Chronic autoimmune thyroiditis and connective tissue system diseases

Autoimmune thyroiditis is often related to non-specific autoimmune organ diseases such as Rheumatoid Arthritis, Sj?gren's syndrome, systemic sclerosis, Systemic Lupus Erythematosus or polymyalgia rheumatica. Etiology of autoimmune diseases has not been clearly discovered yet. In many aspects, mechanisms leading to organ-specific autoimmune diseases are identic with mechanisms causing organ-nonspecific autoimmune disease. In many cases genetic disposal combined with specific antigens can be seen. Another possible factor in terms of endogenesis is genus. External factors are important too, such as undergoing infection, stress situations, exposion to ultraviolet radiation. Authors of this work summarize facts about chronic autoimmune thyroiditis and system connective tissue disease. The most literature supports more frequent appearance of these diseases, while the thyroiditis can appear both in clinical form with typical symptoms and in subclinical form.     

Restriction fragment length polymorphism analysis of T-cell receptor genes in inflammatory bowel disease

The etiology of inflammatory bowel disease is still unknown, but autoimmune phenomena are thought to play an important role. However, only a weak association between HLA or immunoglobulin allotypes and inflammatory bowel diseases has been noted. Recently, DNA markers (restriction fragment length polymorphism (RFLP) pattern) of T-cell receptor gene allotypes have been reported and shown to be linked to susceptibility to autoimmune disease. We investigated the T-cell receptor RFLP pattern in inflammatory bowel diseases. No linkage to the constant region alpha- and beta-chain markers was observed, and no differences in the frequencies of 'genoallotypes' was found between patients and normal blood donors.     

Association of seasonal allergic rhinitis is high in Graves' disease and low in painless thyroiditis.

Hashimoto's thyroiditis is thought to be a T-helper cell type 1 (TH1)-dependent disease, but it is not clear whether Graves' disease is T-helper cell type 2 (TH2)-predominant or not. TH1-predominant diseases are infrequently and TH2-predominant diseases are frequently associated with allergic diseases. We examined the prevalence of seasonal allergic rhinitis to Japanese cedar pollen, a typical TH2-associated disease, in patients with Graves' disease (n = 126), painless thyroiditis (n = 46) and Hashimoto's thyroiditis (n = 88), and compared them to healthy controls (n = 766). Gender and age distribution were not different among patient groups and healthy controls, except for the higher age of patients with Hashimoto's thyroiditis. The prevalence of seasonal allergic rhinitis was significantly high in patients with Graves' disease (42.9%, p < 0.05) and low in patients with painless thyroiditis (13.0%, p < 0.01) but was not different in patients with Hashimoto's thyroiditis (26.1%) compared to that of healthy controls (32.6%). When patients with painless thyroiditis were included in Hashimoto's thyroiditis group, the prevalence of seasonal allergic rhinitis was 21.6% and significantly different from that of healthy controls (p < 0.05). These data indicate that Graves' disease is TH2 predominant and painless thyroiditis is a TH1-predominant disease. Our findings suggest that the shift from TH2 toward TH1 immunogenesis may be important for achieving earlier remission of Graves' disease.     

Usefulness of Screening Program for Celiac Disease in Autoimmune Thyroiditis

We determined the prevalence of celiac disease in subjects with autoimmune thyroiditis compared with sick and healthy subjects. The screening was performed with IgA-class endomysium antibody, by indirect immunofluorescence using human umbilical cord as the antigenic substrate. Six of the 172 patients with autoimmune thyroiditis were found to be anti-endomysium positive (3.4%) and five of these underwent intestinal biopsy, which showed total villous atrophy. By contrast, 3 (0.75%) of 396 patients with nongastroenterologic malignancies and 10 (0.25%) of 4000 blood donors were found to have celiac disease. The prevalence of autoimmune diseases was significantly higher in patients with both celiac disease and autoimmune thyroiditis than in patients with autoimmune thyroiditis alone (P = 0.01). This study confirms that celiac disease is increased among patients with autoimmune thyroiditis. We suggest that these patients may benefit from screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders.     

