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[Intrathyroidal lymphocytes in autoimmune thyroid diseases].

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.

Autoimmune Diseases↗

[The relationship of breast cancer and thyroid diseases].

A relationship between breast cancer and thyroid diseases has been postulated for many years. Several studies have demonstrated an increased risk of breast carcinoma in patients with goiter, chronic thyroiditis (hypothyroidism) or thyroid supplement therapy itself, while others have shown either a slight, nonsignificant excess or none at all. In an overview of the literature, the results were inconclusive and rather controversial in each other. Apart from the thyroid disorders mentioned above, a relationship between thyroid cancer and breast cancer also has been suggested in the recent studies. This is rather probable as a fact, but common risk factors for the two cancers have not been clarified yet and remains in future problem.

Adenoma↗

Hyperparathyroidism and thyroid disease. A study of their association.

The incidence of hyperparathyroidism was prospectively evaluated in a group of patients with thyroid disease, and the incidence of thyroid disease was retrospectively evaluated in a group of patients specifically referred for evaluation of hyperparathyroidism. Hyperparathyroidism was ten times more frequent in thyroid patients than expected in a general medical population and was especially prevalent in patients with nodular goiter. The incidence of thyroid disease in patients with hyperparathyroidism was 38.8%. Although radiation therapy was shown to be a factor in these associations, it alone could not explain the observed frequency.

Goiter, Nodular↗

Thyroid disease and female reproduction.

OBJECTIVE: To review the menstrual function and fertility in thyroid disease, mainly in hyperthyroidism and hypothyroidism. Also to register the consequences of (131)I therapy, which is used widely in the treatment of Graves' disease and thyroid cancer, on subsequent pregnancies and on fertility in these patients. DESIGN: A MEDLINE computer search was used to identify relevant studies. The type of menstrual disturbances and the status of fertility were recorded from all the studies found. Also, the fertility and genetic hazard of female patients with Graves' disease and thyroid cancer who were treated with (131)I were registered. RESULT(S): Both hyperthyroidism and hypothyroidism may result in menstrual disturbances. Menstrual abnormalities are less common now than in previous series. In a recent study, we found that only 21.5% of 214 thyrotoxic patients had some type of menstrual disturbance, compared to 50 to 60% in some older series. The most common manifestations are hypomenorrhea and oligomenorrhea. According to the results of endometrial biopsies, most thyrotoxic women remain ovulatory. Moreover, the genetic hazard incident to radioiodine therapy in Graves' disease and thyroid carcinoma is very small; exposure to (131)I does not cause reduced fecundity, and the risk of loss of fertility is not a contraindication for its use in these patients. mIn hypothyroidism, the frequency of menstrual irregularities has very recently been reported to be 23.4% among 171 hypothyroid patients studied. This is much less than that reported in previous studies, which showed that 50 to 70% of hypothyroid female patients had menstrual abnormalities. The most common manifestation is oligomenorrhea. Severe hypothyroidism is commonly associated with failure of ovulation. Ovulation and conception can occur in mild hypothyroidism. These pregnancies are, however, often associated with abortions, stillbirths, or prematurity. The latter may be of greater clinical importance in infertile women with unexplained infertility. CONCLUSION(S): These new data, mainly concerning menstrual abnormalities in hyperthyroidism and hypothyroidism, are inconsistent with what is generally believed and written in the classic thyroid textbooks and indicate that such opinions should be revised.

Female↗

Investigations of thyroid diseases--an update on diagnostic methods.

Iodine deficiency disorders (IDD) are an important public health problem in India. It requires further refinement and improvements in thyroid disease diagnosis, especially in the early diagnosis of thyroid malfunctioning and risk assessment of autonomously functioning thyroid tissue. Scintigraphy with technetium-99m pertechnetate under exogenous or endogenous thyroid stimulating hormone (TSH) suppression provides the best results. There has been significant improvement in methodology in various laboratory investigations that have resulted from the application of newer luminescent techniques and gene technology in various thyroid function tests. TSH measurement especially by using second or third generation assays has ensured diagnostic accuracy and thyrotropin releasing hormone (TRH) test now almost always unnecessary. Determination of glycosaminoglycans in urine may become a helpful tool in the follow up of endocrine ophthalmopathy. The differentiation of blocking and stimulating TSH receptor antibodies is relevant when discrepant results are obtained with respect to thyroid function. Some newer imaging agents have been used in thyroid disease scintigraphy such as octreotide or in thyroid diseases diagnosis such as fluorodeoxyglucose. Both improve the detectability of thyroid cancer metastasis especially if radioiodine scan is negative.

