Association of preterm birth with poor metabolic outcomes in schoolchildren.

OBJECTIVE: To investigate, at school age, the metabolic profile of children born preterm. METHODS: A cross-sectional study of children 5 to 8 years old, born with gestational age (GA) < 34 weeks and/or weight ≤ 1,500 grams. Clinical and anthropometric data were assessed by a single trained pediatrician. Biochemical measurements were done at the organization's Central Laboratory using standard methods. Data on health conditions, eating, and daily life habits were retrieved from medical charts and through validated questionnaires. Binary logistic and linear regression models were built to identify the association between variables, weight excess, and GA. RESULTS: Out of 60 children (53.3% female), 6.8 ± 0.7 years old, 16.6% presented excess weight, 13.3% showed increased insulin resistance markers and 36.7% had abnormal blood pressure values. Those presenting excess weight had higher waist circumferences and higher HOMA-IR than normal-weight children (OR = 1.64; CI = 1.035-2.949). Eating and daily life habits were not different among overweight and normal-weight children. The small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA, 83.3%) birth weight children did not differ regarding clinical (body weight, blood pressure) or biochemical variables (serum lipids, blood glucose, HOMA-IR). CONCLUSION: Schoolchildren born preterm, regardless of being AGA or SGA, were overweight, and presented increased abdominal adiposity, reduced insulin sensitivity, and altered lipid profile, justifying longitudinal follow-up regarding adverse metabolic outcomes in the future.

Association of preterm birth with poor metabolic outcomes in schoolchildren

Abstract Objective: To investigate, at school age, the metabolic profile of children born preterm. Methods: A cross-sectional study of children 5 to 8 years old, born with gestational age (GA) < 34 weeks and/or weight ≤ 1,500 grams. Clinical and anthropometric data were assessed by a single trained pediatrician. Biochemical measurements were done at the organization's Central Laboratory using standard methods. Data on health conditions, eating, and daily life habits were retrieved from medical charts and through validated questionnaires. Binary logistic and linear regression models were built to identify the association between variables, weight excess, and GA. Results: Out of 60 children (53.3% female), 6.8 ± 0.7 years old, 16.6% presented excess weight, 13.3% showed increased insulin resistance markers and 36.7% had abnormal blood pressure values. Those presenting excess weight had higher waist circumferences and higher HOMA-IR than normal-weight children (OR = 1.64; CI = 1.035-2.949). Eating and daily life habits were not different among overweight and normal-weight children. The small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA, 83.3%) birth weight children did not differ regarding clinical (body weight, blood pressure) or biochemical variables (serum lipids, blood glucose, HOMA-IR). Conclusion: Schoolchildren born preterm, regardless of being AGA or SGA, were overweight, and presented increased abdominal adiposity, reduced insulin sensitivity, and altered lipid profile, justifying longitudinal follow-up regarding adverse metabolic outcomes in the future.

Pharmacogenomic markers of glucocorticoid response in congenital adrenal hyperplasia.

Glucocorticoids (GC) replacement are the mainstay treatment for 21-hydroxylase deficiency (21-OHD), the most common cause of congenital adrenal hyperplasia (CAH), in its classical form. There are novel insights into the genetic basis of the GC action diversity that point to an important role for GC receptor (GR) gene polymorphisms, suggesting a possible modulation in occurrence of metabolic disorders, what may be relevant to clinical management of 21-OHD. The aim of this study was to investigate whether the five GR gene polymorphisms Tth111I, ER22, 23EK, BclI, 9ß (rs10052957, rs6189, rs6190, rs41423247, rs6198) and their combination into haplotypes are associated to different GC response in a cohort of classic 21-OHD subjects. GR genotype-phenotype associations were explored after a dexamethasone suppression test using very low-doses (VLD-DST), 20 and 40 µg/m². The final sample (n = 28) was selected based on the 102 individuals' previous genotypes classification, according to literature data of GC sensitivity or resistance. Thus, only patients with GC increased resistance (n = 18) or increased sensitivity (n = 10) profiles were selected. Out of 28 subjects aged 12 (2-34) years enrolled in this study, 75% were females, 75% presented the salt-wasting form (SW) and 25% the simple virilizing form (SV). Subjects who carried Tth111I and 9ß, associated or not to the ER22/23EK variants, showed an impaired DST response. Results did not differ significantly according to gender or body mass index. SV subjects with GC hypersensitivity-genotypes showed decreased average cortisol levels compared to those with GC resistance-genotypes (p = 0.0023). The Tth111I + 9ß/ Wild or Tth111I + ER22/23EK + 9ß/ Wild genotypes were associated to GC resistance in this population. This finding may be relevant given the challenges posed by therapeutic management with GC in CAH.

Helicobacter pylori Infection Is Associated With Thyroid Dysfunction in Children With Congenital Hypothyroidism.

