桥本氏甲状腺炎2-cme课件

1、桥本甲状腺炎Hashimoto Thyroiditis刘超南京医科大学第一附属医院内容提要一、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、最新进展和展望概述日本学者Hashimoto于1912年首先报道又名：桥本病 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 chronic autoimmune thyroiditis Dr. Hakaru Hashimoto 分型特点1型自身免疫性甲状腺炎（桥本病1型）1A 有甲状腺肿甲状腺功能正常

2、促甲状腺激素（TSH）水平正常，常有抗甲状腺球蛋白（Tg）和甲状腺过氧化物酶（TPO）抗体存在。1B 无甲状腺肿2型自身免疫性甲状腺炎（桥本病2型）2A 有甲状腺肿（经典的桥本病）持续存在甲减TSH水平升高，常有抗Tg和TPO抗体存在，一些2B型伴有阻断型TSH受体抗体存在。2B 无甲状腺肿（原发性粘液性水肿，萎缩性甲状腺炎）2C 暂时加重的甲状腺炎可能开始表现为暂时的甲状腺毒症（血清甲状腺激素升高伴有甲状腺摄碘率减低），然后经常出现暂时性甲减。但患者也可表现为暂时性甲减而没有之前的甲状腺毒症。抗Tg和TPO抗体存在。3型自身免疫性甲状腺炎（Graves病）3A甲状腺功能亢进的Graves病甲

3、状腺功能亢进或甲状腺功能正常而TSH被抑制，有刺激型TSH受体抗体存在，抗Tg和TPO抗体也常存在。3B甲状腺功能正常的Graves病3C甲状腺功能减低的Graves病眼病伴有甲状腺功能减低，有诊断水平的刺激型或阻断型TSH受体抗体可被发现，常有抗Tg和TPO抗体存在。自身免疫性甲状腺炎的分类 Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348:2646-2655. 病因和发病机制遗传因素：HLA 环境因素：高碘自身免疫因素：Fas，ADCCTeng W, Shan Z, Teng X, et al.E

4、ffect of iodine intake on thyroid diseases in China. N Engl J Med. 2006, 354(26):2783-93. Figure1.The TAZ10 transgenic mouse model10 and the immunological basis for Hashimoto thyroiditis.(a) Thyroid follicle and the location of the major thyroid autoantigens: thyroid peroxidase (TPO), thyroglobulin

5、(Tg) and the thyroid-stimulating hormone receptor (TSHR). (b) Immunological mechanisms leading to the spectrum of human autoimmunity with differing pathological and clinical characteristics. Graves hyperthyroidism is caused directly by TSHR autoantibodies that activate the TSHR. Hypothyroidism in Ha

6、shimoto thyroiditis is associated with autoantibodies to TPO (and less commonly to Tg), but the relative contributions to thyrocyte damage by autoantibodies, TPO-specific T cells and/or cytokines is unknown. The TAZ10 model of Quaratino et al. shows that TPO-specific T cells are sufficient to induce

7、 the histopathological and clinical features of Hashimoto disease. However, how CD8+ T cells and cytokines secreted by CD4+ T cells contribute to destruction has yet to be determined. T3, triiodothyronine.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

8、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, Farwel

9、l 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、局部压迫等甲状腺功能异常的表现： 甲亢：心慌、出汗等 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Identical male twins with Hashimotos thyroiditis were photo

10、graphed 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RAIU：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Pat

11、hology 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

12、 lymphocytic infiltrate and lymphoid germinal center formation. 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

13、 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 reduct

14、ion 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 项者可确诊诊断流程及诊断标准 甲状腺肿大、韧、有时峡部大或不对称、或伴结节临床凡患者具有典型的临床表

15、现，只要血中TGAb或TPOAb阳性，就可诊断表现不典型者，需要有高滴度的抗甲状腺抗体测定结果才能诊断，即两种抗体用放免法测定时，连续2次结果大于或等于60以上同时有甲亢表现者，上述高滴度的抗体持续存在半年以上甲状腺穿刺活检方法简便，有确诊价值超声检查对诊断本病有一定意义Diagnosis of Hashimotos thyroiditis (chronic thyroiditis) 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HTFNAB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ATFNAB确诊AT鉴别诊断

16、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. 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措施治疗原则内科治疗手术治疗中医中药局部治疗刘晓云, 刘超, 覃又文, 等. 慢性淋巴细胞性甲状腺炎的局部免疫调节治疗J. 江苏医药, 2007, 33(2):124-126刘晓云, 段宇, 刘超. 桥本甲状腺炎免疫治疗的研

17、究进展J. 医学综述,2006,12(6):344-346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内科治疗病因治疗属于自身免疫性疾病一般不主张全身应用糖皮质激素等免疫抑制药物可局部使用（见后）内科治疗合并临床甲减者 药物：干甲状腺片、L-T4剂量：干甲状腺片20-80mg，L-T4 25-100g原则：小剂量开始，逐步加量，至TSH

18、下降，甲状腺缩小。老年或有缺血性心脏病者，更小剂量用起始，增加剂量应缓慢每6周复查甲状腺功能（妊娠每4周）内科治疗合并亚临床甲减者 TSH在两倍以上需要治疗，同前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. 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：心得安等不用131I治疗及手术治疗手术治疗一般不主张手术治疗有以下情况考虑手术高度怀疑恶性病变压迫明显，药物治疗无法改善合并GD，反复发作术后随访甲状腺功能，注意及时替代治疗中医中药 中医中药在HT治疗方面积累了丰富的临床经验,有一定的实用价值 刘晓云, 段宇, 刘超. 桥本甲状腺炎免疫治疗的研究进展J. 医学综述,2006,12(6):344-346局部治疗原理：应用糖皮质激素局部注射的方法，抑制甲状腺内部的免疫炎症反应方法：每次每侧甲状腺叶内部注射地塞米松5mg，每周1-2次，连续5-10次为一疗程，可2-3个疗程优点：操作简便、副作用小、避免全身糖皮质激素应用的副作用刘晓云, 刘超