硒与自身免疫性甲状腺疾病

硒是人体必需的一种微量元素,以硒蛋白的形式发挥其生物学功能.自身免疫性甲状腺疾病(AITD)患者中,血清硒及硒蛋白水平存在异常.研究表明,硒缺乏可能通过降低多种硒蛋白酶的抗氧化活性、影响辅助性T细胞(Th) 1/Th2平衡、减弱巨噬细胞抗原识别和提呈作用等途径参与AITD的发生.补硒治疗对AITD患者病情缓解可能有一定的作用,但其安全性有待进一步的临床研究提供证据.     

硒与自身免疫性甲状腺炎的关系

自身免疫性甲状腺炎（ AITD）是以高甲状腺过氧化物酶抗体和甲状腺球蛋白抗体为特点的T细胞介导的甲状腺炎症反应。硒在体内作为谷胱甘肽过氧化物酶的活性辅助因子,可抑制甲状腺组织内的氧化反应,保护甲状腺滤泡上皮细胞免受氧化损伤,从而维护膜完整性。给予AITD患者补充硒治疗,可降低体内过氧化物酶抗体,减少自身抗体对甲状腺组织的破坏。     

从致病因素看自身免疫性甲状腺疾病的防治策略

自身免疫性甲状腺疾病(AITD)的发病受内在和外在多种因素的影响。X染色体失活偏移和生育可能是女性好发AITD的重要原因。甲状腺特异基因和免疫调节基因可能是AITD具有家族聚集现象的原因。最近的研究表明,吸烟、饮酒、硒、碘、维生素D、部分药物、感染和应激等因素都可能参与AITD的发病和进展。识别这些易感因素和环境因素,有助于临床医师及早发现并有效治疗AITD。     

自身免疫性甲状腺疾病和丙型肝炎

自身免疫性甲状腺疾病（AITD）和丙型肝炎均为常见病、多发病.近来丙型肝炎病毒（HCV）感染作为导致AITD发病的环境因素引起关注.一些研究发现甲状腺过氧化物酶抗体（TPOAb）和甲状腺球蛋白抗体（TgAb）阳性的患者或桥本甲状腺炎患者的抗-HCV抗体阳性率升高,慢性丙型肝炎患者的甲状腺功能减退症、TPOAb、TgAb的阳性率均增高.而另一些研究未发现丙型肝炎与AITD有关.     

硒与甲状腺

硒是生命必需的一种微量元素.硒在体内最主要的生物活性形式是硒代半胱氨酸,以硒代半胱氨酸为活性中心的蛋白质,称为含硒蛋白.硒主要的生物学作用是抗氧化和抗炎症反应.甲状腺内含有多种含硒蛋白,其中最重要的2种为谷胱甘肽过氧化物酶和脱碘酶,前者是甲状腺组织中重要的抗氧化剂,保护甲状腺细胞免受氧化应激损伤;后者是一组与甲状腺激素代谢相关的酶.硒缺乏与多种甲状腺疾病的发生发展有关.研究表明,低硒可加重自身免疫性甲状腺疾病、增加甲状腺癌发病风险以及促进甲状腺肿的发生发展等.补硒可能具有一定治疗作用,但补硒治疗目前尚不成熟,其有效性、安全性等尚需更多的临床药物研究提供理论依据.     

先天性腋毛缺失-自体免疫性甲状腺疾病的临床研究

随机搜集AITD83例、GD76例、亚甲炎21例、结甲64例和单甲32例,通过临床表现,甲状腺形态,甲状腺功能,甲状腺抗体及甲状腺超声检查进行分析、比较.结果 发现先天性单纯性腋毛缺失与AITD有极密切相关联系,伴腋毛缺失者高达92.77％,伴腋毛稀少者占4.82％.本症候群特点是:①主要见于30 ～ 50岁女性的；②...     

硒蛋白S/VIMP研究现状

硒蛋白具有抗氧化作用,与炎性疾病密切相关.硒蛋白S(SelS)即Tanis/VIMP,是新型葡萄糖调节蛋白,作为血清淀粉样蛋白A的受体将2型糖尿病和炎性反应联系起来,其基因多态性与炎性疾病相关.SelS可以保护细胞免受各种应激原诱导的损伤,调节细胞氧化还原平衡,参与错误折叠蛋白的处理和降解.SelS可能成为炎性疾病防治的突破口.     

