Skip to main content
SpringerLink
Log in

Hypothalamic obesity in patients with craniopharyngioma: treatment approaches and the emerging role of gastric bypass surgery

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Hypothalamic obesity is a potential sequela of craniopharyngioma, arising from hypothalamic damage inflicted by either the tumor and/or its treatment. The marked weight gain that characterizes this disorder appears to result from impaired sympathoadrenal activation, parasympathetic dysregulation, and other hormonal and hypothalamic disturbances that upset the balance between energy intake and expenditure. Given hypopituitarism is commonly present, careful management of hormonal deficits is important for weight control in these patients. In addition, diet, exercise, and pharmacotherapy aimed at augmenting sympathetic output, controlling hyperinsulinism, and promoting weight loss have been used to treat this disease, but these measures rarely lead to sustained weight loss. While surgical interventions have not routinely been pursued, emerging data suggests that surgical weight loss interventions including Roux-en-Y gastric bypass can be safely and effectively used for the management of hypothalamic obesity in patients with craniopharyngioma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bruch H (1993) The Fröhlich syndrome: report of the original case. 1939. Obes Res 1:329–331

    PubMed  CAS  Google Scholar 

  2. Albright AL (ed) (1999) In: Einshaus SL (ed) Principles and practice of pediatric neurosurgery. Craniopharyngioma. Thieme, New York, pp 545–562

  3. Muller HL et al (2001) Obesity after childhood craniopharyngioma–German multicenter study on pre-operative risk factors and quality of life. Klin Padiatr 213(4):244–249

    Article  PubMed  CAS  Google Scholar 

  4. Lee M, Wardlaw SL (2007) The central melanocortin system and the regulation of energy balance. Front Biosci 12:3994–4010

    Article  PubMed  CAS  Google Scholar 

  5. Schwartz MW et al (2000) Central nervous system control of food intake. Nature 404(6778):661–671

    PubMed  CAS  Google Scholar 

  6. Seeley RJ et al (1997) Melanocortin receptors in leptin effects. Nature 390(6658):349

    Article  PubMed  CAS  Google Scholar 

  7. Inoue S (1979) An autonomic hypothesis for hypothalamic obesity. Life Sci 25:561–566

    Article  PubMed  CAS  Google Scholar 

  8. Harris JA, Benedict FG (1918) A biometric study of human basal metabolism. Proc Natl Acad Sci USA 4(12):370–373

    Article  PubMed  CAS  Google Scholar 

  9. Mifflin MD et al (1990) A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr 51(2):241–247

    PubMed  CAS  Google Scholar 

  10. Muller HL et al (2004) Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 89(7):3298–3305

    Article  PubMed  Google Scholar 

  11. Sorva R (1988) Children with craniopharyngioma. Early growth failure and rapid postoperative weight gain. Acta Paediatr Scand 77(4):587–592

    Article  PubMed  CAS  Google Scholar 

  12. de Vile CJ et al (1996) Obesity in childhood craniopharyngioma: relation to post-operative hypothalamic damage shown by magnetic resonance imaging. J Clin Endocrinol Metab 81(7):2734–2737

    Article  PubMed  Google Scholar 

  13. Holmer H et al (2010) 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 95(12):5395–5402

    Google Scholar 

  14. Shaikh MG, Grundy RG, Kirk JM (2008) Reductions in basal metabolic rate and physical activity contribute to hypothalamic obesity. J Clin Endocrinol Metab 93(7):2588–2593

    Article  PubMed  CAS  Google Scholar 

  15. Gobatto CA et al (2002) The monosodium glutamate (MSG) obese rat as a model for the study of exercise in obesity. Res Commun Mol Pathol Pharmacol 111(1–4):89–101

    PubMed  CAS  Google Scholar 

  16. Coutant R et al (2003) Defect in epinephrine production in children with craniopharyngioma: functional or organic origin? J Clin Endocrinol Metab 88(12):5969–5975

    Article  PubMed  CAS  Google Scholar 

  17. Roth CL et al (2007) Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res 61(4):496–501

    Article  PubMed  CAS  Google Scholar 

  18. Mason PW, Krawiecki N, Meacham LR (2002) The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma. Arch Pediatr Adolesc Med 156(9):887–892

    PubMed  Google Scholar 

  19. Ismail D, O’Connell MA, Zacharin MR (2006) Dexamphetamine use for management of obesity and hypersomnolence following hypothalamic injury. J Pediatr Endocrinol Metab 19(2):129–134

    Article  PubMed  CAS  Google Scholar 

  20. Danielsson P et al (2007) Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes. J Clin Endocrinol Metab 92(11):4101–4106

