RESUMO
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a disease of unknown cause characterized by pruritus and biochemical cholestasis in the 3rd trimester of pregnancy. Its pathogenesis may be due to the interaction of abnormalities in the metabolism of estrogens and progesterone, while still unknown environmental factor (s) modulate the expressivity of a genetic predisposing trait. AIMS: To verify if thyroid function tests (TFT) are altered in ICP as in other hepatic diseases and whether a dietary iodine deficiency could be involved. MATERIAL AND METHODS: From 1983 to 1986, 13 normal pregnancies (3rd trimester), 26 ICP patients (with 30 pregnancies) and 4 patients with acute non-A non-B hepatitis in pregnancy, were studied. Serum T3, rT3, T4, fT4 and TSH (before and after TRH) were measured by RIA; in ICP patients, measurements were repeated in puerperium. Urinary 24 h iodine excretion was measured in normal pregnancies and in 6 ICP patients. RESULTS: In normal pregnancies, T3 (3.00 +/- 0.22 nmol/L) and rT3 (0.40 +/- 0.03 nmol/L) were higher than the values detected in non-pregnant women; other TFT were unchanged. Urinary iodine excretion was normal in all individuals tested. Patients with acute hepatitis in pregnancy or with ICP had lower T3 than normal pregnancies (1.82 +/- 0.19 nmol/L in hepatitis; 2.24 +/- 0.12 nmol/L in ICP; p < 0.01) and higher rT3 (0.80 +/- 0.25 nmol/L in hepatitis; 0.54 +/- 0.05 nmol/L in ICP; p < 0.05), while other TFT were unchanged. None of them had clinical signs of hypo or hyperthyroidism. A "euthyroid sick syndrome" was detected in 2 ICP patients and in 2 acute hepatitis in pregnancy. In puerperium of ICP patients, T3 and rT3 returned to levels in non-pregnant women. CONCLUSIONS: In ICP patients, TFT show similar trends than in more severe hepatic and non-hepatic diseases. Although thyroid binding-globulin was not measured in our patients, the pattern of TFT suggests that an impaired peripheral (hepatic?) deiodination of T4 is responsible for these changes. The influence of a dietary iodine deficiency can be ruled out.
Assuntos
Colestase Intra-Hepática/metabolismo , Hepatite C/sangue , Complicações na Gravidez/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Doença Aguda , Estudos de Casos e Controles , Colestase Intra-Hepática/etiologia , Feminino , Humanos , Iodo/urina , Gravidez , Terceiro Trimestre da Gravidez , Testes de Função Tireóidea , Hormônios Tireóideos/metabolismo , Tireotropina/sangueRESUMO
Los demoninados hipospadias son trastornos congénitos frecuentes. Ocurren en uno de cada 300 a 350 varones nacidos vivos. En estos casos siempre se han buscado dos finalidades: restablecer la función y otorgar al pene un aspecto aceptable. En este informe se expone la experiencia de los autores con la corrección de los hipospadias posteriores de 16 pacientes con la técnica de colgajo prepucial vascular transverso de Duckett, la cual se aconseja para tratar esta entidad, ya que la tasa de complicaciones (25 por ciento) es baja en comparación con la de otras técnicas
Assuntos
Criança , Humanos , Masculino , Retalhos Cirúrgicos/métodos , Retalhos Cirúrgicos , Hipospadia/cirurgia , Uretra/cirurgiaRESUMO
In order to measure TSH receptor antibodies (TRAb) we tried to set up a radioreceptor assay using human thyroid membranes. Due to lack of appropriate binding activity of the material obtained, we decided to use a kit which provides solubilized porcine membrane-receptors to TSH instead of human membranes, as well as calibrators that have been standardized in a receptor assay against MRC LATS std B. With these reactives we have measured TRAb in sera from 7 normal controls (C), 54 thyrotoxic patients (43 diffuse goiters [BDH], 8 multinodular goiters [BHM] and 3 Subacute Thyroiditis [TSA]), 3 patients with Hashimoto's Thyroiditis (TH) and in 6 non-hyperthyroid Graves ophthalmopathy patients. Measurement were initially