1、甲状腺功能亢进症甲状腺功能亢进症（thyrotoxicosis）浙江大学医学院附属邵逸夫医院内分泌科 王国兴http:/http:/http:/内内 容容 定义、分类、流行病学资料和发病机理 临床表现 特殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/内内 容容 定义、分类、流行病学资料和发病机理 临床表现 特殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/甲亢定义甲亢定义 由多种病因导致体内甲状腺激素(TH)分泌过多，引起以神经、循环、消化等系统兴奋性增高和代谢亢进为主要表现的一种临床综合征。
2、临床上以弥漫性毒性甲状腺肿(Graves病)最常见，约占85%。http:/http:/http:/http:/http:/http:/流行病学资料流行病学资料http:/http:/http:/Greenspan 8th Edition Endocrine TextHypothalamic-Pituitary-Thyroid Axishttp:/http:/http:/TRHTSHT3,T4INormal FeedbackITSHR-AbT3,T4Graves DiseaseT3TSHTRHhttp:/http:/http:/ThyroidglandThyroid follicularend
3、othelial cellHyperplastic thyroid follicleT3T4ThyrotropinreceptorInterferon-Interleukin-2B cellHelperT cellCD154Thyrotropin-receptorpeptidesAntigen-presentingcellCD40T-cellreceptorMHCclass IITNFInterferon-Anti-thyrotropinreceptorantibodyOrbitalfibroblastExpanded orbitaltissueshttp:/http:/http:/内内 容容
4、 定义、分类、流行病学资料和发病机理 临床表现 特殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/Clinical Symptoms of HyperthyroidismAppetite changeExertional shortness ofbreathFatigueHeadacheHeat intoleranceHyperactivityIncreased perspirationIrritabilityBraverman LE,Utiger RD.In:Werner and Ingbars The Thyroid,7th ed.1996
5、:522.Menstrual disturbancesNervousnessPalpitationsPelvic and pectoral girdle muscle weaknessSleep disturbance TremorWeaknessWeight changehttp:/http:/http:/Clinical Signs of HyperthyroidismGoiterHyperactivityHyperreflexiaMuscle weaknessOphthalmopathy(only Graves disease)Stare and eyelid retractionSys
6、tolic hypertension(widened pulse pressure)Tachycardia/atrial arrhythmiaTremorPretibial MyxedemaWarm,moist,smooth skinhttp:/http:/http:/Goiter in Graves Diseasehttp:/http:/http:/OnycholysisStarehttp:/http:/http:/Pretibial Myxedemahttp:/http:/http:/ATA:Graves病眼征的分级标准病眼征的分级标准NOSPECShttp:/http:/http:/GD
7、眼病活动性的临床评分标准眼病活动性的临床评分标准 包括：自发性的眼球后疼痛感；眼球运动时伴有疼痛 眼睑充血；眼睑水肿；球结膜充血；球结膜水肿；眼阜水肿。以上每点各1分，共7分，大于3分即为GD眼病活动，活动分值越大，表示活动度越高。http:/http:/http:/Graves Ophthalmopathy-Infiltration of Extraocular Muscleshttp:/http:/http:/Extraocular Muscle Thickening from Graves Diseasehttp:/http:/http:/Graves Ophthalmopathyhtt
8、p:/http:/http:/Manifestations of Hyperthyroidism Cardiac-atrial fibrillation,ischemic heart disease.Bone-increased bone turnover,osteoporosis，markedly increased serum alkaline phosphatase Metabolic-weight loss,lowering of cholesterol.GI/Liver-increased gut motility,diarrhea,increased serum alkaline
9、phosphatase and transaminase levels.CNS-sleep disturbance,irritability.Muscular-proximal muscle weakness,periodic paralysis in Orient young man.http:/http:/http:/内内 容容 定义、分类、流行病学资料和发病机理 临床表现 特殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/ 原有甲亢症状加重 高热39 心率快140-240bmphttp:/http:/http:/ 占甲亢1022，随年龄增
