Asunto(s)
Humanos , Femenino , Adulto , Mixedema/fisiopatología , Mucinas/fisiología , Mucinosis/clasificación , Estimulante Tiroideo de Acción Prolongada/fisiología , Receptores de Hormona Tiroidea/fisiología , Mixedema/clasificación , Mixedema/etiología , Hipertiroidismo/complicaciones , Enfermedades de la Tiroides/complicaciones , Mucinas/química , Glicosaminoglicanos , Ácido Hialurónico , Dermatosis de la Pierna/etiología , Dermatosis de la Pierna/fisiopatología , Dermatosis de la Pierna/patologíaAsunto(s)
Humanos , Femenino , Adulto , Estimulante Tiroideo de Acción Prolongada/fisiología , Mucinosis/clasificación , Mucinas/fisiología , Mixedema/fisiopatología , Receptores de Hormona Tiroidea/fisiología , Glicosaminoglicanos , Ácido Hialurónico , Hipertiroidismo/complicaciones , Dermatosis de la Pierna/etiología , Dermatosis de la Pierna/patología , Dermatosis de la Pierna/fisiopatología , Mucinas/química , Mixedema/clasificación , Mixedema/etiología , Enfermedades de la Tiroides/complicacionesAsunto(s)
Autoanticuerpos/fisiología , Enfermedades Autoinmunes/inmunología , Enfermedad de Graves/inmunología , Miastenia Gravis/inmunología , Receptores de Superficie Celular/inmunología , Autoantígenos/inmunología , Diabetes Mellitus/inmunología , Humanos , Idiotipos de Inmunoglobulinas , Insulina/inmunología , Resistencia a la Insulina , Estimulante Tiroideo de Acción Prolongada/fisiología , Receptores Colinérgicos/inmunología , Receptores de Tirotropina/inmunologíaRESUMEN
Graves' disease and Hashimoto's thyroiditis have been previously considered separate clinical and pathologic entities. Current knowledge of the autoimmune cause of specific systemic syndromes has been applied to these seemingly dissimilar diseases and now permit evolution of a unified integrated concept for considering them as two subsets of a single pathologic process. Experimental and clinical data now support the thesis that autoimmune thyroid disease is a genetically conditioned immunologic dysfunction, perhaps an abnormality of suppressor lymphocytes that results in production of humoral and tissue antibodies directed against thyroid gland cells and receptors of other somatic tissues. Thyroid autoantibodies possess hormonally stimulatory qualities and cytotoxic (inflammatory or destructive) properties. They may be present singly or together in the same individual with resulting diverse clinical and biochemical patterns depending upon the predominance or concordance of specific antibodies. Further, antibodies in autoimmune thyroid disease may be directed against other somatic structures such as ocular muscle, skin, hair, pigment cells, hematologic organs, or other endocrine glands. The immune etiology appears to predispose to nonendocrine systemic autoimmune disorders that coincide with thyroid disease. It is not clear at this time how genetic factors influence the onset, course, or ultimate outcome of autoimmune thyroid disease or why certain associated immunopathies tend to cluster with one or the other of these syndromes. Our understanding of the immune etiology common to Graves' and Hashimoto's diseases permits a more precise definition of the terms hyperthyroidism and thyrotoxicosis, the former denoting a pathologic goitrous phenomenon and the latter, a peripheral tissue manifestation of cellular receptor site excess of thyroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedad de Graves/inmunología , Tiroiditis Autoinmune/inmunología , Animales , Anticuerpos/sangre , Anticuerpos/inmunología , Formación de Anticuerpos , Oftalmopatías/inmunología , Cobayas , Antígenos HLA/inmunología , Humanos , Hipertiroidismo/diagnóstico , Estimulante Tiroideo de Acción Prolongada/fisiología , Linfocitos T/fisiología , Tiroglobulina/sangre , Glándula Tiroides/inmunologíaRESUMEN
Two families of thyroid stimulators can be described besides TSH: a) hormonal factors, b) Graves' IgGs. Hormonal factors include: biogenic amines (catecholamines, histamine, serotonine), prostaglandins E and LH and hCG. The stimulating effect of the latters is expressed only at very high concentration. Thyroid stimulating effect of GH, insulin, cortisol, NGF and FGF is probably ancillary. Thyroid stimulating IgG were first represented by the LATS. Graves' IgGs are currently detected by their interaction with human thyroid tissue in vitro: one either detects thyroid stimulation (cAMP or hormone production) or binding inhibition of LATS or TSH. These various activities are denominated: thyroid-stimulating IgG (TSI) or antibodies (TSAb), or LATS-Protector (LATS-P) or thyrotropin binding inhibitory (TBIA). TBIA IgGs are not necessarily TSI. Thyroid growth stimulatory IgGs (TGI) have also been described as well as TSAb or TGI blocking IgG, that also block TSH effects. Graves' IgGs probably include a mosaic of specificities directed against different parts of thyroid cell surface antigens constituting, or near, the TSH receptor complex. TSI represent only one or a few types of these specificities.
