Relations between asthma and obesity: an analysis of multiple factors / Relações entre asma e obesidade: análise de múltiplos fatores

ABSTRACT Objective: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. Methods: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. Results: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. Conclusions: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

RESUMO Objetivo: A asma e a obesidade são doenças prevalentes e inter-relacionadas. Na população pediátrica, o efeito da inflamação sistêmica associada à obesidade, levando à inflamação das vias aéreas, é controverso. Nosso objetivo foi comparar padrões inflamatórios, clínicos e espirométricos entre crianças obesas e aquelas com peso normal. Métodos: Setenta e nove meninos e meninas de 6‒10 anos de idade foram selecionados e divididos em quatro grupos: asmáticos obesos, asmáticos não obesos, não asmáticos obesos e não asmáticos não obesos. Além de dados clínicos e antropométricos, todas as crianças foram submetidas a espirometria e testes cutâneos para alérgenos inalantes. Também foram coletadas amostras de sangue para dosagem de citocinas e adipocinas. Resultados: Obesos asmáticos tiveram um controle significativamente pior da asma do que os não obesos (RP 4,9; IC95% 1,1‒22,1), independentemente do sexo, atividade física e atopia. Não foram observadas diferenças nos níveis de espirometria, citocinas Th1 e Th2 e adipocinas entre os quatro grupos. Os testes cutâneos foram positivos em 81,8 e 80% dos não obesos asmáticos e obesos asmáticos, respectivamente. Conclusões: O grau de controle da asma foi significativamente menor no grupo obeso, apesar de não ter havido diferenças nos achados espirométricos. Esse resultado sugere que fatores extrapulmonares podem ser responsáveis por esse perfil sintomático. A alta positividade do teste cutâneo nos dois grupos, considerado um bom marcador de atopia, demonstrou o componente atópico como preponderante na gênese da asma, tanto em crianças com obesidade quanto naquelas com peso normal.

RELATIONS BETWEEN ASTHMA AND OBESITY: AN ANALYSIS OF MULTIPLE FACTORS.

OBJECTIVE: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. METHODS: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. RESULTS: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. CONCLUSIONS: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

Ultrasound as a method to evaluate the distribution of abdominal fat in obese prepubertal children and the relationship between abdominal fat and metabolic alterations.

Abstract. OBJECTIVE: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. MATERIALS AND METHODS: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. RESULTS: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. CONCLUSION: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.

OBJETIVO: Avaliar, em crianças pré-púberes obesas, a distribuição da gordura no abdome por meio da ultrassonografia e sua possível correlação com as alterações metabólicas decorrentes da obesidade. MATERIAIS E MÉTODOS: Estudo transversal em crianças pré-púberes, sendo 77 obesas (33 meninas e 44 meninos) com média de idade de 7,31 anos e 31 eutróficas (17 meninas e 14 meninos) com média de idade de 7,32 anos. Em todas as crianças foram medidas a espessura da parede abdominal (EPA) e a espessura da gordura intra-abdominal (EIA), pela ultrassonografia. Para a avaliação das alterações metabólicas associadas, foi realizada dosagem sérica de glicemia, HDL-colesterol, triglicerídeos e insulina. RESULTADOS: Observou-se que as crianças obesas apresentaram aumento da gordura abdominal, com predomínio da EPA e sem diferença significativa da EIA e a EPA em relação ao gênero. Foi encontrada associação direta estatisticamente significante entre o índice homeostatic model assessment for insulin resistance (HOMA-IR) e EPA e EIA. CONCLUSÃO: A EPA em pré-púberes obesos, medida pela ultrassonografia, demonstrou ter maior relação com o HOMA-IR, determinante de resistência insulínica, em relação ao metabolismo lipídico e à glicemia.

Ultrasound as a method to evaluate the distribution of abdominal fat in obese prepubertal children and the relationship between abdominal fat and metabolic alterations / A ultrassonografia como método de avaliação da distribuição da gordura abdominal em crianças pré-púberes obesas e sua relação com alterações metabólicas

Abstract Objective: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. Materials and Methods: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. Results: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. Conclusion: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.