Thyroid disease in Sjögren’s syndrome

From 1960 to 2007, an important number of patients with primary Sjögren’s syndrome (pSS) along with thyroid disease diagnosed by laboratory data and clinical presentation were reported. The most common thyroid disorder found was autoimmune thyroiditis and the most common hormonal pattern was subclinical hypothyroidism. The coexistence of SS and thyroiditis is frequent and suggests a common genetic or environmental factor predisposition with similar pathogenic mechanisms. pSS was ten times more frequent in patients with autoimmune thyroid disease and autoimmune thyroiditis was nine times more frequent in pSS. Therefore, SS should be studied in patients with thyroid disease and vice versa. Antigens are shared by both thyroid and salivary glands, which could be responsible for the association between both diseases. Immunogenetic studies had suggested that both diseases have a common genetic predisposition. pSS and thyroid disease patients were mostly women with positive antithyroglobulin, antiparietal cell and antithyroid peroxidase antibodies. Thyroid dysfunction is frequent in pSS patients and those prone to develop thyroid disorders are identified by thyroid-related autoantibodies or by rheumatoid factor and anti-Ro/SSA activity. Patients with pSS have an increased tendency to develop other autoimmune diseases. Hypothyroidism was the most common autoimmune disease developed in pSS patients during follow-up of 10.5 years. Lymphomas are also associated with SS and thyroiditis and a 67-fold increased risk for thyroid mucosa-associated lymphoid tissue (MALT) lymphoma and a 44-fold increased risk for parotid lymphoma is being attributed to autoimmune thyroiditis and pSS. It is suggested that immune mechanism deficiency is a causal factor for B cell lymphoma in pSS and autoimmune thyroid disease. Other studies are necessary to clarify the shared pathogenesis mechanism in SS and autoimmune thyroid disease and to understand this fascinating autoimmune association.     

Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.     

The various presentations of thyroiditis. Diagnostic considerations

The syndromes of thyroiditis include five disorders. Hashimoto's thyroiditis, the commonest, is an autoimmune disease whose principal manifestations are goiter and hypothyroidism. Subacute granulomatous thyroiditis is probably viral in origin and usually presents with a tender goiter. Subacute lymphocytic thyroiditis is of unknown pathogenesis, but the postpartum form may be autoimmune. Its principal manifestations are goiter and spontaneously reversible hyperthyroidism. Acute suppurative thyroiditis results from bacterial or fungal infection causing abscess. Riedel's struma, a disease of unknown cause, presents with a goiter and thoracic inlet obstruction. Thyroiditis may require differentiation from other diseases. The goiter may resemble that of Graves' disease or thyroid lymphoma. Thyroid nodules may resemble neoplasms. Hyperthyroidism may suggest Graves' disease or other hyperthyroid syndromes with low radioactive iodine uptake. Neck pain can also occur with some thyroid malignancies. Local abscess is usually infectious but may be undifferentiated thyroid carcinoma. Finally, hypothyroidism may be transient or permanent.     

Treatment of post-partum thyrotoxicosis

Thyrotoxicosis occurs more frequently during the post-partum period than at other times in women of childbearing age. Graves' disease and post-partum thyroiditis are two major causes of thyrotoxicosis in this period. The major task lies in differentiation of these two diseases in the post-partum period; since throtoxicosis caused by post-partum thyroiditis usually does not require treatment. The radioiodine uptake is elevated or normal in Graves' disease and low in post-partum thyroiditis, and TSH-receptor antibodies are positive in Graves' and negative in post-partum thyroiditis. Post-partum thyrotoxicosis due to Graves' disease may be treated with radioiodine but it requires radiation safety measurements for infant and is contraindicated if the mother is breast-feeding. Antithyroid drugs are the mainstay of the treatment of post-partum thyrotoxicosis. Recent investigations conclude that neither propylthiouracil nor methimazole cause any alterations in thyroid function and physical and mental development of infants breast-fed by lactating thyrotoxic mothers, and both can be safely administered in moderately high doses during lactation.     

Inflammatory diseases associated with Takayasu's arteritis

The etiology of Takayasu's arteritis is unknown; however, abnormality of the immune system plays an important role. To clarify a possible association between inflammatory diseases and Takayasu's arteritis, the authors retrospectively reviewed the medical records of 36 patients (2 men and 34 women), admitted to their department with this diagnosis. They found that 11 of the 36 patients had at least 1 other chronic or subacute inflammatory disease: Chronic tonsillitis, tuberculous lymphadenitis of the neck, chronic hepatitis B (infectious diseases); pyoderma gangrenosum, erythema nodosum (skin lesions); subacute thyroiditis, chronic thyroiditis (autoimmune diseases); Crohn disease, and ulcerative colitis (inflammatory diseases with unknown etiology). The present observation revealed a high prevalence of other inflammatory diseases in patients with Takayasu's arteritis and raises the possibility that Takayasu's arteritis may be associated with abnormality of the immune system activated by other inflammatory diseases, such as infection, autoimmune diseases, or inflammatory diseases of unknown origin.     