    Article  PubMed  CAS  Google Scholar 

  21. James WP et al (2010) Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 363(10):905–917

    Article  PubMed  CAS  Google Scholar 

  22. Gadde KM et al (2011) Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 377(9774):1341–1352

    Article  PubMed  CAS  Google Scholar 

  23. Weintraub M et al (1984) A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination. Arch Intern Med 144(6):1143–1148

    Google Scholar 

  24. Greenway FL, Bray GA (2008) Treatment of hypothalamic obesity with caffeine and ephedrine. Endocr Pract 14(6):697–703

    PubMed  Google Scholar 

  25. Lustig RH et al (1999) Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr 135(2 Pt 1):162–168

    Google Scholar 

  26. Lustig RH et al (2003) Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 88(6):2586–2592

    Article  PubMed  CAS  Google Scholar 

  27. Hamilton JK et al (2011) Hypothalamic obesity following craniopharyngioma surgery: results of a pilot trial of combined diazoxide and metformin therapy. Int J Pediatr Endocrinol 2011:417949

  28. Korner J, Aronne LJ (2004) Pharmacological approaches to weight reduction: therapeutic targets. J Clin Endocrinol Metab 89(6):2616–2621

    Article  PubMed  CAS  Google Scholar 

  29. Muller HL et al (2006) Melatonin treatment in obese patients with childhood craniopharyngioma and increased daytime sleepiness. Cancer Causes Control 17(4):583–589

    Article  PubMed  Google Scholar 

  30. Hochberg Z et al (2004) Hypothalamic regulation of adiposity: the role of 11beta-hydroxysteroid dehydrogenase type 1. Horm Metab Res 36(6):365–369

    Article  PubMed  CAS  Google Scholar 

  31. Tiosano D et al (2003) 11 beta-Hydroxysteroid dehydrogenase activity in hypothalamic obesity. J Clin Endocrinol Metab 88(1):379–384

    Article  PubMed  CAS  Google Scholar 

  32. Fernandes JK et al (2002) Triiodothyronine supplementation for hypothalamic obesity. Metabolism 51(11):1381–1383

    Article  PubMed  CAS  Google Scholar 

  33. Chrisoulidou A et al (2000) Effects of 7 years of growth hormone replacement therapy in hypopituitary adults. J Clin Endocrinol Metab 85(10):3762–3769

    Article  PubMed  CAS  Google Scholar 

  34. Hoffman AR et al (2004) Growth hormone (GH) replacement therapy in adult-onset gh deficiency: effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89(5):2048–2056

    Article  PubMed  CAS  Google Scholar 

  35. Verhelst J et al (2005) Baseline characteristics and response to 2 years of growth hormone (GH) replacement of hypopituitary patients with GH deficiency due to adult-onset craniopharyngioma in comparison with patients with nonfunctioning pituitary adenoma: data from KIMS (Pfizer International Metabolic Database). J Clin Endocrinol Metab 90(8):4636–4643

    Google Scholar 

  36. Buchwald H et al (2004) Bariatric surgery: a systematic review and meta-analysis. JAMA 292(14):1724–1737

    Article  PubMed  CAS  Google Scholar 

  37. Sjöstrom L et al (2007) Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 357(8):741–752

    Article  PubMed  Google Scholar 

  38. Korner J et al (2005) Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab 90(1):359–365

    Article  PubMed  CAS  Google Scholar 

  39. Korner J et al (2009) Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond) 33(7):786–795

    Article  CAS  Google Scholar 

  40. Nakazato M et al (2001) A role for ghrelin in the central regulation of feeding. Nature 409(6817):194–198

    Article  PubMed  CAS  Google Scholar 

  41. Tschöp M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407(6806):908–913

    Article  PubMed  Google Scholar 

  42. Antal S, Levin H (1996) Biliopancreatic Diversion in Prader-Willi Syndrome Associated with Obesity. Obes Surg 6(1):58–62

    Article  PubMed  Google Scholar 

  43. Laurent-Jaccard A et al (1991) Long-term result of treatment of Prader-Willi syndrome by Scopinaro’s Bilio-pancreatic diversion. Study of three cases and the effect of Dextrofenfluramine on the postoperative evolution. Obes Surg 1(1):83–87

    Google Scholar 

  44. Soper RT et al (1975) Gastric bypass for morbid obesity in children and adolescents. J Pediatr Surg 10(1):51–58

    Article  PubMed  CAS  Google Scholar 

  45. Muller HL et al (2007) First experiences with laparoscopic adjustable gastric banding (LAGB) in the treatment of patients with childhood craniopharyngioma and morbid obesity. Klin Padiatr 219(6):323–325

    Article  PubMed  CAS  Google Scholar 

  46. Inge TH et al (2007) Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy. Nat Clin Pract Endocrinol Metab 3(8):606–609

