RESUMO
PURPOSE: The potential benefits of treating subclinical hypothyroidism (SCH) are unclear and still controversial. Thus, we surgically induced SCH in rats and evaluated the effects of thyroxine (T4) replacement on the gene expression levels of deiodinases and thyroid hormone (TH) transporters in different tissues. METHODS: SCH was induced by hemithyroid electrocauterization. The control animals underwent the same surgical procedure but were not subjected to electrocauterization (sham). After 14 days, half of the SCH animals were treated with T4 (SCH + T4). At the end of the experimental protocol, all of the rats were euthanized, serum hormone concentrations were measured, and RNA analyses were performed on different tissues and organs. RESULTS: Consistent with previous studies, we observed increased TSH levels, normal TH levels, and reduced hypothalamic TRH expression in the SCH group. Additionally, Dio2 mRNA expression was downregulated in the hippocampus and pituitary, and Dio1 was upregulated in the kidney and pituitary of the SCH animals. The changes in Dio3 expression were tissue-specific. Concerning TH transporters, Mct10 expression was upregulated in the pituitary, kidney, hypothalamus, and hippocampus, and Mct8 expression was downregulated in the kidney of the SCH group. Crym expression was upregulated in the kidney and pituitary. Notably, T4 replacement significantly attenuated serum TSH levels and reverted Dio1, Dio2, Mct10, and Crym expression in the pituitary, hippocampus, and kidney to levels that were similar to the sham group. Tissue-specific responses were also observed in the liver and hypothalamus. CONCLUSION: Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.
Assuntos
Hipotireoidismo/tratamento farmacológico , Iodeto Peroxidase/metabolismo , Proteínas de Ligação a Tiroxina/metabolismo , Tiroxina/uso terapêutico , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/fisiologia , Hipotireoidismo/etiologia , Iodeto Peroxidase/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Proteínas de Ligação a Tiroxina/genética , Cristalinas muRESUMO
INTRODUÇÃO: Manifestações auto-imunes são frequentes na infecção pelo vírus da hepatite C (VHC). Apesar da associação com doenças auto-imunes de tireóide (DAIT) ser controversa, sabe-se que distúrbios tireoidianos podem surgir ou piorar com tratamento com IFN e ribavirina. Os objetivos deste estudo foram avaliar a função tireoidiana em pacientes infectados pelo VHC, caracterizar distúrbios tireoidianos antes, durante e após tratamento com IFN e estudar as frequências dos genótipos dos polimorfismos do gene CTLA4, correlacionando-os com características clínicas e laboratoriais, presença de disfunção tireoidiana e evolução durante tratamento com IFN. MÉTODOS: Avaliação prospectiva de 112 indivíduos com infecção crônica pelo VHC, 30 tratados com IFN, e 183 controles. Realizaram-se avaliações clínica, hormonal e de auto-imunidade tireoidiana e ultra-sonografia de tireóide no início e durante tratamento. Avaliações de globulina transportadora de hormônios tireoidianos (TBG), de CXCL10 e de biópsia hepática foram feitas pré-tratamento. Análises dos polimorfismos do gene CTLA4 -318C>T, A49G e CT60 foram realizadas por PCR-RFLP e de AT(n) por análise de fragmento através de eletroforese capilar. RESULTADOS: A frequência de DAIT entre infectados por VHC não diferiu dos controles (10,7 vs 13,5%, p=0,585). Os limites de distribuição dos níveis de T3 (T3T) e T4 (T4T) totais foram superiores aos de referência (T3T 112-246 ng/dL; T4T 7,8-15,2 g/dL), assim como de TBG (17-47 mg/L). TBG correlacionou-se com T3T (r=0,654, p<0,001) e T4T (r=0,741, p<0,001). Heterogeneidade (p=0,027) e hipoecogenicidade de parênquima (p=0,002) foram mais frequentes nos pacientes com DAIT. Aumento de vascularização esteve presente em 49,2% dos infectados sem distúrbio tireoidiano. CXCL10 esteve aumentada nos infectados (p=0,006), mas não se relacionou com disfunção tireoidiana. Sua elevação correspondeu ao grau de atividade necro-inflamatória na biópsia hepática...
