Immunoregulatory genes in autoimmune thyroid disease]

Autoimmune thyroid diseases (AITD) has a strong genetic basis. Although several candidate genes have been studied, the AITD causing genes are still unknown. Major candidate immune regulatory genes include human leukocyte antigen (HLA) gene, Ig heavy chain genes, T cell receptor genes, IL-1 receptor antagonist gene, IL-1 alpha gene and cytotoxic T lymphocyte antigen-4 (CTLA-4) gene. The relation between HLA and AITD has extensively been studied. In addition, polymorphism of the 3'-untranslated region and codon 17 of the CTLA-4 gene has been reported to associate positively with AITD. However, no linkage analyses have showed positive relation between AITD and these candidate genes except for HLA.     

Animal models for autoimmune thyroid disease]

Animal models for chronic thyroiditis include (1) experimental autoimmune thyroiditis induced by immunizing rabbits or rodents with thyroid extracts or thyroglobulin and (2) spontaneous thyroiditis in certain species of rodents and chickens. For Graves' disease, no spontaneous animal models are reported. An animal model for Graves' disease has been developed by xenotransplantation of Graves' thyroid tissue plus autologous immune cells to immunodeficient mice. Another animal model for Graves' disease is made by immunizing TSH receptor-peptide or protein to mice. Animal models are very useful for studying etiology of autoimmune thyroid diseases, although no current animal models are satisfactory for human autoimmune thyroid disease.     

Clinical application of ultrasonography to the autoimmune thyroid disease]

US images can detects exactly the size of thyroid gland. B-mode images with high resolution USG shows fine structure of thyroid gland. Furthermore, recent progress of ultrasonography can clarify the vascularity of thyroid gland using 3D-images. The thyroid gland of Graves' disease shows diffuse and remarkably increased vascularity. On the other hand, that of destructive thyroiditis reveals hypovascularity in hypoechoic lesion. There is the possibility that ultrasonographic images is useful tool to clarify the pathogenesis of autoimmune thyroid disease.     

Postpartum autoimmune thyroid syndrome]

Thyroid dysfunction frequently (around 5%) occurs after delivery through immune rebound mechanism. More than half of the patients suffer from postpartum thyroiditis. Initially, patients have a thyrotoxic phase, later passing through euthyroidism to hypothyroidism and, finally, return to euthyroidism. After delivery, other forms of autoimmune thyroid dysfunction also occur, including Graves' disease, transient hypothyroidism without preceding destructive thyrotoxicosis, and persistent hypothyroidism. To include all these conditions, the term postpartum autoimmune thyroid syndrome is often used. To predict who will develop postpartum thyroid dysfunction, the measurement of anti-thyroid microsomal antibody (MCAb) during pregnancy is useful because 62% of subjects with positive MCAb show thyroid dysfunction after delivery.     

Celiac disease and autoimmune thyroid disease

Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders.     

Iodine responsive autoimmune thyroid diseases]

Iodine is an important element for the thyroid and regulates iodine accumulation, thyroid hormone synthesis and hormone release. As a result, dietary iodine deficiency is largely responsible for the production of T3 thyrotoxicosis. Supplemental iodine significantly elevated incidence of iodine induced hyperthyroidism in endemic goiter area. Even in normal iodine area, intake of iodine sometimes accelerates recurrence of hyperthyroid Graves' disease in antithyroid drug treated patients. In contrast, a possible role of iodine on Hashimoto's thyroiditis is not known. As a therapeutic means, excess iodide is used for rapid control of thyrotoxicosis and thyrotoxic crisis. Experimental studies indicated that excess iodide blocks thyroid hormone release by inhibiting thyroid stimulators. This blocking action is ascertained by measuring cAMP, colloid droplets formation and microscopic techniques. Excess iodide does induce hypothyroidism in Hashimoto's thyroiditis.     

甲状腺自身抗体在自身免疫性甲状腺疾病诊断中的应用价值

目的 探究甲状腺自身抗体在自身免疫性甲状腺疾病(AITD)诊断中的应用价值.方法 选择2019年5月至2020年5月我院收治的80例AITD患者作为AITD组,其中34例为桥本甲状腺炎(HT),46例为毒性弥漫性甲状腺肿(Graves病);另选取同期我院50例健康体检者作为对照组.比较各组的促甲状腺激素受体抗体(TRA...     