Goiter, Endemic↗

Thyroid disease in older patients. Diagnosis and treatment.

Thyroid gland dysfunction is a relatively common clinical problem in elderly people and is associated with significant morbidity if left untreated. The clinical features of thyroid disease may be subtle, easily overlooked or misdiagnosed. Therefore, a high index of suspicion is necessary. If potentially serious sequelae are to be avoided, the selection and interpretation of thyroid function tests must be appropriate. It is particularly important to consider both the effect of concurrent illness and the effect of certain drugs on thyroid function tests. With recent methodological advances, thyroid function tests are now more reliable, though in certain situations they still need to be interpreted with caution. Once the diagnosis is established, the management of both hypothyroidism and hyperthyroidism is relatively simple and effective, though there are special considerations relating to elderly patients.

Aged↗

Relation of CD30 molecules on T-cell subsets to the severity of autoimmune thyroid disease.

The prognosis of patients with autoimmune thyroid disease (AITD) varies. To clarify the immunologic differences among patients with various severities of AITD, we examined two types of molecules on peripheral T lymphocytes: CD195 (CCR5), which express dominantly on CD4(+) type 1 helper T (T(H)1) cells, and CD30, which is known as a marker of CD4(+) type 2 helper T (T(H)2) cells and a regulatory molecule of CD8(+) autoreactive cytotoxic T cells. We found presence of patients with high proportion (> 9%) of CD30 expression in CD4(+) cells in a group of patients with Graves' disease (GD) in remission compared to the patients with intractable GD and a decrease in the intensity of CD30 expression on CD8(+) cells from patients with severe Hashimoto's disease (HD) treated for hypothyroidism compared to patients with untreated and euthyroid HD. There was no difference in CD195 expression between these patients with GD or HD with different severities, but there was a decreased intensity of CD195(+) cells in thyrotoxic patients with GD. These results indicate that CD30 molecules on CD4(+) and CD8(+) cells may be related to the severities of GD and HD, respectively.

Adult↗

Autoimmune thyroid disease.

The concept of thyroid autoimmune disease now includes the following clinical entities: 1 degree thyrotoxicosis and goitrous thyroiditis (Hashimoto) with their variants, and 1 degree myxedema (atrophic thyroiditis); some cases of sporadic nontoxic goiters; most cases of neonatal hyperthyroidism; and a proportion of congenital athyreotic cretinism. Endocrine exophthalmos, though clinically associated with Graves' disease, is now considered a separate immunological entity.

Animals↗

Sensitization of T lymphocytes to thyroid antigen in autoimmune thyroid disease as demonstrated by the monocyte procoagulant activity test.

Monocyte procoagulant activity (PCA) production has been reported to have a close relation to cell-mediated immunity (CMI), and the collaboration of T lymphocytes is necessary to induce PCA. Antigen-specific sensitization of lymphocytes in patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) has been demonstrated by means of the production of cell-bound PCA by monocytes following antigen stimulation of whole peripheral blood mononuclear cells (PBM). These cells, obtained from both normal subjects and patients with autoimmune thyroid diseases, produced significant amounts of PCA with non-specific lectin, concanavalin A (Con A) stimulation; however, there was no significant difference between the two groups, suggesting that Con A stimulated T cells induced monocyte PCA nonspecifically. Peripheral mononuclear cells from patients with autoimmune thyroid diseases produced significantly greater amounts of PCA than PBM from normal subjects when stimulated with solubilized and IgG-free thyroid antigen. On the other hand, liver antigen did not induce significant amounts of PCA production in PBM from either normal subjects or patients. Significantly larger amounts of PCA were produced by PBM from patients following thyroid antigen stimulation than with liver antigen stimulation. Although monocytes were the major source of PCA, T cells were necessary to induce PCA in monocytes with thyroid antigen and Con A stimulation. Elimination of lymphocyte subsets in PBM from patients by negative selection (using monoclonal antibodies and complement) suggested that the collaboration of T lymphocytes, especially helper/inducer (T4+) T cells, was necessary to produce PCA with thyroid antigen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Discordant effect of IFN-beta1a therapy on anti-IFN antibodies and thyroid disease development in patients with multiple sclerosis.