INTRODUCTION: Autoimmune disorders are frequent in patients infected by the hepatitis C virus (HCV). Although the association with autoimmune thyroid diseases (AITD) is controversial, thyroid disturbance could occur or worsen with IFN and ribavirin treatment. The aims of the study were evaluate thyroid function in HCV-infected patients, characterize thyroid disturbance prior and after IFN treatment and analyze the frequency of the genotypes of the polymorphisms of CTLA4 gene, and their relation to clinical and laboratorial features, presence of thyroid dysfunction and disturbance along IFN treatment. METHODS: Prospective evaluation of 112 chronically HCV-infected subjects, 30 treated with IFN, and 183 controls. Clinical, hormonal, thyroid autoimmunity and ultrasound exams were performed before and during treatment. Thyroxine-binding globulin (TBG), CXCL10 and hepatic biopsies were also evaluated before treatment. Analysis of polymorphisms of CTLA4 gene -318C>T, A49G and CT60 were made by PCR-RFLP and AT(n) polymorphism analysis by capillary electrophoresis in automatic sequencer. RESULTS: The frequency of AITD among HCV-infected subjects was similar to the rate among controls (10.7 vs 13.5%, p=0.585). Total T3 (T3T) and T4 (T4T) distributions were right shifted (T3T 112-246 ng/dL; T4T 7.8-15.2 g/dL), as was TBG (17-47 mg/L). TBG correlated to both T3T (r=0.654, p<0.001) and T4T (r=0.741, p<0.001). Thyroid heterogeneity (p=0.027) and hipoechogenicity (p=0.002) were associated with AITD and, most notably, increased vascularization was present in 49.2% of HCV-infected patients without thyroid disturbance. CXCL10 was higher in HCV-infected group (p=0.006) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.006) and correlated to T3T (r=0.388, p=0.003), T4T (r=0.444, p=0.001) and TBG (r=0.551, p<0.001). Nineteen percent of subjects treated with IFN presented autoimmune thyroiditis and...
Assuntos
Doenças Autoimunes , Hepatite C , Interferon-alfa , Glândula Tireoide , Proteínas de Ligação a TiroxinaRESUMO
Com objetivo de analisar a freqüência de disfunção tiroideana e de identificar possíveis alterações hormonais decorrentes do envelhecimento, estudamos 198 indivíduos com idade variando de 50 a 85 anos e 106 filhos com idade entre 11 e 49 anos. A prevalência de disfunção tiroideana foi semelhante em ambos grupos (12,6por cento no grupo de estudo e 14,1 por cento entre os filhos). A presença de um ou dois anticorpos anti-tiroideanos positivos foi também semelhante entre os grupos (9,1 por cento e 12,3 por cento para os idosos e filhos respectivamente), embora sem correlação disfunção tiroideana. nos idosos. Os níveis séricos de T3 e FT4 foram significantemente menores entre os indivíduos mais velhos quando comparados com os filhos (1,27ñ0,27 x 1,39ñ0,31 ng/ml e 0,97ñ0,29 x 1,18ñ0,76 ng/dl, respectivamente). Não houve diferença entre os grupos quanto aos níveis de TSH, T4 total e TBG. Concluímos que a prevalência de disfunção tiroideana não foi diferente entre os grupos e que a presença de anticorpos antitiroideanos esteve associada com disfunção da tiróide apenas nos indivíduos mais jovens. A correlação inversa dos níveis de T3 e FT4 com a idade pode refletir uma adaptação à menor necessidade dos hormônios com o envelhecimento.
Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/epidemiologia , Adolescente , Idoso de 80 Anos ou mais , Anticorpos , Hormônios Tireóideos/sangue , Hipertireoidismo , Hipotireoidismo , Tireotropina , Proteínas de Ligação a TiroxinaRESUMO
The association of hyperthyroxinemia and euthyroidism is frequent and characterized by high plasma thyroxin concentrations, normal TSH values and absence of clinical signs of hyperthyroidism. We report an asymptomatic 28 years old male presenting with a serum total plasma thyroxin of 18.5 micrograms/dl (N 6.1-12.5), a free thyroxin of 2.9 ng/dl (N 0.8-1.4), a TSH of 3.4 microIU/ml (N 0.5-5), and a triiodothyronine of 128 ng/dl (N 80-180). Laboratory assessment did not find high thyroxin binding globulin, albumin or prealbumin concentrations or antithyroxin antibodies. The thyroxin binding capacity of albumin was elevated to 58.2 micrograms/dl (N 11.5-34.1). TSH responded normally to TRH stimulus and was suppressed with exogenous triiodothyronine, which caused an hyperthyroid syndrome. We concluded that this patient had a familial dysalbuminemia.
Assuntos
Síndromes do Eutireóideo Doente/complicações , Hipertireoxinemia/complicações , Adulto , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/diagnóstico , Humanos , Hipertireoxinemia/sangue , Hipertireoxinemia/diagnóstico , Masculino , Albumina Sérica/análise , Tireotropina/sangue , Proteínas de Ligação a Tiroxina/análise , Tri-Iodotironina/sangueRESUMO
Foram avaliados 21 pacientes braquicefálicos, com idade inferior a 10 anos, provenientes da Disciplina de Neurocirurgia da Universidade Federal de São Paulo Escola Paulista de Medicina (UNIFESP-EPM), no período de 1994 a 1998, e submetido a avaliação pré-operatória com tomografia computadorizada helicoidal de crânio reconstrução tridimensional (TC3D), realizadas no Laboratório Fleury. A idade d pacientes foi considerada no momento do exame radiológico. Treze pacientes eram d sexo feminino, e oito do masculino. O paciente mais jovem tinha 14 dias de vida e mais velho dez anos. Doze pacientes eram portadores da síndrome de Crouzon, cinco d síndrome de Apert, um apresentava a síndrome de Jackson-Weiss, e três era braquicefalias isoladas. A base do crânio destes pacientes foi comparada com um grupo controle, estudado com TC3D, e provenientes do museu de Craniologia da Disciplina de Anatomia da UNIFESP-EPM. Nesses 63 crânios, foram estudadas sete distâncias e seis ângulos. Para compararmos as diferentes medidas nos dois grupos, usamos o teste de Mann-Whitney, e para compararmos as diferenças dentro do mesmo grupo, nas diferentes faixas etárias, usamos o teste de Kruskal-Wallis, complementado quando necessário, pelo teste de comparações múltiplas. Pudemos verificar que nos pacientes com braquicefalia, a distância interorbitária é muito grande ao nascimento, sugerindo um quadro de hipertelorismo. Com o passar da idade esta distância progressivamente se estabiliza igualando-se ao grupo normal. A distância násio-sela aumentou nos dois grupos, de maneira mais acentuada no grupo normal. O crescimento da fossa anterior do crânio nos portadores de braquicefalia, verificado através das distâncias sela-frontal e esfenofrontal, não demonstrou um crescimento significativo, determinando uma fossa anterior curta. A distância bipterional foi significantemente maior no grupo de braquicéfalos, desde o nascimento, demonstrando um fator compensatório ainda intra-útero. Os resultados das medidas das distâncias pteriorbitária direita e esquerda também foram significantes, demonstrando que nos portadores desta malformação, os ptérios estão anteriorizados. O inverso acontece com a distância ptérigo-básio, também diminuída no grupo afetado, demonstrando uma posteriorização desta estrutura. Com estes resultados pudemos concluir que a asa do esfenóide aderida aos processos pterigóides, atuam como duas lavancas, uma de cada lado, modulando o crescimento do ...(au)
Assuntos
Hipotireoidismo , Biologia Molecular , Proteínas de Ligação a Tiroxina/deficiênciaRESUMO
We measured the levels of thyroxine-binding prealbumin (TBPA), C-reactive protein (CRP), and interleukin-6 (IL-6) in sera from protein-energy undernourished and control children either without or with associated clinical infections. Levels of TBPA were significantly lower in undernourished than in control children without clinical infections. Mean serum TBPA concentration was also significantly lower in both clinically infected undernourished and control children than in those of the same nutritional status but without overt infections. Significant positive correlations were observed between the concentration of TBPA and the Z-scores of weight for age, height for age, and weight for height in all children without clinical infections, which disappeared in clinically infected children. CRP and IL-6 increased to approximately similar levels in sera from undernourished and control children with overt infections. An inverse correlation between the levels of TBPA and CRP and a significant positive correlation between the concentration of CRP and IL-6 were observed in children with associated clinical infections. Serum IL-6 and TBPA showed a small negative relationship in patients with overt infections. Thus, TBPA is a sensitive marker of undernutrition only in the absence of clinical infections, and the capacity to increase production of IL-6 and CRP during infections is preserved in protein-energy undernutrition.