performed using calibrators and the results expressed as U/L; since a very good correlation between the expression U/L and the calculated Inhibition Index (I.I.) was found (r = 0.99, n = 15, p < 0.001), results are shown using latter. In C mean +/- SD value for I.I. was 3.4 +/- 2.37%, so we decided to use, as cut off criteria for differentiating between normal and abnormal results, the figure 11%, which represents the mean +/- 3 SD. According to this, 93% of BDH had elevated TRAb activity while only slightly more than one third of MBH had elevated values, this difference being highly significant (p < 0.0001); both TSA and TH patients showed low TRAb activity while all Graves ophthalmopathy pts had elevated values, thus suggesting that they had a latent disease. We concluded that the methodology that is adequate and practical for clinical purposes.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anticorpos/sangue , Hipertireoidismo/imunologia , Receptores da Tireotropina/imunologia , Estudos de Casos e Controles , Doença de Graves/imunologia , HumanosRESUMO
The aim of this study was to determine whether IGF-1 and INS are able to induce HLA-DR antigen expression (AgHLA-DR) in cultured human thyrocytes. Cytotoxicity assay in thyroid epithelial cells (cultured for 7 days to avoid spontaneous antigen expression) from 14 patients operated due to different thyroidal diseases, was used to assess HLA-DR expression. AgHLA-DR was reinduced adding IFN-delta, IGF-1 or INS to the culture media, alone, combined or associated with TSH or TBII. Both IGF-1 and INS induced HLA-DR expression in a similar way as IFN-delta did, and the response was enhanced with their combination, suggesting that they have different sites of action. Their association with TSH or TBII further augmented the response. To determine if IGF-1 acts via lymphocyte IFN-delta secretion, peripheral lymphocytes from 5 normal subjects were cultured with and without IGF-1 and the supernatant was used as stimulator, observing a stimulation similar to that induced by IFN-delta. This finding supports the hypothesis that IGF-1 acts stimulating a specific tyrosine kinase protein (p56 1ck) which is located in T lymphocyte receptors. According to our results we can conclude that, at least in vitro, both IGF-1 and INS play a role in the immune process, probably exerting a paracrine effect on autoimmunity, acting as perpetuating factors.
Assuntos
Autoimunidade/imunologia , Antígenos HLA-DR/metabolismo , Fator de Crescimento Insulin-Like I/administração & dosagem , Insulina/administração & dosagem , Glândula Tireoide/imunologia , Análise de Variância , Células Cultivadas , Testes Imunológicos de Citotoxicidade , Humanos , Interferon gama/administração & dosagem , Glândula Tireoide/citologiaRESUMO
Aiming to assess the autoimmune origin of certain thyroid diseases, we studied the phenotypic composition and the ability of intrathyroidal lymphocytes to a re-induce HLA-DR expression on autologous thyrocytes coming from patients with graves's disease, nodular goiter and papillary thyroid carcinoma. Lymphocytes coming only from graves's disease patients were capable of reinduce HLA-DR expression on autologous thyrocytes (24.1 +/- 13.6 vs 1.5 +/- 2.54% in nodular goiter and carcinoma), as interferon gamma did (17.4 +/- 8.34%). Phenotypic characterization showed a significant decrease of T-CD3 (total lymphocytes) and T-CD4 (helper) in lymphocytes coming from patients with nodular goiter and carcinoma, and a marked reduction of T-CD8 (suppressor) in lymphocytes coming from patients with graves disease. Thus the T-CD4/T-CD8 ratio varies according to the etiology of the thyroidal disease. The lack of suppressor activity would explain why cells coming only from patients with graves disease, show marked HLA-DR expression. These findings give little support to the autoimmune origin hypothesis for nodular goiter and thyroid carcinoma.