Interferon-beta1b (IFN-beta1b) therapy is associated with a relatively high risk of developing thyroid disease. IFN-beta1a is regarded as less immunogenic than IFN-beta1b because of its structural homology to natural IFN-beta. We assessed the effect of 1 year of IFN-beta1a treatment on thyroid function and autoimmunity in 14 multiple sclerosis (MS) patients. The results were compared with those obtained in a series of 31 MS patients treated with IFN-beta1b. The prevalence of positive binding antibody (BAb) titer and neutralizing (NAb) anti-IFN antibody titer in the two groups was also assessed. The BAb and NAb positivity rate in IFN-beta1a-treated patients was significantly lower than in the group submitted to IFN-beta1b therapy (7% vs. 84% and 0% vs. 30%, respectively). Although the incidence of thyroid dysfunction was slightly higher in IFN-beta1b-treated patients than in those undergoing IFN-beta1a treatment (33% vs. 23%, respectively), it did not reach statistical significance. Thyroid disease was unrelated to the presence of positive serum BAb or NAb titer in both the group undergoing IFN-beta1a therapy and in that treated with IFN-beta1b. In both groups, thyroid disease developed mostly in women (71%) against a background of preexisting thyroiditis and a diffuse hypoechoic ultrasound thyroid pattern (80%). IFN-beta1a treatment was associated with a significantly lower prevalence of both BAb and NAb-positive titers than was IFN-beta1b. Conversely, thyroid disease was similar and unrelated to the presence of positive anti-IFN-beta antibody titer. Therefore, routine thyroid assessment may be advised during IFN-beta1a treatment, especially in patients with preexisting thyroiditis.

Adult↗

[Oncogenic emergency and treatment in thyroid disease].

The urgent treatment of thyroid disease is mainly considered to be that of thyroid neoplasia, especially malignant thyroid tumors. The clinical symptoms produced by malignant neoplasia are acute respiratory failure caused by tumor compression and/or invasion of the trachea. Massive bleeding caused by tumor invasion of the major vessels also requires emergency therapy. In general, thyroid cancer has a favorable prognosis in patients with well-differentiated papillary carcinoma, which makes up more than 90% of thyroid malignancies. However, anaplastic carcinoma, undifferentiated papillary carcinoma, and malignant lymphoma originating from the thyroid sometimes require urgent therapy to save lives. Anaplastic carcinoma that is basically transformed from well-differentiated papillary carcinoma shows rapid growth and invades the surrounding tissue to produce tracheal obstruction. Repeated postoperative recurrences in patient with papillary carcinoma suggest undifferentiated carcinoma that eventually becomes the same endostage as anaplastic carcinoma. Radical surgery is needed in such cases initially, although making a differential diagnosis between well- and undifferentiated carcinoma is extremely difficult. Urgent treatment of these diseases consists of ensuring that the airway remains open to improve quality of life, but does not include radical treatment. Stent insertion is one adequate method for the urgent treatment of respiratory disturbance caused by tumor compression. Malignant lymphoma frequently develops from Hashimoto's thyroiditis. Immediately after making an accurate pathologic diagnosis, chemotherapy and/or radiation therapy are effective in reducing enlarged goiters rather than surgical management.

Emergencies↗

Increased incidence of thyroid disease among men with hypergonadotropic hypogonadism.