Resumo Objetivo: Avaliar, em crianças pré-púberes obesas, a distribuição da gordura no abdome por meio da ultrassonografia e sua possível correlação com as alterações metabólicas decorrentes da obesidade. Materiais e Métodos: Estudo transversal em crianças pré-púberes, sendo 77 obesas (33 meninas e 44 meninos) com média de idade de 7,31 anos e 31 eutróficas (17 meninas e 14 meninos) com média de idade de 7,32 anos. Em todas as crianças foram medidas a espessura da parede abdominal (EPA) e a espessura da gordura intra-abdominal (EIA), pela ultrassonografia. Para a avaliação das alterações metabólicas associadas, foi realizada dosagem sérica de glicemia, HDL-colesterol, triglicerídeos e insulina. Resultados: Observou-se que as crianças obesas apresentaram aumento da gordura abdominal, com predomínio da EPA e sem diferença significativa da EIA e a EPA em relação ao gênero. Foi encontrada associação direta estatisticamente significante entre o índice homeostatic model assessment for insulin resistance (HOMA-IR) e EPA e EIA. Conclusão: A EPA em pré-púberes obesos, medida pela ultrassonografia, demonstrou ter maior relação com o HOMA-IR, determinante de resistência insulínica, em relação ao metabolismo lipídico e à glicemia.

Microcirculation, Adiposity, and Traditional and Emerging Cardiovascular Risk Factors in Prepubertal Children.

PURPOSE: Previous studies have shown that microvascular dysfunction (MD) is associated with a number of cardiovascular risk factors, including obesity. Few studies have assessed microvascular reactivity in children, and in most of these, results were confounded by the effects of puberty. Our aim was to establish whether MD is already present in obese prepubertal children. METHODS: This cross-sectional study included 52 obese, 18 overweight, and 28 eutrophic children, with a mean ± standard deviation age of 7.44 ± 1.22 years. We evaluated cardiovascular risk factors and nutritive microvascular function by using nailfold dynamic videocapillaroscopy and determined functional capillary density (FCD), red blood cell velocity at resting conditions (RBCV) and at peak (RBCVmax), and time to reach peak velocity during the post-occlusive reactive hyperemic response following 1 minute ischemia. RESULTS: On univariate analysis, differences in microvascular reactivity were not observed among the groups. Obese and overweight children had significantly higher scores than eutrophic children for the following parameters: body mass index, waist circumference, waist-to-height ratio, mean arterial pressure, homeostasis model assessment for insulin resistance, levels of insulin, leptin, glucose, triglycerides, total cholesterol, uric acid, and C-reactive protein. Multivariate analysis demonstrated the association between metabolic, anthropometric, and microvascular variables, stratified according to the degree of adiposity and body fat distribution. CONCLUSIONS: Univariate analysis did not show any difference in microvascular reactivity between groups but, by testing these variables by multivariate means, we noticed a common and direct variation between cardiovascular/metabolic risk factors and microvascular reactivity occurring early in life.

Leptin as a predictor of metabolic syndrome in prepubertal children

ABSTRACT Objective Leptin has been suggested as a potential biomarker of cardiovascular risk. This paper aims to ascertain, based on a sample of prepubertal children, which serum leptin value best suited to identify metabolic syndrome (MS). Subjects and methods This observational, cross-sectional study recruited children from the outpatient pediatrics clinic, with the purpose of validating serum leptin level cutoffs to identify MS. All obese and overweight children who met eligibility criteria were included in the study, as was a sample of normal-weight children. The sample underwent clinical assessment and blood fasting glucose, lipid profile, insulin, and leptin were measured. Sensitivity and specificity were estimated for each leptin measurement, using MS as the outcome. These values were used to construct a receiver operating characteristic (ROC) curve. The association between MS and leptin was assessed using logistic models to predict MS. Results A total of 65 normal weight, 46 overweight, and 164 obese children were analyzed (160 boys, 115 girls; age: 93.7 ± 17.8 months). The most appropriate leptin cutoff was 13.4 ng/mL (sensitivity 67.6%; specificity 68.9%; accuracy 72.1%). The logistic model indicated that leptin levels above 13.4 ng/dL were significantly associated with MS and that, for every 1 ng/dL increase in leptin levels, the odds of MS increase by 3% (p = 0.002; OR 1.03; 95% CI 1.01-1.05). Conclusions Leptin may be a useful biomarker of cardiovascular risk in prepubertal children, with an optimal cutoff of 13.4 ng/mL. Identification of potential new risk markers for cardiovascular disease in children could contribute to the development of preventive strategies.

Leptin as a predictor of metabolic syndrome in prepubertal children.

OBJECTIVE: Leptin has been suggested as a potential biomarker of cardiovascular risk. This paper aims to ascertain, based on a sample of prepubertal children, which serum leptin value best suited to identify metabolic syndrome (MS). SUBJECTS AND METHODS: This observational, cross-sectional study recruited children from the outpatient pediatrics clinic, with the purpose of validating serum leptin level cutoffs to identify MS. All obese and overweight children who met eligibility criteria were included in the study, as was a sample of normal-weight children. The sample underwent clinical assessment and blood fasting glucose, lipid profile, insulin, and leptin were measured. Sensitivity and specificity were estimated for each leptin measurement, using MS as the outcome. These values were used to construct a receiver operating characteristic (ROC) curve. The association between MS and leptin was assessed using logistic models to predict MS. RESULTS: A total of 65 normal weight, 46 overweight, and 164 obese children were analyzed (160 boys, 115 girls; age: 93.7 ± 17.8 months). The most appropriate leptin cutoff was 13.4 ng/mL (sensitivity 67.6%; specificity 68.9%; accuracy 72.1%). The logistic model indicated that leptin levels above 13.4 ng/dL were significantly associated with MS and that, for every 1 ng/dL increase in leptin levels, the odds of MS increase by 3% (p = 0.002; OR 1.03; 95% CI 1.01-1.05). CONCLUSIONS: Leptin may be a useful biomarker of cardiovascular risk in prepubertal children, with an optimal cutoff of 13.4 ng/mL. Identification of potential new risk markers for cardiovascular disease in children could contribute to the development of preventive strategies.

Prognostic Factors for Early and Long-Term Remission in Pediatric Differentiated Thyroid Carcinoma: The Role of Sex, Age, Clinical Presentation, and the Newly Proposed American Thyroid Association Risk Stratification System.

BACKGROUND: The incidence of pediatric differentiated thyroid carcinoma (DTC) has been rising in recent years, and the main risk factors for recurrence are lymph node and distant metastasis at diagnosis. Other clinical features remain unclear, such as the impact of age, sex, and puberty. Furthermore, until now, this population has been treated using the same strategies used to treat adults. In 2015, the American Thyroid Association (ATA) published the first guidelines targeted at this age group. The aims of this study were to investigate the prognostic factors for early and long-term remission and also to validate the ATA risk stratification proposal in a population outside the United States. METHODS: Clinical records from 118 patients <18 years old followed in two referral centers were reviewed. The median age was 12 years (range 4-18 years), and 20.3% (24 patients) were <10 years old at diagnosis. The median follow-up was 9.1 years. The majority were female (72%) and received total thyroidectomy and radioiodine therapy (RAI), and 61.8% were treated with more than one dose of RAI. The majority were classified as high risk (48.3%) by the new ATA pediatric guidelines due to distant metastasis (30 patients) or extensive lymph node involvement (27 patients). The remained were classified as low risk (31.3%) and intermediate risk (20.4%). RESULTS: Females with no lymph node or distant metastasis and low ATA pediatric risk were more likely to have no evidence of disease (p < 0.05) within the first year and also in the long term. In this study, age did not significantly predict outcomes. Furthermore, patients also benefitted from multiple doses of RAI, but when the cumulative activity was >400 mCi, this benefit was diminished. CONCLUSIONS: This study shows that the ATA risk stratification proposal for pediatric patients is useful in predicting early and long-term outcomes in pediatric patients with DTC. In addition, it shows that sex and metastatic disease are important prognostic factors in pediatric populations.

Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience.

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children.

BACKGROUND: Early exposure to cardiovascular risk factors creates a chronic inflammatory state that could damage the endothelium followed by thickening of the carotid intima-media. OBJECTIVE: To investigate the association of cardiovascular risk factors and thickening of the carotid intima. SUBJECTS/METHODS: Media in prepubertal children. In this cross-sectional study, carotid intima-media thickness (cIMT) and cardiovascular risk factors were assessed in 129 prepubertal children aged from 5 to 10 year. Association was assessed by simple and multivariate logistic regression analyses. RESULTS: In simple logistic regression analyses, body mass index (BMI) z-score, waist circumference, and systolic blood pressure (SBP) were positively associated with increased left, right, and average cIMT, whereas diastolic blood pressure was positively associated only with increased left and average cIMT (p<0.05). In multivariate logistic regression analyses increased left cIMT was positively associated to BMI z-score and SBP, and increased average cIMT was only positively associated to SBP (p<0.05). CONCLUSIONS: BMI z-score and SBP were the strongest risk factors for increased cIMT.