Helicobacter pylori (H. pylori) infection leads to a systemic low-grade inflammatory state and has been associated causally with a diverse spectrum of extra-gastric disorders. Among them, the infection has been involved in the pathogenesis of autoimmune thyroid disease (ATD), but only one study had evaluated children. Therefore, a cross-sectional study was conducted in a cohort of 142 children and adolescents, randomly assessed among those followed up for thyroid diseases in a university pediatric endocrinology service: 106 with congenital hypothyroidism (CH) and 36 with ATD. All children were asymptomatic, under strict control on levothyroxine replacement, and reported no other diseases or use of drugs. Helicobacter pylori status was evaluated by the 13C-Urea Breath Test (13C-UBT). Antithyroid antibodies (ATPO, antiTg, and TRAb) and serum thyroid hormones (TSH, free T4, and T3) were assessed by standard assays. Data were analyzed in logistic models by the SPSS statistical software package, and a p-value ≤ 0.05 was considered statistically significant. The prevalence of H. pylori infection was 19.44% in children with ATD. Neither the gender nor the serum levels of thyroid hormones and antithyroid antibodies were associated with the H. pylori-positive status. Thirty-seven (34.90%) children with CH were infected with H. pylori. The mean T3 serum level (3.59 ± 0.84) was significantly lower (p = 0.001) in the infected children than in those free from the infection (3.95 ± 0.89), association that remained after adjustment for the other variables in the multivariate analysis. Because no difference was observed in the levels of TSH and T4, the results indicate that the infection may lead to impairment in the thyroid hormonal balance, but not in the hypothalamic-pituitary-thyroid axis function. In as much as H. pylori infection is highly widespread and the prevalence of CH is also not negligible, additional studies are required to confirm our results and to identify the involved mechanisms.

Abordagem da hiperplasia adrenal congênita pela deficiência da enzima 21-hidroxilase em crianças e adolescentes: revisão / Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents: review

Objetivo: Descrever o diagnóstico e manejo clínico da deficiência da 21-hidroxilase (D-21OH), no contexto atual de inclusão da doença nos programas de triagem neonatal, bem como características genéticas, fisiopatológicas e manifestações na infância e adolescência. Fonte de Dados: Revisão integrativa realizada nas bases de dados MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science nos últimos vinte anos, em língua inglesa e portuguesa; população-alvo: crianças da primeira infância à adolescência; com o uso dos termos "triagem neonatal", "hiperplasia adrenal congênita", "deficiência da 21-hidroxilase", "glucocorticoide" e "polimorfismos do gene NR3C1". Síntese de Dados: A hiperplasia adrenal congênita (HAC) constitui um grupo de doenças caracterizadas por deficiências enzimáticas na esteroidogênese do córtex adrenal. A D-21OH é responsável por 95% dos casos e, se não tratada precocemente, pode levar ao óbito no período neonatal em sua forma clássica. A triagem neonatal para a HAC consiste na dosagem do precursor 17-hidroxiprogesterona (17OHP) no sangue de recém-nascidos, permitindo rápida confirmação diagnóstica e instituição da terapêutica. A implantação da triagem neonatal constitui um avanço, mas o controle dos pacientes pediátricos com D-21OH é complexo e deve ser sempre individualizado. Conclusão: A instituição dos programas de triagem neonatal para HAC tem trazido benefícios para o prognóstico das crianças com D-21OH. Seu manejo é multiprofissional, individualizado e ainda um desafio mesmo para o especialista. Ampla divulgação do conhecimento sobre a doença é desejável para permitir melhor condução dessas crianças, especialmente de meninas com a doença que apresentam genitália atípica.

Objective: To describe the diagnosis and clinical management of 21-hydroxylase deficiency (21OH-D), in the current context of including the disease in neonatal screening programs, as well as genetic, pathophysiological characteristics, and manifestations in childhood and adolescence. Data Source: Integrative review performed in MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science databases in the last twenty years, in English and Portuguese; target population: children from early childhood to adolescence; with the use of the terms "neonatal screening"; "congenital adrenal hyperplasia"; "21-hydroxylase deficiency"; "glucocorticoid"; "polymorphisms of the NR3C1 gene". Data Synthesis: Congenital adrenal hyperplasia (CAH) is a group of diseases characterized by enzyme deficiencies in adrenal cortex steroidogenesis. 21OH-D is responsible for 95% of cases and, if not treated early, can lead to death in the neonatal period in its classic form. Neonatal screening for CAH consists of measuring the precursor 17-hydroxyprogesterone (17OHP) in the blood of newborns, allowing rapid diagnostic confirmation and institution of therapy. The implementation of neonatal screening is an advance, but the control of pediatric patients with 21OH-D is complex and must always be individualized. Conclusion: The institution of newborn screening programs for CAH has benefits for the prognosis of children with 21OH-D. Its management is multi-professional, individualized and still a challenge even for the specialist. Wide dissemination of knowledge about the disease is desirable to allow better management of these children, especially girls with the disease who have atypical genitalia.

