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Color Doppler measurement of blood flow in the inferior thyroid artery in patients with autoimmune thyroid diseases.

PURPOSE: The aim of the study is to find out whether the measurement of peak systolic velocity in the inferior thyroid artery (ITA) is a valuable parameter to differentiate autoimmune thyroid diseases (hyper-, normo- or hypofunctional) and to evaluate the efficacy of medical treatment. MATERIAL AND METHODS: The ITA of 31 patients (eight with Graves' disease, 23 with subclinical hypothyroidism) was examined with color Doppler and pulsed Doppler. The final diagnosis was obtained by cytology and by hormonal and antibodies assays. The patients were monitorized by ultrasound for a period of 8 months. RESULTS: In all the patients with Graves' disease the peak systolic velocity was always over 150 cm/s, while in other autoimmune thyroiditis the peak systolic velocity was within the normal range, and never exceeding 65 cm/s. In the first group, the measurement taken in the ITA showed also the efficacy of the pharmacological treatment earlier and more reliably than the color Doppler pattern obtained in the parenchyma. CONCLUSIONS: The color Doppler measurement of the ITA seems to be a promising technique with low-cost and easy approach. In our experience, the color Doppler of the ITA could have a clinical role in the differential diagnosis of diffuse thyroid diseases and in the follow-up of the Graves' disease during medical treatment.

Adolescent↗

Clinical and laboratory assessment of subclinical thyroid disease.

The availability of highly sensitive in vitro tests for the determination of the free fractions of thyroid hormones (FT3 and FT4) and TSH have allowed the identification of latent thyroid disorders (subclinical hyper- and hypothyroidism) where the clinical signs are minor or absent. The TSH determination is the most sensitive in vitro test to define the thyroid function. FT3 is the most suitable for the correct diagnosis of subclinical hyperthyroidism, while FT4 is diagnostic for subclinical hypothyroidism. In patients with acute or chronic non thyroid disease or in case of assumption of drugs which interfere with in vitro diagnostic tests, the interpretation may be difficult.

Female↗

Ion flux and Na+,K+-ATPase activity of erythrocytes and leucocytes in thyroid disease.

In hyperthyroidism, erythrocytes show decreased Na+,K+-ATPase activity, decreased [3H]ouabain binding capacity (an index of the number of sodium pumps) and decreased active sodium and potassium flux rates, with a high intracellular sodium concentration. As erythrocytes are non-nucleated and atypical cells, we have studied electrolyte status in thyroid disease using mixed leucocytes as well; the results obtained differed from those in erythrocytes. When compared with findings in healthy subjects, leucocyte Na+,K+-ATPase activity, [3H]-ouabain binding capacity, total and active rubidium (used instead of potassium) influx were all significantly increased in untreated hyperthyroidism and decreased in untreated hypothyroidism. In hyperthyroidism, there was also a decrease in plasma potassium, an increase in sodium efflux rate and efflux rate constant, but no significant changes in cell sodium and potassium concentrations. All these changes returned to normal in successfully treated patients. There was a significant correlation between these abnormalities of electrolyte status and thyroid disease status (as serum thyroid stimulating hormone and free thyroxine).

Adult↗

The immunoregulatory disturbance in autoimmune thyroid disease.