Nonobese Young Females with Polycystic Ovary Syndrome have Nutritive Microvascular Dysfunction: A Pilot Study.

OBJECTIVE: To investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables. METHODS: Fourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/m2) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCVmax), and time taken to reach RBCVmax (TRBCVmax). RESULTS: Subjects with PCOS had lower RBCV and higher TRBCVmax compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, P<.01) and (5 [5-6] vs. 4 [3-5] s, P<.05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCVmax (ρ = -0.49, P<.05) and to TRBCVmax (ρ = 0.41, P<.05). SHBG correlated with RBCVmax (ρ = 0.52, P<.01) while estradiol (E2) levels correlated with RBCV (ρ = 0.80, P<.001) and RBCVmax (ρ = 0.46, P<.05). CONCLUSION: Microvascular dysfunction characterized by reduced RBCVmax and prolonged TRBCVmax was present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction.

Atualização terapêutica no tratamento dos craniofaringiomas / Therapeutic update on the treatment of craniopharyngiomas

O craniofaringioma é uma neoplasia de natureza benigna, pouco frequente, responsável por 1 por cento a 3 por cento de todos os tumores intracranianos, sendo a mais frequente neoplasia intracraniana não neuroepitelial na criança. Geralmente o tumor é restrito à região selar e ao III ventrículo, mas, em decorrência da infiltração e frequente aderência ao sistema nervoso central, apresenta comportamento clínico muitas vezes desfavorável, sendo classificado pela Organização Mundial de Saúde (OMS) como grau I, caracterizado como tumor de baixo ou incerto potencial de malignização. As sequelas endocrinológicas ganham destaque devido ao importante impacto na qualidade de vida dos pacientes, na maioria das vezes crianças. O hipopituitarismo e a obesidade hipotalâmica são complicações frequentes, sendo o tratamento desse tumor um grande desafio para endocrinologistas e neurocirurgiões. A combinação da cirurgia, radioterapia e aplicação de drogas e radioisótopos intratumorais tem como objetivo maximizar as chances de cura e tentar minimizar as sequelas pós-operatórias, mas, mesmo assim, a recidiva ainda é frequente. A escolha da modalidade de tratamento mais adequado para os craniofaringiomas é uma decisão difícil e que deve sempre ser individualizada para cada paciente. Com o objetivo de explorar as múltiplas opções terapêuticas para o craniofaringioma, foi realizada revisão na literatura com ênfase nas possibilidades terapêuticas e complicações inerentes ao tratamento dessa patologia.

Craniopharyngioma is an uncommon benign neoplasm, accounting for 1 percent-3 percent of all intracranial tumors, and the most common non-neuroepithelial intracranial neoplasm in childhood. Usually, the tumor is confined to the sellar region and the third ventricle, but due to frequent infiltration and adherence to the central nervous system, it often has an unfavorable clinical behavior. Therefore, it is classified by the World Health Organization (WHO) as a tumor of low or uncertain malignant potential. Endocrine after effects, mainly hypothalamic hypopituitarism, obesity and diabetes insipidus are highlighted due to their important impact on the quality of life of patients, mostly children. Optimal treatment of this tumor is a major challenge for neurosurgeons and endocrinologists. The combination of surgery, radiation, and application of radioisotopes and intratumoral drugs, aims at maximizing the chances of cure with minimal complications. Yet, recurrence is still frequent. Choosing the best treatment modality for craniopharyngiomas is a difficult decision, and it should always be specific for each case. In order to explore the multiple therapeutic options for craniopharyngiomas, we reviewed the literature with emphasis on the therapeutic possibilities and complications inherent to the treatment of this disease.

The role of metabolic syndrome components and adipokines in insulin resistance in prepubertal children.

OBJECTIVE: Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipokines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children. METHODS: We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans, age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression. RESULTS: There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05). CONCLUSION: Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer.

BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14). The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up). Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014). The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

[Therapeutic update on the treatment of craniopharyngiomas]. / Atualização terapêutica no tratamento dos craniofaringiomas.