Assuntos
Proteína C-Reativa/análise , Doenças Transmissíveis/sangue , Interleucina-6/sangue , Desnutrição Proteico-Calórica/sangue , Proteínas de Ligação a Tiroxina/análise , Estudos de Casos e Controles , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunodifusão , Técnicas Imunoenzimáticas , Lactente , Modelos Lineares , MasculinoRESUMO
There are few data available about changes in thyroid hormone profiles after hormone replacement therapy (HRT). We analyzed the effect of two different oral estrogens/progestins (E/P) associations on thyroid hormones and thyroxine-binding globulin (TBG) levels in 14 postmenopausal normal women distributed at random into two groups. Both groups received daily for a year 2 mg of estradiol valeriante per os. In Group A (n = 7), estrogen was associated with norethisterone acetate. In Group B, estrogen was associated with promegestone in a similar schedule to Group A. Blood samples were withdrawn to measure estradiol (E2), thyroxine (T4), triiodothyronine (T3), free T4 (fT4), thyroid-stimulating hormone (TSH) and TBG before and after 3, 6 and 12 months of treatment. Estradiol level increased significantly in both groups, being higher in Group A than in B. Under therapy, T4 and TBG levels were increased in both groups, but within the normal range. T4 mean level increased by 34% in Group A and 20% in Group B. TBG increment was slightly significant for Group A (p < 0.02); with only a trend in Group B (p = 0.08). T3, fT4 and TSH levels did not change significantly and remained within the normal range. Oral therapy with associated E/P produces moderate increases in T4 and TBG levels. Our results suggest that in postmenopausal women on oral HRT, fT4 and TSH levels are the most useful tools to evaluate the thyroid axis status.
Assuntos
Estradiol/sangue , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Pós-Menopausa/sangue , Hormônios Tireóideos/sangue , Proteínas de Ligação a Tiroxina/metabolismo , Administração Oral , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Avaliamos 84 pacientescom carcinoma de tireóide atendidos no Hospital de Clínicas da Universidade Federal do Paraná no período compreendido entre janeiro de 1990 e dezembro de 1996. A idade média dos pacientes foi de 40,6 anos (DP 17,4), com predomínio do sexo feminino (82 por cento). Encontramos em nossos pacientes uma elevada associaçäo com doença auto-imune de tereóide (8,5 por cento), 6 pacientes com tireoidite de Hashimoto e 1 com Doença de Graves concomitante. A palpaçäo da tereóide por ocasiäo do diagnóstico do carcinoma, revelou em 84 por cento dos pacientes um nódulo único, sendo a glândula multinodular nos outros 16 por cento. A cintilografia revelou nódulo hipocaptante em 82 por cento dos casos. A PAAF (punçäo aspirativa com agulha fina) diagnosticou a presença de neoplasia em cerca de 82 por cento das vezes. O precedimento cirúrgico foi tireoidectomia total em 90,5 por cento dos casos e subtotal nos restantes. O estudo anatomopatológico mostrou carcinoma papilífero em 64,3 por cento, carcinoma folicular em 32,1 por cento, carcinoma anaplásico em 2,4 por cento e carcinoma medular em 1,2 por cento dos pacientes. O controle para presença de metástase realizado com PCI (pesquisa de corpo inteiro) e/ou tireoglobulina sérica mostrou a presen
Assuntos
Carcinoma , Cintilografia , Proteínas de Ligação a Tiroxina , Glândula Tireoide , Metástase NeoplásicaRESUMO
OBJECTIVE: The abnormalities reported in some thyroid function tests in children with renal disease could be adaptive phenomena, shared by a variety of other nonthyroidal illnesses, or could reflect hypothyroidism. STUDY DESIGN: To answer this question, we studied thyroid function and serum thyroid binding proteins in 36 prepubertal and 23 pubertal patients with renal disease receiving three different therapies: conservative treatment, hemodialysis, and care after renal transplantation. RESULTS: During prepuberty, the serum concentration thyroxine binding globulin (mean +/- SE) in the three groups of patients (294 +/- 18, 303 +/- 18, and 323 +/- 16 nmol/L, respectively) was significantly lower than in prepubertal control subjects (451 +/- 71 nmol/L). Only in prepubertal patients after renal transplantation (3583 +/- 573 nmol/L) were serum thyroxine binding prealbumin values lower than