桥本甲状腺炎临床医师继续教育讲座

桥本甲状腺炎Hashimoto Thyroiditis,内容提要,一、概述二、诊断思路三、治疗措施四、预后五、最新进展和展望,什么是甲状腺炎？(Thyroiditis),指甲状腺组织发生变性、渗出、坏死、增生等炎性病理改变而导致的一系列临床病症,桥本甲状腺炎（Hashmoto Thyroiditis）,Dr. Hakaru Hashimoto (1881-1934).,Japanese surgeon.,1912年首次报告4例患者,1.Hahsimoto H (1912) Zur Kenntniss der lymphomatsen Vernderung der Shilddrse (Struma lymphomatosa). Arch Llin Chir 97:219248 2.Simmonds M (1913) ber lympnatische Herde in der Schilddrsse. Virchows Arch Pathol Anat Physiol 211:7389 3.Heineke (1914) Die chronische Thyreoiditis. Dtsch Z Chir 129:189220 4.Reist A (1922) ber chronische Thyreoiditis. Frankf Z Pathol 28:141200,日本甲状腺协会的LOGO,概述,日本学者Hashimoto于1912年首先报道又名：桥本病(Struma lymphomatosa ) Hashimoto disease 慢性淋巴细胞性甲状腺炎 Chronic lymphocytic thyroiditis 自身免疫性甲状腺炎之一 Chronic autoimmune thyroiditis,什么是桥本甲状腺炎？,桥本甲状腺炎Hashimoto thyroiditis,萎缩性甲状腺炎atrophic thyroiditis,无痛性甲状腺炎painless thyroiditis,产后甲状腺炎postpartum thyroiditis,自身免疫性甲状腺炎autoimmune thyroiditis AITD,自身免疫性甲状腺炎包括哪些？,桥本甲状腺炎Hashimoto thyroiditis,萎缩性甲状腺炎atrophic thyroiditis,慢性淋巴细胞性甲状腺炎chronic lymphocytic thyroiditis,无痛性甲状腺炎painless thyroiditis,产后甲状腺炎postpartum thyroiditis,自身免疫性甲状腺炎autoimmune thyroiditis AITD,自身免疫性甲状腺炎包括哪些？,桥本甲状腺炎的概念,自身免疫性甲状腺炎的一个类型由遗传及免疫因素所致表现为甲状腺肿大甲状腺功能减退或正常甲状腺出现增生淋巴细胞浸润及生发中心出现可有Hrthle细胞增生血中出现甲状腺球蛋白抗体（Tg-Ab)和微粒体抗体（TPO Ab),流行病学,HT是导致甲减的最常见病因，每年5%递增女性多见，女性：男性 9-10：1（1520倍）好发于30-50岁，产后、儿童流行率：23%（国外），0.4-1.5%（中国）发病率：0.8/1000(男),3.5/1000(女)。150/100 000（美国）0-0.5%（中国）高碘地区发病率增高占甲状腺疾病的20-25%以上数字按甲减计，若亚临床计，女性可达1/301/10,且年龄越大，发病率越高,Teng W, Shan Z, Teng X, et al.Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006, 354(26):2783-93.,病因和发病机制,遗传因素：HLA 欧美(DR3,4,B8),日本(B35)环境因素：高碘(Tg碘化抗原效力增强T细胞增殖）感染(Yersinia)自身免疫因素：辅助T细胞1型免疫(Th1) TgAb,TPO-Ab,TSB-Ab, Fas，ADCC（抗体依赖性细胞介导的细胞毒作用）,Teng W, Shan Z, Teng X, et al.Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006, 354(26):2783-93.,TSH-R,TRAb,TSH,TSAb,TSBAb,T G I,HCG,生理效应,TSH受体配体,病理作用,TSH受体与甲状腺功能,TSBAb,桥本甲状腺炎,End-stageHashimotothyroiditis* - Hypothyroidism* initially: goiter w/ inflammation,Graves diseasevvvHyperthyroidism,AUTOIMMUNE THYROID DISEASE(AITD),TSH,TPO-Ab与甲状腺滤泡,TPO,TPO-Ab,+,细胞毒作用,NK细胞,ADCC,细胞凋亡与HT,TPOAb,TPO特异性T细胞,淋巴因子(？),病理,肉眼：甲状腺弥漫性对称性肿大，稍呈结节状，质较韧，60g200g左右，被膜轻度增厚，与周围组织无粘连，切面呈分叶状，色灰白灰黄光镜：实质组织破坏、萎缩，大量淋巴细胞及不等量的嗜酸性粒细胞浸润、淋巴滤泡形成、纤维组织增生，有时可出现多核巨细胞,The specimen in Panel A shows typical changes of Hashimotos thyroiditis, including lymphoid follicles with germinal centers (G), small lymphocytes and plasma cells (P), thyroid follicles with Hrthle-cell metaplasia (H), and minimal colloid material (C).,Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646-2655.,内容提要,一、概述二、诊断思路三、治疗措施四、预后五、最新进展和展望,内容提要,一、概述二、诊断思路三、治疗措施四、预后五、最新进展和展望,诊断思路,临床特点实验室检查和特殊检查 诊断流程及诊断标准 