Adiposidade em pacientes tratados por câncer na infância: entendendo a fisiopatologia da obesidade

As childhood cancer treatment has become more effective, survival rates have improved, and a number of complications have been described while many of these patients reach adulthood. Obesity is a well-recognized late effect, and its metabolic effects may lead to cardiovascular disease. Currently, studies concerning overweight have focused on acute lymphocytic leukemia and brain tumors, since they are at risk for hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation, chemotherapy, and brain surgery) or to primary tumor location. Obesity and cancer have metabolic syndrome features in common. Thus, it remains controversial if overweight is a cause or consequence of cancer, and to date additional mechanisms involving adipose tissue and hypothalamic derangements have been considered, comprising premature adiposity rebound, hyperinsulinemia, leptin regulation, and the role of peroxisome proliferator-activated receptor γ. Overall, further research is still necessary to better understand the relationship between adipogenesis and hypothalamic control deregulation following cancer therapy.Os avanços do tratamento contra o câncer infantil têm resultado no aumento da sobrevida e das complicações, à medida que os pacientes atingem a maioridade. A obesidade é um evento reconhecido, e seus efeitos metabólicos levam à doença cardiovascular. Atualmente, o estudo da obesidade tem enfocado a leucemia linfocítica aguda e os tumores cerebrais, já que ambos têm risco para lesões hipotalâmicas, secundárias às terapias (irradiação cranial, quimioterapia, e cirurgia) ou à localização do tumor. Obesidade e câncer têm em comum fatores para síndrome metabólica. Entretanto, a relação de causa e efeito entre obesidade e câncer permanece controversa, sendo que são considerados outros mecanismos envolvendo o tecido adiposo e lesões hipotalâmicas, como o rebote precoce de adiposidade, hiperinsulinemia, regulação da leptina, e o papel do receptor ativado por proliferadores de peroxissoma γ. Concluindo, mais estudos são necessários para entender a relação entre adipogênese e descontrole hipotalâmico em sobreviventes de câncer.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Divisão de Endocrinologia Pediátrica Departamento de PediatriaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Divisão de Endocrinologia PediátricaUNIFESP, Divisão de Endocrinologia Pediátrica Depto. de PediatriaSciEL

Detection of metabolic syndrome features among childhood cancer survivors: A target to prevent disease

Along with the growing epidemic of obesity, the risk of atherosclerosis, cardiovascular disease morbidity, and mortality are increasing markedly. Several risk factors for cardiovascular disease, such as visceral obesity, glucose intolerance, arterial hypertension, and dyslipidemia commonly cluster together as a condition currently known as metabolic syndrome. Thus far, insulin resistance, and endothelial dysfunction are the primary events of the metabolic syndrome. Several groups have recommended clinical criteria for the diagnosis of metabolic syndrome in adults. Nonetheless, in what concerns children and adolescents, there are no unified definitions, and modified adult criteria have been suggested by many authors, despite major problems. Some pediatric disease states are at risk for premature cardiovascular disease, with clinical coronary events occurring very early in adult life. Survivors of specific pediatric cancer groups, particularly acute lymphocytic leukemia, central nervous system tumors, sarcomas, lymphomas, testicular cancer, and following bone marrow transplantation, may develop metabolic syndrome traits due to: hormonal deficiencies (growth hormone deficiency, thyroid dysfunction, and gonadal failure), drug or radiotherapy damage, endothelial impairment, physical inactivity, adipose tissue dysfunction, and/or drug-induced magnesium deficiency. In conclusion, some primary and secondary prevention remarks are proposed in order to reduce premature cardiovascular disease risk in this particular group of patients

Adiposidade em pacientes tratados por câncer na infância: entendendo a fisiopatologia da obesidade