Ultrasonography of the thyroid gland in pregnancies complicated by autoimmune thyroid disease

Thyroid function and ultrasonographically determined thyroid volume were studied in nine pregnant women with diagnosed autoimmune thyroid disease at regular intervals during pregnancy and two months after delivery. The results were compared to the findings in ten healthy pregnant women. In ultrasound examinations seven of the patients showed definite morphological changes such as hypoechogeneity and inhomogeneity of the thyroid gland, which did not change during the course of pregnancy nor during the post-partum period of eight weeks. There were no morphological changes in the thyroid glands of the control group. The mean thyroid volume did not significantly change during pregnancy and after delivery in both the patient group and controls. The mean thyroid volume was smaller in the study group, with 7.55 ml (SD 6.01) compared to the controls with 11.29 ml (SD 5.61), a difference which was not statistically significant. Neither course of pregnancy nor fetal outcome was influenced by inactive autoimmune disease of the thyroid. © 1993 John Wiley & Sons, Inc.     

Fetal growth and autoimmune thyroid disease

To determine whether fetal and infant growth could influencesusceptibility to autoimmune disease in adults, the occurrenceof thyroid autoantibodies and autoimmune thyroiditis was studiedin 305 women, aged 60–71, born in Hertfordshire and forwhom details of birth weight, infant growth, and feeding wereroutinely recorded. Thyroglobulin autoantibody was detectedin 37% of the women, thyroid peroxidase autoantibody in 41%,and autoimmune thyroiditis, defined as biochemical or clinicalhypothyroidism in association with thyroid autoantibodies, in5.6%. The proportion of women with thyroglobulin and thyroidperoxidase auto antibodies fell with increasing birth weightbut was not related to weight at 1 year of age or the methodof infant feeding. The prevalence of both autoantibodies rosewith increasing adult body mass index but fell as the waistto hip ratio increased. These results demonstrate the importance of early environmentin determining the susceptibility to autoimmune thyroid disease.The contrasting effects of adult body mass index and waist tohip ratio on antibody prevalence could be explained by theirassociations with different hormonal environments.     

Serum interferon gamma levels in autoimmune thyroid disease

The lymphokine, interferon gamma (IFN gamma) is considered to play an important role in the development of autoimmune thyroid disease (AITD); the main source of IFN gamma has been shown to be CD4 cells when stimulated by soluble antigen. We have measured the serum IFN gamma concentration in 42 patients with AITD (24 Graves' disease and 18 Hashimoto's thyroiditis) and 9 normal control subjects, using a sandwich enzyme-linked immunosorbent assay (ELISA) (detectable limit, 1 IU/ml). One of normal controls, 14 of the 24 patients with Graves' disease, and 5 of the 18 patients with Hashimoto's thyroiditis had detectable IFN gamma levels. Patients with Graves' disease were found to have higher concentrations of serum IFN gamma (11.6 +/- 15.8 IU/ml, mean +/- SD) than normal controls (1.1 +/- 0.3 IU/ml). However, the values in patients with Hashimoto's thyroiditis (9.4 +/- 15.5 IU/ml) were not significant when compared to those in normal controls. Serum IFN gamma values in patients with AITD did not correlate with serum anti thyroid autoantibodies (antithyroglobulin, antithyroid microsomal antibody, or TSH binding inhibitory immunoglobulin activity) or with thyroid function. Thus, increased in vivo production of IFN gamma in Graves' disease as evidenced in these serum concentrations might reflect T cell activity, but does not appear to be an accurate reflection of intrathyroidal events.     

Diagnosis and treatment of autoimmune thyroid disease (ATD) complicated by pregnancy]

During pregnancy, distinguishing TBII-negative Graves' disease from HCG-related thyrotoxicosis is important. There has been no convincing evidence for any adverse effects of maternal hyper- or hypothyroidism, or thionamides transferred from the mother on fetal organogenesis. In Graves' disease, maintaining maternal free T4 within normal range with thionamides may be preferable to fetal euthyroidism when toxemia of pregnancy or glucose intolerance develops, since there is little evidence indicating fetal hypothyroidism due to maternal ingestion of thionamides can cause intellectual retardation. TBII and/or TSAb levels should be determined by the 3rd trimester in patients with a history of ablative therapy for Graves' disease, and in patients with primary myxedema, in order to predict or treat fetal hyper- and hypothyroidism.     

Genetic and environmental factors of autoimmune thyroid diseases]

There is a growing consensus that autoimmune thyroid diseases, similar to other autoimmune diseases, is multifactorial: both several genetic and environmental factors interact and produce the clinical phenotype of these disorders. Twin studies and familial aggregation, including clustering within families showed that they are complex diseases with a significant genetic component. Several genetic factors associated with autoimmune thyroid diseases susceptibility have been identified, including the HLA genes, cytotoxic T lymphocyte associated-4 (CTLA-4) gene, TSH receptor and other immunoregulatory genes. Regarding environmental factors, although multiple factors including infection, stress, sex steroids, pregnancy, aging and food, are known as factors precipitating autoimmune thyroid diseases, little progress has been achieved defining them. It will be paradoxically important to identify genetic factors to investigate environmental factors.     

