Патофизиологические механизмы, клинические проявления и методы лечения гипоталамического ожирения

Представлены современные данные литературы о патогенезе, клинических проявлениях и методах лечения гипоталамического ожирения. Повреждение гипоталамуса, связанное с инфильтративными процессами, опухолями и последствиями их лечения, часто приводит к развитию ожирения, характеризующегося быстрым и неуклонным увеличением массы тела (МТ). Прибавление в МТ происходит вследствие нарушения функционирования центров гипоталамуса, ответственных за насыщение, чувство голода и энергетический баланс, что приводит к гиперфагии, вегетативным нарушениям, снижению расхода энергии и гиперинсулинемии. Добиться контроля над МТ путем соблюдения диеты и изменения образа жизни очень сложно. Существующая фармакотерапия, направленная на изменение секреции инсулина и активацию симпатической нервной системы, только в некоторой степени способствует снижению МТ и препятствует ее дальнейшему повышению. Для разработки эффективных терапевтических стратегий лечения данного состояния необходима более детальная информация о его факторах риска и патогенетических механизмах.

гипоталамическое ожирение, меланокортиновая система, гипопитуитаризм, краниофарингиома

1. Hetherington A., Ranson S. Hypothalamic lesions and adiposity in the rat. Anat Rec 1940;78:149-172.

2. Bruch H. The Frohlich syndrome: report of the original case. 1939. Obes Res 1993;1:4:329-331.

3. Bray G.A. Syndromes of hypothalamic obesity in man. Pediatr Ann 1984;13:7:525-536.

4. Farooqi S., O'Rahilly S. Genetics of obesity in humans. Endocr Rev 2006;27:7:710-718.

5. Kim S.F., Huang A.S., Snowman A.M. et al. From the Cover: Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc Natl Acad Sci USA 2007;104:3456-3459.

6. Swaab D.F. Prader-Willi syndrome and the hypothalamus. Acta Paediatr 1997;423:Suppl:50–54.

7. King B.M. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav 2006;87:2:221-244.

8. Lee M., Wardlaw S.L. The central melanocortin system and the regulation of energy balance. Front Biosci 2007;12:3994-4010.

9. Roth C., Wilken B., Hanefeld F. et al. Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. Eur J Endocrinol 1998;138:1:89-91.

10. Murphy K.G., Bloom S.R. Gut hormones and the regulation of energy homeostasis. Nature 2006;444:7121:854-859.

11. Haqq A.M., Farooqi I.S., O'Rahilly S. et al. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. J Clin Endocrinol Metab 2003;88:1:174-178.

12. Goldstone A.P., Thomas E.L., Brynes A.E. et al. Elevated fasting plasma ghrelin in Prader-Willi syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance. J Clin Endocrinol Metab 2004;89:4:1718-1726.

13. Goldstone A.P., Patterson M., Kalingag N. et al. Fasting and postprandial hyperghrelinemia in Prader-Willi syndrome is partially explained by hypoinsulinemia, and is not due to peptide YY3-36 deficiency or seen in hypothalamic obesity due to craniopharyngioma. J Clin Endocrinol Metab 2005;90:5:2681-2690.

14. Daousi C., MacFarlane I.A., English P.J. et al. Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in adults with acquired structural hypothalamic damage? J Clin Endocrinol Metab 2005;90:9:5025-5030.

15. Rohner F., Dufour A.C., Karakash C. et al. Immediate effect of lesion of the ventromedial hypothalamic area upon glucose-induced insulin secretion in anaesthetized rats. Diabetalogia 1977;13:3:239-242.

16. Balkan B., Steffens A.B., Bruggink J.E., Strubbe J.H. Hyperinsulinemia and glucose tolerance in obese rats with lesions of the ventromedial hypothalamus: dependence on food intake and route of administration. Metabolism 1991;40:10:1092–1100.

17. Bray G.A., Inoue S., Nishizawa Y. Hypothalamic obesity. The autonomic hypothesis and the lateral hypothalamus. Diabetologia 1981;20:Suppl:366-377.

18. Inoue S., Bray G.A. The effects of subdiaphragmatic vagotomy in rats with ventromedial hypothalamic obesity. Endocrinology 1977;100:1:108-114.

19. Harz K.J., Muller H.L., Waldeck E. et al. Obesity in patients with craniopharyngioma: assessment of food intake and movement counts indicating physical activity. J Clin Endocrinol Metab 2003;88:11:5227-5231.

20. Schofl C., Schleth A., Berger D. et al. Sympathoadrenal counterregulation in patients with hypothalamic craniopharyngioma. J Clin Endocrinol Metab 2002;87:2:624-629.

21. Fery F., Plat L., van de Borne P. et al. Impaired counterregulation of glucose in a patient with hypothalamic sarcoidosis. N Engl J Med 1999;340:11:852-856.

22. Roth C.L., Hunneman D.H., Gebhardt U. et al. Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma. Pediatr Res 2007;61:4:496-501.

23. Smith D.K., Sarfeh J., Howard L. Truncal vagotomy in hypothalamic obesity. Lancet 1983;1:8337:1330-1331.

24. Lustig R.H., Rose S.R., Burghen G.A. et al. Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr 1999;135:2:Pt 1:162-168.

25. Lustig R.H., Hinds P.S., Ringwald-Smith K. et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2003;88:6:2586-2592.

