Follow-up of children with TSH between 5 and 10 µUI/mL on the neonatal screening test

Orientadores: Sofia Helena Valente de Lemos Marini, André Moreno MorcilloDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: Na busca da detecção de maior número de crianças com alterações leves e moderadas da função tireoidiana, programas de triagem neonatal têm optado por baixar o valor de corte do TSH em papel filtro (TSH-f). O Serviço de Referência em Triagem Neonatal da Universidade Estadual de Campinas utiliza, desde a sua criação, o ponto de corte de 5 µUI/mL, embora atualmente o valor mais utilizado no Brasil seja 10 µUI/mL. Objetivos: Determinar a prevalência de hipotireoidismo congênito (HC), sua etiologia e evolução, além de avaliar possíveis fatores preditores de HC permanente em crianças com TSH-f entre 5 e 10 µUI/mL (sangue total). Métodos: Estudo retrospectivo incluindo crianças triadas de 2003 a 2010, com TSH-f entre 5 e 10 µUI/mL e diagnóstico de HC, definido como TSH sérico igual ou superior a 10 µUI/mL e início de tratamento com levotiroxina até os dois anos de idade. Estudou-se a evolução da função tireoidiana e determinou-se a prevalência de HC no grupo total e a frequência de HC permanente entre as crianças nascidas a termo, sem intercorrências no período neonatal e que haviam sido acompanhadas por pelo menos seis meses após a retirada da medicação; aquelas com HC permanente foram submetidas à cintilografia tireoidiana. Resultados: Dos 380.741 nascidos vivos triados, 3.713 (1,04%) apresentaram TSH-f entre 5 e 10 µUI/mL e, destes, 339 (9,13%) tinham HC. Para a reavaliação, foram excluídas 83 crianças: 32 pré-termos, 13 com Síndrome de Down, duas por intercorrências neonatais graves, uma por hipertireoidismo materno e 35 por perda de seguimento, óbito ou transferência antes do término do período de acompanhamento pré-definido. Das 256 crianças reavaliadas após a suspensão da levotiroxina, 70 (27,34%) apresentavam HC permanente, sendo quatro disgenesias tireoidianas (uma hipoplasia, duas agenesias de lobo e uma redução de lobo) e oito bócios. Os valores de T4 livre na avaliação sérica inicial foram mais baixos no grupo com HC permanente (p=0,001). Em 22,6% das crianças, devido à elevação tardia do TSH, o HC só foi confirmado após os quatro meses de idade. A chance do HC ser permanente foi 4,05 vezes maior nos casos diagnosticados entre seis e 12 meses de idade do que naqueles firmados no primeiro mês de vida (p=0,003). Entre os 70 casos de HC permanente detectados, 25,7% tiveram o diagnóstico definido somente após 120 dias da suspensão da levotiroxina. Conclusão: Conclui-se que 9,13% das crianças com TSH-f entre 5 e 10 µUI/mL têm HC e não seriam detectadas com o uso do valor de corte de 10 µUI/mL. Das 256 crianças com HC reavaliadas, 27,3% apresentavam HC permanente, sendo 17% destas com disgenesia tireoidiana ou bócio. Os únicos parâmetros associados ao HC permanente foram o valor do T4 livre inicial e a idade ao diagnóstico de HC. Portanto, sugere-se a utilização do valor de corte de TSH-f de 5 µUI/mL e o acompanhamento até um ano de idade de pacientes cujo TSH sérico não tenha se normalizado e, por no mínimo seis meses, após retirada do tratamento para afastar o diagnóstico de HC permanenteAbstract: Introduction: Searching to detect the greatest number of children even with mild to moderate alterations in thyroid function, neonatal screening programs have decreased the cutoff value of blood spot TSH (b-TSH) in newborn screening. The Newborn Screening Reference Center of State University of Campinas uses, since its foundation, the cutoff value of 5 µUI/mL, although currently the most commonly used cutoff value in Brazil be 10 µUI/mL. Objectives: To determine the prevalence of congenital hypothyroidism (CH), its etiology and evolution, as well as looking for possible factors that may predict permanent CH among children with b-TSH between 5 and 10 µUI/mL (whole blood). Methods: This retrospective study included children screened between 2003 and 2010 and whose b-TSH was between 5 and 10 µUI/mL. All patients included were diagnosed with CH, defined as serum TSH levels '> or =' 10 µUI/mL and oral levothyroxine treatment initiated until the age of two years. Thyroid function evolution and CH prevalence were studied in the total group. The frequency of permanent CH was also verified among children born at term without intercurrences in the neonatal period and who had been followed for at least six months after medication withdrawal. Children with permanent CH underwent thyroid scintigraphy. Results: From 380,741 newborns screened, 3,713 (1.04%) had b-TSH between 5 and 10 µUI/mL and from them, 339 (9.13%) had CH. For re-evaluation, 83 children were excluded: 32 preterm infants, 13 with Down syndrome, two for severe neonatal intercurrences, one by maternal hyperthyroidism and 35 due to loss of follow-up, death or medical service transference before the end of predetermined follow-up period. From the 256 children re-evaluated after levothyroxine discontinuation, 70 (27.34%) had permanent CH, being 4 thyroid dysgenesis (1 hypoplasia, 2 hemiagenesis and 1 lobe reduction) and 8 goiters. The free T4 serum levels from the initial evaluation were lower in the group with permanent CH (p = 0.001). 22.6% of the children had delayed serum TSH elevation, with the CH confirmation ocurring after four months of age. The chance of CH be permanent was 4.05 times higher in the group diagnosed between six and 12 months of age than in those diagnosed during the first month of life (p = 0.003). Among the 70 cases detected with permanent CH, 25.7% were diagnosed only after 120 days after discontinuation of levothyroxine. Conclusions: CH was present in 9.13% of children with b-TSH between 5 and 10 ?UI/mL and couldn¿t be detected using the cutoff value of 10 ?UI/mL. From 256 children with CH that were re-evaluated, 27.3% had permanent CH, 17% of them with thyroid dysgenesis or goiter. The only parameters associated with permanent CH were the initial free T4 value and the age at diagnosis of CH. Therefore, we suggest the use of b-TSH cutoff of 5 ?UI/mL and the follow-up until one year of age for those patients whose serum TSH has not normalized and at least six months, after treatment withdrawal to exclude the diagnosis of permanent CHMestradoSaude da Criança e do AdolescenteMestra em Saúde da Criança e do Adolescente01-p-03492/2014CAPE

Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

Abstract Objective: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. Data source: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Data synthesis: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. Conclusions: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required

Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

Abstract Objective: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. Data source: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Data synthesis: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. Conclusions: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required

Prevalence of congenital hypothyroidism and thyroid function follow-up of children with Tsh cutoff between 5 and 10 mIU/l in neonatal screening

sem informação862149949955th Annual Meeting of the European Society for Paediatric Endocrinolog