甲状腺机能亢进症Hyperthyroidism 中山大学附属第一医院内分泌科肖海鹏Regulation of Thyroid Hormones Graves 病病因与发病机制免疫功能异常体液免疫TRAb: TSAb TSBAb TGI TPOAb TgAb NIS  眶后成纤维细胞抗体眼外肌自身抗体细胞免疫病因与发病机制  遗传因素家族史HLA 相关感染因素精神因素临床表现甲状腺毒症高代谢综合征疲乏无力怕热多汗多食善饥体重下降精神神经系统多言好动紧张焦虑焦躁易怒失眠不安记忆减退思想不集中手和眼脸震颤甲状腺毒症心血管系统消化系统肌肉骨骼系统甲亢性周期性麻痹甲亢性肌病伴重症肌无力皮肤造血系统生殖系统甲状腺肿大弥漫性对称性质地不等触及震颤闻及血管杂音眼征单纯性突眼轻度突眼(<18mm) Stellwag 征瞬目减少凝视上睑挛缩眼裂增宽(Darymple 征) Von Graefe 征Joffroy 征Mobius 征浸润性突眼甲状腺危象诱因:  感染手术放射碘治疗创伤严重药物反应心梗临床表现高热（39 以上）心率140 次/分以上房颤或房扑大汗淋漓厌食恶心呕吐腹泻烦躁不安、休克、谵妄、昏迷甲亢性心脏病有甲亢症状有心脏病变排除其他器质性心脏病甲亢控制后心脏病变消失淡漠型甲亢T3 或T4 型甲亢亚临床型甲亢妊娠期甲亢胫前黏液性水肿甲状腺功能正常型Graves 眼病Figure 12-6. A case of severe pretibial myxedema showing the coarsened, nodular, infiltrated, pigmented lesions on the lower extremities.  实验室及其他检查 甲状腺功能检查TT3 、TT4  Reverse T3 FT3 、FT4 TSH 123I 或131 I 摄取率TRH 兴奋试验T3 或T4 抑制试验影响TBG 的因素TBG 增加TBG 降低妊娠雄激素雌激素糖皮质激素急性肝炎或慢活肝低蛋白血症药物先天因素先天因素明确病因的检查TSI 或TRAb TPOAb Thyroid Scan 影像学检查B超CT MRI Figure 10-5. (a) This MRI image from a patient with Graves' ophthalmopathy provides a coronal view of the eyes. In this depiction the muscles appear white, and are enormously enlarged, especially in the left eye.  诊断高代谢症状和体征甲状腺肿大伴或不伴血管杂音FT4 增高、TSH 降低浸润性突眼胫前粘液性水肿TRAb (TSI) 鉴别诊断甲亢病因鉴别131I Uptake and scan B 超单纯性甲状腺肿嗜铬细胞瘤神经官能症更年期综合征抑郁症其他：结核、肿瘤、糖尿病、慢性结肠炎、心脏病、眶内肿瘤甲亢的治疗一般治疗甲亢的治疗抗甲状腺药物放射碘(RAI) 治疗手术治疗药物治疗(ATD) 种类与机理硫脲类：甲硫氧嘧啶(methylthiouracil, MTU)  丙硫氧嘧啶(propylthiouracil, PTU) 咪唑类：甲硫咪唑(methimazole, MM 他巴唑) 卡比马唑(carbimazole, CMZ 甲亢平) 机理:  抑制甲状腺激素的合成免疫抑制外周T4 向T3 转化适应证病情轻甲状腺轻中度肿大青少年（20 岁以下），孕妇，年迈体弱有严重肝肾疾病不能手术术前准备，术后复发131I 治疗前后辅助治疗剂量与疗程初治期: MTU / PTU 300 mg - 450 mg /d MM I/ CMZ 30 mg –40 mg / d  甲亢症状缓解，T3 、T4 恢复正常减量期:  每2 –4 周减一次，每次MTU / PTU 50 mg - 100 mg  MMI / CMZ 5 mg –10 mg 甲亢症状完全消失，体征明显好转维持期: MTU / PTU 50 mg - 100 mg /d MMI / CMZ 5 mg –10 mg /d (18 个月)  不良反应粒细胞减少或缺乏药疹胆汁淤积性黄疸、血管神经性水肿、中毒性肝炎停药指征症状消失、甲状腺肿减轻或消失疗程18 个月T3 、T4 、FT3 、FT4 、TSH 均正常TSI 转阴T3 抑制试验恢复正常131I 适应证中度甲亢年龄25 岁以上甲亢药物过敏、长期无效、或治疗后复发心、肝、肾疾病不宜手术、术后复发、或不愿手术131I 禁忌证妊娠、哺乳妇年龄25 岁以下严重心、肝、肾疾病或活动性结核白细胞低于3 109/L ，或中性粒细胞低于1.5 109/L 重症浸润性突眼甲状腺危象甲状腺不能吸碘者131I 剂量与疗程：ATD 停药3-5 天, 戒碘2~4W 80 μCi / g 甲状腺组织半年后仍未缓解，进行第二次治疗131I 并发症:  甲减(一过性和永久性)  甲状腺炎(131I 治疗后7~10d)  诱发甲亢危象突眼加重手术适应证中重度甲亢长期服药无效, 不愿服药, 或停药复发巨大甲状腺,有压迫症状胸骨后甲状腺肿并甲亢结节性甲状腺肿并甲亢手术禁忌证严重的浸润性突眼合并较重心、肝、肾疾病妊娠前1~3 月和6个月后手术术前准备:  药物治疗使症状消失,心率小于80 次/分, T3 T4 恢复正常　复方碘液　３－５滴tid 　７－１０天手术并发症：　　出血　　呼吸道梗阻　　感染　　甲状腺危象　　喉上和喉返神经损伤　　甲状旁腺功能减退　　甲减　　突眼恶化甲状腺危象抑制甲状腺素合成：PTU 600 mg ,250mg q6h  抑制甲状腺素分泌: 复方碘液5滴, q8h  减慢心率:  心得安20-40 mg q6-8h  糖皮质激素: 氢化可的松　50~100mg iv drip q6-8h  降低血甲状腺素浓度：透析支持对症处理Figure 3c-1. Pathways of thyroid hormone metabolism. Figure 6-8. The effect of serum TSH assay sensitivity on the discrimination of euthyroid subject (Euth) from those with thyrotoxicosis (Toxic). (From C. Spencer, Clinical Diagnostics, Eastman Kodak Co., 1992). Figure 13-1. Hot nodule in right lobe of thyroid. Note that uptake of radioactivity in the contralateral lobe issuppressed. Figure 18-3. Scintiscans of thyroid. The scan on the left is normal. A typical scan of a "cold" thyroid nodule failing to accumulate iodide isotope is shown on the right. Incidentally, a pyramidal lobe is also seen on this scan, which might suggest the presence of Hashimoto's Thyroiditis. Figure 6-6. Thyroid Scans.  