RESUMEN
The clinical usefulness of thyroid ultrasonography in the evaluation of patients with autoimmune thyroiditis has been investigated. Thyroid ultrasonography was performed in 1184 consecutive patients attending our clinic, and the echo density of the thyroid parenchyma was evaluated with respect to that of normal thyroid tissue. Diffuse thyroid hypoechogenicity was found in 44 of 238 (18.5%) patients with autoimmune thyroiditis; the degree of hypoechogenicity was significantly correlated with the levels of circulating thyroid autoantibodies. Thyroid function was normal in all 194 patients with normal thyroid echogenicity, whereas hypothyroidism was found in 28 of 44 (63.6%) with reduced thyroid echogenicity. Included in this group were 8 patients, euthyroid at the first observation, who developed hypothyroidism over an 18-month follow-up period. None of the 133 patients with autoimmune thyroiditis and normal thyroid echogenicity followed for the same period of time became hypothyroid. Evidence of diffuse lymphocytic thyroiditis was obtained by histology after thyroidectomy (n = 10) or multiple fine needle aspiration cytology (n = 15) in 25 of the 44 patients with thyroid hypoechogenicity; on the other hand, focal thyroiditis was shown at histology in 8 patients who had normal thyroid echogenicity. In conclusion, diffuse low thyroid echogenicity was found in about 20% of patients with autoimmune thyroiditis. This echographic pattern is indicative of diffuse autoimmune involvement of the gland and is associated with or may predict the development of hypothyroidism.
Asunto(s)
Hipotiroidismo/etiología , Glándula Tiroides/diagnóstico por imagen , Tiroiditis Autoinmune/diagnóstico por imagen , Autoanticuerpos/sangre , Biopsia con Aguja , Humanos , Estudios Prospectivos , Glándula Tiroides/patología , Tiroiditis Autoinmune/complicaciones , Tiroiditis Autoinmune/patología , UltrasonografíaRESUMEN
Although Graves' disease (GD), Hashimoto's thyroiditis (HT) and idiopathic myxoedema (Myx) are clinically distinct autoimmune thyroid diseases, previous studies using crude thyroid preparations as a source of antigens have failed to identify differences in cellular immune responses. In this study, we have assessed cellular immunity in patients with these disorders to two antigen preparations (derived from thyroid gland and cervical fat) enriched in cell membranes and known to share a functional TSH receptor. Using an indirect T-lymphocyte migration inhibitory factor (T-LIF) assay, T-cell immunity to thyroid membranes was demonstrated in 11/11 patients with GD, 4/5 with HT and 4/5 with Myx, but in none of 18 patients with chronic active hepatitis (another organ-specific autoimmune disease) or sixteen healthy controls. In contrast, T lymphocytes responsive to adipocyte membranes were detected only in patients with GD. TSH binding inhibiting antibodies were found exclusively in six patients with GD, and thyroid stimulating antibodies in five of these patients. In co-culture experiments designed to study the activity of antigen-specific suppressor T cells, low numbers of T cells from 6/6 normal controls, 4/4 patients with HT and 5/5 patients with myxoedema suppressed the response to adipocyte membranes of T lymphocytes from patients with Graves' disease. The results of this study demonstrate different patterns of T-cell reactivity to thyroid antigens in patients with Graves' disease, Hashimoto's thyroiditis and myxoedema and suggest that cellular immunity to the TSH receptor is restricted to patients with Graves' disease and associated with a defect in the specific immunoregulatory control of this response.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedad de Graves/inmunología , Receptores de Tirotropina/inmunología , Linfocitos T/inmunología , Glándula Tiroides/inmunología , Tiroiditis Autoinmune/inmunología , Adolescente , Adulto , Anciano , Antígenos de Superficie/inmunología , Membrana Celular/inmunología , Células Cultivadas , Femenino , Hepatitis Crónica/inmunología , Humanos , Inmunidad Celular/inmunología , Masculino , Persona de Mediana Edad , Mixedema/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