An association between hypothyroidism and hypogonadism has been described in the syndrome of autoimmune polyglandular failure and in Klinefelter's syndrome. The incidence of thyroid disease among males with hypogonadism was evaluated. Patients were divided into those with hypergonadotropic hypogonadism (Group I; n = 19) and those with isolated hypogonadotropic hypogonadism (Group II; n = 17), according to their serum concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone. Nine cases of thyroid diseases were encountered in Group I; these included benign and malignant thyroid tumors, hypothyroidism due to Hashimoto's thyroiditis, and hypothyroidism due to amiodarone therapy. Only one case of thyroid disease (hypothyroidism due to Hashimoto's thyroiditis) was found in Group II (p less than 0.01). Patients of Group I were also significantly older than patients of Group II (51 +/- 4 versus 37 +/- 4 years; p less than 0.01); and patients with thyroid diseases were also older than those without thyroid disorders (60 +/- 6 versus 43 +/- 6 years, p less than 0.1). It is concluded that older subjects with hypogonadism and long-term elevation of levels of serum gonadotropins should undergo careful evaluation of thyroid gland morphology and function.

Adult↗

Thyroid disease in pregnancy.

Maternal, fetal, and neonatal thyroid physiology are discussed. Moreover, this article serves as a review of the more common thyroid diseases that are encountered during pregnancy and the postnatal period, their treatments, and their potential effects on pregnancy.

Adaptation, Physiological↗

[Detection of thyroid stimulating antibodies and TSH binding inhibitor immunoglobulins in patients with thyroid diseases and its clinical applications].

Thyroid stimulating antibodies (TSAb) and TSH binding inhibitor immunoglobulins (TBII) were assessed in patients with thyroid diseases. The activity of TSAb and TBII was significantly higher in patients with untreated Graves' disease (GD) as compared with that in patients with remitted GD and Hashimoto's thyroiditis, while the latter two groups had higher TSAb and TBII activity than patients with thyroid adenoma or control subjects. Of 24 patients with untreated GD, TSAb and TBII were detected in 22 and 19 respectively. The positive rates of TSAb and TBII in patients with remitted GD or Hashimoto's thyroiditis were 0.48 and 0.44 or 0.231 and 0.615. Both TSAb and TBII were negative in patients with thyroid adenoma or controls. No statistical correlation was found between TSAb and TBII activity, suggesting the coexistence of heterogeneous populations of TSH receptor antibodies.

Adenoma↗

[Thyroid biopsy in the auto-immune thyroid diseases].

There are three types of thyroid biopsy, fine needle biopsy, large needle biopsy and open biopsy. The aim of thyroid biopsy is not the diagnosis of auto-immune thyroid diseases itself, but the differential diagnosis of coexisting nodular goiter. Though fine needle aspiration biopsy cytology(FNABC) is a safe and valuable method, there is a limit. Large needle biopsy has small part for thyroid field. In case of malignant lymphoma or anaplastic carcinoma, the open biopsy is recommended. By using ultrasonic guide technique, the accuracy of ABC has come to high. Immunohistochemical method or molecular biological technique are now available.

Autoimmune Diseases↗

The value of ultrasonography in predicting autoimmune thyroid disease.

Ultrasonography (US) may demonstrate a diffuse reduction in thyroid echogenicity (low-amplitude echoes) in autoimmune thyroid disease (AITD), which includes chronic lymphocytic thyroiditis and Graves' disease, as well as in subacute thyroiditis. The reported occurrence of this finding in AITD varies from 19% to 95%. To assess the validity of diffuse reduction in thyroid echogenicity as a predictor of AITD, 3,077 patients referred for US of the thyroid were examined prospectively with regard to reduced versus normal thyroid echogenicity. The most frequent reasons for referral were goiter, thyroid dysfunction, neck discomfort, and/or difficulty in swallowing. Ultrasonography demonstrated diffuse reduction in thyroid echogenicity in 485 patients. Of these, 452 patients had available records of fine-needle aspiration biopsy (FNAB), and were included in the study. From the remaining patients, with normal thyroid echogenicity, 100 consecutive patients were selected as controls. In 411 of the 452 study patients (90.9%) there was at least one laboratory finding consistent with possible AITD: cytology indicating lymphocytic thyroiditis, 287 of 363 patients (79.1%) with diagnostic specimens; elevated levels of peroxidase antibodies (TPOAb), 225 of 337 (66.8%); elevated thyrotropin (TSH) levels, 290 of 450 (64.4%); or low TSH levels, 79 of 450 (17.6%). The final diagnosis was: chronic autoimmune (Hashimoto's) thyroiditis in 352 patients; Graves' disease in 47 patients; subacute (granulomatous) thyroiditis in 7 patients; toxic nodular goiter in 3 patients; and toxic adenoma in 2 patients. In the remaining 41 patients, those without laboratory results consistent with AITD, the final diagnosis was colloid goiter in 37 and thyroid cancer in 4 patients. In the 100 controls, laboratory results were consistent with possible AITD in 14 patients: elevated TPOAb levels in 5 of 49 patients with retrieved antibody results; lymphocytic thyroiditis in 2 patients; elevated TSH levels in 2 patients; and low TSH levels in 2 patients. In these controls, the final diagnosis was: chronic autoimmune thyroiditis in 7; toxic nodular goiter in 6 patients, and toxic adenoma in 1 patient. The corresponding positive and negative predictive values of reduced thyroid echogenicity as an indicator of AITD were 399 of 452 (88.3% [95% CI, 85% to 91%]), and 93 of 100 (93.0% [95% CI, 88% to 98%]), respectively. Thus, diffuse reduction in thyroid echogenicity was a valid predictor of AITD.

Adolescent↗

Autoantigens in thyroid diseases.

The autoantigens involved in autoimmune thyroid disease have now been extensively characterised, and the autoantibodies they evoke provide important aids to diagnosis, leading to early treatment of thyroid autoimmunity. The next stage in the puzzle is to determine towards which epitopes on the autoantigens the immune response is directed. We have already come a long way in the identification of immunodominant epitopes and have been able to identify one T cell epitope which has pathogenic capabilities. Identification of other T cell and B cell epitopes will help us understand the cell-mediated and humoral responses in greater detail and in time lead to more specific therapeutic intervention. A greater understanding of the mechanisms underlying one particular autoimmune disease will give us insights into other diseases, due to the belief that there may well be common underlying defects that, due to a multitude of factors, manifest as different diseases. The susceptibility factors in autoimmune thyroidits and autoimmune disease in general are very complex. A greater understanding is required of HLA associations and how particular peptides are presented in vivo. Are susceptible MHC types the ones capable of presenting the pathogenic peptides? Our major T cell thyroiditogenic epitope contains a T4 residue which accounts for over half the molecular weight of the peptide. Its structure is large and consists of a double benzene ring structure with four iodine atoms. It will be interesting to see how such a peptide can be presented and which residues bind T cell receptor or MHC. In summary we can say that autoimmune disease is due to a cocktail of factors which all contrive to tip the delicate balance of the immune system into an autoimmune state. HLA association may play a role in conferring an enhanced ability to select from a restricted repertoire of pathogenic epitopes, those epitopes perhaps only becoming available for presentation after interaction with environmental agents, whatever they may be. Following this, the normal regulation of self presentation and tolerance mechanisms break down and autoimmunity supervenes.

Amino Acid Sequence↗

A preliminary clinical application of sICAM-1 RIA in three kinds of thyroid disease.

OBJECTIVE: To examine serum levels of sICAM-1 from normal controls and patients with thyroid diseases (simple goitre, Graves' disease or Hashimoto's thyroiditis) with (125)I-sICAM-1 RIA established in our lab. METHODS: Using (125)I-sICAM-1 RIA, serum sICAM-1 levels of 400 healthy individuals as the normal group and 1020 patients with simple goitre (SG), Graves' disease (GD) or Hashimoto's thyroiditis (HT) were examined for a comporative chinical study. RESULTS: The serum level of sICAM-1 (x +/- s) in the normal group was 168.43 +/- 36.23 micro g/L. There was no significant difference between the normal and SG groups (P > 0.05), whereas the serum levels of sICAM-1 in autoimmune thyroid diseases (GD or HT) were higher than those in the normal or SG groups (P < 0.05, respectively). After GD patients received one of three medical treatments, their serum sICAM-1 levels decreased (P < 0.05). After GD patients were treated and their thyroid function decreased to normal, their serum sICAM-1 levels were lower than those in relapsed GD patients (P < 0.05). CONCLUSIONS: sICAM-1 RIA can be used to examine autoimmune thyroid diseases. Serum levels of sICAM-1 can be used as a parameter in diagnosing autoimmune thyroid disease and in evaluating the effects of therapy, drug administration or relapse in GD.

Adult↗