自身免疫性甲状腺疾病的诊断和治疗

自身免疫性甲状腺疾病( AITD)是一组有相似遗传和免疫背景但临床表现迥异的疾病.促甲状腺激素受体抗体对Graves病(GD)和Graves眼病(GO)的诊断及预后判断有重要意义.甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体是自身免疫性甲状腺炎(AIT)的标志性抗体.GD的治疗仍以控制甲状腺功能亢进症为主,重度GO则需免疫抑制治疗.硒治疗是目前有循证医学证据的降低AIT患者TPOAb水平的方法.针对AITD病因的免疫治疗仍有待开发及循证医学证据支持.     

硒治疗自身免疫性甲状腺疾病的荟萃分析

目的 评价元素硒治疗自身免疫性甲状腺疾病(AITD)的有效性和安全性.方法 通过5个数据库(MEDLINE,Cochrane Central Register of Controlled Trials,中国期刊全文数据库,中国生物医学文献数据库和维普数据库)检索所有研究元素硒治疗AITD的随机对照试验(RCT).由两名研究者独立筛选文献、提取数据和进行结果的统计分析.将结果数据形式一致的同类临床试验的结果进行荟萃分析,对不能荟萃分析的数据进行描述性分析.共纳入30项RCT,涉及2 963例AITD患者.结果 (1)与对照组相比,硒治疗组桥本甲状腺炎患者甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)水平明显下降[标准化均数差(SMD)=-1.35,95％ CI:-1.93～-0.67,P ＜0.000 01和SMD=-0.92,95％ CI:-1.53～-0.31,P＜0.01].(2)硒治疗组与对照组相比,Graves病患者促甲状腺激素受体抗体(TRAb)水平降低(均数差=-2.5,95％ CI:-2.99～-2.01,P＜0.000 01).(3)元素硒可以降低Graves病患者血清游离T3(FT3)和游离T4(FT4)水平(均数差=-1.57,95％ CI:-2.56～-0.58,P＜0.001和均数差=-3.74,95％ CI:-5.65～-1.82,P=0.000 01),但对桥本甲状腺炎患者FT3、FT4和促甲状腺激素的作用不明显(P均＞0.05).结论 对AITD患者使用200 μg∥d的元素硒治疗3～12个月,能够有效降低抗甲状腺自身抗体(TPOAb,TgAb和TRAb)的水平,并具有较好的安全性.     

维生素D与自身免疫性甲状腺疾病

近年来较多的研究表明,维生素D具有调节免疫的特性,在一些自身免疫性疾病动物模型中表现出一定的防治作用.自身免疫性甲状腺疾病(AITD)是一种器官特异性自身免疫性疾病.研究证实,维生素D相关基因多态性与AITD相关,如维生素D受体基因、1α-羟化酶(CYP2781)基因、维生素D结合蛋白基因等.AITD患者存在维生素D缺乏,一些研究表明应用维生素D对AITD具有一定的防治作用.维生素D及其类似物防治AITD的可能机制在于它们能够调节AITD患者的细胞因子表达,并对其甲状腺细胞凋亡具有调节作用.因此认为,维生素D及其类似物在AITD的临床应用前景广阔.     

硒与甲状腺疾病

硒是人体所必需的一种微量元素,在机体中发挥多种生物学作用,如抗氧化、提高免疫功能、抗肿瘤等。硒和碘一样,参与甲状腺激素的合成、活化及代谢过程,从而影响甲状腺功能。在甲状腺肿、自身免疫性甲状腺疾病、甲状腺癌等患者中,血清硒的水平都存在异常。后者可能通过影响甲状腺滤泡上皮细胞内多种含硒基蛋白酶和(或)影响机体的免疫功能而导致甲状腺疾病的发生与发展。给与某些甲状腺疾病患者含硒制剂可以改善甲状腺功能,这为甲状腺疾病的治疗另辟蹊径。     

Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations

In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.     

肠道菌群与甲状腺稳态的关系

肠道菌群是人体胃肠道系统内一个数目庞大的微生物有机群体.近年发现,肠道菌群参与人体心血管、内分泌与代谢等系统生理功能的调节.甲状腺是人体内分泌系统的重要调节器官.碘离子是甲状腺激素分子结构中重要的构成元素;同时,微量元素硒在甲状腺激素T4向L的转化中起到必不可少的作用.肠道菌群的组成结构异常,不仅参与了自身免疫性甲状腺疾病的免疫调节,而且影响甲状腺激素相关物质如外源性甲状腺素、碘以及硒元素的吸收和代谢,进而影响甲状腺稳态.目前,对于肠道菌群与甲状腺稳态的关系,相关研究仅呈现冰山一角,更多、更深入的机制有待进一步探讨.     