Activated (Ia+) T-lymphocytes and their subsets in autoimmune thyroid diseases: analysis by dual laser flow microfluorocytometry

Peripheral blood lymphocytes of patients with autoimmune thyroid diseases were studied using monoclonal antibodies reacting with cell surface antigens of activated T-cells (Ia+T), as well as their helper-inducer (Ia+TH/I) and suppressor-cytotoxic (Ia+TS/C) subsets, using two-color dye labeling and dual laser activated cell sorter analyses. Compared to normal subjects, hyperthyroid Graves' disease patients had significantly higher percent Ia+T values in association with an increase in percent Ia+TH/I as well as a reduction in percent Ia+TS/C; whereas patients with hypothyroid Hashimoto's thyroiditis as well as those with postpartum thyroiditis studied in the hyperthyroid phase also had a significant but lesser increase in percent Ia+T-cells, but their percent Ia+TH/I subset was significantly decreased, whereas the percent Ia+TS/C subset was increased; and patients with toxic nodular goiter or factitious hyperthyroidism (nonimmunogenic causes of hyperthyroidism) had a significant increase in percent Ia+T-cells without a significant difference in their Ia+T subsets or their ratios in comparison to controls. These studies demonstrated the feasibility of detecting Ia+T-cells and their subset characteristics using two-color dye labeling and dual laser flow microfluorocytometric methodology. In both the active and treated phases of Graves' disease, Hashimoto's thyroiditis, and postpartum thyroiditis, the percent Ia+T-cells was increased compared to normal subjects, with the highest values occurring in hyperthyroid Graves' disease. Furthermore, patients with hyperthyroid Graves' disease had the opposite changes in percent Ia+TH/I and Ia+TS/C subsets as compared to patients with either untreated hypothyroid Hashimoto's disease or the hyperthyroid phase of postpartum thyroiditis, suggesting that the pathogenic mechanisms involved in Hashimoto's disease and the destructive hyperthyroidism of painless thyroiditis are similar, and that they are both distinctly different from that of hyperthyroid Graves' disease.     

Environmental triggers of thyroiditis: hepatitis C and interferon-α

Autoimmune thyroid diseases (AITD) are postulated to develop as a result of a complex interplay between several genetic and environmental influences. The pathogenesis of AITD is still not clearly defined. However, among the implicated triggers (e.g. iodine, infections, medications), more recent data confirmed strong associations of AITD with the hepatitis C virus (HCV) infection and interferon-α (IFNα) therapy. Moreover, it is likely that HCV and IFN act in synergism to trigger AITD in patients. Indeed, approximately 40% of HCV patients develop either clinical or subclinical disease while receiving IFNα. Interferon induced thyroiditis (IIT) can manifest as non-autoimmune thyroiditis (presenting as destructive thyroiditis, or non-autoimmune hypothyroidism), or autoimmune thyroiditis [presenting with clinical features of Graves' disease (GD) or Hashimoto's thyroiditis (HT)]. Although not yet clearly understood, it is thought that IFNα can induce thyroiditis via both immune stimulatory and direct toxic effects on the thyroid. In view of the high frequency of IIT, routine screening and surveillance of HCV patients receiving IFNα is recommended to avoid the complications, such as cardiac arrhythmias, associated with thyrotoxicosis. In summary, IIT is a common clinical problem that can be readily diagnosed with routine thyroid function screening of HCV patients receiving IFN. The treatment of IIT consists of the standard therapy for differing clinical manifestations of IIT such as GD, HT, or destructive thyroiditis. However, anti-thyroid medications are not recommended in this setting since they can potentially be hepatotoxic.     

Prevalence and Relative Risk of Other Autoimmune Diseases in Subjects with Autoimmune Thyroid Disease

Background

Common autoimmune disorders tend to coexist in the same subjects and to cluster in families.

Methods

We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents.

Results

The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases (P = .005). Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative “clustering” of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases.

Conclusion

This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.     

The role of Fas-mediated apoptosis in thyroid disease

Recent evidence has emphasized the importance of apoptosis in the maintenance of tissue homeostasis and the pathogenesis of malignant and immune diseases. Autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease, as well as other autoimmune endocrine diseases, have been associated with dysregulation of apoptotic signaling pathways. In particular, dysfunction of the Fas apoptotic pathway or production of soluble factors including soluble Fas and soluble Fas ligand may be involved in the pathogenesis of these disorders. On the other hand, malignant thyroid cells may avoid Fas-mediated suicide possibly by expression of inhibitors of apoptosis and evade the immune system by inducing apoptosis on infiltrating lymphocytes. The delicate balance between cell proliferation and cell death through the Fas pathway may also play an important role in the control of thyroid cell mass and goitrogenesis. This review analyzes the current evidence on the role of Fas-mediated apoptosis in the pathogenesis of thyroid diseases including Hashimoto's thyroiditis, Graves' disease, thyroid cancer and goiter. However, the exact mechanisms involved in the regulation of apoptosis in thyroid disease remain unclear. Further investigation is needed.     

