内分泌内科-甲亢

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,RegulationofThyroidHormones,Figure4-3.Basicelementsintheregulationofthyroidfunction.TRHisanecessarytonicstimulustoTSHsynthesisandrelease.TRHsynthesisisregulateddirectlybythyroidhormones.T4isthepredominantsecretoryproductofthethyroidgland,withperipheraldeiodinationofT4toT3intheliverandkidneysupplyingroughly80%ofthecirculatingT3.BothcirculatingT3andT4directlyinhibitTSHsynthesisandreleaseindependently;T4viaitsrapidconversiontoT3.SRIH=somatostatin.,甲状腺毒症(thyrotoxicosis)的常见原因甲状腺功能亢进症：弥漫性毒性甲状腺肿（Graves病diffusetoxicgoiter）桥本甲状腺毒症(Hashitoxicosis)新生儿甲状腺功能亢进症多结节性毒性甲状腺肿(Toxicmultiplenodulargoiter)甲状腺自主高功能腺瘤(Plummerdisease)滤泡状甲状腺癌碘致甲状腺功能亢进症（IHH）HCG相关性甲状腺功能亢进症（绒毛膜癌、葡萄胎等）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亚急性肉芽肿性甲状腺炎（亚急性甲状腺炎）亚急性淋巴细胞性甲状腺炎（无痛性甲状腺炎）慢性淋巴细胞性甲状腺炎（桥本甲状腺炎、萎缩性甲状腺炎）产后甲状腺炎（PPT）外源甲状腺激素替代异位甲状腺激素产生（卵巢甲状腺肿等）,Graves病,病因与发病机制免疫功能异常体液免疫TRAb:TSAbTSBAbTGITPOAbTgAbNIS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,Figure7-15PossiblesequenceandclinicaloutcomeinAITD,indicatingtheinterrelationofenvirenmentalandgeneticfactors,anddependenceoftheclinicalpictureonthetypeofimmuneresponse.,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,Figure10-7.Plummersnailchanges,showingthinningofthenailandmarkedposteriorerosionofthehyponychium.,Thyroidacropachy,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)VonGraefe征Joffroy征Mobius征浸润性突眼,Palpebraledema,WideningofpalpepralFissures,Lidretraction,ParalysisofrightRectusmuscle,Conjuntivalinjectionandchemosis,Failuretocloselid,ParalysisofupwardGazeontheright,Figure12-3.Endstageinsevereinvolvementofextraocularmusclesinophthalmopathy,a.ExtraocularmusclefromapatientwithGravesdiseaseandinfiltrativeophthalmopathy.Thelymphocyticinfiltrationandfibrosisarecharacteristicfindings.,b.Edematousorbitalfatandcellularinfiltrate.,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、vonGraefe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）,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,Figure10-9.Congestiveheartfailureinducedinanotherwisehealthyyoungwoman(a),whichreceded(b),andreturnedtonormal(c),duringandaftertherapy.,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,胫前粘液性水肿,Figure12-6.Acaseofseverepretibialmyxedemashowingthecoarsened,nodular,infiltrated,pigmentedlesionsonthelowerextremities.,Figure12-7.(a)Massiveinfiltrative,localizedmyxedemainafemalepatientwithGravesdiseaseandprogressiveexophthalmos.Thelesionshavebecomeconfluentoverthelowerextremities.(b)Inthesamepatient,localizedmyxedema,involvingthephalanges,isevident.,实验室及其他检查,甲状腺功能检查TT3、TT4ReverseT3FT3、FT4TSH123I或131I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,Figure3c-1.Pathwaysofthyroidhormonemetabolism.,Figure6-8.TheeffectofserumTSHassaysensitivityonthediscriminationofeuthyroidsubject(Euth)fromthosewiththyrotoxicosis(Toxic).(FromC.Spencer,ClinicalDiagnostics,EastmanKodakCo.,1992).,明确病因的检查,TSI或TRAbTPOAbThyroidScan,Figure13-1.Hotnoduleinrightlobeofthyroid.Notethatuptakeofradioactivityinthecontralaterallobeissuppressed.,Figure18-3.Scintiscansofthyroid.Thescanontheleftisnormal.Atypicalscanofacoldthyroidnodulefailingtoaccumulateiodideisotopeisshownontheright.Incidentally,apyramidallobeisalsoseenonthisscan,whichmightsuggestthepresenceofHashimotosThyroiditis.,Figure6-6.ThyroidScans.Normalthyroidimagedwith123I.Coldnoduleintherightlobeimagedby99mTc.Elderlywomanwithobviousmultinodulargoiterandthecorrespondingradioiodidescanontheright.,Figure17-5.(A)Crosssectionofmultinodulargoiter.(B)Grossradioautographofthethyroidinparta.Observethevariationin131Iuptakeindifferentareas.,影像学检查,B超CTMRI,(b)Inthistransverseviewtheenlargedmusclesareseen(appearingdarkagainstthelightfatsignal)andtheexophthalmosisapparrent.,Figure10-5.(a)ThisMRIimagefromapatientwithGravesophthalmopathyprovidesacoronalviewoftheeyes.Inthisdepictionthemusclesappearwhite,andareenormouslyenlarged,especiallyinthelefteye.,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131IUptakeandscanB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/PTU300mg-450mg/dMMI/CMZ30mg40mg/d甲亢症状缓解，T3、T4恢复正常减量期:每24周减一次，每次MTU/PTU50mg-100mgMMI/CMZ5mg10mg甲亢症状完全消失，体征明显好转维持期:MTU/PTU50mg-100mg/dMMI/CMZ5mg10mg/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,其他药物治疗碘剂术前准备甲亢危象B-阻断剂,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3109/L，或中性粒细胞低于1.5109/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24W80Ci/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710d)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13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,T3T4恢复正常复方碘液滴tid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：PTU600mg,250mgq6h抑