Asunto(s)
Enfermedad de Graves/inmunología , Inmunoglobulina G/fisiología , Glándula Tiroides/fisiología , Tirotropina/fisiología , Autoanticuerpos/análisis , Autoanticuerpos/fisiología , Humanos , Inmunoglobulinas Estimulantes de la Tiroides , Técnicas Inmunológicas , Estimulante Tiroideo de Acción Prolongada/fisiología , Receptores de Superficie Celular/inmunología , Receptores de Tirotropina , Terminología como Asunto , Tirotropina/inmunologíaRESUMEN
A new sensitive in vitro assay for human thyroid stimulator (HTS) was developed using human thyroid adenoma cells in monolayer culture. After being cultured for 2 days, the cells were incubated in 0.3 ml Hank's solution without 0.8% NaCl (medium 1) and with thyroid stimulator (bovine TSH or 3 mg patient serum immunoglobulin G) at 37 C for 2 h. The cAMP generated in the cells and the medium during the incubation was measured by RIA. The assay was sensitive enough to elicit a 1.7- to 7.9-fold increase in cAMP at a TSH concentration of 10 microU/ml. HTS was detected in 33 (82.5%) of the 40 patients with untreated graves' disease using this assay system. In Hank's solution (medium 2), however, HTS was detected in only 5 (23.8%) of the 21 patients with untreated GRaves' disease. cAMP increment upon stimulation by either TSH or HTS in medium 1 was larger than that in medium 2, and the difference in the response to HTS using the two media was much greater than that in the response to TSH. Therefore, all HTS-immunoglobulin G studies showed higher activity using medium 1 than using medium 2 when expressed as bovine TSH equivalent. Analysis by the Lineweaver-Burk plot of dose-response curves of the effect of TSH and HTS stimulation on cAMP increment showed an increase in the Km upon the addition of NaCl to the medium. A similar inhibitory effect of NaCl (150 mM) was also observed in the assay system of human thyroid adenylate cyclase stimulator using crude plasma membrane fractions. In summary: 1) an assay for HTS measuring cAMP production in cultured thyroid adenoma cells was developed and the assay using low NaCL medium was found to be the most sensitive, and 2) the inhibitory effect of NaCl on the response to HTS was much greater than that on the response to TSH. These data suggest different behaviors of these two stimulators at their receptor sites.
Asunto(s)
Adenoma/metabolismo , AMP Cíclico/metabolismo , Inmunoglobulina G/análisis , Estimulante Tiroideo de Acción Prolongada/análisis , Cloruro de Sodio/farmacología , Neoplasias de la Tiroides/metabolismo , Bioensayo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Enfermedad de Graves , Humanos , Inmunoglobulina G/fisiología , Estimulante Tiroideo de Acción Prolongada/fisiología , Tirotropina/farmacologíaAsunto(s)
Enfermedades Autoinmunes/etiología , Enfermedad de Graves/etiología , Estimulante Tiroideo de Acción Prolongada/inmunología , Animales , Autoanticuerpos/inmunología , Enfermedad de Graves/inmunología , Humanos , Estimulante Tiroideo de Acción Prolongada/análisis , Estimulante Tiroideo de Acción Prolongada/fisiología , RatonesAsunto(s)
Adenilil Ciclasas/metabolismo , AMP Cíclico/metabolismo , Enfermedad de Graves/enzimología , Animales , Anticuerpos , Bovinos , Activación Enzimática , Humanos , Inmunoensayo , Inmunoglobulina G , Estimulante Tiroideo de Acción Prolongada/fisiología , Receptores de Superficie Celular/metabolismo , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/enzimología , Glándula Tiroides/fisiopatología , Tirotropina/farmacología , Tirotropina/fisiologíaAsunto(s)
Glándula Tiroides/fisiopatología , Tiroiditis/etiología , Genes MHC Clase II , Antígenos HLA/genética , Humanos , Hipertiroidismo/etiología , Hipotiroidismo/etiología , Tolerancia Inmunológica , Inmunidad Celular , Yodo/metabolismo , Estimulante Tiroideo de Acción Prolongada/fisiología , Tiroiditis/genética , Tiroiditis/fisiopatología , Tirotropina/metabolismo , Tirotropina/fisiologíaRESUMEN
To obtain an in vitro method of LATS assay which is equally sensitive to a McKenzie bioassay, we compared the quality of cAMP generation-stimulation, thyroidal adenyl cyclase stimulation, and the stimulation of T3-release from mouse thyroid slices. Among those indicators of thyroid stimulation, stimulation by IgG of the release of T3 from incubated thyroid slices is the most sensitive, reproducible and reliable indicator, reflecting faithfully the results of a McKenzie bioassay. Stimulation of cAMP generation in slice manifested less sensitivity, but reasonable reproducibility. However, adenyl cyclase stimulation by IgG of patients with Graves' disease was erratic in two successive experiments, probably due to a non-specific effect of IgG. When adenyl cyclase stimulation was adopted as a sole indicator of thyroid stimulation, the results must be interpreted cautiously.