Glucocorticoid receptor Gene (NR3C1) Polymorphisms and Haplotypes in patients with congenital adrenal hyperplasia.

BACKGROUND: Lifelong glucocorticoid (GC) replacement is the mainstay treatment of congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). Challenges posed by therapeutic management of these patients are well known, but novel insights into the variability in clinical response to GC highlight a role for single nucleotide polymorphisms (SNPs) of the glucocorticoid receptor gene (NR3C1). AIM: To assess whether six commonly studied NR3C1 SNPs, which were previously associated with modified response to GC, are associated with CAH. We further assessed the linkage disequilibrium (LD) among these NR3C1 SNPs and their combination into haplotypes. METHODS: Genotypes were determined by Taqman allele discrimination assays for Tth111I (rs10052957), ER22 (rs6189), 23 EK (rs6190), N363S (rs56149945), BclI (rs41423247) and 9ß (rs6198) in a Brazilian cohort of 102 unrelated 21-OHD patients and 163 unrelated healthy subjects (controls). Haplotypes were estimated using Haplo.stats, and LD among SNPs using Haploview. RESULTS: Heterozygous subjects for Tth111I were more frequent in 21-OHD patients (P = 0.004), while heterozygous for BclI were more frequent in controls (P = 0.049). We found a strong LD among the six NR3C1 SNPs, and four out of six common haplotypes contained the Tth111I-variant. Although we found no significant differences in overall haplotype analysis, the BclI-haplotype was less frequent among 21-OHD patients (P = 0.0180). CONCLUSIONS: BclI-haplotype was less common and heterozygous for Tth111I were more frequent in 21-OHD patients, while heterozygous for BclI were more frequent in controls. Our novel findings may contribute to further clinical studies on the prognostic value of NR3C1 haplotypes towards individualized treatment for 21-OHD patients.

[Formula: see text]Socioeconomic aspects are crucial to better intellectual outcome in early-treated adolescents with congenital hypothyroidism.

Congenital hypothyroidism (CH) is an important cause of preventable intellectual disability. Implementation of CH neonatal screening programs leading to early treatment has improved cognitive outcome. However, more subtle cognitive impairments are still reported, and there is lack of clarity regarding factors that impact long-term cognitive outcome. Research to better understand these factors can lead to further improvements in the cognitive prognosis for these patients. The current study aimed to evaluate the cognitive performance of adolescents who were early-treated for primary permanent CH and possible associated variables. Neurocognitive evaluation was carried out in 66 adolescents, 11 to 16 years old: 34 with CH and 29 paired controls. Intellectual quotient (IQ), verbal fluency, processing speed, executive functions, and memory were investigated. CH patients and control subjects were comparable regarding sex, age, schooling, family's socioeconomic status and caregiver's educational level. Both groups presented not only similar IQ scores but also equivalent performances regarding Perceptual Reasoning, Working Memory and Processing Speed index scores. Patients presenting different CH etiologies (dysgenesis and dyshormonogenesis) showed similar cognitive performance. Socioeconomic aspects along with the initial levothyroxine dose were the main variables to positively influence the cognitive performance, the family's socioeconomic status having the strongest association with patients' cognitive skills.

Elaboração, validação e adequação de protocolo para aplicativo em diabetes tipo 1 / Elaboración, validación y adaptación de protocolo para aplicación en diabetes tipo 1 / Development, validation and adaptation of a protocol for a self-management app targeting adolescents with type 1 diabetes

Resumo Objetivo Elaborar, efetuar a validação de conteúdo e a adequação cultural do protocolo AGITO no autocuidado em diabetes tipo 1. Métodos Estudo metodológico realizado no período de fevereiro de 2017 a março de 2019, abrangendo três etapas: elaboração, validação de conteúdo e adequação cultural. Foram contemplados os principais temas de práticas de autocuidado em diabetes tipo 1, concernentes a aspectos educacionais, psicossociais e comportamentais. Na 2ª etapa, 32 profissionais da área da Saúde foram convidados a participar do Comitê de Juízes. A etapa final compreendeu dois ciclos de testes face a face do protocolo com 10 adolescentes com diabetes tipo 1. Resultados O protocolo de autocuidado em diabetes tipo 1 nomeado AGITO foi consolidado em seis seções, denominadas: Glicemia de Jejum; Glicemia antes do almoço; Glicemia antes do lanche da tarde; Glicemia antes do jantar; Glicemia antes do lanche de dormir; e Saúde Emocional. Cada seção do protocolo tem opções de respostas que o adolescente poderá marcar de acordo com a situação vivenciada para o controle glicêmico. A concordância entre os avaliadores e a população-alvo quanto à clareza e relevância dos itens foi confirmada pelo Índice de Validade de Conteúdo, que apresentou variação das médias entre 0,90 e 1,0. As principais alterações realizadas foram a inclusão de termos mais utilizados no cotidiano dos adolescentes. Conclusão Este estudo fornece o protocolo AGITO com conteúdo validado, configurando-se um componente passível de ser utilizado como uma estratégia para o autocuidado em diabetes tipo 1 para adolescentes.

