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Abstract Objective The present study aimed to evaluate the effects of GH treatment on the body composition of children born with SGA. Methods This study is a systematic review of the literature. CINAHL, Embase; Medline/Pubmed, Scopus and Web of Science were searched from inception to March 2022. Results Four studies met the inclusion criteria, with an intervention time of 1 to 3 years, using doses from 0.03 to 0.07 mg/kg/day of GH. Bone densitometry by dual-energy X-ray absorptiometry (DXA) with whole-body scans was the most used method to assess body composition. Most studies (n= 3) had SGA children as a control group with the same characteristics as the case group; the mean age was similar between the groups (minimum of 5.1 ± 1.4 years and maximum of 6.7 ± 1 0.8 years) and all participants had an average height ≤ -3DP. The Lean Mass (LM) and Fat Mass (FM) outcomes of the studies were not presented in a standardized manner; thus, they cannot be compared. There was a significant increase in LM in the group treated with GH in relation to the pre-treatment period and in comparison, to the untreated control group. Three studies showed a significant decrease in FM at the end of the intervention period, and in two studies, this decrease occurred in the control group. Conclusions Despite the differences in the presentation of results and in the evaluation periods, the results of the studies showed that growth hormone favors the gain and maintenance of lean mass, and it also affects fat mass reduction and redistribution.
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OBJECTIVE: The present study aimed to evaluate the effects of GH treatment on the body composition of children born with SGA. METHODS: This study is a systematic review of the literature. CINAHL, Embase; Medline/Pubmed, Scopus and Web of Science were searched from inception to March 2022. RESULTS: Four studies met the inclusion criteria, with an intervention time of 1 to 3 years, using doses from 0.03 to 0.07 mg/kg/day of GH. Bone densitometry by dual-energy X-ray absorptiometry (DXA) with whole-body scans was the most used method to assess body composition. Most studies (n = 3) had SGA children as a control group with the same characteristics as the case group; the mean age was similar between the groups (minimum of 5.1 ± 1.4 years and maximum of 6.7 ± 1 0.8 years) and all participants had an average height ≤ -3DP. The Lean Mass (LM) and Fat Mass (FM) outcomes of the studies were not presented in a standardized manner; thus, they cannot be compared. There was a significant increase in LM in the group treated with GH in relation to the pre-treatment period and in comparison, to the untreated control group. Three studies showed a significant decrease in FM at the end of the intervention period, and in two studies, this decrease occurred in the control group. CONCLUSIONS: Despite the differences in the presentation of results and in the evaluation periods, the results of the studies showed that growth hormone favors the gain and maintenance of lean mass, and it also affects fat mass reduction and redistribution.
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Hormônio do Crescimento , Hormônio do Crescimento Humano , Criança , Pré-Escolar , Humanos , Recém-Nascido , Composição Corporal , Estatura , Idade Gestacional , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/farmacologia , Recém-Nascido Pequeno para a Idade Gestacional , Lactente , AdolescenteRESUMO
Objectives Adequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients. Methods Clinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls). Results Median chronological age (CA) at treatment initiation was 24 days, and mean initial levothyroxine dose was 11.7 ± 1.9 µg/kg/day; mean CA at puberty onset was 11.5 ± 1.3 years (boys) and 9.7 ± 1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1 ± 1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04). Conclusions In this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.
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Desenvolvimento do Adolescente/fisiologia , Hipotireoidismo Congênito/fisiopatologia , Puberdade/fisiologia , Adolescente , Desenvolvimento do Adolescente/efeitos dos fármacos , Adulto , Estatura/efeitos dos fármacos , Estatura/fisiologia , Brasil/epidemiologia , Criança , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/tratamento farmacológico , Hipotireoidismo Congênito/epidemiologia , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Triagem Neonatal , Puberdade/efeitos dos fármacos , Valores de Referência , Tiroxina/uso terapêuticoRESUMO
The antitumor effect of metformin has been demonstrated in several types of cancer; however, the mechanisms involved are incompletely understood. In this study, we showed that metformin acts directly on melanoma cells as well as on the tumor microenvironment, particularly in the context of the immune response. In vitro, metformin induces a complex interplay between apoptosis and autophagy in melanoma cells. The anti-metastatic activity of metformin in vivo was assessed in several mouse models challenged with B16F10 cells. Metformin's activity was, in part, immune system-dependent, whereas its antitumor properties were abrogated in immunodeficient (NSG) mice. Metformin treatment increased the number of lung CD8-effector-memory T and CD4+Foxp3+IL-10+ T cells in B16F10-transplanted mice. It also decreased the levels of Gr-1+CD11b+ and RORγ+ IL17+CD4+ cells in B16F10-injected mice and the anti-metastatic effect was impaired in RAG-1-/- mice challenged with B16F10 cells, suggesting an important role for T cells in the protection induced by metformin. Finally, metformin in combination with the clinical metabolic agents rapamycin and sitagliptin showed a higher antitumor effect. The metformin/sitagliptin combination was effective in a BRAFV600E/PTEN tamoxifen-inducible murine melanoma model. Taken together, these results suggest that metformin has a pronounced effect on melanoma cells, including the induction of a strong protective immune response in the tumor microenvironment, leading to tumor growth control, and the combination with other metabolic agents may increase this effect.