As childhood cancer treatment has become more effective, survival rates have improved, and a number of complications have been described while many of these patients reach adulthood. Obesity is a well-recognized late effect, and its metabolic effects may lead to cardiovascular disease. Currently, studies concerning overweight have focused on acute lymphocytic leukemia and brain tumors, since they are at risk for hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation, chemotherapy, and brain surgery) or to primary tumor location. Obesity and cancer have metabolic syndrome features in common. Thus, it remains controversial if overweight is a cause or consequence of cancer, and to date additional mechanisms involving adipose tissue and hypothalamic derangements have been considered, comprising premature adiposity rebound, hyperinsulinemia, leptin regulation, and the role of peroxisome proliferator-activated receptor γ. Overall, further research is still necessary to better understand the relationship between adipogenesis and hypothalamic control deregulation following cancer therapy.Os avanços do tratamento contra o câncer infantil têm resultado no aumento da sobrevida e das complicações, à medida que os pacientes atingem a maioridade. A obesidade é um evento reconhecido, e seus efeitos metabólicos levam à doença cardiovascular. Atualmente, o estudo da obesidade tem enfocado a leucemia linfocítica aguda e os tumores cerebrais, já que ambos têm risco para lesões hipotalâmicas, secundárias às terapias (irradiação cranial, quimioterapia, e cirurgia) ou à localização do tumor. Obesidade e câncer têm em comum fatores para síndrome metabólica. Entretanto, a relação de causa e efeito entre obesidade e câncer permanece controversa, sendo que são considerados outros mecanismos envolvendo o tecido adiposo e lesões hipotalâmicas, como o rebote precoce de adiposidade, hiperinsulinemia, regulação da leptina, e o papel do receptor ativado por proliferadores de peroxissoma γ. Concluindo, mais estudos são necessários para entender a relação entre adipogênese e descontrole hipotalâmico em sobreviventes de câncer.190200Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Detection Of Metabolic Syndrome Features Among Childhood Cancer Survivors: A Target To Prevent Disease

