RESUMO
A woman receiving thyroxine substitution therapy for acquired hypothyroidism caused by autoimmune thyroiditis gave birth to three babies who had transient primary hypothyroidism. All three babies had elevated thyrotropin levels on neonatal screening, but one had normal thyroxine values. Thyrotropin receptor-blocking antibodies were present in maternal serum and in the three neonates. Each baby also had a different congenital malformation. The neurodevelopmental outcome of the children appeared related in part to maternal thyroxine levels, which suggests that transplacental transfer of thyroxine may protect the fetal brain.
Assuntos
Hipotireoidismo Congênito , Complicações na Gravidez/tratamento farmacológico , Tireoidite Autoimune/tratamento farmacológico , Tiroxina/sangue , Tiroxina/uso terapêutico , Adulto , Pré-Escolar , Feminino , Seguimentos , Cardiopatias Congênitas/epidemiologia , Hérnia Umbilical/epidemiologia , Humanos , Hipotireoidismo/epidemiologia , Recém-Nascido , Rim/anormalidades , Masculino , Gravidez , Complicações na Gravidez/sangue , Tireoidite Autoimune/sangue , Tireoidite Autoimune/complicações , Tireotropina/sangue , Fatores de TempoRESUMO
Thymic epithelial cell physiology is known to be under neuroendocrine control. In particular, thyroid hormones modulate thymic hormone secretion by thymic epithelial cells in vivo and in vitro, thus suggesting the existence of specific receptors for those hormones in this component of the thymic microenvironment. Yet, thyroid hormone-binding sites have previously been detected only in crude thymus fractions and lymphocytes. We, thus, decided to search for T3 receptors in the thymic epithelium, by using an antinuclear T3 receptor monoclonal antibody. In situ immunohistochemical analysis of thymic frozen sections showed nuclear labeling of both lymphoid and nonlymphoid cells in the cortex and medulla. Moreover, in vitro studies using thymic epithelial cell lines and the so-called thymic nurse cells revealed a positive reaction in the chromatin, with nucleoli remaining negative. Immunoblot data clearly showed a single protein band of 57K reactive with the antinuclear T3 receptor antibody in murine thymus extracts as well as in the thymic epithelial cell lines. Lastly, in vitro treatment of these cells with T3 resulted in a transient, yet profound, down-modulation of the receptor. In conclusion, our findings provide molecular evidence that the action of thyroid hormones on thymic epithelium occurs via the typical 57K nuclear T3 receptors.
Assuntos
Núcleo Celular/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Timo/metabolismo , Animais , Anticorpos Monoclonais , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Ensaio de Imunoadsorção Enzimática , Células Epiteliais , Epitélio/metabolismo , Epitélio/ultraestrutura , Feminino , Immunoblotting , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Imunoeletrônica , Peso Molecular , Ratos , Ratos Endogâmicos , Receptores dos Hormônios Tireóideos/análise , Timo/citologia , Timo/ultraestrutura , Tri-Iodotironina/farmacologiaRESUMO
A prospective study of the mental development of hypothyroid infants detected by the Quebec Network for Genetic Medicine began in January, 1976. The mean age at initiation of thyroid hormone therapy was 27 days. Forty-five hypothyroid infants and 37 normal control subjects were assessed at age 12 months with the Griffiths mental development test; 77 and 41, respectively, were assessed at age 18 months, and 59 and 40, respectively, at 36 months. There were no statistically significant differences in the various test scores between the two populations at age 12 months, but at age 18 and 36 months the hypothyroid infants had lower scores in hearing-speech performance scales and practical reasoning (36 months) which also decreased their global quotient. The mean scores were still above 100 and only nine were below 85. Further assessment of the influence of early therapy on mental development at age 6 years is needed before definitive statements can be made about the long-term mental development in these subjects.