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Não há consenso sobre quais são os valores ideais da vitamina D em crianças saudáveis. Porém, níveis séricos altos ou baixos parecem ter influência na fisiopatologia das doenças alérgicas. Há dados na literatura atual que demonstram os potenciais efeitos da vitamina D em aumentar a atividade dos peptídeos antimicrobianos e suprimir a resposta inflamatória, apontando uma relação inversa entre os níveis de vitamina D e a gravidade da dermatite atópica. O objetivo do presente trabalho foi revisar artigos publicados sobre a relação entre níveis séricos de vitamina D e dermatite atópica, uma vez que a vitamina D tem sido implicada em várias ações imunomoduladoras e alguns estudos têm descrito sua influência na gravidade da dermatite atópica, porém com resultados conflitantes. Este estudo baseou-se em revisão de artigos originais, artigos de revisão e consensos publicados nos últimos 10 anos, obtidos a partir da pesquisa dos termos vitamin D e atopic dermatitis, nos bancos de dados online. Concluímos que a suplementação da vitamina D pode trazer benefícios no tratamento da dermatite atópica. No entanto, mais pesquisas são necessárias para determinar se existe alguma relação entre os níveis de vitamina D e a gravidade da dermatite atópica.
There is no consensus about optimal values of vitamin D in normal children. However, high or low serum levels seem to influence the pathophysiology of allergic diseases. There is evidence supporting the potential effects of vitamin D on increasing the activity of antimicrobial peptides and suppressing the inflammatory response, indicating an inverse relationship between vitamin D levels and the severity of atopic dermatitis. Our objective was to review published articles on the relationship between serum vitamin D levels and atopic dermatitis, as vitamin D has been implicated in several immunoregulatory actions, and some studies have reported an influence on the severity of atopic dermatitis, with conflicting results. The present study reviewed original articles, review articles, and consensus documents published in the past 10 years, retrieved in online databases using the keywords vitamin D and atopic dermatitis. We conclude that vitamin D supplementation may be beneficial in the treatment of atopic dermatitis. However, more research is needed to determine whether there is any relationship between vitamin D levels and atopic dermatitis severity.
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Humanos , Peptídeos Catiônicos Antimicrobianos , Dermatite Atópica , Fatores Imunológicos , Deficiência de Vitamina D , Técnicas e Procedimentos Diagnósticos , Inflamação , MétodosRESUMO
BACKGROUND: Congenital hypothyroidism (CH) is mainly due to developmental abnormalities leading to thyroid dysgenesis (TD). TD encompasses very distinct morphologic subtypes of disease. This study examined and compared the phenotype in TD variants and searched for genetic alterations in sporadic thyroid hypoplasia (TH), the most misdiagnosed form of CH. This was a longitudinal study over a 14-year period (1990-2004). METHODS: A continuous series of 353 children with TD was identified using thyroid function tests [thyroxine (T4) and TSH], scintigraphy, and ultrasound as diagnostic tools. Individual phenotypes were analyzed in 253 children with TD. Mutations in the most likely candidate genes were studied in 35 cases of TH. RESULTS: The overall birth prevalence of permanent CH was 1:4795. Ectopy represented 37% of all cases of permanent primary CH, dyshormonogenesis 28%, agenesis 24%, hypoplasia 10%, and hemiagenesis 1%. The lowest screening T4 level and the highest TSH level were in the agenetic group, followed by TH. The TH group had an improvement in the thyroid function showing less-severe phenotype with aging. In the molecular analysis, one patient was identified with a mutation in the PAX8 gene (155G>C; R52P); four patients had a heterozygous G>C substitution in position -569; two patients showed a (234C>A; P52T) or (2181C>G; D727E) polymorphic variants of the TSH-R gene; and one patient presented a novel heterozygous nonsynonymous substitution, 293G>A; S98N, in the NKX2.5 gene. CONCLUSIONS: The prevalence of CH was within the previously reported range of 1:3000-4000. Ectopy was the most common etiology. Clinical analysis revealed distinct hormonal patterns in TH subgroup when compared with other variants of TD, with genetic abnormalities identified only in few cases in the TSH-R, PAX8, and NKX2.5 genes.