Resumen Objetivo Elaborar, realizar la validación de contenido y adaptación cultural del protocolo AGITO para el autocuidado en diabetes tipo 1. Métodos Estudio metodológico realizado en el período de febrero de 2017 a marzo de 2019, que incluyó tres etapas: elaboración, validación del contenido y adaptación cultural. Fueron contemplados los principales temas sobre prácticas de autocuidado en diabetes tipo 1, relacionados con aspectos educativos, psicosociales y de comportamiento. En la segunda etapa, se invitó a 32 profesionales de la salud para participar en el Comité de Jueces. La etapa final consistió en dos ciclos de pruebas del protocolo cara a cara con 10 adolescentes con diabetes tipo 1. Resultados El protocolo de autocuidado en diabetes tipo 1 llamado AGITO fue consolidado en seis secciones denominadas: Glucemia en ayunas, Glucemia antes del almuerzo, Glucemia antes de la colación de la tarde, Glucemia antes de la cena, Glucemia antes de la colación de dormir y Salud emocional. Cada sección del protocolo tiene opciones de respuestas que el adolescente podrá marcar de acuerdo con la situación vivida para el control glucémico. La concordancia entre los evaluadores y la población destinataria respecto a la claridad y relevancia de los ítems fue confirmada por el Índice de Validez de Contenido, que presentó variación de los promedios entre 0,90 y 1,0. Las principales modificaciones realizadas fueron inclusiones de términos más utilizados en el día a día de los adolescentes. Conclusión Este estudio proporciona el protocolo AGITO con contenido validado y, de esta forma, se convierte en un componente apto para utilizarse como estrategia para el autocuidado en diabetes tipo 1 para adolescentes.

Abstract Objective To develop, validate and adapt a protocol for a self-management app targeting adolescents with type 1 diabetes. Methods Methodological study conducted from February 2017 to March 2019 in three stages: development; content validation; and adaptation. In stage 1, the main issues about self-management practices in type 1 diabetes were discussed regarding educational, psychosocial and behavioral aspects. In stage 2, 32 healthcare professionals were invited to participate as members of the Expert Committee. Stage 3 comprised two of face-to-face tests of the protocol with 10 type 1 diabetes adolescents. Result The type 1 diabetes self-management protocol called AGITO was developed covering six sections: Fasting blood sugar level, blood sugar level before lunch, blood sugar level before an afternoon snack, blood sugar level before dinner, blood sugar level before a bedtime snack, and emotional health. Each section of the protocol has multiple items that are answered by each adolescent according to his/her glycemic control situation. Agreement between the evaluators and the target population regarding the clarity and relevance of the items was confirmed by the content validity index, which ranged from 0.90 to 1.0. Adaptation was carried out to make sure the language in the protocol is closely patterned upon the vocabulary most frequently used by adolescents in their daily lives. Conclusion The AGITO protocol was developed and its content validated, allowing it to be used as a self-management strategy for adolescents with type 1 diabetes.

Análise das emissões otoacústicas transitórias por banda de frequência em adolescentes com diabetes mellitus tipo 1 / Transient otoacoustic emissions analysis by frequency bands in adolescents with type 1 diabetes mellitus

Introdução: A associação entre perda auditiva e Diabetes Mellitus tipo 1 (DM1) é ainda pouco estudada. A perda auditiva é uma das complicações crônicas relacionadas ao grau de controle glicêmico, que os pacientes podem apresentar com a progressão da doença. Objetivo: Investigar o comprometimento auditivo por meio das emissões otoacústicas transitórias (EOAT) por banda de frequência em adolescentes com DM1 e relação com o controle glicêmico. Métodos: Foram incluídos 80 adolescentes, 50% do gênero masculino, entre 10 e 19 anos de idade: 40 com DM1 e 40 controles saudáveis, pareados por gênero e idade. Os dados clínicos e laboratoriais foram pesquisados nos prontuários médicos. O controle glicêmico foi avaliado por meio dos exames de hemoglobina glicada e os pacientes com DM1 analisados de acordo com o controle glicêmico. A avaliação auditiva foi realizada por meio da imitanciometria, audiometria, e posteriormente EOAT, em sala tratada acusticamente, pelo protocolo "TE Test" de clique não-linear (1 KHz a 4 kHz) a 80 dB NPS de intensidade (AuDX - Biologic). Resultados: As respostas às EOAT foram ausentes em 5,12% em pacientes com DM1, com diferença significativa em relação aos controles (p=0,04). A análise das EOAT por bandas de frequência mostrou maior proporção de alteração nos adolescentes com DM1 mal controlados quando comparados aos bem controlados, nas frequências de 1000Hz, 2000Hz e 3000Hz (p<0,05). Conclusão: As EOAT por bandas de frequência permitiram a identificação precoce de comprometimento auditivo em adolescentes com DM1 e mostraram associação entre DM1 mal controlado e perda auditiva. (AU)