Along with the growing epidemic of obesity, the risk of atherosclerosis, cardiovascular disease morbidity, and mortality are increasing markedly. Several risk factors for cardiovascular disease, such as visceral obesity, glucose intolerance, arterial hypertension, and dyslipidemia commonly cluster together as a condition currently known as metabolic syndrome. Thus far, insulin resistance, and endothelial dysfunction are the primary events of the metabolic syndrome. Several groups have recommended clinical criteria for the diagnosis of metabolic syndrome in adults. Nonetheless, in what concerns children and adolescents, there are no unified definitions, and modified adult criteria have been suggested by many authors, despite major problems. Some pediatric disease states are at risk for premature cardiovascular disease, with clinical coronary events occurring very early in adult life. Survivors of specific pediatric cancer groups, particularly acute lymphocytic leukemia, central nervous system tumors, sarcomas, lymphomas, testicular cancer, and following bone marrow transplantation, may develop metabolic syndrome traits due to: hormonal deficiencies (growth hormone deficiency, thyroid dysfunction, and gonadal failure), drug or radiotherapy damage, endothelial impairment, physical inactivity, adipose tissue dysfunction, and/or drug-induced magnesium deficiency. In conclusion, some primary and secondary prevention remarks are propose in order to reduce premature cardiovascular disease risk in this particular group of patients. © 2008 Siviero-Miachon et al, publisher and licensee Dove Medical Press Ltd.44825836Adan, L., Trivin, C., Sainte-Rose, C., GH deficiency caused by cranial irradiation during childhood: Factors and mukers in young adults (2001) J Clin Endocrinol Metab, 86, pp. 5245-5251Ahmet, A., Blaser, S., Stephens, D., Weight gain in craniopharyngioma -a model for hypothalamic obesity (2006) J Pediatr Endocrinol Metab, 19, pp. 121-128Alberti, K.G.M.M., Zimmet, P.Z., World Health Organisation (WHO)-Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation (1998) Diabet Med, 15, pp. 539-553National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (1992) Pediatrics, 89 (PART 2), pp. 525-584. , American Academy of PediatricsType 2 diabetes in children and adolescents (2000) Diabetes Care, 23, pp. 381-389. , American Diabetes AssociationArgüelles, B., Barrios, V., Buño, M., Anthropometric parameters and their relationship to serum growth hormone-binding protein and leptin levels in children with acute lymphoblastic leukemia: A prospective study (2000) Eur J Endocrinol, 143, pp. 243-250Baker, K.S., Ness, K.K., Steinberger, J., Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: A report from the Bone Marrow Transplantation Survivor Study (2007) Blood, 109, pp. 1765-1772Balkau, B., Charles, M.A., European Group for the Study of Insulin Resistance (EGIR) - Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (1999) Diabet Med, 16, pp. 442-443Barker, D.J., Fetal origins of coronary heart disease (1995) BMJ, 311, pp. 171-174Brydøy, M., Fosså, S.D., Dahl, O., Gonadal dysfunction and fertility problems in cancer survivors (2007) Acta Oncol, 46, pp. 480-489Bülow, B., Link, Y., Ahren, B., Survivors of childhood acute lymphoblastic leukaemia, with radiation-induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment (2004) Clin Endocrinol (Oxf), 61, pp. 683-691Chatterjee, R., Palla, K., MeGarrigle, H.H., Syndrome "X" in adult female recipients of bone marrow transplantation for haematological malignancies (2005) Bone Marrow Transplant, 35, pp. 209-210Colao, A., Di Somma, C., Rota, F., Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: A prospective study after GH withdrawal and restarting GH replacement (2005) J Clin Endocrinol Metab, 90, pp. 2659-2665Cook, S., Weitzman, M., Auinger, P., Prevalence of a metabolic syndrome phenotype in adolescents: Findings from the third National Health and Nutrition Examination Survey, 1988-1994 (2003) Arch Pediatr Adolesc Med, 157, pp. 821-827Cruz, M.L., Weigensberg, M.J., Huang, T.T., The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity (2004) J Clin Endocrinol Metab, 89, pp. 108-113Dalton, V.K., Rue, M., Silverman, L.B., Height and weight in children treated for acute lymphoblastic leukemia: Relationship to CNS treatment (2003) J Clin Oncol, 21, pp. 2953-2960DeFerranti, S.D., Gauvreau, K., Ludwig, D.S., Prevalence of the metabolic syndrome in American adolescents (2004) Circulation, 110, pp. 2494-2497Einhom, D., Reaven, G.M., Cobin, R.H., The American College of Endocrinology - American College of Endocrinology position statement on the insulin resistance syndrome (2003) Endocr Pract, 9, pp. 237-252Florin, T.A., Fryer, G.E., Miyoshi, T., Physical inactivity in adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study (2007) Cancer Epidenziol Biomarkers Prev, 16, pp. 1356-1363Genuth, S., Alberti, K.G., Bennett, P., Follow-up report on the diagnosis of diabetes mellitus. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Diabetes Care, 26, pp. 3160-3167Gleeson, H.K., Shalet, S.M., The impact of cancer therapy on the endocrine system in survivors of childhood brain tumors (2004) Endocr Relat Cancer, 11, pp. 589-602Grundy SM, Brewer Jr HB, Cleeman JI, et al. 2004. Definition of metabolic syndrome. Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation, 109:433-8Guo, C.Y., Halton, J.M., Barr, R.D., Hypomagnesemia associated with chemotherapy in patients treated for acute lymphoblastic leukemia: Possible mechanisms (2004) Oncol Rep, 11, pp. 185-189Gurney, J.G., Ness, K.K., Sibley, S.D., Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia (2006) Cancer, 107, pp. 1303-1312Harish, K., Dharmalingam, M., Himanshu, M., Study protocol: Insulin and its role in cancer (2007) BMC Endocr Disord, 7, p. 10Harz, K.J., Müller, H.L., Waldeck, E., Obesity in patients with craniopharyngioma: Assessment of food intake and movement counts indicating physical activity (2003) J Clin Endocrinol Metab, 88, pp. 5227-5231Heikens, J., Ubbink, M.C., Van der Pal, H.P.J., Long term survivors of childhood brain cancer have an increased risk for cardiovascular disease (2000) Cancer, 88, pp. 2116-2121Hickman, T.B., Briefel, R.R., Carroll, M.D., Distributions and trends of serum lipid levels among United States children and adolescents ages 4-19 years: Data from the Third National Health and Nutrition Examination Survey (1998) Prev Med, 27, pp. 879-890Higgins, K., Noon, C., Cartwright, V., Features of the metabolic syndrome present in bone marrow transplantation in adulthood (2004) Bone Marrow Transplant, 33 (SUPPL. 1), pp. S216-S217Hodgkinson, E., Neville-Webbe, H.L., Coleman, R.E., Magnesium depletion in patients receiving cisplatin-based chemotherapy (2006) Clin Oncol (R Coll Radiol), 18, pp. 710-718Hoffman, K.E., Derdak, J., Bernstein, D., Metabolic syndrome traits in long-term survivors of pediatric sarcoma (2008) Pediatr Blood Cancer, 50, pp. 341-346Hsu, I.R., Kim, S.P., Kabir, M., Metabolic syndrome, hyperinsulinemia, and cancer (2007) Am J Clin Nutr, 86, pp. S867-S871Hu, G., Qiao, Q., Tuomilehto, J., Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women (2004) Arch Intern Med, 164, pp. 1066-1076. , for the DECODE Study Group(2006) The IDF consensus worldwide definition of the metabolic syndrome, , http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf, online, Accessed on January 10, 2008. URLJaniszewski, P.M., Oeffinger, K.C., Church, T.S., Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia (2007) J Clin Endocrinol Metab, 92, pp. 3816-3821Jarfelt, M., Lannering, B., Bosaeus, I., Body composition in young adult survivors of childhood acute lymphoblastic leukaemia (2005) Eur J Endocrinol, 153, pp. 81-89Jones, K.L., The dilemma of the metabolic syndrome in children and adolescents: Disease or distraction? (2006) Pediatr Diabetes, 7, pp. 311-321Kavey RE, Allada V, Daniels SR, et al. 2006. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Sciencethe Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Diseaseand the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation, 114:2710-38Kourti, M., Tragiannidis, A., Makedou, A., Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy (2005) J Pediatr Hematol/Oncol, 27, pp. 499-501Link, K., Moëll, C., Garwicz, S., Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood (2004) J Clin Endocrinol Metab, 89, pp. 5003-5012Lustig, R.H., Autonomic dysfunction of the β-Cell and the pathogenesis of obesity (2003) Rev Endocr Metab Disord, 4, pp. 23-32Lustig, R.H., Post, S.R., Srivannaboon, K., Risk factors for the development of obesity in children surviving brain tumors (2003) J Clin Endocrinol Metab, 88, pp. 611-616Mertens, A.C., Yasui, Y., Neglia, J.P., Late mortality experience in five-year survivors of childhood and adolescent cancer: The Childhood Cancer Survivor Study (2001) J Clin Oncol, 19, pp. 3163-3172Mohamed-Ali, V., Pinkney, J.H., Coppack, S.W., Adipose tissue as an endocrine and paracrine organ (1998) Int J Obes, 22, pp. 1145-1158Moser, E.C., Noordijk, E.M., Carde, P., Late non-neoplastic events in patients with aggressive non-Hodgkin's lymphoma in four randomized European Organisation for Research and Treatment of Cancer trials (2005) Clin Lymphoma Myeloma, 6, pp. 122-130National Center for Health Statistics. 2000 CDC Growth Charts: United States [updated 2007 February 12cited 2007 November 08] [online]. Accessed on January 10, 2008. URL: http://www.cdc.gov/ growthcharts[NCEP-ATP III] National Cholesterol Education Program Adult Treatment Panel III - Expert panel on the detection, evaluation, and treatment of high blood cholesterol in adults. 2001. Executive summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 285:2486-97National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. 1996. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. Pediatrics, 98:649-58National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. 