in respective control subjects (5999 +/- 908 nmol/L). The serum total thyroxine concentration in the three groups of patients (108 +/- 41.9, 121 +/- 5.7, and 123 +/- 5.5 nmol/L, respectively) was significantly lower than in prepubertal control subjects (149 +/- 10 nmol/L), whereas serum free thyroxine and serum albumin-bound thyroxine concentrations were similar to those in control subjects. The serum total triiodothyronine level in the three groups of patients (2.29 +/- 0.82, 2.13 +/- 0.13, and 2.01 +/- 0.20 nmol/L respectively) was significantly lower than in prepubertal control subjects (3.04 +/- 0.24 nmol/L), whereas serum levels of free triiodothyronine and serum albumin-bound triiodothyronine were similar to those in prepubertal control subjects. During puberty, serum thyroxine binding globulin and serum thyroxine binding prealbumin levels in the three groups of patients were not statistically different from those in pubertal control subjects (309 +/- 47 and 4950 +/- 1230 nmol/L, respectively). Serum levels of total thyroxine, free thyroxine, albumin-bound thyroxine, total triiodothyronine, free triiodothyronine, and albumin-bound triiodothyronine were similar to those in pubertal control subjects except for pubertal patients undergoing hemodialysis. In all clinical groups the basal serum thyrotropin concentration was similar to those in respective control subjects. The frequency of goiter was increased in patients undergoing hemodialysis, probably as a result of iodide washout with dialysis. CONCLUSION: Children and adolescents with chronic renal insufficiency or endstage renal disease or after renal transplantation do not have a primary abnormality of thyroid function and therefore are not candidates for thyroid hormone treatment.
Assuntos
Falência Renal Crônica/terapia , Testes de Função Renal , Transplante de Rim/fisiologia , Complicações Pós-Operatórias/sangue , Puberdade/sangue , Diálise Renal , Proteínas de Ligação a Tiroxina/metabolismo , Adolescente , Assistência ao Convalescente , Fatores Etários , Criança , Pré-Escolar , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Falência Renal Crônica/sangue , Complicações Pós-Operatórias/diagnóstico , Valores de Referência , Tiroxina/sangue , Tri-Iodotironina/sangueAssuntos
Diálise Peritoneal Ambulatorial Contínua , Hormônios Tireóideos/análise , Adulto , Glicemia/análise , Proteínas Sanguíneas/análise , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , Creatinina/sangue , Soluções para Diálise/análise , Feminino , Humanos , Hipotireoidismo/etiologia , Masculino , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Proteínas/análise , Tireotropina/análise , Tireotropina/sangue , Hormônio Liberador de Tireotropina , Tiroxina/análise , Tiroxina/sangue , Proteínas de Ligação a Tiroxina/análise , Tri-Iodotironina/análise , Tri-Iodotironina/sangueRESUMO
Serum thyroid hormones, serum thyroxine-binding proteins and serum thyroid hormone fractions have been measured in children with congenital heart disease before and after open cardiac surgery. Twenty prepubertal patients, mean (+/- SD) age 3.6 +/- 3.7 yr, were studied before, immediately after, and 24 and 48 h after surgery. A control group of 6 normal prepubertal children was also studied in basal conditions. Serum TSH was normal in all samples collected. Significantly low mean levels of serum TBG (261 +/- 57 vs 456 +/- 71 nmol/L in normals), serum TBPA (2692 +/- 1119 vs 5999 +/- 2226 nmol/L), serum TBG-bound T4, serum TBPA-bound T4, serum TT3, serum TBG-bound T3 and free T3 were found before cardiac surgery in the patients. While serum binding proteins did not change after surgery, significant decrements in serum TT4, serum TBG-bound T4, serum TT3, serum TBG-bound T3, serum albumin-bound T3 and free T3 were observed after surgery. Free T4 and albumin-bound T4 remained normal. Our study shows that many features of nonthyroidal illness were present in our patients before surgery. In this context, the stress of surgery induced further alterations in several parameters of thyroid metabolism. It is concluded that the changes occurring in this model of chronic, as well as acute, nonthyroidal illness reflect adaptative changes, rather than altered thyroid function, as shown by normal serum free T4, serum albumin-bound T4 and serum TSH.