Normal thyroid imaged with 123I.  Cold nodule in the right lobe imaged by 99mTc.  Elderly woman with obvious multinodular goiter and the corresponding radioiodide scan on the right. Figure 17-5. (A) Cross section of multinodular goiter. (B) Gross radioautograph of the thyroid in part a. Observe the variation in 131I uptake in different areas. (b) In this transverse view the enlarged muscles are seen (appearing dark against the light fat signal) and the exophthalmos is apparrent.  其他药物治疗碘剂术前准备甲亢危象B- 阻断剂* Figure 4-3. Basic elements in the regulation of thyroid function. TRH is a necessary tonic stimulus to TSH synthesis and release. TRH synthesis is regulated directly by thyroid hormones. T4 is the predominant secretory product of the thyroid gland, with peripheral deiodination of T4 to T3 in the liver and kidney supplying roughly 80% of the circulating T3. Both circulating T3 and T4 directly inhibit TSH synthesis and release independently; T4 via its rapid conversion to T3. SRIH = somatostatin.  甲状腺毒症(thyrotoxicosis) 的常见原因甲状腺功能亢进症：⒈弥漫性毒性甲状腺肿（Graves 病diffuse toxic goiter ）⒉桥本甲状腺毒症(Hashitoxicosis) ⒊新生儿甲状腺功能亢进症⒋多结节性毒性甲状腺肿(Toxic multiple nodular goiter) ⒌甲状腺自主高功能腺瘤(Plummer disease) ⒍滤泡状甲状腺癌⒎碘致甲状腺功能亢进症（IHH ）⒏HCG 相关性甲状腺功能亢进症（绒毛膜癌、葡萄胎等）⒐垂体TSH 瘤或增生致甲状腺功能亢进症非甲状腺功能亢进类型⒈亚急性肉芽肿性甲状腺炎（亚急性甲状腺炎）⒉亚急性淋巴细胞性甲状腺炎（无痛性甲状腺炎）⒊慢性淋巴细胞性甲状腺炎（桥本甲状腺炎、萎缩性甲状腺炎）⒋产后甲状腺炎（PPT ）⒌外源甲状腺激素替代⒍异位甲状腺激素产生（卵巢甲状腺肿等）Figure 7-15 Possible sequence and clinical outcome in AITD, indicating the interrelation of envirenmental and genetic factors, and dependence of the clinical picture on the type of immune response. Figure 10-7. Plummer's nail changes, showing thinning of the nail and marked posterior erosion of the hyponychium. Thyroid acropachy Palpebral edema Widening of palpepral Fissures Lid retraction Paralysis of right Rectus muscle Conjuntival injection and chemosis Failure to close  lid Paralysis of upward Gaze on the right Figure 12-3. End stage in severe involvement of extraocular muscles in ophthalmopathy a. Extraocular muscle from a patient with Graves' disease and infiltrative ophthalmopathy. The lymphocytic infiltration and fibrosis are characteristic findings. b. Edematous orbital fat and cellular infiltrate. Graves 病眼征的分级标准（美国甲状腺学会ATA )  级别眼部表现0  无症状和体征无症状，体征有上睑挛缩、Stellwag 征、von Graefe 征等2  有症状和体征，软组织受累3  突眼（﹥18mm) 眼外肌受累角膜受累视力丧失（视神经受累）Figure 10-9. Congestive heart failure induced in an otherwise healthy young woman (a), which receded (b), and returned to normal (c), during and after therapy.  胫前粘液性水肿Figure 12-7. (a) Massive infiltrative , localized myxedema in a female patient with Graves' disease and progressive exophthalmos. The lesions have become confluent over the lower extremities. (b) In the same patient, localized myxedema, involving the phalanges, is evident. *