2004. Fourth report of the Task Force on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children. Pediatrics, 114:555-76Neville, K.A., Cohn, R.J., Steinbeck, K.S., Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: Prevalence and risk factors (2006) J Clin Endocrinol Metab, 91, pp. 4401-4407Nuver, J., Smit, A.J., Postma, A., The metabolic syndrome in long-term cancer survivors, an important target for secondary preventive measures (2002) Cancer Treat Ver, 28, pp. 195-214Nuver, J., Smit, A.J., Wolffenbuttel, B.H., The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer (2005) J Clin Oncol, 23, pp. 3718-3725Oeffinger, K.C., Buchanan, G.R., Eshelman, D.A., Cardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia (2001) J Pediatr Hematol/Oncol, 23, pp. 424-430Oeffinger, K.C., Mertens, A.C., Sklar, C.A., Obesity in adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study (2003) J Clin Oncol, 21, pp. 1359-1365Oeffinger, K.C., Are survivors of acute lymphoblastic leukemia (ALL) at increased risk of cardiovascular disease? (2008) Pediatr Blood Cancer, 50, pp. 462-467Pollak, M.N., Insulin, insulin-like growth factors, insulin resistance, and neoplasia (2007) Am J Clin Nutr, 86, pp. S820-S821Razzouk, B.I., Rose, S.R., Hongeng, S., Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma (2007) J Clin Oncol, 25, pp. 1183-1189Reaven, G.M., Banting lecture 1988: Role of insulin resistance in human disease (1988) Diabetes, 37, pp. 1595-1607Reilly, J.J., Kelly, A., Ness, P., Premature adiposity rebound in children treated for acute lymphoblastic leukemia (2001) J Clin Endocrinol Metab, 86, pp. 2775-2778Ross, J.A., Oeffinger, K.C., Davies, S.M., Genetic variation in the leptin receptor gene and obesity in survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study (2004) J Clin Oncol, 22, pp. 3558-3562Roth C, Wilken B, Hanefeld F, et al. 1998. Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. Eur J Endocrinol, 138-89-91Rutter, M.M., Rose, R.S., Long-term endocrine sequelae of childhood cancer (2007) Curr Opin Pediatr, 19, pp. 480-487Saini, A., Al-Shanti, N., Stewart, C.E., Waste management - cytokines, growth factors and cachexia (2006) Cytokine Growth Factor Rev, 17, pp. 475-486Sarti, C., Gallagher, J., The metabolic syndrome: Prevalence, CHD risk, and treatment (2006) J Diabetes Compl, 20, pp. 121-132Shalitin, S., Phillip, M., Stein, J., Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence (2006) Bone Marrow Transplant, 37, pp. 1109-1117Shoelson, S.E., Lee, J., Goldfine, A.B., Inflammation and insulin resistance (2006) J Clin Invest, 116, pp. 1793-1801Siviero-Miachon, A.A., Spinola-Castro, A.M., Tosta-Hernandez, P.D.C., Leptin assessment in acute lymphocytic leukemia survivors: Role of cranial radiotherapy? (2007) J Ped Hematol/Oncol, 29, pp. 776-782Sklar, C.A., Mertens, A.C., Walter, A., Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: Role of cranial irradiation (2000) Med Pediatr Oncol, 35, pp. 91-95Sklar, C.A., Mertens, A.C., Mitby, P., Premature menopause in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (2006) J Natl Cancer Inst, 98, pp. 890-896Soares, D.V., Spina, L.D., de Lima, Oliveira Brasil, R.R., Carotid artery intima-media thickness and lipid profile in adults with growth hormone deficiency after long-term growth hormone replacement (2005) Metabolism, 54, pp. 321-329Srinivasan, S., Ogle, G.D., Garnett, S.P., Features of the metabolic syndrome after childhood craniopharyngioma (2004) J Clin Endocrinol Metab, 89, pp. 81-86Szczepaniska-Kostro, J., Tolwinska, J., Urban, M., Cardiac mass and function, carotid artery intima media thickness, homocysteine and lipoprotein levels in children and adolescents with growth hormone deficiency (2004) J Pediatr Endocrinol Metab, 17, pp. 1405-1413Talvensaari, K.K., Lanning, M., Tapanainen, P., Long-term survivors of childhood cancer have an increased risk of manifesting the metabolic syndrome (1996) J Clin Endocrinol Metab, 81, pp. 3051-3055Taskinen, M., Lipsanen-Nyman, M., Tiitinen, A., Insufficient growth hormone secretion is associated with metabolic syndrome after allogeneic stem cell transplantation in childhood (2007) J Pediatr Hematol/ Oncol, 29, pp. 529-534Trimis, G., Moschovi, M., Papassotiriou, I., Early indicators of dysmetabolic syndrome in young survivors of acute lymphoblastic leukemia in childhood as a target for preventing disease (2007) J Ped Hematol/ Oncol, 29, pp. 309-314Waychenberg, B.L., Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome (2000) Endocr Rev, 21, pp. 697-738Weiss, R., Dziura, J., Burgett, T.S., Obesity and the metabolic syndrome in children and adolescents (2004) N Engl J Med, 350, pp. 2362-2374Zimmet P, Alberti G, Kaufinan F, et al. on behalf of the International Diabetes Federation Task Force on Epidemiology and Prevention of Diabetes. 2007. The metabolic syndrome in children and adolescents. Lancet, 369:2059-61Zhou JR, Blackburn GL, Walker WA. 2007. Symposium introduction: metabolic syndrome and the onset of cancer. Am J Clin Nutr, 86: S817-S81