UNLABELLED: The incidence and the significance of TSH-receptor antibodies in Graves' disease and in various thyroid disorders have been evaluated. TSH-binding inhibiting antibodies (TBIAb) and thyroid stimulating antibodies (TSAb) were detected in a large proportion of Graves' disease patients (TBIAb in 68.8% and TSAb in 77.8%), in a small number of patients with idiopathic myxoedema or Hashimoto's thyroiditis, and were not detected in patients with endemic euthyroid goitre, differentiated thyroid carcinoma and toxic adenoma. Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%). When TSH-receptor and other thyroid autoantibodies were compared, it was found that 13 of the 15 Graves' patients with negative tests for thyroglobulin and thyroid microsomal antibodies were positive for TSH-receptor antibodies. On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies. No significant differences in the prevalence of TSH-receptor antibodies were found in Graves' patients irrespective of the presence of ophthalmopathy or pretibial myxoedema. Elevated TBIAb activity at the end of anti-thyroid drug treatment was found in 52.9% of Graves' patients who subsequently relapsed, while in Graves' patients in remission TBIAb was always negative. TSH-receptor antibody results were not predictive of the outcome of radioiodine treatment in Graves' disease. Finally no correlation could be found between TBIAb and TSAb in Graves' disease and Hashimoto's thyroiditis. IN CONCLUSION: the high incidence of TSH-receptor antibodies in Graves' disease confirms their pathogenetic role in the development of hyperthyroidism; TSH-receptor antibodies in Graves' disease are not significantly associated with the presence of ophthalmopathy or pretibial myxoedema; TSH-receptor antibody assays may be useful for the diagnosis of Graves' disease in the absence of other signs of autoimmunity. TBIAb seems to be a good predictor of relapse in Graves' patients treated with anti-thyroid drugs; a fraction of toxic multinodular goitre could be a nodular variant of Graves' disease.
Asunto(s)
Autoanticuerpos/sangre , Receptores de Tirotropina/inmunología , Enfermedades de la Tiroides/inmunología , Bocio/inmunología , Enfermedad de Graves/diagnóstico , Enfermedad de Graves/etiología , Enfermedad de Graves/inmunología , Humanos , Inmunoglobulinas Estimulantes de la Tiroides , Mixedema/inmunología , Pronóstico , Tiroglobulina/inmunología , Glándula Tiroides/inmunología , Tiroiditis Autoinmune/inmunologíaRESUMEN
Previous studies by us and others have shown that Graves' immunoglobulins G (IgGs) behaved as agonists or even antagonists of TSH. In this paper we have looked for the existence of IgG preparations without any thyroid stimulatory activity but able to significantly block the action of TSH in 128 hyperthyroid Graves' patients. The presence of TSH-binding inhibiting antibodies (TBIAb) and that of thyroid stimulating antibodies (TSAb) was evaluated by a radioreceptor assay using solubilized thyroid plasma membranes and by assaying the adenylate cyclase (AC) function of thyroid plasma membranes, respectively. Seventeen IgGs were negative for TSAb but positive for TBIAb in the screening, using only one concentration of IgG. Three kinds of activity were investigated in these IgGs at different doses: (1) TSH-binding inhibiting activity; (2) thyroid AC stimulating activity; and (3) the inhibition of TSH-induced AC stimulation. The results showed that the level of activity was not always dose-dependent. A significant (greater than 20%) inhibition of the TSH-dependent AC stimulation was present in 15 of the 17 IgGs examined: this inhibition was more elevated at lower than at higher doses in two preparations. No significant correlation was found between the three activities. In short, we have been able to demonstrate the existence of 'blocking' antibodies, apparently without any stimulatory activity, in some patients with Graves' disease. The diphasic pattern of the dose-response curves of some IgGs and the lack of correlation between the different activities can be explained by the co-existence in the sera of Graves' patients of different autoantibodies varying in concentration, binding affinity constant and intrinsic biological activity.