鉴别诊断,临床特点,发病隐匿，早期无特殊表现颈部增粗的表现：咽部不适、局部压迫等甲状腺弥漫性、无痛性轻、中度肿大，质硬不对称，不光滑，有结节甲状腺功能异常的表现： 甲亢：心慌、出汗等（一过性甲亢或合并Graves 病） 甲减：怕冷、乏力、皮肤干燥、胸闷、心包积液等特殊表现：桥本脑病、不孕等合并症：淋巴瘤、其他自身免疫疾病等,甲状腺功能减退,甲状腺功能亢进,Identical male twins with Hashimotos thyroiditis were photographed at age 12. At age 8, they had the same height and appearance. During the intervening 4 years, small goiters developed and the growth of the twin on the right almost stopped. Biopsy indicated Hashimotos thyroiditis in each twins thyroid.,实验室检查和特殊检查,甲状腺功能：20%甲减，5%甲亢，余可正常自身抗体： TPoAb， TgAb甲状腺超声：甲状腺肿大呈弥漫性病变， 回声减低、不均核素扫描：不作为诊断常规FNAB：滤泡细胞嗜酸性变特征性改变, 背景较多淋巴细胞,实验室检查和特殊检查,TRIU：可低于正常也可高于正常,多数病人在正常水平 过氯酸钾排泌试验：60患者阳性,Pathology of Hashimotos thyroiditis. In this typical view of severe Hashimotos thyroiditis, the normal thyroid follicles are small and greatly reduced in number, and with the hematoxylin and eosin stain are seen to be eosinophilic. There is marked fibrosis. The dominant feature is a profuse mononuclear lymphocytic infiltrate and lymphoid germinal center formation.,Lymphocytes and Plasma cells.,Image Description: A dense infiltrate of plasma cells and lymphocytes with germinal center formation is seen in this thyroid. Cells of the individual colloid follicles often display abundant pink granular cytoplasm, which is referred to as oncocytic change, in this setting. These cells are referred to as Hurthle cells or oncocytes - these are metaplastic.,Fluorescent thyroid scan in thyroiditis. The normal thyroid scan (left) allows identification of a thyroid with normal stable (127I) stores throughout both lobes. A marked reduction in 127I content is apparent throughout the entire gland involved with Hashimotos thyroiditis (right).,诊断流程及诊断标准,典型的HT病例诊断并不困难，临床不典型病例容易漏诊或误诊Fisher于1975年提出5项指标诊断方案甲状腺弥漫性肿大,质坚韧,表面不平或有结节TGAb或TPOAb阳性TSH 升高甲状腺扫描有不规则浓聚或稀疏过氯酸钾排泌试验阳性5 项中有2 项者可拟诊为HT ,具有4 项者可确诊,诊断标准,甲状腺肿大+TPOAb+TRAb升高，诊断可成立甲状腺无肿大，抗体升高+甲减，萎缩性甲状腺炎,甲亢表现,甲状腺肿大,甲减表现,和或,和或,甲状腺功能TPoAb，TgAb,甲状腺超声或ECT,临床诊断HT,FNAB,确诊HT,临床表现典型，抗体升高,临床表现不典型，抗体显著升高,甲减伴甲状腺萎缩,临床诊断AT,FNAB,确诊AT,诊断流程,鉴别诊断,Riedel 甲状腺炎Graves病甲状腺癌甲状腺恶性淋巴瘤无痛性甲状腺炎,Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646-2655.,甲状腺炎鉴别诊断,病理鉴别,正常甲状腺,桥本病,亚急性甲状腺炎,单纯甲状腺肿,内容提要,一、概述二、诊断思路三、治疗措施四、预后五、最新进展和展望,内容提要,一、概述二、诊断思路三、治疗措施四、预后五、最新进展和展望,治疗原则,目前尚无法根治纠正继发的甲状腺功能异常和缩小显著肿大的甲状腺 一般轻度弥漫性甲状腺肿又无明显压迫症状,不伴有甲状腺功能异常者勿需特殊治疗,可随诊观察 对甲状腺肿大明显并伴有压迫症状者，采用L-T4制剂治疗可减轻甲状腺肿 如有甲减者，则需采用TH替代治疗 一般不宜手术治疗，除非考虑恶性可能或解除压迫,治疗方法,限制碘摄入量在安全范围（尿碘100200ug),可能阻止进展左甲状腺素的应用：可减轻甲状腺肿，但无阻病情发展的证据甲减必用甲肿用无甲减？,治疗方法,合并亚临床甲减者 （T3、T4正常，TSH升高TSH在两倍以上需要治疗TSH在两倍以内，评估危险因素老年人孕妇及不孕症者生长发育期的儿童应接受治疗,JAMA2004 Jan 14;291(2):228-38.,治疗方法,糖皮质激素：甲状腺迅速增大、伴疼痛有压迫症状时使用。强的松mg/day压迫症状明显，药物效果不佳，可手术治疗。但术后多数发生甲减,内科治疗,合并甲亢 一般不主张抗甲亢药物治疗若用，小剂量、短程、密切复查甲功对症治疗：