Craniopharyngioma is an uncommon benign neoplasm, accounting for 1%-3% of all intracranial tumors, and the most common non-neuroepithelial intracranial neoplasm in childhood. Usually, the tumor is confined to the sellar region and the third ventricle, but due to frequent infiltration and adherence to the central nervous system, it often has an unfavorable clinical behavior. Therefore, it is classified by the World Health Organization (WHO) as a tumor of low or uncertain malignant potential. Endocrine after effects, mainly hypothalamic hypopituitarism, obesity and diabetes insipidus are highlighted due to their important impact on the quality of life of patients, mostly children. Optimal treatment of this tumor is a major challenge for neurosurgeons and endocrinologists. The combination of surgery, radiation, and application of radioisotopes and intratumoral drugs, aims at maximizing the chances of cure with minimal complications. Yet, recurrence is still frequent. Choosing the best treatment modality for craniopharyngiomas is a difficult decision, and it should always be specific for each case. In order to explore the multiple therapeutic options for craniopharyngiomas, we reviewed the literature with emphasis on the therapeutic possibilities and complications inherent to the treatment of this disease.

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14). The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5 percent and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up). Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014). The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review.

Spindle epithelial tumor with thymus-like element (SETTLE) is a rare malignant neoplasm of the thyroid, occurring predominantly in children, adolescents, and young adults. SETTLE usually presents itself as a thyroid mass, without metastases at diagnosis. It is believed to derive from branchial pouch or thymic remnant tissue showing primitive thymic differentiation. This article reports the clinical, cytological, histological and immunohistochemical features of a SETTLE in a 3-year-old girl. Microscopic exam revealed a nodular, highly cellular neoplasm displayed in the classic biphasic pattern, with mixture of prominent spindle cell component and a minor glandular component lined by mucinous or respiratory-type epithelium. The immunohistochemical study showed strong and diffuse positivity for pan-CK, vimentin and smooth muscle actin. The present case is the first SETTLE case reported in Brazil. To date, the patient described remains without evidence of recurrence or metastasis 5 years after surgery.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review / Tumor epitelial de células fusiformes com diferenciação thymus-like da tireoide (SETTLE): relato de caso e revisão da literatura

Spindle epithelial tumor with thymus-like element (SETTLE) is a rare malignant neoplasm of the thyroid, occurring predominantly in children, adolescents, and young adults. SETTLE usually presents itself as a thyroid mass, without metastases at diagnosis. It is believed to derive from branchial pouch or thymic remnant tissue showing primitive thymic differentiation. This article reports the clinical, cytological, histological and immunohistochemical features of a SETTLE in a 3-year-old girl. Microscopic exam revealed a nodular, highly cellular neoplasm displayed in the classic biphasic pattern, with mixture of prominent spindle cell component and a minor glandular component lined by mucinous or respiratory-type epithelium. The immunohistochemical study showed strong and diffuse positivity for pan-CK, vimentin and smooth muscle actin. The present case is the first SETTLE case reported in Brazil. To date, the patient described remains without evidence of recurrence or metastasis 5 years after surgery.

O tumor epitelial de células fusiformes com elemento thymus-like é uma rara neoplasia maligna da tireoide, ocorrendo predominantemente em crianças, adolescentes e adultos jovens. Habitualmente, esse tumor se apresenta como massa tireoideana, sem metástases ao diagnóstico. Acredita-se derivar de arco branquial ou tecido remanescente tímico, apresentando diferenciação tímica primitiva. Este artigo descreve os aspectos clínicos, citológicos, histológicos e imuno-histoquímicos de um caso de SETTLE diagnosticado em uma menina de 3 anos de idade. O aspecto microscópico encontrado no tumor foi de uma lesão nodular, hipercelular, disposta em aspecto bifásico clássico, com componente de células fusiformes, e de tecido glandular acompanhado por epitélio mucinoso e respiratório. O estudo imuno-histoquímico foi positivo para pan-CK, vimentina e actina de músculo liso. Esse caso é o primeiro relato de SETTLE no Brasil. A paciente descrita permanece sem evidência de doença em atividade cinco anos após o tratamento cirúrgico.