The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (Aids) patients

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.As primeiras descrições da síndrome da imunodeficiência adquirida (Aids) associavam-se à síndrome de emaciamento, e os distúrbios metabólicos às alterações na composição corporal. Após a introdução da terapia anti-retroviral altamente ativa (HAART), houve declínio na desnutrição, e surge a lipodistrofia como importante distúrbio metabólico. A Aids também se caracteriza por distúrbios hormonais, principalmente no eixo hormônio de crescimento/fator de crescimento insulina-like tipo 1 (GH/IGF-1). O uso do GH recombinante humano (hrGH) foi inicialmente indicado na síndrome de emaciamento, a fim de aumentar a massa muscular. Embora também não existam dúvidas quanto aos efeitos do hrGH na lipodistrofia, a diminuição na sensibilidade à insulina limita o seu uso, o qual ainda não está oficialmente aprovado. A diversidade nos esquemas de tratamento é outro limitante do uso dessa medicação em pacientes com Aids. Esta revisão apresenta os principais distúrbios endócrino-metabólicos associados à Aids e ao uso do hrGH nessas condições.Universidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Serviço de Endocrinologia PediátricaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de PediatriaUnicamp FCM Departamento de PediatriaUNIFESP, Depto. de Pediatria Serviço de Endocrinologia PediátricaSciEL

Short stature in chronic kidney disease: physiopathology and treatment with growth hormone