Assuntos
Doenças Autoimunes/imunologia , Antígenos HLA-DR/imunologia , Linfócitos T/imunologia , Doenças da Glândula Tireoide/imunologia , Glândula Tireoide/imunologia , Doenças Autoimunes/patologia , Carcinoma Papilar/imunologia , Bócio Nodular/imunologia , Doença de Graves/imunologia , Humanos , Contagem de Leucócitos , Linfócitos T/patologia , Doenças da Glândula Tireoide/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/imunologiaRESUMO
The purpose of this paper is to study some of the mechanisms by which antigen presentation, one of the first steps in the immune process, is modulated. Three different experiments are performed: a) Using thyroid tissue from patients operated on for Graves' Disease, spontaneous HLA-DR and TPO antigen expressions were measured through the Cytotoxicity Assay; these findings were correlated with the presence of antiTPO in the sera of these patients. It was found that only patients whose thyroid tissue spontaneously expressed both antigens had circulating antiTPO in their sera, thus demonstrating that dual expression is basic for antibody production. b) Blood samples from other Graves' patients were obtained; peripheral lymphocytes were isolated and cultured in complete media for 5 days, then supernatant was separated and IFN-g concentration was measured by a sandwich type RIA; the same procedure was done in 12 normal controls in order to compare the results. It was found that lymphocytes from Graves' patients secreted significantly more IFN-g than normal controls (20.9 +/- 13.54 U/ml vs 3.7 +/- 3.22 U/ml respectively, p < 0.001) confirming that they were sensitized, so this determination could be used as a marker of immune process, if other infectious conditions are excluded; also it was found that IFN-g hypersecretion persists once hyperthyroidism has been treated, pointing out that the immune abnormality is still present.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença de Graves/imunologia , Antígenos HLA-DR/metabolismo , Interferon gama/metabolismo , Iodeto Peroxidase/imunologia , Apresentação de Antígeno , Antígenos CD4 , Doença de Graves/metabolismo , Antígenos HLA-DR/imunologia , Humanos , Iodeto Peroxidase/metabolismo , Linfócitos T/imunologiaRESUMO
The purpose of this work was to study if TSH has a role in TPO antigen expression in vivo. Using the cytotoxicity assay we measured TPO expression and correlated it with TSH serum levels in 3 groups of rats: control, hypothyroid and hypothyroid supplemented with thyroxine. For comparative purposes, in the cytotoxicity assay we used rat monoclonal antiTPO or human sera with high titles for antiTPO antibodies. Hypothyroid rats showed marked elevations of TSH serum levels and TPO antigen expression in their thyrocytes when compared to the control and supplemented group. A positive correlation between TPO antigen and TSH levels was observed (r = 0.69, p < 0.001). There was an excellent correlation between TPO results using rat monoclonal or human sera antibodies (r = 0.94 p < 0.0001). It is concluded that TSH modulates TPO antigen expression. These data are of clinical relevance considering that TSH modulates the expression of other antigens that can maintain the immune response and perpetuate the immune disease in patients with Graves disease treated with antithyroid drugs. Thus, the avoidance of TSH hypersecretion with administration of thyroxine could be useful to treat these patients.
Assuntos
Iodeto Peroxidase/sangue , Tireotropina/sangue , Análise de Variância , Animais , Peso Corporal , Humanos , Hipotireoidismo/tratamento farmacológico , Masculino , Metimazol/farmacologia , Ratos , Ratos Sprague-Dawley , Tireotropina/farmacologia , Tiroxina/sangue , Tiroxina/uso terapêutico , Fatores de TempoRESUMO
The aim of this study is to determine whether antithyroid drugs (ATD) act via inhibiting thyroid hormone synthesis or by interfering with the immune process which leads to autoimmune disease. Previously we had demonstrated that ATD do not affect HLA-DR and TPO antigen expressions induced by appropriate stimulus in normal thyrocytes, so we decided to study what happens when the same experiments are performed using autoimmune thyrocytes. Cultured thyroid tissue from patients operated on for Graves' Disease or Hashimoto's Thyroiditis were stimulated with TSH or TBII alone or associated with ATD; TPO antigen expression was evaluated by the Cytotoxicity Assay using human monoclonal antiTPO. When autoimmune thyrocytes were cultured and no stimulus was used or with the addition of MMI or PTU alone, very low values of TPO expression were noted (8.6 +/- 6.7, 5.0 +/- 7.1 and 4.2% +/- 2.3% respectively); if they were stimulated with TSH or TBII, a sharp rise of TPO antigen expression was detected (54.4 +/- 23.3 and 62.6 +/- 16.5%), these figures being significantly different from unstimulated cells (p < 0.001). If both stimulus were used associated with ATD, the high TPO antigen expression was unaffected. It is concluded that, at least in vitro, ATD have no effect upon induced-antigen expression in autoimmune thyrocytes. Since they do not alter antigen presentation, a primary step in the immune process, it is difficult to accept that their mechanism of action is through interference with the immune response.