Assuntos
Hipotireoidismo Congênito , Deficiência Intelectual/prevenção & controle , Programas de Rastreamento , Pré-Escolar , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/psicologia , Lactente , Recém-Nascido , Testes de Inteligência , Masculino , Estudos Prospectivos , Quebeque , Hormônios Tireóideos/uso terapêuticoRESUMO
Data regarding the incidence and effect of maternal thyroid antibodies on neonatal thyroid function are conflicting. In order to elucidate this aspect, antimicrosomal thyroid antibodies were measured: (1) in cord serum of a normal populations, (2) in the eluate of blood spots of infants with normal filter paper spot T4 and TSH, (3) in the eluate of blood spots from our recalled population (low T4 and normal TSH), and (4) in serum of detected hypothyroid infants. The incidence of MCA with titer greater than 1/40 in cord sera was 8% (115 of 1.383). There was no statistical difference in cord serum T4' T3' or TSH concentrations in these newborn infants compared to the MCA negative population. In 1,000 spots with normal T4 and TSH, 11 or 1.1% were positive for MCA. In 1,630 spots with low T4' 18 positive cases were discovered, or 1.1%. There was excellent correlation between maternal MCA titers and newborn infant titers either in sera or spots when paired samples were available. Finally, only one of 104 detected infants with primary hypothyroidism had detectable MCA. These results indicate a high incidence (8%) of MCA in our presumed normal newborn population, MCA does not decrease serum T4' T3' and TSH concentration or filter paper spot T4 and TSH, and thyroid autoimmunity is not a frequent cause of congenital hypothyroidism.
Assuntos
Autoanticorpos/análise , Hipotireoidismo/imunologia , Glândula Tireoide/imunologia , Hipotireoidismo Congênito , Feminino , Humanos , Recém-Nascido , Programas de Rastreamento , Troca Materno-Fetal , Microssomos/imunologia , Gravidez , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Pilot programs for screening of newborn infants for congenital hypothyroidism began in North America in 1972. To date, the five oldest programs (Quebec, Pittsburgh, Toronto, Oregon Regional, and New England Regional) have screened 1,046,362 infants. A total of 277 infants with congenital hypothyroidism have been detected and seven have been missed, resulting in a total of 284 affected infants in the screened population and an overall incidence of one in 3,684 live births. Of the affected infants, 246 were determined to have primary hypothyroidism, an incidence of one in 4,254 births. Ten infants with secondary-tertiary hypothyroidism were detected in Quebec, Oregon, and Toronto, an incidence of one in 68,200 births. Of all the infants with primary hypothyroidism who were adequately studied, 63% were determined to have aplastic or hypoplastic glands, 14% normal or enlarged glands, and 23% ectopic thyroid tissue. The estimated minimum incidence of infants with TBG deficiency is one in 8,913 births. Only 8 of the 277 detected infants were suspected clinically to have congenital hypothyroidism prior to the time of confirmation of the diagnosis at 4 to 8 weeks of age. The cost of screening varied from $0.70 to $1.60 per infant, depending on which costs were included in the estimate. Preliminary evidence from Quebec suggests that infants treated in the program have normal developmental testing scores at 18 months of age.
Assuntos
Hipotireoidismo Congênito , Programas de Rastreamento , alfa-Globulinas/deficiência , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Lactente , Recém-Nascido , Programas de Rastreamento/economia , América do Norte , Proteínas de Ligação a Tiroxina/deficiência , Instituições Filantrópicas de SaúdeRESUMO
From our experience in the screening of 212,000 newborn infants, we have devised a flow chart for processing T4 and TSH measurements obtained from initial filter paper blood spots. To date, all infants with thyroid dysfunction or TBG deficiency have been detected. Of the population screened, 1.84% require a spot TSH determination, and 1.1% require repeat determinations of T4.