Assuntos
Cardiopatias Congênitas/sangue , Proteínas de Ligação a Tiroxina/análise , Tiroxina/sangue , Tri-Iodotironina/sangue , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Masculino , Fatores de TempoRESUMO
We examined the results of the Northwest Regional Screening Program from May 1975 to June 1991 to determine the prevalence of inherited thyroxine-binding globulin (TBG) deficiency and its effect on thyroid hormone concentrations in infants. Serum thyroxine (T4), triiodothyronine resin uptake (T3RU), and thyrotropin values were requested of physicians caring for all infants with a single filter paper T4 level < 38.6 nmol/L (3 micrograms/dl) or a T4 level < 3rd percentile on two filter paper tests (at birth and 2 to 6 weeks of age). From 1,367,724 infants screened in five states, TBG deficiency, an X-linked disorder, was identified in 317 infants (285 boys). For the entire screening program the calculated frequency of TBG deficiency was 1:4315 infants (1:2400 for boys). In Oregon, where 95% of infants have two screening tests performed, the calculated frequency was somewhat higher (1:3080 infants; 1712 boys) and is probably more accurate. The mean serum T4 concentration for TBG-deficient boys was 41.9 nmol/L (3.26 micrograms/dl); 31% had values < 25.7 nmol/L (2.0 micrograms/dl). The mean serum T4 concentration for TBG-deficient girls was 60.2 nmol/L (4.68 micrograms/dl), with none < 2.0 micrograms/dl. The mean T3RU value was 0.472 in TBG-deficient boys, and 0.412 in TBG-deficient girls; the T3RU value was > 0.55 in 24% of TBG-deficient boys but was > 0.55 in only one girl. Free serum T4 levels were normal in all 56 TBG-deficient infants studied, and TBG levels were low in all 20 infants studied. Inherited TBG deficiency is common in boys in the Northwest, with a frequency of 1:1700 and a male/female ratio of 8.9:1. Boys with TBG deficiency have mild, moderate, or severe alterations in total T4 and T3RU values, but severe deficiency is rare in girls.
Assuntos
Triagem Neonatal , Proteínas de Ligação a Tiroxina/deficiência , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Noroeste dos Estados Unidos/epidemiologia , Oregon/epidemiologia , Prevalência , Fatores Sexuais , Tireotropina/sangue , Tiroxina/sangue , Proteínas de Ligação a Tiroxina/análise , Tri-Iodotironina/sangueRESUMO
During 3 years 1632 newborns from Gorgas Army hospital had their cord blood screened for congenital hypothyroidism by determining serum thyroxine levels (T4). Fifty-five had serum levels below 7 mcg/dl and 80% of them went into a confirmatory evaluation for hypothyroidism. Three of those (1.8/1000 live birth) had a familiar deficiency of thyroid binding globulin (TBG). All of them were male newborns born at 38 weeks of gestation. The average T4 from the umbilical cord was 2.4 +/- 1.3 mcg/dl. This value was significantly lower than the values from those with an initial T4 below 7 mcg/dl who did not have TBG deficiency. The prevalence of TBG deficiency in this study was about 10 times higher than the prevalence reported by other authors for both the general population and the male population.