Introduction: The association between hearing loss and type 1 diabetes mellitus (DM1) is still poorly studied. Hearing loss is one of the chronic complications related to the degree of glycemic control that patients may present with the progression of the disease. Objective: To investigate auditory impairment through transient otoacoustic emissions (TEOAE) by frequency band in adolescents with DM1 and in relation to glycemic control. Methods: Were included 80 adolescents, 50% males, between 10 and 19 years of age: 40 with DM1 and 40 healthy controls, matched by gender and age. Clinical and laboratory data were taken from the medical records. Glycemic control was evalueted by glycated hemoglobin and the patients with DM1 were analyzed according to glycemic control. To the auditory evaluation were used the immittance and audiometry, and the TEOAE. The test was performed in the acoustically treated room, the non-linear TE test protocol (1 KHz to 4 kHz) at 80 dB SPL (AuDX - Biologic ). Results: TEOAE responses were absent in 5.12% of patients with DM1, with a significant difference in relation to controls (p = 0.04). The analysis of TEOAE by frequency bands showed a higher proportion of alteration in adolescents with DM1 poorly controlled when compared to well controlled ones, in the frequencies of 1000Hz, 2000Hz and 3000Hz (p <0.05). Conclusion: TEOAE by frequency bands allowed the early identification of auditory impairment in adolescents with DM1 and showed an association between poorly controlled DM1 and hearing loss. (AU)

Intima-media thickness of the carotid arteries is affected by pubertal maturation in healthy adolescents / Espessura médio-intimal das artérias carótidas é relacionada à maturação puberal em adolescentes saudáveis

ABSTRACT Objective: To contribute to the assessment of normal parameters of carotid intima-media thickness (CIMT) in healthy adolescents. Methods: A cross-sectional study was conducted through clinical, laboratory and ultrasound evaluation in 61 healthy adolescents. The inclusion criteria consisted of being in good health. The exclusion criteria were: presence or history of any chronic disease; being obese or overweight according to the World Health Organization (WHO) established criterion; continuous use of medication; or presenting a febrile condition or requiring medication within 48-hours prior to assessment. The pubertal stages were evaluated using the Tanner criteria. The high-resolution B-mode ultrasound examinations were performed according to the recommendations of the Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Results: Adolescents were 14±2.6 years old, 62.3% female, 19 (31%) at early puberty (Tanner II and III), and 38 (62%) at late puberty (Tanner IV and V). They presented normal clinical and laboratorial parameters. CIMT values were 0.46±0.04 to 0.55±0.04 mm on the right and 0.48±0.02 to 0.53±0.04 mm on the left, according to pubertal maturation. CIMT values increased significantly on the right and left sides, according to pubertal stage (p<0.001 and p=0.016), and maximum internal diameters of the common carotid artery (p<0.025 and p<0.003). It was higher in males compared to females. Conclusions: An increase in CIMT in the healthy adolescents group, according to both age, and the degree of pubertal maturation should be considered when evaluating adolescents in diagnostic procedures.

RESUMO Objetivo: Contribuir para a avaliação dos parâmetros normais da espessura médio-intimal carotídea (EMIC) em adolescentes saudáveis. Métodos: Estudo transversal realizado por meio de avaliações clínicas, laboratoriais e ultrassonográficas em 61 adolescentes saudáveis. O critério de inclusão foi ter boa saúde. Os critérios de exclusão foram: presença ou histórico de doença crônica; obesidade ou sobrepeso segundo os parâmetros estabelecidos pela Organização Mundial da Saúde (OMS); uso contínuo de medicação; e quadro febril ou que necessitasse de uso de medicação nas 48 horas anteriores à avaliação. Os estágios puberais foram avaliados pela escala de Tanner. As ultrassonografias em modo B de alta resolução foram realizadas seguindo as recomendações do Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force (Declaração de Consenso da Força Tarefa da Sociedade Americana de Ecocardiografia sobre Espessura Médio-Intimal Carotídea). Resultados: Os adolescentes tinham 14±2,6 anos, 62,3% eram do sexo feminino, 19 (31%) estavam em estágios iniciais da puberdade (2 e 3) e 38 (62%) em estágios avançados (4 e 5) de acordo com a escala de Tanner. Todos apresentavam parâmetros clínicos e laboratoriais normais. Os valores da EMIC variaram de 0,46±0,04 a 0,55±0,04 mm do lado direito e 0,48±0,02 a 0,53±0,04 mm do lado esquerdo, conforme a maturação puberal. Houve aumento significativo nos valores da EMIC em ambos os lados de acordo com o estágio puberal (p<0,001 e p=0,016) e os diâmetros internos máximos da artéria carótida comum (p<0,025 e p<0,003). A EMIC foi maior em participantes do sexo masculino em relação ao feminino. Conclusões: O aumento da EMIC em adolescentes saudáveis, conforme a idade e o grau de maturação puberal, deve ser levado em consideração nas avaliações diagnósticas.