There is now considerable evidence for a genetically induced antigen-specific defect in suppressor T lymphocytes as the basis for AITD, derived from several laboratories and via different types of experimental techniques. In addition, there is now evidence for additive effects on reducing generalized suppressor T lymphocyte numbers and/or function by environmental factors as well as hyperthyroidism itself, and these effects would be superimposed upon the organ-specific defect. Such effects on generalized suppressor T lymphocyte numbers may act as precipitating and self-perpetuating factors, in Graves' disease at least. Presentation of the antigen by the thyroid cell via HLA-DR expression on its membrane does occur as a result of interferon gamma production by T lymphocytes. This in turn appears to be secondary to the initial specific immune assault and is not a primary inductive step. However, it may be important as an amplifying intermediate factor but cannot perpetuate the process in the absence of the underlying immune disorder. There is, however, no evidence for an underlying antigenic abnormality or stimulus in human autoimmune thyroid disease, and the initiating event would appear to be due to perturbation of the generalized immune system superimposed on the organ-specific abnormality. Variations in the serological and clinical expression of AITD would appear to depend on the severity of the original organ-specific disturbance in suppressor T lymphocyte function, plus the added factor of environmental influences playing upon generalized suppressor T lymphocyte function and numbers. Remissions in Graves' disease brought about by antithyroid drugs may well be via their effect on modulating the thyroid cell activity; this will then reduce thyrocyte-immunocyte signalling, allowing remission to occur in those patients with a partial organ-specific defect in suppressor T lymphocytes.

Animals↗

Angiogenesis in benign and malignant thyroid disease.

CONTEXT: Angiogenesis has been recognized as an important process contributing to the pathophysiology of many benign and malignant diseases. It is not surprising, therefore, that this complex process is proving to be an important regulator of both benign and malignant disease processes in the thyroid gland. This paper will review the general principles of angiogenesis and lymphangiogenesis, as well as the importance of the balance between angiogenic stimulators and inhibitors in the normal thyroid gland. We will also review how this balance is disturbed in benign and malignant thyroid conditions. Finally, we will address the role manipulation of this process may play in the development of novel treatment strategies for diseases of the thyroid. OBJECTIVE: To review the literature concerning the role of angiogenesis in the thyroid gland. CONCLUSIONS: Angiogenesis is an important process which has been shown to be involved in the pathophysiology of benign and malignant diseases of the thyroid gland. Manipulation of this process holds great promise for the development of novel treatments for these disorders. As the mechanisms regulating angiogenesis in the thyroid become increasingly clear, researchers will come ever closer to turning this promise into clinical reality.

Animals↗

Thyroid disease in pregnancy.

It has long been known that there is a close relationship between pregnancy and the thyroid gland-iodine insufficiency, goitre development, and abnormal thyroid function are common during pregnancy. Autoimmune thyroid disease and thyrotoxicosis may also affect pregnant women, and their management requires the understanding of the interaction between the neuroendocrine and immune systems. In this article, the physiology of the thyroid gland during pregnancy and the interrelationship between pregnancy and autoimmune thyroid disease are discussed.

Journal Article↗

Frequent detection of thyroid peroxidase-specific IgG+ memory B cells in blood of patients with autoimmune thyroid disease.

Centrocytes in germinal centers on selection differentiate into plasma cells and/or memory B cells. Cells that have acquired autoreactivity by somatic mutation generally fail to undergo positive selection and die by apoptosis. Presence of isotype-switched high-affinity autoantibodies in serum of autoimmune patients suggests that autoreactive plasma cells eventually emerge from a germinal center reaction. Currently, it is still unclear to which extent the same is true for autoreactive memory B cells. To address this question, we have analyzed whether IgG-bearing memory B cells with specificity for thyroid peroxidase (TPO) can be found in blood of patients with autoimmune thyroid disease and in normal blood donors. Autoreactive TPO-specific IgG+ memory B cells were identified using a previously described assay combining two-step immunomagnetic enrichment with flow cytometric detection. Autoreactive IgG+ memory B cells were found in 65% of the patients with autoimmune thyroid disease and in 17% of normal blood donors; 40% of the latter had no detectable TPO-specific IgG in the serum. The specificity of enriched TPO-specific IgG+ memory B cells was confirmed by in vitro proliferation and differentiation into antibody-secreting cells at limiting dilution and analysis of the supernatants for the presence of TPO-specific IgG. Detection of TPO-specific IgG+ memory B cells in most patients with clinically manifested autoimmune thyroid disease and few normal blood donors may argue for a role of circulating memory B cells in onset of disease.

