RESUMO
OBJECTIVE: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. SUBJECTS AND METHODS: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. RESULTS: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). CONCLUSIONS: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.
Assuntos
Proteína Homeobox Nkx-2.5/genética , Mutação/genética , Fator de Transcrição PAX8/genética , Receptores da Tireotropina/genética , Disgenesia da Tireoide/genética , Brasil , Pré-Escolar , Estudos de Coortes , Hipotireoidismo Congênito/diagnóstico por imagem , Hipotireoidismo Congênito/etiologia , Hipotireoidismo Congênito/genética , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Disgenesia da Tireoide/complicações , Disgenesia da Tireoide/diagnóstico por imagem , Tireotropina/sangue , Tiroxina/sangue , Fatores de Transcrição HES-1/genética , UltrassonografiaRESUMO
INTRODUCTION: National programs of salt iodization were implemented in Brazil to combat iodine deficiency (ID) in children of school age. Currently, there are limited data in Brazil on those still vulnerable to this deficiency and the state of nutritional iodine status in the northeast region of Brazil, where children are vulnerable to malnutrition. OBJECTIVE: The aim of this study was to analyze the iodine nutritional status, household food insecurity, socioeconomic and demographic characteristics among schoolchildren from the public school system living in state the state of Bahia, Brazil. METHODS: A cross-sectional study was conducted on 1419 schoolchildren in Bahia between the ages of 6 and 14 years old. Anthropometric parameters, urinary iodine concentrations (UIC), and thyrotropin (TSH) measurements were evaluated from blood spots on filter paper. RESULTS: The mean UIC was 206.4 ± 80.5 µg/L, with a median of 221.6 µg/L, indicating sufficient iodine intake in the region. Low urinary iodide concentration (<100 µg/L) was detected in 12.3% of the schoolchildren (n = 174), with 6.2% with mild (<100 µg/L), 3.0% with moderate (20-49 µg/L), and 3.1% with severe ID (<20 µg/L). Moreover, 9.4% (n = 134) had a urinary iodide concentration of >300 µg/L, indicating the coexistence of excessive iodine intake (EII). The mean TSH was 1.0 ± 0.6 mIU/L. The body mass index category "overweight/obesity" was a protective factor against EII (odds ratio [OR] = 0.64 [confidence interval (CI) 0.4-1.0]; p = 0.07). Urban areas (73%) had a mean UIC of 213.1 ± 80 µg/L compared with 176.8 ± 76.1 µg/L in rural areas. The risk for EII increased in children living in a house with more than six people (OR = 1.62 [CI 0.9-2.6]; p < 0.05) and water consumption from shallow wells (OR = 1.70 [CI 0.9-3.1]; p = 0.09). The risk of ID was increased by 70% in schoolchildren who had moderate or severe food insecurity (OR = 1.70 [CI 0.9-3.0]; p > 0.05). CONCLUSION: A significant proportion of schoolchildren still have ID or EII in the northeast region of Brazil, emphasizing the importance of committed public policies to address this problem. Socioeconomic factors and the lack of education about nutritional importance of iodine were important influencing factors in the presence of ID in schoolchildren.
Assuntos
Deficiências Nutricionais/epidemiologia , Abastecimento de Alimentos/estatística & dados numéricos , Iodo/urina , Fatores Socioeconômicos , Tireotropina/sangue , Adolescente , Índice de Massa Corporal , Brasil/epidemiologia , Criança , Estudos Transversais , Deficiências Nutricionais/sangue , Deficiências Nutricionais/urina , Água Potável , Feminino , Humanos , Masculino , Estado Nutricional , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Fatores de Proteção , Características de Residência , Fatores de Risco , População Rural , Instituições Acadêmicas , População UrbanaRESUMO
OBJECTIVE: To search for genetic alteration in NKX2.5 gene in patients presenting both congenital heart disease (CHD) and TD. SUBJECTS AND METHODS: Individual phenotypes were carefully analyzed in 86 children with thyroid dysgenesis (TD) using thyroid function tests, scintigraphy, ultrasound and echocardiography. DNA was extracted and NKX2.5 gene coding region was amplified by polymerase chain reaction (PCR) and sequenced. RESULTS: CHD were found in 8.1% of patients with TD. The mutation screening revealed two known polymorphisms in patients with isolated TD or TD associated with CHD. None of them are predicted to result in codon change in conserved domain. The c.63A>G polymorphism was detected in 54/86 patients (49 with isolated TD and 5 with TD combined with CHD). There was a significant association of c.63A>G polymorphism with hypoplasia (p < 0.036). The c.541G>A polymorphism was observed in only one patient with isolated thyroid hypoplasia. CONCLUSION: NKX2.5 mutations were not found. The c.63A>G polymorphism might be associated with thyroid hypoplasia.
Assuntos
Proteínas de Homeodomínio/genética , Polimorfismo Genético , Disgenesia da Tireoide/genética , Glândula Tireoide/anormalidades , Fatores de Transcrição/genética , Feminino , Estudos de Associação Genética , Proteína Homeobox Nkx-2.5 , Humanos , Recém-Nascido , Masculino , Linhagem , Testes de Função TireóideaRESUMO
ABSTRACT Objective: To evaluate the candidate genes PAX-8, NKX2-5, TSH-R and HES-1 in 63 confirmed cases of thyroid dysgenesis. Subjects and methods: Characterization of patients with congenital hypothyroidism into specific subtypes of thyroid dysgenesis with hormone levels (TT4 and TSH), thyroid ultrasound and scintigraphy. DNA was extracted from peripheral blood leukocytes and the genetic analysis was realized by investigating the presence of mutations in the transcription factor genes involved in thyroid development. Results: No mutations were detected in any of the candidate genes. In situ thyroid gland represented 71.1% of all cases of permanent primary congenital hypothyroidism, followed by hypoplasia (9.6%), ectopia (78%), hemiagenesis (6.0%) and agenesis (5.5%). The highest neonatal screening TSH levels were in the agenesis group (p < 0.001). Conclusions: Thyroid dysgenesis is possibly a polygenic disorder and epigenetic factors could to be implicated in these pathogeneses.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Receptores da Tireotropina/genética , Proteína Homeobox Nkx-2.5/genética , Fator de Transcrição PAX8/genética , Mutação/genética , Brasil , Análise Mutacional de DNA , Testes Genéticos , Estudos de Coortes , Ultrassonografia , Hipotireoidismo Congênito/etiologia , Hipotireoidismo Congênito/genética , Hipotireoidismo Congênito/diagnóstico por imagem , Disgenesia da Tireoide/genéticaRESUMO
Objective To search for genetic alteration in NKX2.5 gene in patients presenting both congenital heart disease (CHD) and TD. Subjects and methods Individual phenotypes were carefully analyzed in 86 children with thyroid dysgenesis (TD) using thyroid function tests, scintigraphy, ultrasound and echocardiography. DNA was extracted and NKX2.5 gene coding region was amplified by polymerase chain reaction (PCR) and sequenced. Results CHD were found in 8.1% of patients with TD. The mutation screening revealed two known polymorphisms in patients with isolated TD or TD associated with CHD. None of them are predicted to result in codon change in conserved domain. The c.63A>G polymorphism was detected in 54/86 patients (49 with isolated TD and 5 with TD combined with CHD). There was a significant association of c.63A>G polymorphism with hypoplasia (p < 0.036). The c.541G>A polymorphism was observed in only one patient with isolated thyroid hypoplasia. Conclusion NKX2.5 mutations were not found. The c.63A>G polymorphism might be associated with thyroid hypoplasia.