INTIMA-MEDIA THICKNESS OF THE CAROTID ARTERIES IS AFFECTED BY PUBERTAL MATURATION IN HEALTHY ADOLESCENTS.

OBJECTIVE: To contribute to the assessment of normal parameters of carotid intima-media thickness (CIMT) in healthy adolescents. METHODS: A cross-sectional study was conducted through clinical, laboratory and ultrasound evaluation in 61 healthy adolescents. The inclusion criteria consisted of being in good health. The exclusion criteria were: presence or history of any chronic disease; being obese or overweight according to the World Health Organization (WHO) established criterion; continuous use of medication; or presenting a febrile condition or requiring medication within 48-hours prior to assessment. The pubertal stages were evaluated using the Tanner criteria. The high-resolution B-mode ultrasound examinations were performed according to the recommendations of the Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. RESULTS: Adolescents were 14±2.6 years old, 62.3% female, 19 (31%) at early puberty (Tanner II and III), and 38 (62%) at late puberty (Tanner IV and V). They presented normal clinical and laboratorial parameters. CIMT values were 0.46±0.04 to 0.55±0.04 mm on the right and 0.48±0.02 to 0.53±0.04 mm on the left, according to pubertal maturation. CIMT values increased significantly on the right and left sides, according to pubertal stage (p<0.001 and p=0.016), and maximum internal diameters of the common carotid artery (p<0.025 and p<0.003). It was higher in males compared to females. CONCLUSIONS: An increase in CIMT in the healthy adolescents group, according to both age, and the degree of pubertal maturation should be considered when evaluating adolescents in diagnostic procedures.

Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

INTRODUCTION: Oral corticosteroids (OCS) are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS) trial. METHOD: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006). RESULTS: In all, 140 children (0.3-15 years old) with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29) nor in the last OCS course duration (p=0.20). The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89). CONCLUSION: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing.

Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that? / Uso de corticosteroides orais nas exacerbações da asma pode estar associado à supressão adrenal: os médicos estão alertas?

Summary Introduction: Oral corticosteroids (OCS) are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS) trial. Method: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006). Results: In all, 140 children (0.3-15 years old) with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29) nor in the last OCS course duration (p=0.20). The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89). Conclusion: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing.

Resumo Introdução: A corticoterapia oral (CO) é um dos pilares do tratamento na exacerbação da asma, e cursos de curta duração são geralmente considerados seguros. No entanto, crianças submetidas a repetidos cursos estão sujeitas a disfunção do eixo hipotálamo-hipófise-adrenal (HHA). Objetivo: Investigar a integridade do eixo HHA em crianças com asma persistente ou sibilância recorrente com indicação para corticoterapia inalatória (CI). Método: Avaliação do cortisol sérico basal antes da introdução da CI e 30, 60 e 90 dias após iniciado o tratamento, utilizando-se o imunoensaio ImmuliteÒ Siemens Medical Solutions Diagnostic chemiluminescent (Los Angeles, EUA; 2006). Resultados: Das 140 crianças avaliadas (0,3 a 15 anos de idade) com asma persistente ou sibilância recorrente, 40% relataram ter recebido CO no último mês antes da avaliação. Cerca de 12,5% delas apresentaram supressão adrenal bioquímica e evoluíram com recuperação do eixo HHA durante os primeiros três meses em CI. O número de dias livres de CO e a duração do último curso antes da avaliação do cortisol não foram significativamente diferentes entre as crianças com ou sem supressão adrenal (p=0,29 e p=0,20, respectivamente). O número de cursos de curta duração relatados no ano anterior à avaliação também não esteve associado à supressão adrenal (p=0,89). Conclusão: A utilização dos corticosteroides nas doses convencionais, em cursos de curta duração, pode colocar as crianças em risco de disfunção do eixo HHA. A recuperação desse eixo é possível durante a CI. Profissionais de saúde devem estar atentos para a possibilidade de resposta inadequada ao estresse durante o acompanhamento de crianças com asma persistente ou sibilância recorrente.

Imaging methods for bone mass evaluation during childhood and adolescence: an update.