Apoptosis in chronic obstructive pulmonary disease]

Apoptosis is a critical mechanism controlling cellularity in various tissues. It is so far unknown whether apoptosis plays a critical role in the pathogenesis and development of chronic obstructive pulmonary disease (COPD). However, recent evidence suggests that apoptosis may occur in vascular endothelial cells and/or alveolar epithelial cells in COPD lungs, thereby potentially contributing to lung tissue destruction seen in COPD. Apoptosis may also influence cellular infiltrates into the lung, another pathologic feature of COPD, because the survival of inflammatory cells such as neutrophils, lymphocytes, and macrophages are critically determined by the mechanism of apoptosis.     

Thyroid disease in autoimmune liver diseases]

It has been reported that autoimmune liver diseases, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis, complicate thyroid disorder. According to the Nationwide survey in Japan, hypothyroidism most of which are due to chronic thyroiditis was seen in both autoimmune hepatitis and primary biliary cirrhosis, at 12% and 5.8%, respectively. It is sometimes happen that the manifestation of thyroid disorder proceeds the symptoms of liver disease. Because middle-aged women preferably tend to suffer from both autoimmune liver disease and autoimmune thyroid disease, it is important that we should be concerned both diseases when we are making diagnosis in these patients.     

Assessment of serum dipeptidyl peptidase-IV levels in autoimmune thyroid disease

ObjectiveDecreased serum dipeptidyl peptidase-IV (sDPPIV) levels have been reported in patients with autoimmune diseases. However, few studies have analyzed the association between sDPPIV levels and autoimmune thyroid disease (AITD). This study aimed to evaluate the association between sDPPIV levels and three types of AITD: Graves’ disease (GD), Graves’ ophthalmopathy (GO), and Hashimoto’s thyroiditis (HT).MethodsPatients newly diagnosed with GD (n = 65), GO (n = 22), and HT (n = 27) and healthy individuals (n = 30) were recruited. Clinical characteristics and thyroid function data were collected. sDPPIV was measured using enzyme-linked immunosorbent assays.ResultsCompared with controls (786.3 ± 46.95), patients with GD and GO had significantly lower sDPPIV levels (662.2 ± 38.81 and 438.4 ± 31.78). Additionally, sDPPIV levels were negatively associated with antithyroid peroxidase antibody (r = −0.20) and antithyroglobulin antibody (r = −0.19), but there was no significant relationship between thyroid hormone and sDPPIV levels. GO cases were divided by proptosis with and without muscle thickening; sDPPIV levels were lower in the muscle thickening group than those in the without muscle thickening group. Logistic regression analysis showed that sDPPIV was negatively correlated with GO and GD.ConclusionssDPPIV concentrations were abnormal in patients with GD and GO, and reduced sDPPIV expression may be involved in the progression of GO and GD.     

Celiac disease occurring in a patient with hypoparathyroidism and autoimmune thyroid disease

Patients with an underlying autoimmune endocrine disorder are at an increased risk of developing other autoimmune diseases. We describe a patient with idiopathic autoimmune hypoparathyroidism who developed hyperthyroidism due to Graves disease and subsequently was diagnosed with celiac disease. Malabsorption of L-thyroxine was the only clue regarding the presence of celiac disease. This particular association of these three autoimmune disorders occurring in the same patient has not, to our knowledge, been previously reported. The presentation, investigations performed, and treatment provided are discussed and the literature pertaining to similar cases is reviewed.     

Immunological tolerance and autoimmune disease]

The immune system must remain tolerant to self-antigens so as not to destroy what it has evolved to protect. There appears several mechanism for this purpose; deletion, anergy, sequestration of autoantigen and active suppression. These mechanism cooperate, constituting a fail-safe system, although the strategy against each autoantigen is determined by the nature of the autoantigen, i.e., the amount, timing and location of the expression. Here, we review and discuss on the pathogenesis of autoimmune disease as a consequence of the breakdown of the surveillance network, based on the recent advances in immunology.     

维生素D与自身免疫性甲状腺疾病的研究进展

自身免疫性甲状腺疾病(AITD)是一种T淋巴细胞介导的器官特异性自身免疫性疾病,主要包括桥本甲状腺炎(HT)和Grave病(GD),其发病机制尚不明确,可能与遗传、环境及免疫等有关。维生素D除具有调节骨和钙磷代谢,防治骨质疏松外,近年研究发现维生素D可能通过影响T淋巴细胞的增殖与分化,参与免疫调节,维持免疫内稳态。本文综述维生素D与AITD相关性的研究进展,旨在为AITD的预防与治疗提供新的思路。