Assuntos
Antitireóideos/farmacologia , Autoantígenos/sangue , Doença de Graves/imunologia , Iodeto Peroxidase/sangue , Tireoidite Autoimune/imunologia , Doença de Graves/sangue , Antígenos HLA-DP/imunologia , Humanos , Técnicas In Vitro , Glândula Tireoide/imunologia , Tireoidite Autoimune/sangueRESUMO
The aim of this study was to update the thyroid hormone profile in normal pregnant women with adequate iodine nutrition, to analyze the physiological changes that occur during pregnancy and to know the role that TBG and bHCG exert on these changes. One hundred six pregnant women without goiter, former thyroid diseases or positive antimicrosomal antibodies were studied. Fifty three of them were prospectively followed during the gestational period. Thirty age matched non pregnant women were studied as a control group. Serum T3t, T4t, T41, conventional and IRMA TSH, rT3, TBG, bHCG, antimicrosomal antibodies and urinary iodine content were measured. Median urinary iodine content was 18.9 ug/ml in pregnant women, discarding iodine deficiency, the main observed changes occurred between weeks 6 and 14 with significant elevations of T3t, T4t, T41, rT3, TBG and bHCG and TSH decrease. There was a positive correlation between TBG and T3t and T4t indicating a causal relationship. There was a negative correlation between T41 and TSH and between TSH and bHCG and a positive correlation between T41 and bHCG, suggesting a thyroid stimulator effect of bHCG which would raise T41 and thus inhibit TSH secretion.
Assuntos
Gravidez/sangue , Hormônios Tireóideos/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Iodo/urina , Primeiro Trimestre da Gravidez/sangue , Segundo Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/sangueRESUMO
The spontaneous expression of Class II molecules (HLA-DR) was studied in cultured thyrocytes obtained from patients with Graves Disease (n = 7), Hashimoto's Thyroiditis (n = 5), euthyroid nodular goiter, (n = 12), papillary carcinoma (n = 5), and laryngeal carcinoma (3 normal thyroid glands). If nodular goiters and papillary carcinoma are of autoimmune origin, as Graves Disease and Hashimoto's Thyroiditis, they should spontaneously express HLA-DR antigen on their cell surface as this has been considered one of the initial steps of autoimmunity. The study was performed using the cytotoxicity assay. Immediately after the thyroid glands were obtained, thyrocytes were labelled with 51-Cr and incubated overnight; the cells were destroyed by adding monoclonal antiHLA-DR antibody and rabbit complement. The cytotoxicity index (CI% + SD) which reflects 51-Cr release from lyzed cells was used to measure antigen expression. While Graves Disease's and Hashimoto's Disease's thyrocytes expressed HLA-DR in high proportion, normal thyrocytes and thyroid cells from other diseases did so in minimal proportion (28.12 +/- 10.71 vs 2.26 +/- 2.32, p < 0.001). These findings strongly suggest that nodular goiters and papillary carcinoma are not of autoimmune origin since they are unable to express HLA-DR on their cell surface. It is postulated that HLA-DR expression is the result of the influence of T lymphocytes previously sensitized to thyroid antigens.
Assuntos
Doenças Autoimunes/imunologia , Antígenos HLA-DR/análise , Doenças da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/imunologia , Testes Imunológicos de Citotoxicidade/métodos , HumanosRESUMO
An autoimmune disease can be the cause of thyroid disfunction. Determination of autoantibodies titers is the best way of demonstrating its existence. We studied 172 thyroid patients (146 females, 26 males) with ages ranging from 15 to 81 years. Thyroid microsomal autoantibodies (TMA) were detected by a modified agglutination test (SERA-TEK kit, Ames Div); a dilution greater than or equal to 1/1600 was considered as diagnostic of autoimmune disease. Patients were classified according to morphological and functional status in 3 groups: GI = non toxic goiter, n = 98 (71 diffuse, 20 multi and 7 uninodular); GII = toxic goiter, n = 62 (52 diffuse, 4 multi, 2 uninodular and 4 subacute thyroiditis); G III = hypothyroidism, n = 12 (5 primary hypothyroidism and 7 chronic thyroiditis). A control group of 30 normal individuals, ages ranging from 19 to 85 years was also studied. Diagnostic titers of TMA were found in 30.8% of group I, 88.5% of group II, 91.6% of group III and only in 6.6% of controls. The high incidence of positive TMA in toxic diffuse goiter (96.1%) as well as in hypothyroid patients was expected since these are typical examples of thyroid autoimmune disease. In the non toxic goiter group, positive TMA were present in 50% of multinodular, 28% of uninodular and 25% of diffuse goiters and the incidence of positive TMA varied according to age, being higher over the age of 40 years and lower under the age of 20 years. We postulate that this unexpected high incidence of positive TMA in non toxic goiter is due to amelioration of chronic iodine deficiency inducing the expression of latent autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)