10、长而增加 甲亢心的诊断标准：多年不愈的甲亢病史 有心律失常、心脏扩大及心力衰竭之一 排除其它器质性心脏病：风心病、高心病、冠心病等 甲亢控制后，大多数心律失常、心脏增大、心力衰竭恢复甲亢性心脏病甲亢性心脏病http:/http:/http:/http:/http:/http:/Orbital fibroblastThyrotropinreceptorCD40CD154AntithyrotropinReceptor antibodyProadipogenicprostaglandinsT cellOrbitaladipocytesExpandedadipose tissueElevated an
11、tithyrotropin-receptorantibody levelsInterleukin-6B cellPlasma cellMacrophageInterleukin-1Interleukin-1HelperT cellInterleukin-16RANTESIGF-IreceptorOrbitalfibroblastInterferon-TNFHyaluronanProstaglandin E2TGF-Thy-1Extraocular muscleMyofibroblastExtraocularmuscle enlargementFibrosisRANTES(regulated u
12、pon activation normal T-cellexpressed and secreted)http:/http:/http:/ 老年患者多见 表情淡漠、消瘦 起病隐袭，易误诊 以厌食、恶心、呕吐及心血管疾病表现为主诉http:/http:/http:/ T3 型：疾病早期、治疗中、治疗后复发、缺碘地区 甲亢 症状轻，FT3、TT3增高，FT4、TT4正常，TSH水平 降低，131I吸收率增加，不受外源T3抑制 T4 型：GD伴严重躯体疾病或碘甲亢 TT4、FT4升高，TT3、FT3正常或偏低 http:/http:/http:/ FT3、FT4正常，TSH降低 疾病早期、治疗后 可
13、持续存在 转为典型甲亢 无症状或有某些表现 排除下丘脑垂体疾病等致低TSHhttp:/http:/http:/ TRAb 阴性，血HCG显著升高妊娠合并甲亢妊娠合并甲亢HCG相关性甲亢相关性甲亢绒毛膜癌、葡萄胎、多胎妊娠绒毛膜癌、葡萄胎、多胎妊娠http:/http:/http:/内内 容容 定义、分类、流行病学资料和发病机理 临床表现 特殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/FT3、FT4：不受血清TBG影响，直接反映甲状腺功能状态，敏感性、特异性均高于TT3、TT4 TT3、TT4：判定甲状腺功能最基本指标 血清中99.95与蛋白
14、结合，80-90与TBG结合 受结合量、结合力变化的影响 TBG在妊娠、雌激素、病毒性肝炎 ，雄激素、低蛋白血 症、泼尼松http:/http:/http:/uTSH波动较T3、T4迅速、显著 是反映下丘脑垂体甲状腺轴功能的最敏感指标 对亚临床甲亢和亚临床甲减的诊断意义重大 uTSH0.5mU/L可诊断甲亢 http:/http:/http:/ 诊断符合率90 缺碘性甲状腺肿也升高，但无高峰前移 受多种食物、含碘药物影响 受许多疾病影响，肾病时、应激、腹泻、吸收不良时 正常值：3小时 525 24小时 2045 高峰 24小时 现多被甲状腺摄锝率代替 http:/http:/http:/未治疗
15、GD血TSAb检出率80-100早期诊断，判断病情活动、复发、治疗后停药指标TRAb新诊断GD患者75%96%阳性，仅反映针对TSH抗体存在，不能反映抗体功能未治GD者的母体TSAb可通过胎盘，致新生儿甲亢lTGAb和和TPOAb http:/http:/http:/http:/http:/http:/内内 容容 定义、分类、流行病学资料和发病机理 临床表现 特殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/ 甲 亢：病 史、体 征 甲 状 腺 肿 大 FT4FT3 TSH GD：甲亢 弥漫性甲肿眼征和/或胫前粘液性水肿+摄碘率/摄鍀率增高和/
16、或血TRAb（+）http:/http:/http:/ 有结节者：与高功能甲状腺结节、多结节性甲肿伴甲亢、腺瘤、癌等鉴别 亚甲炎伴甲亢：发热，咽痛，甲状腺肿大伴压痛+摄131I率低 桥本氏甲状腺炎：摄131I率低+TGAb、TPOAb高滴度阳性http:/http:/http:/Hyperfunctioning“hot”left noduleThese“hot”nodulesdo not need to be aspiratedhttp:/http:/http:/http:/http:/http:/http:/http:/http:/内内 容容 定义、分类、流行病学资料和发病机理 临床表现 特
17、殊临床表现与类型 实验室及辅助检查 诊断与鉴别诊断 甲亢的治疗http:/http:/http:/ 忌碘饮食 休息 营养 镇静 http:/http:/http:/ 药物、手术、放射性碘 根据年龄、性别、病情、病程 病理、并发症、伴发症以及意愿 经济情况决定http:/http:/http:/Treatment of Graves Disease Antithyroid Drugs:First line,chance of remission(approximately 30%at 1 year overall)greatest with mild to moderate thyroid en