Asunto(s)
Estimulante Tiroideo de Acción Prolongada/fisiología , Adenilil Ciclasas/fisiología , Animales , Bioensayo , AMP Cíclico/análisis , Enfermedad de Graves/sangre , Humanos , Inmunoglobulina G/fisiología , Masculino , Ratones , Glándula Tiroides/análisis , Triyodotironina/sangreRESUMEN
Thyroid-stimulating immunoglobulins (TSIs) were measured by radioreceptor assay in serum from 51 patients with a multinodular goitre, divided into four groups according to thyroid function, and in 30 normal people. In 9 patients who were euthyroid and had non-autonomous thyroid function and in 6 patients who were hyperthyroid, TSI index was normal . Of 21 euthyroid patients with autonomous function only 2 had a slightly abnormal TSI index (66 in both, normal greater than or equal to 68). Another series of 15 clinically euthyroid patients also had a normal TSI index. These results suggest that TSIs do not contribute to the pathogenesis of multinodular goitre, as has been suggested by others.
Asunto(s)
Bocio Nodular/etiología , Inmunoglobulinas/análisis , Estimulante Tiroideo de Acción Prolongada/fisiología , Glándula Tiroides/inmunología , Adulto , Anciano , Femenino , Bocio Nodular/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Ensayo de Unión Radioligante/métodos , Pruebas de Función de la Tiroides , Glándula Tiroides/fisiopatologíaAsunto(s)
Hormonas Tiroideas/metabolismo , Animales , AMP Cíclico/fisiología , Dieta , Humanos , Yodo/fisiología , Estimulante Tiroideo de Acción Prolongada/fisiología , Mastocitos/fisiología , Prostaglandinas/fisiología , Sistema Nervioso Simpático/fisiología , Enfermedades de la Tiroides/fisiopatología , Glándula Tiroides/inervación , Glándula Tiroides/fisiología , Hormonas Tiroideas/sangre , Hormona Liberadora de Tirotropina/metabolismoRESUMEN
The prevalence of serum thyroid-stimulating immunoglobulins (T.S.I.) in a variety of thyroid diseases was determined in 96 patients and 35 normal controls. Significantly elevated levels of T.S.I. were found not only in patients with Graves' disease and Hashimoto's thyroiditis but also in those with non-toxic and toxic multinodular goitre, whereas patients with a single autonomously functioning thyroid nodule, with subacute thyroiditis, and with "hyperthyroiditis" had levels which did not differ from those in the controls. We postulate that non-toxic multinodular goitre, like Graves' disease, may result from increased circulating T.S.I., which in some cases may be present in sufficient concentration to cause thyrotoxicosis.
Asunto(s)
Bocio Nodular/etiología , Hipertiroidismo/etiología , Inmunoglobulina G , Estimulante Tiroideo de Acción Prolongada/fisiología , Adolescente , Adulto , Anciano , Bocio Nodular/inmunología , Enfermedad de Graves/inmunología , Humanos , Hipertiroidismo/inmunología , Estimulante Tiroideo de Acción Prolongada/aislamiento & purificación , Persona de Mediana Edad , Tiroiditis/inmunología , Tiroiditis Autoinmune/inmunologíaRESUMEN
Alpha-amanitin was shown to inhibit triiodothyronine (T3)-induced increases in mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytoplasmic malic enzyme activity in the livers of male Sprague-Dawley rats. A 3-fold increase in alpha-GPD observed 24 h after the iv injection of 3 microngT3/100 g BW was completely inhibited by administration of alpha-amanitin at 0 and 8 h. Similarly, alpha-amanitin blocked a two- to four-fold increase in malic enzyme 24 h following iv injection of 3 mg T3/100 g BW into euthyroid rats. After the initial inhibition of enzyme induction by alpha-amanitin was dissipated, however, a delayed but striking increase in enzyme activity occurred. In hypothyroid animals, alpha-GPD activity rose after the initial 24 h inhibition and reached levels at 72 h equal to those observed in hypothyroid rats treated with T3 only. In euthyroid animals treated with T3 and alpha-amanitin, a delayed increase in malic enzyme activity was observed at 72 h and attained values at 96 h similar to those in euthyroid animals injected with T3 only. The delayed rise in enzyme response is most easily explained by the formation of a long-lived intermediate during the exposure of the nuclear sites to T3.