    Article  PubMed  Google Scholar 

  47. Cummings DE et al (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346(21):1623–1630

    Article  PubMed  Google Scholar 

  48. Geloneze B et al (2003) Ghrelin: a gut-brain hormone: effect of gastric bypass surgery. Obes Surg 13(1):17–22

    Article  PubMed  Google Scholar 

  49. Faraj M et al (2003) Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab 88(4):1594–1602

    Article  PubMed  CAS  Google Scholar 

  50. Holdstock C et al (2003) Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab 88(7):3177–3183

    Article  PubMed  CAS  Google Scholar 

  51. Kotidis EV et al (2006) Serum ghrelin, leptin and adiponectin levels before and after weight loss: comparison of three methods of treatment—a prospective study. Obes Surg 16(11):1425–1432

    Google Scholar 

  52. Schultes B et al (2009) Distal gastric bypass surgery for the treatment of hypothalamic obesity after childhood craniopharyngioma. Eur J Endocrinol 161(1):201–206

    Article  PubMed  CAS  Google Scholar 

  53. Carey DG et al (2006) Body composition and metabolic changes following bariatric surgery: effects on fat mass, lean mass and basal metabolic rate. Obes Surg 16(4):469–477

    Article  PubMed  Google Scholar 

  54. Flancbaum L et al (1997) Changes in measured resting energy expenditure after Roux-en-Y gastric bypass for clinically severe obesity. Surgery 122(5):943–949

    Article  PubMed  CAS  Google Scholar 

  55. Das SK et al (2003) Long-term changes in energy expenditure and body composition after massive weight loss induced by gastric bypass surgery. Am J Clin Nutr 78(1):22–30

    PubMed  CAS  Google Scholar 

  56. Leibel RL, Rosenbaum M, Hirsch J (1995) Changes in energy expenditure resulting from altered body weight. N Engl J Med 332(10):621–628

    Article  PubMed  CAS  Google Scholar 

  57. Ravussin E et al (1985) Energy expenditure before and during energy restriction in obese patients. Am J Clin Nutr 41(4):753–759

    PubMed  CAS  Google Scholar 

  58. Leibel RL, Hirsch J (1984) Diminished energy requirements in reduced-obese patients. Metabolism 33(2):164–170

    Article  PubMed  CAS  Google Scholar 

  59. Elliot DL et al (1989) Sustained depression of the resting metabolic rate after massive weight loss. Am J Clin Nutr 49(1):93–96

    PubMed  CAS  Google Scholar 

  60. Carrasco F et al (2007) Changes in resting energy expenditure and body composition after weight loss following Roux-en-Y gastric bypass. Obes Surg 17(5):608–616

    Article  PubMed  Google Scholar 

  61. Faria SL, Kelly E, Faria OP (2009) Energy expenditure and weight regain in patients submitted to Roux-en-Y gastric bypass. Obes Surg 19(7):856–859

    Article  PubMed  Google Scholar 

  62. Korner J et al (2008) Sex differences in visceral adipose tissue post-bariatric surgery compared to matched non-surgical controls. Int J Body Composit Res 6(3):93–99

    Google Scholar 

  63. Stegen S et al (2011) Physical fitness in morbidly obese patients: effect of gastric bypass surgery and exercise training. Obes Surg 21(1):61–70

    Article  PubMed  Google Scholar 

  64. Bond DS et al (2009) Becoming physically active after bariatric surgery is associated with improved weight loss and health-related quality of life. Obesity 17(1):78–83

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the participation of our patient in this study and the expert technical assistance of Gerardo Febres and Irene M. Conwell. This project was supported by NIH/NIDDK RO1 DK072011 and NIH/NCRR UL1RR024156. JK has research support from Covidien.

Author information

Authors and Affiliations

  1. Department of Medicine, Columbia University College of Physicians and Surgeons, William Black Medical Research Building, 650 West 168th Street, Room 905, New York, NY, 10032, USA

    Gabrielle Page-Wilson, Sharon L. Wardlaw & Judith Korner

  2. Department of Radiology, Columbia University College of Physicians and Surgeons, 177 Fort Washington Avenue, MHB4-156, New York, NY, 10032, USA

    Alexander G. Khandji

Authors
  1. Gabrielle Page-Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon L. Wardlaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander G. Khandji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Judith Korner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Judith Korner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Page-Wilson, G., Wardlaw, S.L., Khandji, A.G. et al. Hypothalamic obesity in patients with craniopharyngioma: treatment approaches and the emerging role of gastric bypass surgery. Pituitary 15, 84–92 (2012). https://doi.org/10.1007/s11102-011-0349-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-011-0349-5

Keywords

Search

Navigation