18、largement(less than 2-fold),lower serum T3/T4,lower TSI(rare agranulocytosis).Radioiodine:Most frequently used definitive treatment.Surgery:Refractory Graves(e.g.,with amiodarone or ATD allergy),pregnancy,refusal to have radioiodine.Complications are rare with experienced surgeon(hypoparathyroidism,
19、recurrent laryngeal nerve damage).http:/http:/http:/ 硫脲类：MTU、PTU 咪唑类：MM、CMZ 40%-60%治愈率治愈率http:/http:/http:/其他药物治疗其他药物治疗 复方碘液：术前准备和甲亢危象 受体阻滞剂：改善初期症状，抑制T4转化T3 也可用于术前准备，131I治疗前后 哮喘和喘息性慢支可用阿替洛尔或美托洛尔 http:/http:/http:/Radioiodine Therapy of Graves Disease Treatment of choice for most adults Hypothyroidis
20、m inevitable,not a“side-effect”:50%at 1 year,2-3%/yr afterwards(lifelong f/u needed)Takes 2-6 months for full effect Cure in 80%of patients with 1 dose 15-20%of patients develop transient hypothyroidism after 2-3 monthshttp:/http:/http:/Radioiodine Therapy of Graves Disease No evidence for infertili
21、ty,birth defects,cancer Absolutely contraindicated in pregnancy Transient worsening of thyroid function after RAI reported in 1%of patients rationale for ATD pretreatment in older pts.Pretreatment with PTU may lower cure rate May worsen pre-existing Graves eye diseaseConcerns:http:/http:/http:/手术治疗手
22、术治疗 中、重度甲亢 长期服药无效、易复发 甲状腺巨大有压迫症状 胸骨后甲肿伴甲亢 结节性甲肿伴甲亢l严重浸润性突眼l严重心、肝、肾疾病，不耐受手术l妊娠前3个月及6个月后http:/http:/http:/甲亢危象治疗甲亢危象治疗http:/http:/http:/Weetman NEJM 343:1237,2000http:/http:/http:/Therapeutic Implications of GO Infliximab,adalimumab:TNF-specific monoclonal antibodies,Reduction in inflammation,leukocyt
23、e recruitment,and hyaluronan透明质烷 production.Etanercept:TNF receptorIgG Fc fusion molecule,Reduction in inflammation,leukocyte recruitment,and hyaluronan production.Anakinra:Interleukin-1receptor antagonist,Reduction in inflammation,leukocyte recruitment,and hyaluronan production.Tocilizumab:Interleu
24、kin-6 receptorspecific monoclonal antibody,Reduction in inflammation,leukocyte recruitment,and hyaluronan production.http:/http:/http:/ Lerdelimumab,GC1008:TGF-specific monoclonal antibodies,Reduction in fibrosis.(Oxygen free radicals)Selenium:Essential trace element,Antiinflammatory activity.Rituxi
25、mab,ocrelizumab,ofatumumab:Partially or fully humanized CD20-specific monoclonal antibodies,Decreased antigen presentation and T-cell activation;possible modulation of antithyrotropin-receptor antibody productionhttp:/http:/http:/妊娠期甲亢治疗妊娠期甲亢治疗 ATD：PTU，初300mg/日，后50-150mg，维持FT4上限 普萘洛尔致子宫收缩，胎儿发育不良、早产等，慎用 哺乳者PTU不宜过大：300mg/d安全 妊娠12-14周，胎儿有甲状腺聚碘功能，禁用放射性治疗 妊娠期不宜手术，若手术，宜于妊娠中期（4-6月）http:/http:/http:/甲亢性心脏病甲亢性心脏病 首选放射性碘治疗 不适应：改ATD 普萘洛尔：20-40mg，q6-8hhttp:/http:/http:/
