in Google Scholar PubMed

96. Weiss R. URL: http://clinicaltrials.gov/ ct2/show/NCT00076362.Search in Google Scholar

97. Hamilton JK, Conwell LS, Syme C, Ahmet A, Jeffery A, et al. Hypothalamic obesity following craniopharyngioma surgery: results of a pilot trial of combined diazoxide and metformin therapy. Int J Pediatr Endocrinol 2011;2011:417949.10.1155/2011/417949Search in Google Scholar

98. Cettour-Rose P, Burger AG, Meier CA, Visser TJ, Rohner- Jeanrenaud F. Central stimulatory effect of leptin on T3 produc- tion is mediated by brown adipose tissue type II deiodinase. Am J Physiol Endocrinol Metab 2002;283:E980–7.10.1152/ajpendo.00196.2002Search in Google Scholar

99. Fernandes JK, Klein MJ, Ater JL, Kuttesch JF, Vassilopoulou-Sellin R. Triiodothyronine supplementation for hypothalamic obesity. Metabolism 2002;51:1381–3.10.1053/meta.2002.35591Search in Google Scholar

100. Danielsson P, Janson A, Norgren S, Marcus C. Impact of sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes. J Clin Endocrinol Metab 2007;92:4101–6.10.1210/jc.2007-0826Search in Google Scholar

101. Apovian CM, Bergenstal RM, Cuddihy RM, Qu Y, Lenox S, et al. Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. Am J Med 2010;123:468.e9–17.10.1016/j.amjmed.2009.11.019Search in Google Scholar

102. Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009;374:1606–16.10.1016/S0140-6736(09)61375-1Search in Google Scholar

103. Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. Br Med J 2012;344:d7771.10.1136/bmj.d7771Search in Google Scholar PubMed PubMed Central

104. Shirazi R, Palsdottir V, Collander J, Anesten F, Vogel H, et al. Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6. Proc Natl Acad Sci USA 2013;110:16199–204.10.1073/pnas.1306799110Search in Google Scholar PubMed PubMed Central

105. Zoicas F, Droste M, Mayr B, Buchfelder M, Schöfl C. GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases. Eur J Endocrinol 2013;168:699–706.10.1530/EJE-12-0997Search in Google Scholar PubMed

106. Simmons JH, Shoemaker AH, Roth CL. Treatment with glucagon-like peptide-1 agonist exendin-4 in a patient with hypothalamic obesity secondary to intracranial tumor. Horm Res Paediatr 2012;78:54–8.10.1159/000339469Search in Google Scholar PubMed

107. Thondam SK, Cuthbertson DJ, Aditya BS, Macfarlane IA, Wilding JP, et al. A glucagon-like peptide-1 (GLP-1) receptor agonist in the treatment for hypothalamic obesity complicated by type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2012;77:635–7.10.1111/j.1365-2265.2012.04368.xSearch in Google Scholar PubMed

108. Ando T, Haraguchi A, Matsunaga T, Natsuda S, Yamasaki H, et al. Liraglutide as a potentially useful agent for regulating appetite in diabetic patients with hypothalamic hyperphagia and obesity. Intern Med 2014;53:1791–5.10.2169/internalmedicine.53.1646Search in Google Scholar PubMed

109. She M, Deng X, Guo Z, Laudon M, Hu Z, et al. NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats. Pharmacol Res 2009;59:248–53.10.1016/j.phrs.2009.01.005Search in Google Scholar PubMed

110. Oxenkrug GF, Summergrad P. Ramelteon attenuates age-associated hypertension and weight gain in spontaneously hypertensive rats. Ann NY Acad Sci 2010;1199:114–20.10.1111/j.1749-6632.2009.05355.xSearch in Google Scholar PubMed

111. Müller HL, Gebhardt U, Wessel V, Schröder S, Kolb R, et al. First experiences with laparoscopic adjustable gastric banding (LAGB) in the treatment of patients with childhood craniopharyngioma and morbid obesity. Klin Padiatr 2007;219:323–5.10.1055/s-2007-985848Search in Google Scholar PubMed

112. Schultes B, Ernst B, Schmid F, Thurnheer M. Distal gastric bypass surgery for the treatment of hypothalamic obesity after childhood craniopharyngioma. Eur J Endocrinol 2009;161:201–6.10.1530/EJE-09-0079Search in Google Scholar PubMed

113. Inge TH, Pfluger P, Zeller M, Rose SR, Burget L, et al. Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy. Nat Clin Pract 2007;3:606–9.10.1038/ncpendmet0579Search in Google Scholar PubMed

114. Bretault M, Boillot A, Muzard L, Poitou C, Oppert JM, et al. Clinical review: bariatric surgery following treatment for craniopharyngioma: a systematic review and individual- level data meta-analysis. J Clin Endocrinol Metab 2013;98:2239–46.10.1210/jc.2012-4184Search in Google Scholar PubMed

115. Elowe-Gruau E, Beltrand J, Brauner R, Pinto G, Samara-Boustani D, et al. Childhood craniopharyngioma: hypothalamus-sparing surgery decreases the risk of obesity. J Clin Endocrinol Metab 2013;98:2376–82.10.1210/jc.2012-3928Search in Google Scholar PubMed

116. Clark AJ, Cage TA, Aranda D, Parsa AT, Sun PP, et al. A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma. Childs Nerv Syst 2013;29:231–8.10.1007/s00381-012-1926-2Search in Google Scholar PubMed

117. Spoudeas HA, Saran F, Pizer B. A multimodality approach to the treatment of craniopharyngiomas avoiding hypothalamic morbidity: a UK perspective. J Pediatr Endocrinol Metab 2006;19:447–51.Search in Google Scholar

118. Puget S, Garnett M, Wray A, Grill J, Habrand JL, et al. Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg 2007;106:3–12.10.3171/ped.2007.106.1.3Search in Google Scholar PubMed

119. Mallucci C, Pizer B, Blair J, Didi M, Doss A, et al. Management of craniopharyngioma: the Liverpool experience following the introduction of the CCLG guidelines. Introducing a new risk assessment grading system. Childs Nerv Syst 2012;28:1181–92.10.1007/s00381-012-1787-8Search in Google Scholar PubMed

Received: 2014-12-11
Accepted: 2015-1-29
Published Online: 2015-3-14
Published in Print: 2015-5-1

©2015 by De Gruyter

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