合并2型糖尿病的甲状腺疾病的管理

甲状腺疾病和2型糖尿病是内分泌代谢性疾病中最常见的两种疾病.糖尿病对甲状腺疾病会产生影响,糖尿病急症或严重感染可能会诱发甲状腺危象;甲状腺疾病及抗甲状腺药物或糖皮质激素等另一方面又影响到糖代谢,导致血糖波动甚至心血管风险增加,故合并2型糖尿病的甲状腺疾病患者病情较复杂.文章就合并2型糖尿病的甲状腺疾病包括甲状腺功能亢进...     

Detection of enterovirus RNA in postoperative thyroid tissue specimens

Context  Autoimmune thyroiditis is a very common disease. A genetic predisposition and environmental factors such as viruses are thought to contribute to the development of autoimmune thyroiditis. Enteroviruses, which are involved in other autoimmune diseases, are attractive candidates.
Objective  To investigate the presence of enteroviral genome sequences in postoperative thyroid tissues with lymphocytic infiltration, a common histological feature of thyroiditis.
Subjects and methods  Postoperative thyroid specimens collected prospectively from 86 patients were blindly frozen at –80 °C. The presence of EV genome sequences in the samples was blindly investigated by real-time RT-PCR. Clinical data, histological findings and levels of anti-TPO antibodies were collected.
Results  EV-RNA detection was positive (up to 36 cycles) or weakly positive (37–39 cycles) in 22 out of 86 patients (25%). EV-RNA (positive or weakly positive signal) was detected in 5 out of 27 (18·5%) thyroid specimens with lymphocytic infiltration, and in 17 out of 59 (29%) thyroid specimens without lymphocytic infiltration ( P =  0·4). No correlation was observed between EV-RNA detection in thyroid and the presence of anti-TPOAb. EV-RNA was detected in 3 out of 11 patients histologically diagnosed as thyroiditis (27·3%) and in 18 out of 74 patients (24·3%) with thyroid tumours (multinodular goitre, adenoma and carcinoma) ( P =  0·5) and in one patient with a normal thyroid.
Conclusion  EV-RNA can be detected in thyroid tissue from patients with various thyroid diseases, but there is no relationship between the presence of EV-RNA and thyroiditis. Further studies are needed to clarify the role of EV in thyroid diseases.     

Diagnosis and therapy of thyroiditis

In general a heterogeneous group of diseases of the thyroid gland which have a common histological picture of an inflammatory infiltration is referred to as thyroiditis. In the last years increasingly is paid attention to these diseases, since they apparently become more frequent and diagnostics and also therapy have improved. In a review the diagnostic and therapeutic possibilities are discussed, whereby the most frequent forms, the Hashimoto and de Quervain thyroiditis, are described in detail. The individual forms of thyroiditis and particularly the thyroid malignoma are to be distinguished differential-diagnostically.     

Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.     

Autoimmune thyroid disease (Graves' disease and hashimoto's thyroiditis) in two patients with Crohn's disease: case reports and literature review

An increased prevalence of the association between autoimmune thyroid diseases and ulcerative colitis has been suggested, however, not with Crohn's disease, as only 7 cases of thyroid disease coexisting with Crohn's disease have been reported. Herein, we describe 2 patients with Crohn's disease complicated with Graves' disease or autoimmune thyroiditis, and also review other cases with those complications. Some immunological processes are suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.     

Rheumatic manifestations of autoimmune thyroid disease: the other autoimmune disease

Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.     

Epidemiologic study of autoimmune thyroid disease in south Tunisia

In order to study incidence and prevalence of autoimmune thyroid diseases (AITDs), we studied a retrospective cohort of 1,079 patients explored in the department of Endocrinology of Sfax (south of Tunisia). The overall incidence of AITDs was 9.9%. Mean age was 39.6+15 years; sex ratio 5 F/1M. Graves' disease was the most frequent (45%). Atrophic thyroiditis was present in 32.2% of patients and Hashimoto's thyroiditis in 22.8%. The incidence of AITDs increased from 1990 to 2000 and by 2003 it had fallen to 67 cases per year. TPO antibody was present in two-thirds of patients with Hashimoto thyroiditis, and half of those with atrophic thyroiditis. TG antibodies were less frequent (one-third of patients). Association with other autoimmune diseases was noted in 6.3% of patients: type I diabetes mellitus, adrenal insufficiency and vitiligo. Statistic analysis did not disclose any association between autoantibody levels and thyroid dysfunction. There was an association between TG antibody and TSH levels among patients with Graves' disease and between TG antibody level and age in atrophic thyroiditis patients (p<0.05); a correlation was also noted between these antibodies and other autoimmune diseases (p=0.05). It is difficult to assess the frequency of ATD in the clinical setting. Characteristic features of AITDs in patients seen in south Tunisia were found to be similar to those described in the literature. Other more large-scale representative studies would be useful to establish the epidemiology of AITDs in Tunisia.