Adolescent↗

Autoimmune thyroid disease accompanied by recurring episodes of painful thyroid ameliorated by thyroidectomy.

A 71-yr-old female initially presented with clinical and biochemical hyperthyroidism with high TSH binding inhibitory immunoglobulin (TBII) and anti-thyroid peroxidase antibody (TPOAb) titers. Histological findings of the thyroid revealed hyperplasia with a focal germinal center, indicating Graves' disease and mild focal chronic thyroiditis. Four episodes of painful and tender thyroid occurred over the next 2 yr accompanied by acute inflammatory reactions. The first episode that developed while the patient was in a hyperthyroid state was soon followed by hypothyroidism associated with further increases in anti-thyroglobulin antibody (TGAb) and TPOAb titers. The subsequent 3 episodes occurred during the hypothyroid state, when the TGAb titer progressively increased with each episode. We performed subtotal thyroidectomy to prevent further episodes. Specimens obtained at thyroidectomy showed that extreme fibrosis had replaced the thyroid parenchyma with collapsed follicles and moderate lymphocyte infiltration. No further episodes occurred after thyroidectomy, and during a 3-yr follow-up period, TBII and thyroid-stimulating antibody (TSAb) disappeared and TGAb and TPOAb titers decreased. This case report provides further evidence supporting the notion that thyroid epithelial destruction progresses during relatively short periods of recurrent painful thyroid and that thyroidectomy helps patients affected by this condition that are unresponsive to other treatment strategies.

Aged↗

[Autoimmune thyroid diseases--cell mediated immunity].

Some aspects of cellular immunity of autoimmune thyroid diseases are reviewed. Changes in number subpopulations and functions of T-lymphocytes in Graves' and Hashimoto's diseases with special attention to leucocyte migration inhibition test are described. Correlation between cellular and humoral immune factors is discussed.

Antibody Formation↗

The codon 620 single nucleotide polymorphism of the protein tyrosine phosphatase-22 gene does not contribute to autoimmune thyroid disease susceptibility in the Japanese.

The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD), and Hashimoto's thyroiditis (HT) is largely unknown. However, genetic susceptibility is believed to play a major role. The lymphoid tyrosine phosphatase (LYP), encoded by the protein tyrosine phosphatase-22 (PTPN22) gene, is a powerful inhibitor of T cell activation. Recently, a single-nucleotide polymorphism (SNP), encoding a functional arginine to tryptophan residue change at PTPN22 codon 620 in Caucasians has been shown to be associated with GD and other autoimmune diseases. We have used a polymerase chain reaction (PCR)-restriction fragment (XcmI) assay to examine genotypes at the codon 620 polymorphism in 334 unrelated patients with AITD and 179 controls. None of the patients with AITD and controls had the tryptophan allele. These data suggest that the codon 620 polymorphism of the PTPN22 gene does not have a causal role for AITD in the Japanese. However, we cannot exclude the PTPN22 region as harboring another susceptibility locus for AITD in linkage disequilibrium with the Trp/Arg SNP.

Asian People↗

Thyroid disease in the elderly.