Assuntos
Hipotireoidismo/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Programas de Rastreamento , Filtração , Humanos , Hipotireoidismo/sangue , Recém-Nascido , Quebeque , Tireotropina/sangue , Tiroxina/sangueRESUMO
A female infant born to a mother with active Graves disease and a strongly positive LATS developed neonatal thyrotoxicosis. The diagnosis was confirmed rapidly by the markedly elevated filter paper spot T4 (5.45 ng/40 microliter) taken on the fifth day of life as part of the Quebec Screening Program for Neonatal Hypothyroidism. Although the infant's serum was negative for LATS, it reacted strongly (as did the maternal serum) in the lipolytic assay for LATS. This case illustrates the ability of screening programs for neonatal hypothyroidism to detect cases of neonatal thyrotoxicosis and supports the hypothesis that this condition is secondary to the placental transfer of a thyroid-stimulating immunoglobulin.
Assuntos
Hipertireoidismo/diagnóstico , Hipotireoidismo/diagnóstico , Imunoglobulinas/metabolismo , Doenças do Recém-Nascido/diagnóstico , Programas de Rastreamento , Troca Materno-Fetal , Feminino , Humanos , Recém-Nascido , Metabolismo dos Lipídeos , Estimulador Tireóideo de Ação Prolongada/análise , Gravidez , Radioimunoensaio , Tiroxina/metabolismoAssuntos
alfa-Globulinas/deficiência , Doenças do Recém-Nascido/sangue , Tireotropina/sangue , Proteínas de Ligação a Tiroxina/deficiência , Tiroxina/sangue , Diagnóstico Diferencial , Feminino , Humanos , Hipotireoidismo/diagnóstico , Recém-Nascido , Masculino , Razão de Masculinidade , Tri-Iodotironina/sangueRESUMO
Various aspects of the thyroid function have been measured in 28 cases of neonatal hypothyroidism detected by means of the Quebec Screening Program for Metabolic Diseases. In all instances the T4 value in the blood of filter paper spot was below 2 SD of the mean of the day, averaging 0.39 +/- 0.04 ng/40 mul (mean +/- SEM) of eluted blood. The T4 value of a second similar sample averaged 0.22 +/- 0.04 ng/mul of eluted blood; this value was significantly lower than the first one. The serum T4 concentration was decreased in all the infants, whereas three of them had a normal serum TSH concentration. At least three groups of patients could be identified: (1) patients with primary thyroid failure, (2) those with secondary or tertiary hypothyrodism, and (3) those with abnormal synthesis of thyroid hormone.
Assuntos
Hipotireoidismo/fisiopatologia , Doenças do Recém-Nascido/fisiopatologia , Glândula Tireoide/fisiopatologia , Feminino , Humanos , Hipotálamo/fisiopatologia , Recém-Nascido , Masculino , Hipófise/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
A sensitive radioimmunoassay for the measurement of TSH in the eluate of blood spotted on filter paper has been developed. The method is consistently sensitive to 0.1 to 0.25 muU of TSH and enables the detection of values equivalent to 6 to 15 muU/ml of serum. The measurement of TSH in the filter paper spot in all infants with low filter paper spot T4 has permitted rapid confirmation of 10 cases of neonatal hypothyroidism. However, cases of hypothalamic hypothyroidism with low or normal filter paper spot TSH concentrations would have been missed using only this method. Since these patients represent approximately 10% of our neonatal hypothyroid population, we do not recommend this method as a primary screening procedure, but rather as a confirmatory test which will accelerate the diagnosis and therefore the onset of therapy.
Assuntos
Hipotireoidismo/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Tireotropina/sangue , Filtração , Humanos , Recém-Nascido , Métodos , RadioimunoensaioRESUMO
We have recently developed an immunoassay that can measure thyroxine rapidly and accurately in the eluate of 40 mul of dried blood spotted on filter paper at the fifth day of life. The method is completely automated and by using the samples received by the Central Laboratory of the Quebec Network for Genetic Medicine and their follow-up facilities, we are now screening every newborn in the province of Quebec for neonatal hypothyroidism. To date, from 47,000 measurements, three newborn infants with abnormally low TBG and seven hypothyroid infants have been detected. From these data we conclude that the frequency of congenital hypothyroidism is about one in 7,000 births and that our method is effective in detecting thyroid hormone abnormalities with an acceptable percentage of false positive measurements; no false negative results have occurred to our knowledge.