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Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/fisiopatologia , Proteínas de Homeodomínio/genética , Mutação/genética , Fatores de Transcrição Box Pareados/genética , Fenótipo , Receptores da Tireotropina/genética , Fatores de Transcrição/genética , Brasil , Feminino , Genótipo , Proteína Homeobox Nkx-2.5 , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Fator de Transcrição PAX8 , Linhagem , Prevalência , Cintilografia , Testes de Função Tireóidea , Glândula Tireoide/diagnóstico por imagem , Tireotropina/sangue , Tiroxina/sangue , UltrassonografiaRESUMO
INTRODUCTION: Amiodarone (AMD) is an antiarrhythmic agent which contains 37% of iodine. It can reach the fetus by transplacental passage and induce transient congenital hypothyroidism (TCH). We report two cases of TCH caused by gestational exposure to AMD, detected by the Newborn Screening Program for Congenital Hypothyroidism of the State of Paraná-Brazil. CLINICAL CASE 1 (C1): Neonatal TSH value was 78.2 mU/L (normal<15 mU/L). AMD had been given to the mother during pregnancy to treat maternal arrhythmia. The screening results were confirmed by serum thyroid function tests. Levothyroxin (L-T4) (50 microg/day) was started on the first visit, on the 14th day of life (dl). CLINICAL CASE 2 (C2): Neonatal TSH value was 134.0 mU/L. AMD had been given to the mother in the third trimester of pregnancy to treat maternal arrhythmia. The screening results were confirmed by serum thyroid function tests: L-T4 (50 microg/day) was started on the first visit, with 13 dl. FOLLOW-UP: TSH and T4 normalized on 51 dl (C1) and 36 dl (C2); L-T4 could be diminished gradually and stopped within 16 months (C1) and 10 months (C2). They were followed-up until 22 months (C1) and 16 months (C2) with normal thyroid function tests. Their growth and mental development, evaluated by the Cognitive Adaptive Test/Clinical Linguistic & Auditory Milestone Scale (CAT/CLAMS test), were normal. CONCLUSION: Evaluation of thyroid function and mental development should be performed if AMD is used during pregnancy. Treatment of TCH must be started as soon as the diagnosis is made.
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Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Transtornos Cognitivos/etiologia , Hipotireoidismo Congênito/induzido quimicamente , Transtornos Cognitivos/diagnóstico , Hipotireoidismo Congênito/psicologia , Feminino , Humanos , Recém-Nascido , Inteligência , Gravidez , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacosRESUMO
INTRODUÇÃO: A amiodarona (AMD) é uma droga antiarrítmica que contém 37 por cento de iodo. A AMD pode alcançar o feto por via transplacentária e causar hipotireoidismo congênito (HC) ou transitório (HCT). Relatamos dois casos de HCT em virtude de exposição gestacional à AMD, detectados pelo programa de triagem neonatal para HC no Estado do Paraná, Brasil. CASO CLÍNICO 1 (C1): TSH neonatal 78,2 mU/L (normal < 15 mU/L). A AMD foi utilizada durante toda a gestação em virtude de arritmia materna. As dosagens séricas iniciais confirmaram o HC; e na primeira consulta [aos 14 dias de vida (dv)], foi iniciada levotiroxina (L-T4), 50 µg/dia. CASO CLÍNICO 2 (C2): TSH neonatal 134 mU/L. A AMD foi utilizada no último trimestre da gestação em virtude de arritmia materna. As dosagens séricas iniciais confirmaram o HC; aos 13 dv, foi iniciada L-T4 50 µg/dia. ACOMPANHAMENTO: TSH e T4 estavam normais aos 51 dv (C1) e aos 36 dv (C2) sendo então gradativamente reduzida a dose da medicação e suspensa aos 16 meses (C1) e aos dez meses (C2). As pacientes foram acompanhadas até 22 meses (C1) e 16 meses (C2) com testes de função tireoidiana normais. O crescimento e o desenvolvimento neuropsicomotor (DNPM), avaliados pelo teste CAT/CLAMS, eram normais. CONCLUSÃO: As avaliações da função tireoidiana e do DNPM são necessários quando a AMD é utilizada na gestação. O tratamento do HCT deve ser instituído tão logo o diagnóstico seja realizado.