The objective of the work was to prepare an update on imaging methods for bone evaluation during childhood and adolescence. The text was based on original and review articles on imaging methods for clinical evaluation of bone mass in children and adolescents up to 20 years old. They were selected from BIREME and PUBMED by means of the following keywords: bone density; osteoporosis/diagnosis; densitometry; tomography; ultrasonography; magnetic resonance imaging; and radiogrammetry and published in Portuguese or English, in the last 10 years (2006-2016). The article was organized into topics with the description of peculiarities, advantages and disadvantages of each imaging method and their possible clinical applicability. Despite the emergence of new technologies, dual energy X-ray absorptiometry (DXA) remains the gold standard method for low bone mass diagnosis in all age groups. However, interpretation is complex in children and adolescents and demands skilled people. Quantitative computed tomography (QCT) [central QCT, peripheral QCT (pQCT) and high resolution-pQCT (HR-pQCT)] and magnetic resonance imaging (MRI) evaluate real bone density, but are not yet available for routine use. Quantitative bone ultrasound (QUS) shows good perspectives for its use in primary prevention actions. Automated radiogrammetry shows promise as a method able to flag individuals who might benefit from a complete bone assessment, but the clinical value of the measures still needs to be established.

Increased carotid intima-media thickness in Brazilian adolescents with type 1 diabetes mellitus.

BACKGROUND: Increased carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is an independent predictor of future cardiovascular events, and has been reported in children with various chronic diseases, including type 1 diabetes mellitus (DM1). OBJECTIVES: Evaluate CIMT and its association with cardiovascular risk factors in Brazilian adolescents with DM1. METHODS: Cross-sectional study of 118 adolescents, 57 with DM1 and no chronic complications related to the disease, and 61 healthy individuals. Clinical, biochemical, and high-resolution B-mode ultrasonographic evaluations according to the Consensus Statement of the American Society of Echocardiography CIMT Task Force were performed. RESULTS: Adolescents with diabetes (66.6% female) were 14.5 ± 2.9 years old and had 9.0 ± 4.0 years of disease duration. The healthy adolescents (62.3% female) were 14.3 ± 2.6 years old. All the adolescents had blood pressure within their reference ranges. In 66% of DM1 adolescents the systolic blood pressure was >50th percentile. Increased CIMT was observed in adolescents with diabetes compared with those in the control group: 0.53 vs 0.51 mm (p < 0.004) on the right side, and 0.55 vs 0.51 mm (p < 0.001) on the left side. CIMT presented independent and positive associations with diabetes duration, total cholesterol level, low-density lipoprotein cholesterol level, and systolic blood pressure percentile in DM1 adolescents. CONCLUSIONS: Increased CIMT was observed in young Brazilian adolescents with DM1, and was associated with cardiovascular risk factors. CIMT assessment may be useful for the early identification and monitoring of cardiovascular risk in this age group.

Cardiovascular risk factors and increased carotid intima-media thickness in young patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Increased arterial intima-media thickness has been observed in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). CAH has also been associated with obesity, insulin resistance, and hypertension. The aim of the present study was to compare youths with CAH with healthy, normal-weight individuals, evaluating carotid intima-media thickness (CIMT) and indicative factors of cardiovascular risk to seek for abnormalities in the CAH group. SUBJECTS AND METHODS: Clinical, biochemical, and ultrasonographic evaluations, according to published criteria, were performed in 113 subjects (5 to 20 years old): 40 patients with 21-OHD and 73 healthy individuals matched for gender, pubertal status, and age. RESULTS: Most CAH patients were female (80%), salt-losers (72.5%), and pubescent (80%); 10 (25%) patients were overweight. An increase in CIMT was observed both on the right (p = 0.0240) and left (p = 0.0003) sides in 38 CAH patients compared with the healthy individuals. The body mass index, BMI/age Z score, and systolic blood pressure (SBP) were higher in patients compared with controls (p < 0.000 and p = 0.0219, respectively). CONCLUSIONS: Findings of increased CIMT, BMI, and SBP in young patients with 21-OHD indicate the need for early identification and intervention regarding cardiovascular risk. Validating these findings might result in improved therapeutic approaches for children with 21-OHD in the future.

Cardiovascular risk factors and increased carotid intima-media thickness in young patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

ABSTRACT Objective Increased arterial intima-media thickness has been observed in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). CAH has also been associated with obesity, insulin resistance, and hypertension. The aim of the present study was to compare youths with CAH with healthy, normal-weight individuals, evaluating carotid intima-media thickness (CIMT) and indicative factors of cardiovascular risk to seek for abnormalities in the CAH group. Subjects and methods Clinical, biochemical, and ultrasonographic evaluations, according to published criteria, were performed in 113 subjects (5 to 20 years old): 40 patients with 21-OHD and 73 healthy individuals matched for gender, pubertal status, and age. Results Most CAH patients were female (80%), salt-losers (72.5%), and pubescent (80%); 10 (25%) patients were overweight. An increase in CIMT was observed both on the right (p = 0.0240) and left (p = 0.0003) sides in 38 CAH patients compared with the healthy individuals. The body mass index, BMI/age Z score, and systolic blood pressure (SBP) were higher in patients compared with controls (p < 0.000 and p = 0.0219, respectively). Conclusions Findings of increased CIMT, BMI, and SBP in young patients with 21-OHD indicate the need for early identification and intervention regarding cardiovascular risk. Validating these findings might result in improved therapeutic approaches for children with 21-OHD in the future. Arch Endocrinol Metab. 2015;59(6):541-7.