Asunto(s)
Anticuerpos/análisis , Enfermedad de Graves/inmunología , Inmunoglobulina G/análisis , Adenilil Ciclasas/metabolismo , Unión Competitiva , Membrana Celular/análisis , Humanos , Inmunoglobulinas Estimulantes de la Tiroides , Glándula Tiroides/análisisRESUMEN
We report the incidence of thyroid cancer in a series of 1832 consecutive patients seen for thyrotoxicosis of any etiology during 1970 and 1985 in our department. Surgical treatment for thyrotoxicosis was selected as the treatment of choice in 179 patients (9.8%), 86 with toxic diffuse goiter (TDG), 21 with toxic nodular goiter (TNG) and 40 with toxic adenoma (TA). The presence of thyroid cancer was found in 11 patients for a total incidence of 6.1%. Six patients had TDG (percent incidence in this group 6.9%), 4 patients had TNG (7.5%) and 1 had TA (2.5%). While the presence of thyroid cancer was totally unsuspected in TNG and TA, in TDG 4 out of 6 patients found to have a cancer, had been suspected before surgery. When a thyroid nodule was present in a toxic diffuse goiter the possibility to face with a malignant lesion reached 22.2% of the cases (4 out of 18 cases), while only 2 out of 68 patients (2.9%) with TDG and no nodule had thyroid cancer. These results confirm recent other series reporting the frequent association of hyperthyroidism and thyroid cancer and suggest that in thyrotoxic patients any nodule must be screened carefully to rule out malignancy.
Asunto(s)
Neoplasias de la Tiroides/complicaciones , Tirotoxicosis/cirugía , Adenoma/diagnóstico , Adenoma/patología , Adolescente , Adulto , Anciano , Autoanticuerpos/análisis , Femenino , Bocio/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Tirotoxicosis/complicaciones , Tirotoxicosis/patologíaRESUMEN
Amiodarone, an iodine containing drug, may induce thyrotoxicosis by an uncertain mechanism. In this study the role of thyroid autoimmunity was evaluated in 28 consecutive patients referred to us because they had become hyperthyroid during long-term amiodarone administration. Titres of thyroglobulin and thyroid microsomal antibodies, TSH binding-inhibitory and thyroid stimulating antibodies were evaluated. Underlying thyroid disorders were demonstrated in 20 patients (9 of them had toxic diffuse goitre, seven toxic multinodular goitre and four toxic adenoma), while eight patients did not show any apparent thyroid gland abnormality. Circulating thyroid autoantibodies could be found in all amiodarone iodine-induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients. These studies suggest that thyroid autoimmunity has little if any role in the development of thyrotoxicosis in amiodarone treated patients without underlying thyroid disorders. Furthermore, in amiodarone-iodine-induced thyrotoxicosis associated with various thyroid diseases, the humoral markers of thyroid autoimmunity show an incidence similar to that observed in spontaneous hyperthyroidism.
Asunto(s)
Amiodarona/efectos adversos , Autoanticuerpos/análisis , Glándula Tiroides/inmunología , Tirotoxicosis/inmunología , Adulto , Anciano , Formación de Anticuerpos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tirotoxicosis/inducido químicamente , Factores de TiempoRESUMEN
The majority of Graves' immunoglobulins have the capacity to stimulate thyroid adenylate cyclase (AC) activity in vitro. So far, the exact events leading to AC activity stimulation by thyroid stimulating antibody (TSAb) are not known. It has been suggested that TSAb activates thyroid AC through prostaglandin (PG) synthesis, implying the concept that TSH and TSAb stimulate AC in different ways. If this is so, the inhibition of PG synthesis should notably reduce the response of thyroid plasma membrane to TSAb. We have, therefore, investigated the effect of 2 inhibitors of PG synthesis on the TSAb-stimulated AC activity in a crude human thyroid plasma membrane preparation. Neither indomethacin, nor hydrocortisone, even at concentrations able to completely inhibit PG synthesis, had any significant effect on the thyroid plasma membrane response to TSAb. The results suggest, therefore, that, at least under our experimental conditions, PG does not mediate the AC activation by TSAb. Consequently, the aforementioned suggestion should not be used to claim that TSH and TSAb activate thyroid AC through different pathways. The data, however, do not exclude that TSAb may determine PG synthesis in thyroid cells through the phosphatidylinositol signal system (Pl system).