INTRODUCTION: Amiodarone (AMD) is an antiarrhythmic agent which contains 37 percent of iodine. It can reach the fetus by transplacental passage and induce transient congenital hypothyroidism (TCH). We report two cases of TCH caused by gestational exposure to AMD, detected by the Newborn Screening Program for Congenital Hypothyroidism of the State of Paraná - Brazil. CLINICAL CASE 1 (C1): Neonatal TSH value was 78,2mU/L (normal < 15 mU/L). AMD had been given to the mother during pregnancy to treat maternal arrhythmia. The screening results were confirmed by serum thyroid function tests. Levothyroxin (L-T4) (50µg/day) was started on the first visit, on the 14th day of life (dl). CLINICAL CASE 2 (C2): Neonatal TSH value was 134,0 mU/L. AMD had been given to the mother in the third trimester of pregnancy to treat maternal arrhythmia. The screening results were confirmed by serum thyroid function tests: L-T4 (50µg/day) was started on the first visit, with 13 dl. FOLLOW-UP: TSH and T4 normalized on 51 dl (C1) and 36 dl (C2); L-T4 could be diminished gradually and stopped within 16 months (C1) and 10 months (C2). They were followed-up until 22 months (C1) and 16 months (C2) with normal thyroid function tests. Their growth and mental development, evaluated by the Cognitive Adaptive Test/Clinical Linguistic & Auditory Milestone Scale (CAT/CLAMS test), were normal. CONCLUSION: Evaluation of thyroid function and mental development should be performed if AMD is used during pregnancy. Treatment of TCH must be started as soon as the diagnosis is made.
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Feminino , Humanos , Recém-Nascido , Gravidez , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Transtornos Cognitivos/etiologia , Hipotireoidismo Congênito/induzido quimicamente , Transtornos Cognitivos/diagnóstico , Hipotireoidismo Congênito/psicologia , Inteligência , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacosRESUMO
Tumores tireoideanos são raros na infância e adolescência. Foram revisados os prontuários de quinze pacientes (8 do sexo feminino) com idades entre 5,8 e 15,2 anos, atendidos na Unidade de Endocrinologia Pediátrica (UEP) do HC-UFPR entre fevereiro de 1988 e março de 2003. Nódulo cervical anterior foi a queixa inicial mais freqüente. Dez pacientes eram portadores de carcinoma papilífero (CP), quatro apresentavam carcinoma medular (CMT; dos quais, três com NEM-2B) e um, carcinoma folicular. Dois pacientes com NEM-2B apresentam mutação de novo (Met918Thr) do proto-oncogene RET. PAAF, efetuada em dez pacientes, foi positiva para neoplasia em cinco deles. Todos os pacientes foram submetidos a tireoidectomia total. Terapia adjuvante com 131I foi realizada em dez pacientes. Dois pacientes faleceram por doença não relacionada ao tumor. Nove pacientes não apresentam evidência clínica ou laboratorial do tumor; um (CP) apresentou recidiva 5 anos após o tratamento inicial e três (1 CP, 2 CMT) ainda têm evidência da doença. Nossos dados estão de acordo com a literatura em relação ao prognóstico e manifestações clínicas. Entretanto, a prevalência de CMT (27 por cento), a distribuição por sexo e os resultados da PAAF diferem da maioria das casuísticas publicadas, o que pode ser atribuído ao número de casos aqui relatado.
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Adolescente , Criança , Feminino , Humanos , Masculino , Neoplasias da Glândula Tireoide , Seguimentos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Thyroid tumors are rare in childhood and adolescence. A retrospective analysis was done of fifteen patients (8 female) with thyroid carcinoma attended in the Pediatric Endocrinology Unit of the HC-UFPR, from February 1988 to March 2003. The most frequent initial complaint was an anterior cervical nodule. Ten patients were papillary carcinoma (PTC) bearers, four had medullary carcinoma (MTC; three of them with MEN-2B) and one had follicular carcinoma. Two patients with MEN-2B have de novo proto-oncogene RET mutation (Met918Thr). Fine needle aspiration (FNA) was performed in ten patients and was malignancy positive in only five of them. All patients underwent total thyroidectomy. Adjuvant radioiodine (131I) therapy was made in ten patients. Two patients died from unrelated diseases. Nine patients presented no clinical or laboratorial evidence of disease; one (PTC) developed recurrence 5 years after initial treatment and three (1 PTC, 2 MTC) have disease evidence yet. Our prognosis and clinical manifestations data are according to the literature. However, MTC prevalence (27%), sex distribution and FNA results differ from the majority of published casuistics, that can be attributed to the number of cases reported here.