Hábitos alimentares e perfil de ingestão de energia e nutrientes de crianças eadolescentes com diabetes mellitus tipo 1 / Eating habits and energy and nutrient intake profile in children and adolescents with type 1 diabetes mellitus

Introdução: a adoção de hábitos alimentares adequados, fundamental para o controlemetabólico da criança com diabetes mellitus tipo 1 (DM1), necessita do envolvimentoe participação efetiva da família e pode implicar mudanças nos padrões alimentares jáestabelecidos. Objetivo: avaliar o perfil alimentar de crianças e adolescentes com DM1e sua adequação às recomendações atuais. Casuística e métodos: foram estudadas146 pessoas com idade entre sete e 19 anos e no mínimo um ano de diagnóstico deDM1, atendidos na Divisão de Endocrinologia Pediátrica do Hospital das Clínicas daUniversidade Federal de Minas Gerais. A dieta foi avaliada por meio de questionárioquantitativo de frequência alimentar, testado e validado previamente em projeto-piloto.Resultados: o percentual médio de calorias ingeridas como proteínas e gordurapoli-insaturada estava dentro das recomendações adotadas; o de gordura saturadae colesterol superou a recomendação em toda a população estudada. A ingestão degordura monoinsaturada e a de carboidratos nos indivíduos com até 14 anos de idadenão atingiu a recomendação adotada. Adolescentes entre 15 e 19 anos ingeriram altopercentual de calorias provenientes de carboidratos, enquanto as crianças entre sete e10 anos de idade ingeriram mais gorduras e proteínas. Os adolescentes de 15 a 19 anosapresentaram hábitos alimentares mais inadequados. Conclusão: constituem motivode preocupação a dieta com perfil lipídico insatisfatório e hábitos alimentares inapropriados,inadequações nutricionais que contribuem para o mau controle de DM1.

Introduction: adopting proper eating habits is crucial for the metabolic control of diabetesmellitus type 1 (DM1) in children and requires the involvement and effective participationof the family implying in changes in established eating patterns. Objective: toevaluate the dietary profile of children and adolescents with DM1 and their adaptation tocurrent recommendations. Patients and methods: we studied 146 individuals aged betweenseven and 19 years old with at least one year of DM1 diagnosis and treated at theDivision of Pediatric Endocrinology of the General Hospital, Federal University of MinasGerais. The diet was assessed by a quantitative food frequency questionnaire, previouslytested and validated in a pilot project. Results: the average percentage of ingestedcalories as protein and polyunsaturated fat was within the adopted recommendations;that of saturated fat and cholesterol exceeded the recommendation in the entire studypopulation. The monounsaturated fat and carbohydrates intake in individuals under 14years of age did not reach the adopted recommendation. Adolescents between 15 and19 years old ingested a high percentage of calories from carbohydrates while childrenbetween seven and ten years old ingested more fat and protein. Adolescents between15 and 19 years old presented the most inadequate eating habits. Conclusion: a diet with poor lipid profile, inappropriate eating habits, andnutritional inadequacies that contribute to poor controlof DM1 are of concern.

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.

Morning serum Basal cortisol levels are affected by age and pubertal maturation in school-aged children and adolescents.

BACKGROUND: The same reference values for cortisol have been used for adults and children, but laboratory results obtained from an adult population might not be suitable for pediatric patients. AIMS: To determine morning serum basal cortisol levels in children and adolescents. METHODS: The study was conducted on 120 suitable reference individuals, healthy Brazilian children and adolescents from both genders aged 4-19 years old. The method used for cortisol assessment was the chemiluminescent enzyme immunoassay (VITROS® 5600 MicroWell; Johnson & Johnson, High Wycombe, UK, 2009), and the kit reference interval was 4.46-22.7 µg/dl (122.7-626.2 nmol/l). The setting limits were calculated according to the Clinical Laboratory Standards Institute guidelines. RESULTS: The morning serum basal cortisol levels increased with age and pubertal maturation, but there were no differences based on gender. The cortisol reference values were established based on the 2.5th and 97.5th percentiles as 2.97 µg/dl [81.9 nmol/l, 90% confidence interval (CI) 1.44-3.69 µg/dl] and 23.4 µg/dl (645.5 nmol/l; 90% CI 16.3-26.4 µg/dl), respectively. CONCLUSIONS: The assessment of the morning serum basal cortisol levels showed a unique pattern, with a different lower limit for the cohort compared to current values established for adult subjects.