[Etiological assessment of hyperthyrotropinemia in children with Down's syndrome]. / Avaliação etiológica da hipertirotropinemia em crianças com síndrome de Down.

OBJECTIVE: To study the prevalence of increased TSH level and its probable cause in children with Down's syndrome treated at Policlínica Antônio Cândido. METHODS: The data were collected using medical records of 169 patients. Of these, 46 patients, whose TSH increased at some time during their follow-up, were re-evaluated. In these patients, TSH, free T4, total T4 and thyroid peroxidase autoantibody (anti-TPO) levels were measured. Thyroid ultrasound, iodine-131 scintigraphy, and a perchlorate discharge test were performed. RESULTS: In 169 children, 86 (50.8%) of whom were male, aged between 1-16 years (median 4 years), 67 (39.6%) presented increased TSH levels. Out of these 67 patients, 46 were prospectively studied. In 31 (67.4%) of them serum TSH returned to normal levels; in 11, TSH remained between 5 and 10 microU/ml, three (6.5%) had a TSH level over 10 microU/ml and one (2.2%) had hyperthyroidism. The diagnoses in 34 patients who were fully studied were: goiter in five (14.7%); Hashimoto's thyroiditis in four (5.9%); hypoplasia in three (8.8%) and iodide organification defect in one (2.9%). The increased TSH levels had a statistically positive relationship with anti-TPO (p = 0.02), but not with gender, abnormal ultrasound or scintigraphy findings. TSH levels did not have any relationship with persistent hyperthyrotropinemia. CONCLUSIONS: In patients with Down's syndrome, slightly elevated and transient TSH levels are frequently detected. Positive anti-TPO antibody test is a key factor in the follow-up of these patients because of its potential risk of progression to manifest thyroid disease.

[Congenital transient hypothyroidism: characteristics of children identified at Newborn Screening Program of the State of Minas Gerais, Brazil]. / Hipotiroidismo congênito transitório: perfil das crianças identificadas no Programa Estadual de Triagem Neonatal de Minas Gerais, Brasil.

Early diagnosis and treatment of congenital hypothyroidism are the main goals of the neonatal screening programs. A retrospective analysis was carried out to assess the characteristics and etiologies of congenital transient hypothyroidism (CTH) in the Newborn Screening Program of the State of Minas Gerais, Brazil. To reach a diagnosis of CTH, altered screening and serum confirmatory T4 and TSH tests and normal serum free T4 and TSH at 4 and 8 weeks after the withdrawal of levothyroxine were used. We studied 21 children with CTH who represented 4.23% of the whole group with detected hypothyroidism and followed them up in the Screening Program. These patients received LT4 therapy for a variable period of one month to three years. Serum confirmatory TSH levels varied from 10.4 to 583.4 microUI/mL. Maternal antibodies, TRAB and anti-TPO, were associated to CTH in two children and iodine overload in one of them. We concluded that CTH is an important component in neonatal screening and hormonal treatment during the first months of the life is essential. The TSH initial levels are not relevant to determine whether the thyroid dysfunction is transient or permanent.

Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect.

The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99% perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.

Congenital hypothyroidism: the clinical profile of affected newborns identified by the Newborn Screening Program of the State of Minas Gerais, Brazil.

OBJECTIVE: To evaluate the clinical profile of newborns with congenital hypothyroidism identified by the Newborn Screening Program of the State of Minas Gerais, Brazil, between 2000 and 2006. METHODS: Analysis of factors involved in this profile, including: TSH and FT4 levels (determined by chemiluminescence, with limits of normality set at 0.3-5.0 microUI/mL and 0.8-1.8 ng/dL, respectively), age at diagnosis and age at treatment. The study sample consisted of 443 children, 55.8% were female and 95% were seen before completing 60 days of life. RESULTS: The most prevalent clinical signals were: umbilical hernia (51%), enlarged anterior fontanel (50.3%), and open posterior fontanel (47.2%). Hypotonia, macroglossia and feeding difficulties were the clinical signs most frequently associated with the biochemical severity of the disease. A delay in bone age was present in 32.1% of the children at diagnosis. The median of serum TSH and FT4 was 120 microUI/mL and 0.62 ng/dL, respectively. The median age at start of treatment was 28 days. CONCLUSION: There are some early clinical signs that suggest a diagnosis of congenital hypothyroidism. Therefore, when presented with a child exhibiting these signs, serum TSH and FT4 should be assayed in order to confirm or rule out the disease, irrespective of the result of screening. Age at start of treatment remains high, but strategies are being implemented to reduce it.

Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect / Mutação monoalélica no gene da tireoperoxidase em paciente com hipotireoidismo congênito com defeito total de incorporação de iodeto

The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99 percent perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.

O objetivo deste estudo foi identificar defeitos genéticos em paciente com hipotireoidismo congênito (HC) por disormonogênese e defeito total de incorporação de iodeto (DIIT). Neonato do sexo masculino com HC diagnosticado pelo rastreamento neonatal. Exames clínicos e radiológicos confirmaram que o paciente apresentava HC severo e permanente com DIIT (teste de perclorato: 99 por cento). A região codificadora dos genes TPO, DUOX2, DUOXA2 e 2957 pares de bases (pb) do promotor de TPO foram sequenciados. No paciente foi identificada a duplicação em heterozigose GGCC no éxon 8 do gene TPO (c.1186_1187insGGCC). Nenhuma outra mutação foi localizada nos genes TPO, incluindo o promotor, DUOX2 ou DUOXA2. Descrevemos paciente com grave defeito de organificação de iodeto, provocando HC severo com bócio, em consequência de uma única mutação monoalélica no gene TPO. A expressão monoalélica no tecido tireoideano explicaria a associação de uma doen­ça autossômica recessiva com uma única mutação monoalélica.

Hipotireoidismo congênito: perfil clínico dos recém-nascidos identificados pelo Programa de Triagem Neonatal de Minas Gerais / Congenital hypothyroidism: the clinical profile of affected newborns identified by the Newborn Screening Program of the State of Minas Gerais, Brazil

OBJETIVO: Avaliar o perfil clínico de recém-nascidos com hipotireoidismo congênito identificados pelo Programa Estadual de Triagem Neonatal de Minas Gerais entre 2000 e 2006. MÉTODOS: A frequência das manifestações clínicas de hipotireoidismo congênito foi analisada em relação aos níveis de hormônio estimulante da tireoide T4L (determinados por quimioluminescência, valores de referência de 0,3 a 5,0 µUI/mL e 0,8 a 1,8 ng/dL, respectivamente) e idades ao diagnóstico e tratamento. Estudou-se 443 crianças, sendo 55,8 por cento do sexo feminino e 95 por cento delas com menos 60 dias de vida. RESULTADOS: Os sinais clínicos mais prevalentes foram: hérnia umbilical (51 por cento), fontanela anterior ampla (50,3 por cento) e fontanela posterior aberta (47,2 por cento). Hipotonia, macroglossia e sucção débil foram os sinais mais associados com a gravidade bioquímica da doença. Em 32,1 por cento das crianças houve atraso na idade óssea ao diagnóstico. As medianas de TSH e T4L séricos foram 120 µUI/mL e 0,62 ng/dL, respectivamente. A mediana da idade de início de tratamento foi de 28 dias. CONCLUSÃO: Existem sinais clínicos precoces que sugerem o diagnóstico de hipotireoidismo congênito. Portanto, diante de uma criança com esses sinais, devem ser avaliados TSH e T4L séricos para confirmar ou excluir a doença, independentemente do resultado do teste de triagem. A idade de início de tratamento ainda foi elevada, mas o programa vem adotando estratégias para redução da mesma.

OBJECTIVE: To evaluate the clinical profile of newborns with congenital hypothyroidism identified by the Newborn Screening Program of the State of Minas Gerais, Brazil, between 2000 and 2006. METHODS: Analysis of factors involved in this profile, including: TSH and FT4 levels (determined by chemiluminescence, with limits of normality set at 0.3-5.0 µUI/mL and 0.8-1.8 ng/dL, respectively), age at diagnosis and age at treatment. The study sample consisted of 443 children, 55.8 percent were female and 95 percent were seen before completing 60 days of life. RESULTS: The most prevalent clinical signals were: umbilical hernia (51 percent), enlarged anterior fontanel (50.3 percent), and open posterior fontanel (47.2 percent). Hypotonia, macroglossia and feeding difficulties were the clinical signs most frequently associated with the biochemical severity of the disease. A delay in bone age was present in 32.1 percent of the children at diagnosis. The median of serum TSH and FT4 was 120 µUI/mL and 0.62 ng/dL, respectively. The median age at start of treatment was 28 days. CONCLUSION: There are some early clinical signs that suggest a diagnosis of congenital hypothyroidism. Therefore, when presented with a child exhibiting these signs, serum TSH and FT4 should be assayed in order to confirm or rule out the disease, irrespective of the result of screening. Age at start of treatment remains high, but strategies are being implemented to reduce it.

