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. Arq Bras Endocrinol Metab. 2009;53(2):190-200. KeywordsAdiposity; precursor cell lymphoblastic leukemia-lymphoma; brain neoplasms; radiotherapy; drug therapy; leptin resumo 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 síndro-me 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. Arq Bras Endocrinol Metab. 2009;53(2):190-200. Descritores

BackgroundAdvances 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.MethodsA 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.ResultsCranial 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.ConclusionsAdolescent 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.

Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L-L (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.

Leptin has been hypothesized to play a role in the development of obesity in leukemia survivors, particularly those who have received cranial radiotherapy. This cross-sectional study evaluated the relationship between leptin levels and body mass index (BMI) in a sample of 26 acute lymphocytic leukemia survivors of both sexes, treated with and without cranial irradiation, aged 7.6 to 17 years, at a mean 3.4+/-2.0 years off treatment. There were significantly more males among the irradiated group (P<0.001), even though no differences were encountered in pubertal stage (P=1.000), BMI standard deviation score (mean+/-SD) (0.68+/-1.00 vs. 1.19+/-0.78; P=0.164), or leptin concentrations (17.01+/-17.04 vs. 23.3+/-13.4; P=0.309). Nonetheless, there was a positive correlation between the natural logarithm of leptin and BMI standard deviation score [t(22)=2.348, P=0.028], however, no differences were recorded among irradiated and nonirradiated patients [F(2,22)=0.384, P=0.685]. When this relationship was compared between sexes, a significant difference was encountered [F(2,22)=4.907, P=0.017], with males having the strongest association (R(2)males=65.5%, R(2)females=34.7%). Leptin is a reliable adiposity index as it strongly correlates with BMI. Overall, the current data suggest that cranial irradiation did not play a role upon this relationship; however, sex differences influenced positively this correlation.

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RESUMOo 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 evidên-cias 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. H istoricamente, o termo insuficiência renal crônica (IRC) tem sido usado para descrever pacientes com ritmo de filtração glomerular (RFG) menor que 75 mL/min/1,73 m 2 de área corporal (1). Mais recentemente, a National Kidney Foundation (NKF) introduziu o termo doença renal crônica (DRC), bem como a classificação do quadro, a fim de propiciar a detecção precoce, retardar a progressão e prevenir complicações relacionadas. Essa classificação descreve cinco estágios da DRC considerando a presença de lesão

PurposeThe aim of this study was to evaluate the relationship between body composition, metabolic profile, adipokines, and carotid intima-media thickness (cIMT) in young survivors of childhood acute lymphocytic leukemia (ALL).Patients and methodsThis cross-sectional study compared 55 ALL survivors, of chronological age between 15 years and 24 years, assigned into two groups according to the exposure to cranial radiation therapy (CRT; 25 irradiated and 30 nonirradiated) with 24 leukemia-free controls, and assessed body fat mass (dual-energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, blood pressure (BP), adipokines, and cIMT by a multiple regression analysis.ResultsTreatment with CRT had an effect on all of the variables derived from the computed tomography scan: visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (P<0.050). In a multiple linear regression model, cIMT positively correlated with exposure to CRT (P=0.029), diastolic BP (P=0.016), and leptin-to-adiponectin ratio (P=0.048), while negatively related to SAT (P=0.007).ConclusionIn young survivors of childhood ALL, CRT modified the distribution of fat and played a critical role in determining cIMT. Leptin-to-adiponectin ratio, a biomarker of abdominal obesity and metabolic syndrome, and diastolic BP also influenced cIMT, a marker of subclinical atherosclerosis. Nonetheless, adiposity-associated vascular disease might be attenuated by SAT. Changes in body fat must be evaluated in this group of patients in the early course of survivorship in order to avoid premature cardiovascular disease associated with atherosclerosis. Yet, further research as regards the possible protective effect of SAT on vascular disease is warranted.