O impacto da obesidade sobre os componentes da síndrome metabólica e as adipocitoquinas em crianças pré-púberes / Impact of obesity on metabolic syndrome components and adipokines in prepubertal children

OBJETIVO: Verificar o impacto da obesidade sobre os componentes da síndrome metabólica e sobre os níveis de adipocitoquinas em crianças pré-púberes. MÉTODOS: Estudo transversal comparando 30 crianças obesas, 31 com sobrepeso e 33 eutróficas, oriundas do ambulatório de pediatria geral de um hospital universitário, quanto às médias de glicose, lipídios séricos, insulina, HOMA-IR (homeostasis model assessment-insulin resistance), relação glicose/insulina, adiponectina e leptina. Compararam-se as frequências de acantose nigricans e das alterações de cintura, pressão arterial, glicose, lipídios séricos e insulina. Avaliou-se a correlação entre escore z de índice de massa corporal (IMC) e adipocitoquinas. RESULTADOS: Houve diferença nas médias dos obesos, quanto a HDL-colesterol e adiponectina, e nas dos eutróficos, quanto a insulina, HOMA-IR, relação glicose/insulina e leptina (p < 0,001). O mesmo ocorreu em relação às frequências dos obesos quanto a acantose nigricans e alteração de cintura e HDL-colesterol (p < 0,005). O escore z de IMC se correlacionou positivamente com leptina (p < 0,001) e negativamente com adiponectina (p = 0,001). Na regressão linear múltipla, esta correlação se manteve apenas para leptina; o HDL-colesterol se correlacionou com adiponectina (p = 0,007) e o HOMA-IR com ambas (p < 0,05). CONCLUSÃO: Os achados comprovam a influência da obesidade sobre os componentes da síndrome metabólica e sobre os níveis de adipocitoquinas já nas crianças pré-púberes e apontam para a importância destas na gênese da doença cardiovascular.

OBJECTIVE: To verify the impact of obesity on metabolic syndrome components and adipokine levels in prepubertal children. METHODS: This cross-sectional study compared 30 obese, 31 overweight and 33 eutrophic children attending a university hospital-based outpatient pediatric clinic. Parameters assessed included glucose, serum lipids, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), glucose/insulin relation, adiponectin, and leptin. We compared the frequency of acanthosis nigricans and changes in waist, blood pressure, glucose, serum lipids, and insulin. The correlation between body mass index (BMI) z score and adipokines was evaluated. RESULTS: Among obese children, there was a difference in the mean values of HDL cholesterol and adiponectin, whereas among the eutrophic children, there was a difference in the mean values of insulin, HOMA-IR, glucose/insulin relation, and leptin (p < 0.001). A difference was also observed regarding the frequency of acanthosis nigricans and alteration in waist and HDL cholesterol (p < 0.005) in the obese group. The BMI z score showed a positive correlation with leptin (p < 0.001) and a negative correlation with adiponectin (p = 0.001). In multiple linear regression, this correlation was maintained only for leptin; HDL-cholesterol correlated with adiponectin (p = 0.007) and HOMA-IR correlated with both variables (p < 0.05). CONCLUSION: These findings provide evidence of the influence of obesity on metabolic syndrome components and on adipokine levels in prepubertal children, indicating that these components may contribute to the beginning of cardiovascular diseases.

Impact of obesity on metabolic syndrome components and adipokines in prepubertal children.

OBJECTIVES: To verify the impact of obesity on metabolic syndrome components and adipokine levels in prepubertal children. METHODS: This cross-sectional study compared 30 obese, 31 overweight and 33 eutrophic children attending a university hospital-based outpatient pediatric clinic. Parameters assessed included glucose, serum lipids, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), glucose/insulin relation, adiponectin, and leptin. We compared the frequency of acanthosis nigricans and changes in waist, blood pressure, glucose, serum lipids, and insulin. The correlation between body mass index (BMI) z score and adipokines was evaluated. RESULTS: Among obese children, there was a difference in the mean values of HDL cholesterol and adiponectin, whereas among the eutrophic children, there was a difference in the mean values of insulin, HOMA-IR, glucose/insulin relation, and leptin (p < 0.001). A difference was also observed regarding the frequency of acanthosis nigricans and alteration in waist and HDL cholesterol (p < 0.005) in the obese group. The BMI z score showed a positive correlation with leptin (p < 0.001) and a negative correlation with adiponectin (p = 0.001). In multiple linear regression, this correlation was maintained only for leptin; HDL-cholesterol correlated with adiponectin (p = 0.007) and HOMA-IR correlated with both variables (p < 0.05). CONCLUSIONS: These findings provide evidence of the influence of obesity on metabolic syndrome components and on adipokine levels in prepubertal children, indicating that these components may contribute to the beginning of cardiovascular diseases.