As people in our society live longer, it is important for clinicians to know more about problems commonly seen in the elderly. Thyroid problems are especially important to understand because they do occur with rather high frequency, and their mode of presentation is frequently different from those seen in younger patients. The thyroid gland does undergo certain age-related changes in anatomy and physiology, but overall the thyroid is able to produce a normal amount of thyroid hormone throughout the years. Hypothyroidism is frequently difficult to diagnose in the elderly, because many of the symptoms of hypothyroidism can easily be confused with symptoms of aging. When hypothyroidism is looked for in large population studies of elderly patients, the incidence varies from 1% to as high as 17%, with women being more commonly affected than men, and subclinical hypothyroidism being more common than overt hypothyroidism. Virtually all cases of hypothyroidism are due to autoimmune thyroid disease, with most patients having measurable titers of thyroid autoantibodies. The therapy of hypothyroidism is done with extreme caution, as older patients are frequently very sensitive to the effects of excess thyroid hormone. In addition, the metabolism of thyroid hormone slows down with age, making the full replacement dose much less in an older patient than in a younger one. Hyperthyroidism is also quite common, occurring in from 0.5% to 3% of all elderly patients. The presentation is frequently atypical, as patients often lack the hyperdynamic symptomatology and instead have a more sedated, apathetic presentation. Weight loss and cardiac symptoms frequently predominate, and the presence of a goiter is frequently absent, making the diagnosis less obvious than in a younger patient. Therapy is usually radioactive iodine, after an adequate course of antithyroid drugs, to render the patient euthyroid. Thyroid nodules do occur with increasing frequency in the elderly, but most of them are not malignant. Fine-needle aspiration for cytology is very helpful in determining which patients should be referred for surgery. Well-differentiated cancers do predominate, but their course is frequently less predictable than in younger patients. Lymphoma of the thyroid and undifferentiated cancers do occur with increasing frequency in the elderly. Multinodular goiter, usually of longstanding, is frequently seen in elderly patients, and thyroid hormone suppressive therapy not only is not indicated but may contribute to exogenous hyperthyroidism.

Aged↗

[Puncture cytologic diagnosis of thyroid diseases: potentialities and limitations of the method].

The role of fine-needle aspiration biopsy in cytological diagnosis of thyroid diseases is reviewed. This method allows not only to determine whether the condition is benign or malignant, but also diagnose nosological variants of thyroid pathology. The difficulties lie in the diagnosis of combined thyroid pathology, differential diagnosis of follicular adenoma with follicular carcinoma, lymphoma with autoimmune thyroiditis, follicular tumor with adenomatous goiter.

Adenocarcinoma, Follicular↗

[Studies on the production of anti-thyroglobulin autoantibody in vitro in patients with autoimmune thyroid diseases].

We have studied the production of anti-thyroglobulin autoantibody (ATA) in vitro in patients with autoimmune thyroid diseases to test the hypothesis that these patients have a deficiency in T suppressor cell function. Lymphocytes were cultured for 7 days with or without pokeweek mitogen (PWM). ATA and IgG concentrations in the culture supernatant were measured by enzyme immunoassays. In 15 patients with Hashimoto's disease (HD), ATA production in vitro was detected. These patients had very high titers of ATA in their sera. In 5 patients with HD who had low ATA titers in their sera, and in 20 normal individuals, ATA production was not detected. Therefore, ATA production in vitro was positively correlated with ATA concentration in the serum. The stimulating effect of PWM was not clear in ATA production, but apparent in IgG production. In another experiment, concanavalin A (Con A) was used to induce T suppressor cells, and the activities of these cells were detected in the PWM driven culture system of fresh lymphocytes. In 5 patients with HD, ATA production was inhibited by Con A induced autologous suppressor cells. And the degree of suppression in ATA production was the same as that seen in IgG production. Furthermore, in 2 patients we have compared the suppressing effect on ATA production of autologous Con A activated cells with that of normal Con A activated cells. There was no difference between the two. Therefore, we could not demonstrate the defect in Con A induced, non-specific suppressor cell activities in patients with HD. Finally, we cultured the lymphocytes with the specific antigen, Tg (10-100 micrograms/ml). The responses of ATA production to Tg were variable among patients, which may suggest the variety of the status of presensitized lymphocytes or antigen specific suppressor cells. Further studies are necessary to elucidate the antigen specific T cell function in autoimmune thyroid diseases.

Autoantibodies↗

Incidental detection of familial medullary thyroid carcinoma by calcitonin screening for nodular thyroid disease.