Growth failure is frequent and a clinically important issue in children with chronic kidney disease (CKD). Many factors contribute to impaired growth in these children, including abnormalities in the growth hormone (GH) - insulin-like growth factor 1 (IGF-1) axis, malnutrition, acidosis, renal bone disease and glucocorticoid associated treatment. The management of growth failure in children with CKD is complicated by the presence of other-disease related complications requiring medical intervention. Despite evidence of GH efficacy and safety in this population, this therapy is still underutilized. This review shows the impact, the causes and the treatment of growth failure in children with CKD.O atraso no crescimento é freqüente e grave em crianças com doença renal crônica (DRC). Vários fatores contribuem para o comprometimento do crescimento nestas crianças, incluindo as alterações no eixo hormônio de crescimento (GH) - insulin-like growth factor 1 (IGF-1), desnutrição, acidose, doença renal óssea e uso de corticóides. Em crianças com DRC, o tratamento do atraso no crescimento é difícil em virtude da presença de doenças associadas que necessitem de adequado tratamento médico. Apesar de as evidências a respeito da segurança e de a eficácia do GH nesta população, este tratamento ainda é pouco utilizado. Esta revisão mostra o impacto, as causas e o tratamento do atraso no crescimento em crianças com DRC.Universidade Estadual de Campinas Faculdade de Ciências Médicas Clínica MédicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Programa de Pós-graduação do Curso de PediatriaUNIFESP-EPM Departamento de PediatriaUnicamp FCM Departamento de PediatriaUNIFESP, EPM, Programa de Pós-graduação do Curso de PediatriaUNIFESP, EPM Depto. de PediatriaSciEL

Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

Background: Advances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. the aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia.Methods: A comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance.Results: Cranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance.Conclusions: Adolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Div Pediat Endocrinol, Dept Pediat, UNIFESP EPM, São Paulo, BrazilIOP GRAACC, Pediat Oncol Inst, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent & Social Med, Div Biostat, UNIFESP EPM, São Paulo, BrazilUniv Estadual Campinas, Lab Invest Metab & Diabet LIMED, Fac Med Sci, UNICAMP, Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imaging, UNIFESP EPM, São Paulo, BrazilUniv Estadual Campinas, Dept Pediat, Div Pediat Endocrinol, Fac Med Sci,UNICAMP, Campinas, SP, BrazilUniversidade Federal de São Paulo, Div Pediat Endocrinol, Dept Pediat, UNIFESP EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Prevent & Social Med, Div Biostat, UNIFESP EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imaging, UNIFESP EPM, São Paulo, BrazilFAPESP: 06/06162-9Web of Scienc

The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (Aids) patients

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.As primeiras descrições da síndrome da imunodeficiência adquirida (Aids) associavam-se à síndrome de emaciamento, e os distúrbios metabólicos às alterações na composição corporal. Após a introdução da terapia anti-retroviral altamente ativa (HAART), houve declínio na desnutrição, e surge a lipodistrofia como importante distúrbio metabólico. A Aids também se caracteriza por distúrbios hormonais, principalmente no eixo hormônio de crescimento/fator de crescimento insulina-like tipo 1 (GH/IGF-1). O uso do GH recombinante humano (hrGH) foi inicialmente indicado na síndrome de emaciamento, a fim de aumentar a massa muscular. Embora também não existam dúvidas quanto aos efeitos do hrGH na lipodistrofia, a diminuição na sensibilidade à insulina limita o seu uso, o qual ainda não está oficialmente aprovado. A diversidade nos esquemas de tratamento é outro limitante do uso dessa medicação em pacientes com Aids. Esta revisão apresenta os principais distúrbios endócrino-metabólicos associados à Aids e ao uso do hrGH nessas condições.525818832Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions

Fatores precoces para síndrome metabólica em sobreviventes de câncer pediátrico: resultados em adolescentes e adultos jovens tratados por meduloblastoma na infância