Assuntos
Proteínas de Ligação a Tiroxina/deficiência , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Recém-Nascido , Masculino , Triagem Neonatal , Projetos Piloto , Prevalência , Tiroxina/sangueRESUMO
Recent advances in molecular biology and the use of modern techniques made possible the identification and cloning of DNA portions of the human genome encoding proteins that are important for the synthesis, storage, transport and action of thyroid hormones. These achievements have led to the diagnosis of the basic defects at the DNA level and the understanding of the biochemical disturbance in the genetic disorders of thyroid metabolism. In patients with defective expression of thyroid peroxidase (TPO) the presence of polymorphism (RFLP) associated with Bgl-I segregates with the affected individual with goiter, hypothyroidism and positive perchlorate discharge test. Defects in the thyroglobulin are either quantitative (no Tg is synthetized) or qualitative (an abnormal Tg is expressed). Low messenger RNA codifying for Tg was present in one of the families with virtual absence of Tg in serum and thyroid tissue. In another family absence of sialic acid incorporation into the Tg molecule produced a Tg with structural defect, incapable of T3 and T4 generation. A point mutation in the nucleotide 281 of exon 5 has been claimed as the mutation producing a defective TBG. Finally, the resistance to thyroid hormone action is linked to a mutation in the c-erb-A beta, detected by the presence of a polymorphism EcoRV, that will encode a defective protein or will produce a protein that might block the T3 binding to the receptor.
Assuntos
Hormônios Tireóideos/deficiência , Animais , Clonagem Molecular , DNA Recombinante , Resistência a Medicamentos , Biblioteca Genômica , Humanos , Hipotireoidismo/enzimologia , Hipotireoidismo/genética , Iodeto Peroxidase/deficiência , Linhagem , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/metabolismo , Tireoglobulina/deficiência , Proteínas de Ligação a Tiroxina/genética , Proteínas de Ligação a Tiroxina/metabolismoRESUMO
1. Se analizan las interrelaciones entre T4 total, tiroxina libre y globulinas transportadoras. 2. Se resalta la importancia del perfil tiroideo parcial en el diagnóstico correcto de la función tiroidea. 3. Se fundamenta la importancia de la relación T4/T4L en el establecimiento de los niveles de TBG. 4. Se analiza la incidencia de las 11 posibilidades diagnósticas que se pueden establecer con el perfil tiroideo parcial. 5. Se compara el diagnóstico por el Laboratorio con el diagnóstico Clínico
Assuntos
Humanos , Masculino , Feminino , Glândula Tireoide/fisiologia , Testes de Função Tireóidea/métodos , Proteínas de Ligação a Tiroxina/fisiologia , Tiroxina/fisiologia , Peru , Soroglobulinas , Proteínas de Ligação a Tiroxina , TiroxinaRESUMO
Abnormal binding of thyroxin (T4) to serum albumin of subjects with familial dysalbuminemic hyperthyroxinemia (FDH) is generally demonstrated by the T4-loaded charcoal uptake test, with T4 added in excess (0.1 mmol/L) to accentuate T4 binding to albumin in FDH. I describe a binding study involving T4 tracer in which thyroxin-binding globulin is denatured in samples by treatment with mild acid at pH less than 3.0. The tracer is bound to the serum albumin and, to a greater extent, to the FDH albumin, because the binding by thyroxin-binding prealbumin is blocked by barbital buffer. The result of the [125I]T4 binding to the albumin is expressed as a T4 binding index, based on results for pooled sera from patients with normal thyroid function as a reference. The mean index in FDH was 4.08 (SD 0.92, n = 5); in hypoalbuminemia, 0.66 (SD 0.18, n = 8); in normal subjects, 1.00 (SD 0.11, n = 20). This albumin-binding index enables the rapid and unequivocal diagnosis of subjects with FDH, without the addition of unlabeled T4.