ABSTRACT
OBJECTIVES: To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. SUBJECTS AND METHODS: Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor (TSHR) gene in those with hypoplasia. RESULTS: In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. CONCLUSION: Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development.
Subject(s)
Congenital Hypothyroidism/genetics , Homeodomain Proteins/genetics , Mutation , Paired Box Transcription Factors/genetics , Thyroid Dysgenesis/genetics , Thyrotropin/genetics , Transcription Factors/genetics , Adolescent , Child , Child, Preschool , Female , Homeobox Protein Nkx-2.5 , Humans , Male , PAX8 Transcription Factor , Thyroid Dysgenesis/diagnosis , Young AdultABSTRACT
OBJECTIVES: To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. SUBJECTS AND METHODS: Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor (TSHR) gene in those with hypoplasia. RESULTS: In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. CONCLUSION: Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development.
OBJETIVOS: Classificar corretamente as várias formas de DT e depois rastrear por mutações em genes que participam no desenvolvimento da tireoide. SUJEITOS E MÉTODOS: Os pacientes realizaram ultrassonografia, cintilografia e tireoglobulina sérica para o diagnóstico preciso de DT. DNA foi extraído de leucócitos periféricos. Os genes PAX8 e NKX2.5 foram estudados em todos os pacientes e o gene do receptor do TSH (TSHR) foi estudado na hipoplasia. RESULTADOS: Avaliaram-se 27 pacientes sem consanguinidade com DT, dos quais 13 foram diagnosticados com ectopia, 11 com hipoplasia e 3 com atireose. Nenhuma mutação foi detectada nos genes estudados. CONCLUSÃO: Casos esporádicos de DT são provavelmente causados mais por fatores epigenéticos do que por mutações em fatores de transcrição ou genes envolvidos no desenvolvimento tireoidiano.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Young Adult , Congenital Hypothyroidism/genetics , Homeodomain Proteins/genetics , Mutation , Paired Box Transcription Factors/genetics , Thyroid Dysgenesis/genetics , Thyrotropin/genetics , Transcription Factors/genetics , Thyroid Dysgenesis/diagnosisABSTRACT
Methods currently employed to establish the etiology of congenital hypothyroidism include thyroid ultrasound and scintigraphic exams. Thyroglobulin is a protein almost exclusively secreted by thyroid tissue and indirectly reflects the amount of follicular cells. Even though thyroglobulin is easy to measure, it has been not frequently used because of discordant results to distinguish mainly athyreosis and ectopy (dysgenesis). Knowing the differences in inheritance and prognosis of thyroid dysgenesis and dyshormonogenesis, it is important to define the etiology of CH, combining tools that are easy, fast and available in most medical centers. Our objective was to evaluate and compare color Doppler ultrasound and serum thyroglobulin with radionuclide scan to define the etiology of congenital hypothyroidism. We evaluated 38 children above 3 years-old off-treatment that performed serum thyroglobulin by immunofluorometric assay, color Doppler ultrasound and radionuclide study. On color Doppler ultrasound, 11 patients had athyreosis, 5 ectopic glands, being 1 associated to hemiagenesis. Twenty one had topic thyroid (3 goiters, 10 normal, 8 hypoplastic). Hemiagenesis and cystic lesion were not revealed by radionuclide scan. We observed substantial agreement between color Doppler ultrasound and radionuclide scan (kappa=0.745, p<0.0001). Serum thyroglobulin in athyreosis ranged from <1.0 to 18.7 micro g/L. Patients with ectopic glands showed wider thyroglobulin range (4.5 to 123 micro g/L, median 28.4 micro g/L). Only one patient showed thyroglobulin deficiency. By using color Doppler ultrasound and serum thyroglobulin levels as valuable combined tools, we established the etiology of congenital hypothyroidism limiting excessive and harmful exams in children, like radionuclide scan.