Hipotiroidismo congênito transitório: perfil das crianças identificadas no programa estadual de triagem neonatal de Minas Gerais, Brasil / Congenital transient hypothyroidism: characteristics of children identified at newborn screening program of the state of Minas Gerais, Brazil

O diagnóstico e o tratamento precoces do hipotiroidismo congênito (HC) constituem os principais objetivos dos programas de triagem neonatal. Neste estudo avaliou-se o perfil hormonal e os possíveis fatores responsáveis pelo HC transitório (HCT). Os dados foram colhidos dos prontuários das crianças acompanhadas no Hospital das Clínicas da UFMG, triadas pelo Programa Estadual de Triagem Neonatal de Minas Gerais. Para o diagnóstico de HCT considerou-se: exames de triagem e sérico confirmatório alterados; TSH e T4 livre normais em 4 e 8 semanas após suspensão do tratamento hormonal para avaliação etiológica. As 21 crianças com HCT representavam 4,23 por cento das crianças acompanhadas pelo Programa e receberam tratamento com L-tiroxina por um mês a três anos. Os valores de TSH no primeiro exame sérico variaram de 10,4 a 583,4æUI/ml, não se correlacionando, portanto, à gravidade da doença. Possivelmente a presença de anticorpos maternos em duas crianças, anti-TPO (anticorpo anti-tireoperoxidase) em uma e o anticorpo anti-receptor de TSH associado à exposição ao iodo em outra foram responsáveis pelo hipotiroidismo. Concluímos que o HCT é uma entidade importante na triagem neonatal, sendo essencial o tratamento hormonal nos primeiros meses de vida e que os níveis iniciais de TSH não são úteis para definir se a disfunção tiroidiana será transitória ou permanente.

Avaliação etiológica da hipertirotropinemia em crianças com síndrome de Down / Etiological assessment of hyperthyrotropinemia in children with Down's syndrome

OBJETIVO: Analisar a prevalência de hipertirotropinemia e estudar sua possível etiologia em crianças com síndrome de Down atendidas na Policlínica Municipal Antônio Cândido, em Belo Horizonte. MÉTODOS: Foram utilizados os dados dos prontuários de todas as crianças com síndrome de Down atendidas na policlínica para o cálculo da prevalência da alteração do hormônio estimulante da tireóide (TSH). As crianças que tiveram TSH elevado (maior que 5 µUI/ml) em pelo menos um exame foram convocadas para novas dosagens de TSH, T4livre, T4total e auto-anticorpo antiperoxidase (ATPO), realização de ultra-som da tireóide, tireograma com iodo-131 e teste de descarga do perclorato. As alterações encontradas nos exames das crianças que permaneceram com TSH elevado foram comparadas com as das que normalizaram os valores de TSH. RESULTADOS: Foram encontradas, em 169 crianças com síndrome de Down, 86 (50,8 por cento) masculinas, idade entre 1-6 anos (mediana de 4 anos), 67 (39,6 por cento) com TSH aumentado, as quais foram convocadas para novas avaliações, comparecendo 46. Nesses pacientes, o TSH se normalizou em 31 (67,4 por cento); em 11 (23,9 por cento) permaneceu entre 5-10 µUI/ml; em três (6,5 por cento) ficou acima de 10 µUI/mL; e em uma (2,2 por cento) constatou-se hipertireoidismo. Os diagnósticos realizados nos pacientes com propedêutica completa (n = 34) foram: bócio (14,7 por cento), hipoplasia (8,8 por cento), tireoidite de Hashimoto (5,9 por cento), defeito na organogênese de iodo (2,9 por cento). Não se evidenciou relação entre as amplitudes dos valores de TSH e a persistência da hipertirotropinemia. Crianças com ATPO positivo estavam associadas a TSH elevado (p = 0,02). CONCLUSÕES: Na síndrome de Down, são freqüentes valores de TSH discretamente elevados e instáveis, sendo suas etiologias variáveis. A presença de ATPO mostrou-se importante no seguimento dessas crianças pelo risco potencial de evolução para doença tireoidiana manifesta.