26. Mason P.W., Krawiecki N., Meacham L.R. The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma. Arch Pediatr Adolesc Med 2002;156:9:887-892.

27. Pinto G., Bussieres L., Recasens C. et al. Hormonal factors influencing weight and growth pattern in craniopharyngioma. Horm Res 2000;53:4:163-169.

28. Muller H.L., Emser A., Faldum A. et al. Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma. J Clin Endocrinol Metab 2004;89:7:3298-3305.

29. Muller H.L., Bueb K., Bartels U. et al. Obesity after childhood craniopharyngioma - German multicenter study on preoperative risk factors and quality of life. Klin Padiatr 2001;213:4:244-249.

30. Muller H.L., Gebhardt U., Etavard-Gorris N. et al. Prognosis and sequela in patients with childhood craniopharyngioma - results of HIT-ENDO and update on KRANIOPHARYNGEOM 2000. Klin Padiatr 2004;216:6:343-348.

31. de Vile C.J., Grant D.B., Hayward R.D. et al. Obesity in childhood craniopharyngioma: relation to post-operative hypothalamic damage shown by magnetic resonance imaging. J Clin Endocrinol Metab 1996;81:7:2734-2737.

32. Lustig R.H., Post S.R., Srivannaboon K. et al. Risk factors for the development of obesity in children surviving brain tumors. J Clin Endocrinol Metab 2003;88:2:611-616.

33. Daousi C., Dunn A.J., Foy P.M. et al. Endocrine and neuroanatomic features associated with weight gain and obesity in adult patients with hypothalamic damage. Am J Med 2005;118:1:45-50.

34. Belojevic G., Maric-Zivkovic J. Sarcoidosis and obesity. Med Pregl 2005;58:Suppl 1: 44-45.

35. Montaurier C., Morio B., Bannier S. et al. Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation. Brain 2007;130 Pt. 7:1808-1818.

36. Lustig R.H. Hypothalamic obesity: the sixth cranial endocrinopathy. Endocrinologist 2002;12:210-217.

37. Ahmet A., Blaser S., Stephens D. et al. Weight gain in craniopharyngioma - a model for hypothalamic obesity. J Pediatr Endocrinol Metab 2006;19:2:121-127.

38. Reeves A.G., Plum F. Hyperphagia, rage, and dementia accompanying a ventromedial hypothalamic neoplasm. Arch Neurol 1969;20:6:616-624.

39. Gobatto C.A., Mello M.A., Souza C.T., Ribeiro I.A. The monosodium glutamate (MSG) obese rat as a model for the study of exercise in obesity. Res Commun Mol Pathol Pharmacol 2002;111:1-4:89-101.

40. Scomparin D.X., Grassiolli S., Marcal A.C. et al. Swim training applied at early age is critical to adrenal medulla catecholamine content and to attenuate monosodium L-glutamate-obesity onset in mice. Life Sci 2006;79:22:2151-2156.

41. Martins A.C., Souza K.L., Shio M.T. et al. Adrenal medullary function and expression of catecholamine-synthesizing enzymes in mice with hypothalamic obesity. Life Sci 2004;74:26:3211-3222.

42. Muller H.L., Heinrich M., Bueb K. et al. Perioperative dexamethasone treatment in childhood craniopharyngioma - influence on short-term and long-term weight gain. Exp Clin Endocrinol Diabetes 2003;111:6:330-334.

43. Tiosano D., Eisentein I., Militianu D. et al. 11 beta-Hydroxysteroid dehydrogenase activity in hypothalamic obesity. J Clin Endocrinol Metab 2003;88:1:379-384.

44. Friedberg M., Zoumakis E., Hiroi N. et al. Modulation of 11 beta-hydroxysteroid dehydrogenase type 1 in mature human subcutaneous adipocytes by hypothalamic messengers. J Clin Endocrinol Metab 2003;88:1:385-393.

45. Fernandes J.K., Klein M.J., Ater J.L. et al. Triiodothyronine supplementation for hypothalamic obesity. Metabolism 2002;51:11:1381-1383.

46. Hoffman A.R., Kuntze J.E., Baptista J. et al. 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 2004;89:5:2048-2056.

47. Schoenle E.J., Zapf J., Prader A. et al. Replacement of growth hormone (GH) in normally growing GH-deficient patients operated for craniopharyngioma. J Clin Endocrinol Metab 1995;80:2:374-378.

48. Geffner M., Lundberg M., Koltowska-Haggstrom M. 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;89:11:5435-5440.

49. Verhelst J., Kendall-Taylor P., Erfurth E.M. et al. 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 Int Metabol Database 2005;90:8:4636-4643.

50. Muller H.L., Gebhardt U., Wessel V. et al. First experiences with laparoscopic adjustable gastric banding (LAGB) in the treatment of patients with childhood craniopharyngioma and morbid obesity. Klin Padiatr 2007;219:6:323-325.

51. Inge T.H., Pfluger P., Zeller M. et al. Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy. Nat Clin Pract Endocrinol Metab 2007;3:8:606-609.

52. Muller H.L., Handwerker G., Brigitte W. et al. Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients. J Clin Endocrinol Metab 2002;87:8:3993-3996.

53. Muller H.L., Handwerker G., Gebhardt U. et al. Melatonin treatment in obese patients with childhood craniopharyngioma and increased daytime sleepiness. Cancer Causes Control 2006;17:4:583-589.