OBJECTIVE: To analyze traits of metabolic syndrome (MetS) in medulloblastoma survivors. SUBJECTS AND METHODS: Sixteen childhood medulloblastoma survivors aged 18.0 (4.4) years, with history of craniospinal radiation therapy (RT) were compared with nine control subjects matched by age, gender, and body mass index, according to fat distribution, metabolic and cardiovascular variables. RESULTS: Medulloblastoma patients showed increases in waist circum-ference and its relationships (all p < 0.05), and HOMA1-IR (p = 0.006), which were modified by growth hormone (GH) secretion status. However, these increases were within normal range. CONCLUSIONS: Adolescent and young adult survivors of medulloblastoma showed centripetal fat deposition and decreased insulin sensitivity, associated with GH status. Pediatric brain tumor survivors following RT should be monitored for the diagnosis of MetS traits predisposing to cardiovascular disease.OBJETIVO: Analisar características que predispõem para síndrome metabólica (SM) em sobreviventes de meduloblastoma. SUJEITOS E MÉTODOS: Dezesseis sobreviventes de meduloblastoma pediátrico, 18,0 (4,4) anos, história de radioterapia (RT) cranioespinhal, comparados a nove controles pareados por idade, sexo e índice de massa corporal, de acordo com distribuição de gordura, variáveis metabólicas e cardiovasculares. RESULTADOS: Pacientes com meduloblastoma mostraram aumento da cintura e relações (todos p < 0,05) e HOMA1-IR (p = 0,006), modificados pela secreção do hormônio de crescimento (GH), mas dentro dos limites de normalidade. CONCLUSÕES: Sobreviventes adolescentes e adultos jovens de meduloblastoma apresentaram deposição centrípeta de gordura e diminuição da sensibilidade à insulina, associados ao estado do GH. Sobreviventes de tumor cerebral pediátrico que receberam RT devem ser monitorados para diagnosticar fatores para SM predispondo à doença cardiovascular.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of PediatricsUNIFESP-EPM Department of MedicineUniversidade de São Paulo Department of Food Science and Experimental Nutrition Pharmaceutical Science SchoolUNIFESP-EPM Department of PediatricsUNIFESP, EPM, Department of PediatricsUNIFESP, EPM Department of MedicineUNIFESP, EPM Department of PediatricsSciEL

O uso da hibridação in situ com fluorescência no diagnóstico de mosaicismo oculto: a propósito de três casos de anomalias de cromossomos sexuais

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51FISH tem sido usado como um complemento para a citogenética clássica na detecção de mosaicismo em anomalias de cromossomos sexuais. O objetivo deste trabalho é descrever três casos nos quais o diagnóstico final só foi obtido por meio de FISH. O caso 1 é uma menina de 8 anos, 46,XY, com genitália feminina normal, encaminhada ao nosso setor devido à baixa estatura. A análise de linfócitos por FISH com sondas centroméricas de X e Y identificou a constituição 45,X/46,X,idic(Y) e estabeleceu o diagnóstico de síndrome de Turner. O caso 2 é um menino de 21 meses, 46,XY, com ambiguidade genital (hipospadia peniana, testículo à direita e gônada disgenética à esquerda). FISH de linfócitos e mucosa oral identificou o cariótipo 45,X/46,XY, levando ao diagnóstico de disgenesia gonadal mista. O caso 3 é um rapaz de 19 anos, 47,XYY, com atraso de desenvolvimento neuromotor, dificuldade de aprendizado, problemas psicológicos, alta estatura, testículos pequenos, gonadotrofinas elevadas e azoospermia. FISH de linfócitos e mucosa oral identificou a constituição 47,XYY/48,XXYY. Os casos 1 e 2 ilustram a variabilidade fenotípica do mosaico 45,X/46,XY e a importância da detecção da linhagem 45,X na avaliação e na condução dos casos. No caso 3, a função gonadal anormal pôde ser explicada pela linhagem 48,XXYY. O uso de FISH na prática clínica é particularmente relevante quando a análise citogenética clássica traz resultados normais ou incertos em pacientes com quadro sugestivo de uma aneuploidia de cromossomos sexuais. Arq Bras Endocrinol Metab. 2012;56(8):545-51Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Genética MédicaUnicamp FCM Grupo Interdisciplinar de Estudos da Determinação e Diferenciação do SexoUnicamp FCM Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL