RESUMO
Introduction: It is rare for a euthyroid mother to carry a child with a fetal goiter. However, cases of congenital hypothyroidism (CH) caused by thyroid dyshormonogenesis have been reported. Even though gene mutations associated with fetal goiter have been reported in a few studies, the effects on intellectual development have not been investigated. This study aimed to characterize and investigate the underlying genetic mechanism of CH and neuropsychological development and growth of two siblings with CH-induced fetal goiters. Case report: Two male siblings from a non-consanguineous marriage with CH and fetal goiter were diagnosed by ultrasonography at 32- and 26-weeks of gestation. This condition was confirmed by cordocentesis in the first pregnancy (TSH: 135 µIU/ml). The mother was euthyroid, and no intra-amniotic levothyroxine treatment was performed. Peripheral blood DNA was screened for TPO mutations. The new deletion p.Cys296Alafs*21 and the p.Arg665Trp mutation, inherited from heterozygous parents, were identified in both patients. Functional analysis showed both mutations reduced the TPO enzyme activity and impaired the membrane localization. The p.Cys296Alafs*21 mutation produces a protein product with a drastically reduced molecular weight. Additionally, a complete clinical and neuropsychological evaluation was also performed. The WISC IV test was employed to provide an overall measure of the siblings' cognitive and intellectual abilities. No growth retardation was detected in either child. In general, both children showed normal neuropsychological development; however, they exhibited slight reduction of Processing Speed Index scores, which are sensitive to neurological and attentional factors and motor maturation activity. Notably, the younger sibling obtained significantly low scores in the Operational Memory Index, a measure of attention capacity and psychoneurological immaturity. Conclusion: We described a new TPO compound heterozygosity that severely impaired the TPO activity and membrane localization leading to severe CH and fetal goiter. This is the first report showing the neuropsychological evaluation in patients with dyshormonogenetic fetal goiter. More studies are needed to understand the neurodevelopmental outcomes of neonates with CH-induced fetal goiters.
Assuntos
Autoantígenos/genética , Hipotireoidismo Congênito/diagnóstico por imagem , Bócio/diagnóstico por imagem , Iodeto Peroxidase/genética , Proteínas de Ligação ao Ferro/genética , Mutação , Hipotireoidismo Congênito/genética , Análise Mutacional de DNA , Feminino , Bócio/genética , Humanos , Recém-Nascido , Masculino , Gravidez , Ultrassonografia Pré-NatalRESUMO
Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatment may be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.
As complicações fetais da tireoide na gravidez são incomuns e são comumente relacionadas à passagem de substâncias pela placenta. A ingestão excessiva de iodo durante a gravidez é um mecanismo bem conhecido de aumento da tireoide ou bócio fetal, e procedimentos invasivos foram propostos para o tratamento de patologias da tireoide fetal. No presente relato de caso, demonstramos dois casos de diferentes centros de diagnóstico pré-natal de aumento da tireoide fetal e/ou bócio em três fetos (um par de gêmeos, em que ambos os fetos foram afetados, e uma gravidez única). A anamnese revelou a ingestão de iodo pelos pacientes prescrita por suplementação inadequada de vitaminas. Nos dois casos, a interrupção da ingestão de suplemento de iodo resultou em uma redução acentuada do volume das glândulas tireoides fetais, demonstrando que o tratamento conservador pode ser uma opção nestes casos. Além disso, os médicos devem estar cientes de que as pacientes podem ser expostas a doses ou substâncias nocivas durante a gravidez.
Assuntos
Suplementos Nutricionais/efeitos adversos , Doenças Fetais/etiologia , Bócio/etiologia , Iodo/efeitos adversos , Cuidado Pré-Natal , Adulto , Doenças em Gêmeos/diagnóstico por imagem , Doenças em Gêmeos/etiologia , Feminino , Doenças Fetais/diagnóstico por imagem , Bócio/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Iodo/administração & dosagem , Imageamento por Ressonância Magnética , Gravidez , Cuidado Pré-Natal/métodos , Autocuidado/efeitos adversos , Ultrassonografia Pré-NatalRESUMO
Abstract Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatmentmay be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.
