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OBJECTIVE: In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS: Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS: Children with obesity (N=11) had longer T2 relaxation times, consistent with gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N=9; p=0.004). Moreover, there was a highly significant group*region interaction (p=0.002), demonstrating that signs of gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity including visceral fat percentage (p=0.01). Mean glucose-induced hypothalamic BOLD signal change did not differ between groups (p=0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (p

Results of gonadotropins measurements according to age in TS girls. (DOCX 20 kb)

Objetivos: comparar o estado nutricional de meninas de nove a 17 anos na cidade de Cascavel (PR) segundo três referências para índice de massa corporal (IMC). Métodos: estudo transversal com 2759 meninas. Verificou-se o peso e a estatura obtendo-se o IMC além da avaliação da maturidade sexual e do nível socioeconômico. O estado nutricional foi classificado pelos pontos de corte do IMC propostos por Conde e Monteiro, WHO, e CDC. Resultados: as frequências dos estados nutricionais não diferiram significativamente na mesma referência para IMC por faixa etária, por nível socioeconômico e por tipo de escola. Por nível de maturidade sexual, apenas a referência da WHO apresentou valores de obesidade e sobrepeso maiores para o estadio de mamas grau 5. No entanto, quando comparadas as três referências entre si, o CDC apresentou frequências significativamente menores de sobrepeso e obesidade por faixa etária, por nível de maturidade sexual, por nível socioeconômico e por tipo de escola. Apesar das três referências apresentarem concordância entre si, esta foi maior entre os de Conde e Monteiro, e da WHO. Conclusões: a referência do CDC identificou menor percentual de meninas com sobrepeso e obesidade. As referências propostas por Conde e Monteiro e WHO apresentaram resultados semelhantes. Objectives: to compare the nutritional status of girls aged between nine and seventeen years in the city of Cascavel (in the Brazilian State of Paraná) according to three body mass index (BMI) references. Methods: a cross-sectional study was conducted with 2759 girls. Weight and height were measured to obtain the BMI and the sexual maturity and socioeconomic status of the girls evaluated. Nutritional status was classified using the BMI cut-off points proposed by Conde & Monteiro, the WHO, and the CDC. Results: the frequencies for different nutritional states did not differ significantly when the same BMI reference was used according to age, socioeconomic status or type of school attended. In terms of sexual maturity, only the WHO reference WHO produced higher levels of obesity and overweight for girls with Stage 5 breasts. However, when the three references were compared with one another, the CDC produced significantly lower frequencies for overweight and obesity by age group, level of sexual maturity, socioeconomic status and type of school. All three references were in agreement, this was greater between Conde & Monteiro, and the WHO. Conclusions: the CDC reference identified a smaller percentage of overweight and obese girls. The references proposed by Conde & Monteiro and the WHO produced similar results.

Supplemental Information. Table S1. NPHS2 specific primers. Table S2. WT1 exons 8 and 9 especific primers. Table S3. NPHS1 specific primers. Methods (PCR reactions and sequencing). Table S4. NPHS2 and NPHS1 missenses in silico predictions. (DOC 84 kb)

The objective of this study was to review the growth curves for Turner syndrome, evaluate the methodological and statistical quality, and suggest potential growth curves for clinical practice guidelines. The search was carried out in the databases Medline and Embase. Of 1006 references identified, 15 were included. Studies constructed curves for weight, height, weight/height, body mass index, head circumference, height velocity, leg length, and sitting height. The sample ranged between 47 and 1,565 (total = 6,273) girls aged 0 to 24 y, born between 1950 and 2006. The number of measures ranged from 580 to 9,011 (total = 28,915). Most studies showed strengths such as sample size, exclusion of the use of growth hormone and androgen, and analysis of confounding variables. However, the growth curves were restricted to height, lack of information about selection bias, limited distributional properties, and smoothing aspects. In conclusion, we observe the need to construct an international growth reference for girls with Turner syndrome, in order to provide support for clinical practice guidelines.

Frasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms' tumor suppressor gene (WT1) located in 11p23. Patients with the 46,XY karyotype present normal female genitalia with streak gonads, and have higher risk of gonadal tumor, mainly, gonadoblastoma. Therefore, elective bilateral gonadectomy is indicated. Nephropathy in FS consists in nephrotic syndrome (NS) with proteinuria that begins early in childhood and progressively increases with age, mainly due to nonspecific focal and segmental glomerular sclerosis (FSGS). Patients are generally unresponsive to steroid and immunosuppressive therapies, and will develop end-stage renal failure (ESRF) during the second or third decade of life. We report here four cases of FS diagnosis after identification of WT1 mutations. Case 1 was part of a large cohort of patients diagnosed with steroid-resistant nephrotic syndrome, in whom the screening for mutations within WT1 8-9 hotspot fragment identified the IVS9+5G>A mutation. Beside FS, this patient showed unusual characteristics, such as urinary malformation (horseshoe kidney), and bilateral dysgerminoma. Cases 2 and 3, also bearing the IVS9+5G>A mutation, and case 4, with IVS9+1G>A mutation, were studied due to FSGS and/or delayed puberty; additionally, patients 2 and 4 developed bilateral gonadal tumors. Since the great majority of FS patients have normal female external genitalia, sex reversal is not suspected before they present delayed puberty and/or primary amenorrhea. Therefore, molecular screening of WT1 gene is very important to confirm the FS diagnosis. Arq Bras Endocrinol Metab. 2012;56(8):525-32 A síndrome de Frasier (SF), caracterizada por disgenesia gonadal e nefropatia, é causada por mutações específicas no gene supressor do tumor de Wilms (WT1) localizado em 11p23. Pacientes com cariótipo 46,XY apresentam genitália feminina normal com gônadas disgenéticas e alto risco de tumor gonadal, principalmente o gonadoblastoma. Por isso, a gonadectomia bilateral eletiva está indicada. A nefropatia na SF consiste de síndrome nefrótica com proteinúria que se inicia na infância e aumenta progressivamente com a idade, principalmente devido à glomeruloesclerose focal e segmentar (GESF). Esses pacientes não respondem ao tratamento com esteroides e imunossupressores e desenvolverão insuficiência renal crônica durante a segunda ou terceira década de vida. Neste trabalho, são relatados quatro casos de SF cujo diagnóstico foi definido após o rastreamento molecular do gene WT1. O caso 1 faz parte de um grande grupo de pacientes que tiveram diagnóstico de síndrome nefrótica corticorresistente e no qual o rastreamento de mutações no fragmento 8-9 do gene WT1 identificou a mutação IVS9+5G>A. Além da SF, essa paciente apresentou características incomuns, tais como malformação urinária (rins em ferradura) e disgerminoma bilateral. Os casos 2 e 3 também apresentaram a mutação IVS9+5G>A, e, no caso 4, foi identificada a mutação IVS9+1G>A, sendo que esses três casos foram encaminhados para estudo molecular em decorrência de GESF e/ou atraso no desenvolvimento puberal. Além disso, as pacientes 2 e 4 desenvolveram tumor gonadal bilateral. Visto que a maioria dos pacientes com SF apresenta genitália externa feminina, não há suspeita de sexo reverso até apresentarem atraso puberal e/ou amenorreia primária. Portanto, o rastreamento molecular do gene WT1 é de fundamental importância para se confirmar o diagnóstico de SF. Arq Bras Endocrinol Metab. 2012;56(8):525-32

To analyze the effects of the aerobic training on components of physical fitness in adult women. Forty women aged above 40 years were selected; 20 of them participated regularly on the program (Experimental Group), with above 55% of maximum heart rate, one hour a day, five times a week, during five months. The control group was composed by the others 20 women. The Rikli and Jones (1999) tests were used to evaluate physical fitness. Non-parametric statistics were used to compare the scores of components of physical fitness with p < 0.05. The two Groups did not differ significantly in relation to age, body mass index, family income and the results of the tests at the beginning of the program. After five months of the program, the experimental group showed a significant improvement in the performance in the tests in comparison with pre-program and control group. The regular practice of oriented walking used in this study contributed to the improvement of the health-related physical fitness in a group of adult women submitted to five months of aerobic training. O trabalho teve como objetivo analisar os efeitos de um treinamento aeróbio sobre os componentes da aptidão física em mulheres adultas. Foram selecionadas 40 mulheres com idade superior a 40 anos, das quais 20 participaram regularmente do programa (grupo-experimento), com freqüência cardíaca máxima superior a 55%, em exercícios com duração de uma hora por dia e freqüência de cinco vezes por semana, durante cinco meses, e as demais formaram o grupo-controle. Para avaliação da aptidão física foram utilizados os testes propostos por Rikli e Jones (1999) antes e após cinco meses do programa. Para análise dos dados foram utilizados procedimentos de estatística não-paramétrica na comparação dos escores dos componentes da aptidão física, com p < 0,05. Observou-se que os dois grupos não apresentaram diferenças estatisticamente significativas em relação aos fatores idade, índice de massa corporal, renda familiar e resultados dos testes antes do início do programa. Após cinco meses, o grupo-experimento apresentou significativo incremento na performance nos testes em relação aos resultados pré-programa e ao grupo-controle. Concluiu-se que prática regular da caminhada orientada definida neste estudo contribuiu para a melhora da aptidão física relacionada à saúde em um grupo de mulheres adultas submetido a cinco meses de treinamento aeróbio.