Serum calcitonin screening has recently been found to be a useful supplement to fine-needle aspiration biopsy, ultrasound and radionuclide imaging in the evaluation of thyroid nodules. We describe a case where introduction of routine calcitonin screening in nodular thyroid disease led to the detection of a family with medullary thyroid carcinoma. The benefits and problems of basal and stimulated serum calcitonin testing and ret-proto-oncogene mutation studies are exemplified and we discuss the appropriate use and interpretation of these tests. We conclude that routine basal serum calcitonin measurement in nodular thyroid disease and thoughtful use of ret-mutation analysis is cost-effective in detecting medullary thyroid carcinoma and multiple endocrine neoplasia type II.

Adult↗

Heterogeneity of the thyroglobulin epitopes associated with circulating thyroid hormone autoantibodies in hashimoto's thyroiditis and non-autoimmune thyroid diseases.

We previously implicated TG leakage from fine-needle aspiration biopsy (FNAB) as responsible for circulating thyroid hormone autoantibodies (THAb). However, THAb were not always associated with TGAb. In the literature these negative findings have been interpreted against a role of TG as the antigen for THAb. To evaluate the TGAb status more fully and to gain information on TG epitopes involved in THAb development, we measured: 1) TGAb with an independent hemagglutination assay (HA), and 2) epitope specificity in a competitive ELISA using 2 monoclonal Abs (mAb) against TG: mAb 42C3 and mAb 134C2. MAb 42C3 recognizes a cross-reactive iodinated epitope, whereas 134C2 is specific for human TG. We tested 12 Hashimoto's thyroiditis (HT) and 35 non-HT patients sampled prior to, 1 and 3 months after FNAB. We found that, irrespective of thyroid disease or post-FNAB THAb status, certain patients previously classified as TGAb negative by IRMA tested TGAb positive by HA or by competition ELISA and vice versa. A post FNAB positive response to the 42C3 iodinated epitope in only one THAb IgM-T4+ve HT and a few THAb negative non-HT patients was observed. Furthermore, we observed that the 3 non-HT patients who expressed IgM-T3 THAb failed to bind either TG-mAb epitope. We conclude that a single TGAb assay is not sufficient to define the TGAb status, which can be achieved reliably only by using multiple TGAb assays. In addition, the TG-iodinated epitope recognized by 42C3 is not a major epitope in post-FNAB THAb, and the T3-epitope involved in THAb remains distinct from the mAb epitopes. In light of recent data in the literature, we further suggest that the responsible epitopes are more likely to be expressed in leaked TG fragments, rather than leaked intact TG.

Antibodies, Monoclonal↗

[Level of neopterin in blood serum in selected thyroid diseases].

The aim of our study was to estimate the levels of neopterin (NTP), anti thyroglobulin antibodies (ATG), anti thyroid microsomal antibodies (MAB), immunoglobulins (IgG, IgA and IgM) and creatinine in the serum of patients with thyroid diseases. The clinical material consisted of 71 patients (64 women and 7 men) with non-toxic nodular goitre (30 persons), neoplasms (33 persons: 22 with thyroid adenoma and 11 with thyroid carcinoma) and thyroiditis (8 persons). The control group consisted of 30 healthy women. In studied groups the mean serum levels of NTP and creatinine were in normal range. The highest levels of NTP were found in patients with thyroid carcinoma (7.14 +/- 5.95 nmol/l) and with non-toxic nodular goitre (5.13 +/- 3.57 nmol/l). It was statistically significant in comparison with control group (p < 0.05). Anti thyroglobulin antibodies (ATG) were detected in serum of 36 patients (50.7%) and anti thyroid microsomal antibodies (MAB) were in serum of 28 patients (39.4%). Mean levels of these autoantibodies were significantly higher than in control group (< 0.05). In patients with autoantibodies (ATG and/or MAB) mean serum level of NPT was significantly higher than in patients without these autoantibodies (p < 0.05). We did not find a significant correlation between the level of NPT and the levels of ATG and MAB.

Adolescent↗