Resumo As complicações fetais da tireoide na gravidez são incomuns e são comumente relacionadas à passagem de substâncias pela placenta. A ingestão excessiva de iodo durante a gravidez é um mecanismo bem conhecido de aumento da tireoide ou bócio fetal, e procedimentos invasivos foram propostos para o tratamento de patologias da tireoide fetal. No presente relato de caso, demonstramos dois casos de diferentes centros de diagnóstico pré-natal de aumento da tireoide fetal e/ou bócio em três fetos (um par de gêmeos, em que ambos os fetos foram afetados, e uma gravidez única). A anamnese revelou a ingestão de iodo pelos pacientes prescrita por suplementação inadequada de vitaminas. Nos dois casos, a interrupção da ingestão de suplemento de iodo resultou em uma redução acentuada do volume das glândulas tireoides fetais, demonstrando que o tratamento conservador pode ser uma opção nestes casos. Além disso, os médicos devem estar cientes de que as pacientes podem ser expostas a doses ou substâncias nocivas durante a gravidez.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Cuidado Pré-Natal/métodos , Suplementos Nutricionais/efeitos adversos , Bócio/etiologia , Iodo/efeitos adversos , Autocuidado/efeitos adversos , Imageamento por Ressonância Magnética , Ultrassonografia Pré-Natal , Imageamento Tridimensional , Doenças em Gêmeos/etiologia , Doenças em Gêmeos/diagnóstico por imagem , Doenças Fetais/etiologia , Doenças Fetais/diagnóstico por imagem , Bócio/diagnóstico por imagem , Iodo/administração & dosagemRESUMO
Thyroglobulin is a glycoiodoprotein that is produced by thyroid follicular cells; it is stored in follicles in structures known as colloids. The main function of this protein is to stock the hormones triiodothyronine (T3) and thyroxine (T4) until the body requires them. This study aims to demonstrate that infrared spectral imaging with appropriate multivariate analysis can reveal biochemical changes in this glycoprotein. The results achieved herein point out biochemical differences in the colloid samples obtained from normal and goiter patients including glycosylation and changes in the secondary conformational structure. We have presented the first spectral histopathology-based method to detect biochemical differences in thyroid colloids, such as TG iodination, glycosylation, and changes in the secondary structure in normal and goiter patients. The observed changes in the colloids were mainly due to the alterations in amide I and amide II (secondary conformation of proteins) and there is a correlation with different glycosylation between normal and goiter tissues.
Assuntos
Bócio , Tireoglobulina , Bócio/diagnóstico por imagem , Humanos , Espectrofotometria Infravermelho , Tiroxina , Tri-IodotironinaRESUMO
Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain.
Assuntos
Hipotireoidismo Congênito/genética , Bócio/genética , Mutação/genética , Tireoglobulina/genética , Adolescente , Sequência de Aminoácidos , Sequência de Bases , Criança , Pré-Escolar , Segregação de Cromossomos/genética , Hipotireoidismo Congênito/diagnóstico por imagem , Análise Mutacional de DNA , Família , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Bócio/diagnóstico por imagem , Haplótipos/genética , Humanos , Recém-Nascido , Masculino , Linhagem , Tireoglobulina/químicaRESUMO
Hypothyroidism was documented by cordocentesis at 19 weeks in a fetus with non-immune goiter. Intra-amniotic thyroxine was injected at 25 weeks when amniotic fluid volume increased. Psychomotor outcome was normal. We argue that intra-amniotic thyroxine should not be used to treat the hypothyroidism but only to correct the development of polyhydramnios.