Morning glory syndrome (MGS) is a congenital optic disc dysplasia often associated with craniofacial anomalies, especially basal encephalocele and hypopituitarism. Clinical signs are varied and often occult. The PAX6 gene is involved in ocular morphogenesis and is expressed in numerous ocular tissues during development especially in the developing central nervous system. The aim of the present study is to evaluate PAX6 in MGS associated with isolated growth hormone deficiency. Three pre-pubertal males (A, B and C) with MGS and short stature due to growth hormone deficiency, treated with recombinant human growth hormone with limited response, were reported. Two of them had basal encephalocele. Coding and non-coding sequences corresponding of PAX6 different transcripts were analyzed by direct sequencing. Nucleotide variations causing putative aminoacid change were not observed. Patient A presented the new IVS2+9G>A transition, whereas patients A and C were heterozygous for known single nucleotide polymorphisms (SNP) within the intron 4. In addition, two SNP heterozygoses were observed for patient C in both intron 9 and 13. Sequencing also revealed several nucleotide variations in patient B. Two heterozygoses for known polymorphisms were identified along with a novel C>A nucleotide change in intron 4. This patient also presented a low number on the TG repeat in intron 9 and a new IVS11+33A>T transversion. Gene regulation and transcription of PAX6 are complex processes; there are two major protein isoforms, PAX6(-5a) and PAX6(+5a), and nine transcripts described. Furthermore, extra transcription regulatory elements have been postulated within PAX6 introns. Considering that neither population distributions on PAX6 polymorphism nor their linkeages with diseases have been reported, a functional effect due to alterations described here cannot be discarded. A síndrome de Morning Glory (SMG) é uma displasia óptica congênita associada a anomalias craniofaciais, principalmente encefalocele basal e hipopituitarismo. Os sinais clínicos são variados e muitas vezes ocultos. O gene PAX6 está envolvido na morfogênese ocular e se expressa em vários tecidos oculares durante o desenvolvimento do sistema nervoso central. O objetivo deste estudo foi avaliar o gene PAX6 na SMG associada com deficiência isolada de hormônio de crescimento. Foram relatados três pacientes pré-púberes (A, B e C) com SMG e baixa estatura por deficiência de hormônio de crescimento tratados com hormônio de crescimento recombinante humano. As seqüências codificadoras e não-codificadoras correspondentes ao PAX6 em diferentes transcritos foram analisadas por seqüenciamento direto. Variações nucleotídeas com trocas pontuais de aminoácidos não foram encontradas. O paciente A apresentou uma transição nova IVS2+9G>A, enquanto os pacientes A e C foram heterozigotos para um polimorfismo (SNP) no íntron 4. Ainda, dois SNPs em heterozigose nos íntrons 9 e 13 foram observados no paciente C. O seqüenciamento também mostrou várias variações nucleotídeas no paciente B. Dois SNPs conhecidos com a alteração nucleotídea nova C>A no íntron 4 foram observados em heterozigose. Este paciente também apresentou um baixo número de repetições TG no íntron 9 e uma nova transversão IVS11+33A>T. A regulação e a transcrição do gene PAX6 são um processo complexo; existem 2 isoformas principais da proteína, PAX6(-5a) e PAX6(+5a) e 9 transcritos descritos. Considerando que nem a distribuição de SNPs no PAX6 e nem as suas ligações com as doenças foram relatadas, um defeito funcional devido às alterações descritas não pode ser descartado.

Adriana Aparecida Siviero-Miachon1, Angela Maria Spinola-Castro1, Gil Guerra-Junior21Division of Pediatric Endocrinology, Department of Pediatrics, Federal University of Sao Paulo – UNIFESP/EPM, Brazil; 2Division of Pediatric Endocrinology, Department of Pediatrics, State University of Campinas – FCM/UNICAMP, BrazilAbstract: 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.Keywords: metabolic syndrome X, cardiovascular diseases, insulin resistance, obesity, growth hormone/deficiency, endothelium, vascular/physiopathology

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. 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.

SummaryObjectiveTo evaluate the influence of body composition on bone mass in children and adolescents.MethodsA cross-sectional study with 267 healthy students of both sexes (141 males and 126 females) aged 8 to 18 years. Weight, height, body mass index, lean mass, fat mass, fat mass index, body fat percentage, waist and hip circumferences, and waist-to-hip ratio were evaluated. Bone mass was assessed using ultrasound of hand phalanges (DBM Sonic BP – IGEA, Carpi, Italy).ResultsFemales showed greater bone mass in relation to males with advances in age and pubertal stage. In both sexes, the bone mass showed significant and positive correlations with age, weight, height, body mass index, lean mass, waist and hip circumferences; and negative correlations with waist-to-hip ratio. In females, there was also a positive correlation with fat mass, fat mass index, and body fat percentage. Age and lean mass were predictors for bone mass in males, and age, pubertal stage and fat mass index were predictors in females.ConclusionThe correlation between bone mass and body composition occurred in both sexes, with lean mass and fat mass index being the predictor of bone mass in males and females, respectively.