Pediatric Endocrinology 2011

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaIrmandade da Santa Casa de Misericórdia de São Paulo Unidade de Endocrinologia Pediátrica Departamento de Pediatria e PuericulturaUniversidade Estadual de Campinas Unidade de Endocrinologia Pediátrica, Faculdade de Ciências Médica Departamento de PediatriaUNIFESP, EPM, Depto. de PediatriaSciEL

Disorders Of Sex Development And Hypogonadism: Genetics, Mechanism, And Therapies.

201282037

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

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 proposed in order to reduce premature cardiovascular disease risk in this particular group of patients

Efeitos dos esportes de combate sobre a massa óssea: revisão sistemática

To determine the influence of combat sports on bone mass. Methods: A systematic review was performed according to the PRISMA method, with searches in the Pubmed, Bireme, Embase and Web of Science databases covering the period 1900 to 2015, using the keywords "martial arts", "fight", "combat","karate","kung fu","tae kwon do","judo","aikido","bone mass","bone health","bone tissue","bone density", and "bone mineral contents The articles were searched for and retrieved electronically and manually, by two independent reviewers. Results: Seventy-nine articles were identified, of which 25 were duplicates, leaving 54 for reading and evaluation of the titles; next, articles about diseases such as bone and/or orthopedic injuries, maxillofacial, surgeries, fractures, osteoporosis and osteopenia in women, prevention of falls, and physical fitness were excluded, leaving 15 articles. Of the articles selected and retrieved in full, all were published between 2002 and 2015. One article was a case control study; two were longitudinal studies, two were randomized studies; and 10 were cross-sectional studies. A total of 1368 children, adolescents, adults and elderly subjects were involved in combat sports and had bone evaluation by imaging. Factors such as calorie intake, calcium and/or vitamin D, intensity and volume of the exercise, hormonal aspects as bone markers, and characteristics of menopause are not conclusive in relation to bone mass, and further studies are needed. Conclusion:The practice of combat sports shows a significant improvement in bone mass at all ages253240244COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESVerificar a influência dos esportes de combate sobre a massa óssea. Foi realizada revisão sistemática da literatura de acordo com o método PRISMA, com buscas nas bases de dados Pubmed, Bireme, Embase e Web of Science, referente ao período de 1900 a 2015, com os descritores “martial arts”, “fight”, “combat”, “karate”, “kung fu”, “tae kwon do”, “judo”, “aikido”, “bone”, “bone mass”, “bone health”, “bone tissue”, “bone density”, “bone mineral contents”. A busca e a recuperação dos artigos foram realizadas por meio eletrônico e manual, executadas por dois revisores independentes. Foram identificados 79 artigos, dos quais, 25 eram duplicados, restando 54 artigos para leitura e avaliação dos títulos; posteriormente, foram excluídos os que tratavam de doenças como lesões ortopédicas e/ou ósseas, maxilofaciais, cirurgias, fraturas, mulheres osteopênicas e osteoporóticas, prevenção de quedas e aptidão física, restando 15 artigos. Dos estudos selecionados e encontrados na íntegra, todos foram publicados entre 2002 e 2015. Apenas um era estudo de caso controle, dois eram estudos longitudinais, dois estudos randomizados e 10 estudos transversais. Verificou-se um total de 1.368 crianças, adolescentes, adultos e idosos envolvidos em esportes de combate e avaliação óssea por imagem. Fatores como ingestão calórica, de cálcio e/ou vitamina D, intensidade e volume do exercício, aspectos hormonais como marcadores ósseos e características da menopausa não são conclusivos com relação à massa óssea e requerem um número maior de estudos. A prática de esportes de combate evidencia melhora significativa na massa óssea em todas as idadesLaboratorio de Crescimento e Desenvolvimento do CIPED, Biblioteca - FCM - UNICAMP; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brazil (CAPES)CAPES [001

Influence of physical training on bone mineral density in healthy young adults: a systematic review

Sem informação6581102110

Uso da fish em mucosa oral para investigação de mosaicismo com linhagem 45,x: estudo com homens saudáveis e pacientes com distúrbios da diferenciação do sexo

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOObjective: To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium. © ABE&M todos os direitos reservados.To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Subjects and methods: Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. Results: The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Conclusions: Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium584328334FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2011/50189-7Verificar se a hibridização in situ por fluorescência (FISH) em células de mucosa oral poderia ser empregada para detectar criptomosaicismo com linhagem 45,X em pacientes 46,XY. Sujeitos e métodos: Amostra de 19 jovens saudáveis 46,XY e cinco pacientes com distúrbios da diferenciação do sexo (DDS), quatro 45,X/46,XY e um 46,XY. FISH com sondas específicas para X e Y em núcleos interfásicos de linfócitos e mucosa oral para investigar aproporção de núcleos contendo apenas o sinal do cromossomo X. Resultados: A frequência de núcleos contendo apenas o sinal do X nos dois tecidos dos homens saudáveis não diferiu (p =0,69). Em todos os pacientes com DDS essa frequência foi significativamente maior, e tambémnão houve diferença entre os dois tecidos (p = 0,38). Conclusões: A investigação de mosaicismo com linhagem 45,X em pacientes com DDS 46,XY ou esterilidade pode ser feita por FISHdiretamente em células de mucosa ora

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

Clinical and molecular data from 61 Brazilian cases of Congenital Hyperinsulinemic Hypoglycemia

Objective: To study the clinical and molecular characteristics of a sample of Brazilian patients with Congenital Hyperinsulinemic Hypoglycemia (CHH).Methods: Electronic message was sent to members from Endocrinology Department-Brazilian Society of Pediatrics requesting clinical data for all cases of CHH. A whole blood sample from living patients was requested for DNA extraction followed by a search for mutations of the genes ABCC8, KCNJ11, GCK, GLUD1, HADH, SLC16A1 and HNF4A.Results: of the 61 patients evaluated, 36 (59%) were boys, and only 16 (26%) were born by normal delivery. Gestational age ranged from 32 to 41 weeks (mean = 37 weeks and 6 days). Birth weight ranged from 1590 to 5250 g (mean = 3430 g). Macrossomia occurred in 14 cases (28%). Age at diagnosis ranged from 1 to 1080 days (mean = 75 days). DNA for molecular analysis was obtained from 53 of the 61 patients. Molecular changes in the ABCC8 gene were detected in 15 (28%) of these 53 cases, and mutations in the KCNJ11 gene were detected in 6 (11%). Mutations in the GLUD1 gene were detected in 9 cases (17%) of the total series. Mutations of the GCK gene in heterozygosis were detected in 3 cases. No mutations were detected in the sequencing of genes HADH, SLC16A1 and HNF4A.Conclusion: the present study conducted in Brazil permitted the collaborative compilation of an important number of CHH cases and showed that the present clinical and molecular data are similar to those of published global series.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto, SP, BrazilState Univ Campinas UNICAMP, Dept Pediat, Sch Med Sci, Campinas, SP, BrazilUniv São Paulo, Hosp Clin, Inst Crianca, Pediat Endocrine Unit, São Paulo, SP, BrazilUniv Fed Minas Gerais, Dept Pediat, Med Sch, Hosp Clin, Belo Horizonte, MG, BrazilFAPESP: 2011/09355-0Web of Scienc