Assuntos
Hipotireoidismo Congênito/terapia , Doenças Fetais/terapia , Bócio/congênito , Tiroxina/administração & dosagem , Adulto , Líquido Amniótico , Hipotireoidismo Congênito/diagnóstico por imagem , Cordocentese , Feminino , Doenças Fetais/diagnóstico por imagem , Bócio/diagnóstico por imagem , Humanos , Masculino , Poli-Hidrâmnios/prevenção & controle , Gravidez , Segundo Trimestre da Gravidez , Tireotropina/sangue , Ultrassonografia Pré-NatalAssuntos
Bócio/diagnóstico , Doença de Graves/diagnóstico , Adulto , Antitireóideos/uso terapêutico , Feminino , Bócio/diagnóstico por imagem , Bócio/etiologia , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Humanos , Metimazol/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
The aim of the present study was to estimate the prevalence of goiter in schoolchildren in a formerly iodine-deficient region in southern Brazil by assessing the relationship between body surface area (m2 ) and thyroid volume (ml) measured by ultrasonography. A population-based sample of 1,094 randomly selected schoolchildren (6 to 14 years; 556 boys and 538 girls) underwent clinical evaluation. A total of 119 (10.9%) children were diagnosed with goiter upon clinical examination according to WHO criteria (grade Ia: 65, grade Ib: 24, grade II: 29, grade III: 1). Of these, 85 underwent ultrasonography. In order to ascertain the absence of goiter in the 975 schoolchildren with a negative result upon clinical examination, one of ten children was randomly selected for ultrasonography. Sixty-two children agreed to be submitted to the exam. Thus, 147 schoolchildren were evaluated by ultrasonography (7.5-MHz transducer). Goiter was considered to be present when the thyroid volume:body surface area index was >6.2 ml/m . The estimated prevalence of goiter if all schoolchildren had been submitted to thyroid volume measurement by ultrasound was 7.2%; it was higher in the lower socioeconomic class (8.2%) than in the upper (7.8%) and middle classes (6.5%). In conclusion, the prevalence of goiter in schoolchildren of this region was higher than in other iodine-sufficient areas, especially in lower socioeconomic classes. Goiter in this region may be associated with naturally occurring goitrogens that operate more intensively among less privileged individuals.
Assuntos
Bócio/epidemiologia , Glândula Tireoide/diagnóstico por imagem , Adolescente , Superfície Corporal , Brasil/epidemiologia , Distribuição de Qui-Quadrado , Criança , Feminino , Bócio/diagnóstico por imagem , Humanos , Masculino , Prevalência , Fatores Socioeconômicos , UltrassonografiaRESUMO
A fetal goiter was detected by ultrasonography in a woman receiving potassium iodide. After this medication was discontinued at 29 weeks, a fetal hypothyroidism was confirmed by cordocentesis, and two doses of levothyroxine were administered by amniocentesis. At 34 weeks repeated cordocentesis showed fetal euthyroidism and ultrasonography shrinkage of the goiter. Growth and development normal at 1 year.
Assuntos
Doenças Fetais/diagnóstico por imagem , Bócio/diagnóstico por imagem , Iodeto de Potássio/efeitos adversos , Adulto , Feminino , Doenças Fetais/induzido quimicamente , Doenças Fetais/tratamento farmacológico , Bócio/induzido quimicamente , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Iodeto de Potássio/administração & dosagem , Gravidez , Tiroxina/uso terapêutico , Ultrassonografia Pré-NatalRESUMO
A large and highly inbred kindred including patients with incomplete and complete forms of Pendred's syndrome was studied. Blood samples were collected from 42 individuals (23 affected and 19 normal), and serum thyroid hormones, TSH, Tg, and anti-TPO autoantibodies were assayed. Thyroid function studies have indicated euthyroidism in all 42 individuals. The affected subjects, however, had significantly elevated serum Tg levels (19.4 +/- 6.8 ng/dL) as compared with normals (9.6 +/- 2.9 ng/dL). Nineteen subjects had clinical and or ultrasonographic evidence of a multinodular goiter. In addition, 13 individuals had impaired hearing with or without goiter. Computer axial tomography scan studies in six patients confirmed the presence of a defective cochlea (Mondini's cochlear defect) in three of these subjects. It has been suggested that thyroperoxidase (TPO) in patients with Pendred's syndrome might be defective for coupling but could be partially effective for iodide organification. We have investigated possible abnormalities in the TPO gene by Southern blot analysis. Genomic DNA was obtained from peripheral blood leukocytes of 40 subjects (22 affected and 18 normal). DNA samples were digested with five restriction enzymes and hybridized with the pM5 probe (831 bp). Polymorphic fragment patterns obtained with three of the five enzymes employed were equally distributed in normal and affected subjects of this kindred. Lod score analysis did not disclose any linkage of TPO gene polymorphisms with the phenotypic characteristics observed in this family. Our findings may be explained in two different ways. First one might have hitherto undetected mutations in the TPO gene, and, second, the pathology may in fact be due to a genetic defect lying elsewhere.