Selenium and the thyroid gland: more good news for clinicians

The thyroid is the organ with the highest selenium content per gram of tissue because it expresses specific selenoproteins. Since the discovery of myxoedematous cretinism and thyroid destruction following selenium repletion in iodine‐ and selenium‐deficient children, data on links between thyroid metabolism and selenium have multiplied. Although very minor amounts of selenium appear sufficient for adequate activity of deiodinases, thus limiting the impact of its potential deficiency on synthesis of thyroid hormones, selenium status appears to have an impact on the development of thyroid pathologies. The value of selenium supplementation in autoimmune thyroid disorders has been emphasized. Most authors attribute the effect of supplementation on the immune system to the regulation of the production of reactive oxygen species and their metabolites. In patients with Hashimoto's disease and in pregnant women with anti‐TPO antibodies, selenium supplementation decreases anti‐thyroid antibody levels and improves the ultrasound structure of the thyroid gland. Although clinical applications still need to be defined for Hashimoto's disease, they are very interesting for pregnant women given that supplementation significantly decreases the percentage of postpartum thyroiditis and definitive hypothyroidism. In Graves' disease, selenium supplementation results in euthyroidism being achieved more rapidly and appears to have a beneficial effect on mild inflammatory orbitopathy. A risk of diabetes has been reported following long‐term selenium supplementation, but few data are available on the side effects associated with such supplementation and further studies are required.     

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.     

The pathogenesis of Graves' disease

The abnormally increased thyroid activity that is characteristic of Graves' disease is caused by immunoglobulins which specifically interact with the thyroid cell and stimulate it. Increases and decreases in thyroid activity in Graves' disease can be clearly related to rise and fall of these immunoglobulin-mediated activities. The level of immunoglobulin stimulatory activity can be used for prediction of the likelihood of neonatal Graves' disease and of recurrence of disease after cessation of treatment with antithyroid drugs. Investigation of patients with Graves' disease and their families has led to identification of particular human leukocyte antigens and genetically linked markers on immunoglobulins which both appear to incur increased susceptibility to certain autoimmune diseases. Differences in immune function, when compared with control populations, have been found in patients with these genetically linked markers. Protection against autoimmune disease is maintained by purposeful inhibition of any self-directed activity within each function of the immune system and by the controlling interaction of other immune functions. No single deficiency of immune function can be selected as giving the major risk of autoimmune disease, but rather a sum of relative defects resulting in an increased risk. In some patients with Graves' disease the self-protection mechanisms regain sufficient control of the immune functions to reduce the activity of the autoimmune disease, and the patient may achieve clinical remission. Often, however, there is evidence that abnormal immune activity directed against thyroid tissue has persisted with liability to recurrence of the Graves' disease.     

FOXP3与自身免疫性甲状腺疾病

叉状头／翅膀状螺旋转录因子（FOXP3）作为CD4^＋CD25^＋调节T（Treg）细胞表面的特征性标志,是Treg细胞发育和功能维持的关键因素,在维持机体免疫耐受和免疫应答稳态方面具有非常重要的作用。FOXP3基因突变可引发多种自身免疫性疾病,目前研究发现,FOXP3基因表达异常在自身免疫性甲状腺疾病的发病中发挥重要作用。     

The importance of selenium to human health

The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.     

催乳素与甲状腺疾病

催乳素(PRL)在哺乳动物的生长、繁殖及免疫调节中起重要作用.甲状腺疾病与高PRL血症关系密切,PRL可能参与了这些疾病的发生、发展.自身免疫性甲状腺疾病时,PRL可通过刺激辅助性T细胞分泌多种细胞因子而促进甲状腺自身抗体的产生.甲状腺功能减退时,雌激素、促甲状腺激素释放激素(TRH)及垂体血管活性肠肽(VIP)水平可能影响了PRL的分泌.甲状腺癌时PRL可能作为抗细胞凋亡因子或有丝分裂原而发挥作用.     

Why is the thyroid so prone to autoimmune disease?

The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients.