爱爱医资源甲状腺功能减退症

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,甲状腺功能减退症hypothyroidism,甲状腺激素合成及分泌不足或,组织不能很好利用甲状腺激素,导致甲状腺功能绝对或相对不足的全身性疾病,人每日需要补充100,g的甲状腺素(T,4,) 合成这些T,4,所用的碘，即每日最低需碘量为65g,碘几乎100%从胃肠道吸收,其中90%从尿排出,10%从粪便排泄,.,正常碘摄入时,.每天尿碘浓度应达到100g/L,碘超足量（MUI 201-300g/L）和碘过量（MUI 300g/L）,自身免疫甲状腺炎和甲减的患病率显著增加，,促进甲状腺自身抗体阳性人群发生甲减；,可以促进亚临床甲减发展为临床甲减。,维持碘摄入量在,尿碘,100-200g/L,安全范围是防治甲减的基础措施,对于有遗传背景、甲状腺自身抗体阳性和亚临床甲减的易感人群尤重要,理想碘摄入量：,青春期前儿童,120g/d,青少年和成人,150g/d,怀孕和哺乳期妇女,200g/d,一 甲状腺激素的合成及调节,过多的活性碘, 占据过氧化物酶的功能键，抑制其活性 干扰酪氨酸的碘化,使甲状腺激素的合成和释放受损Wolff-chaikoff效应,有潜在的致甲状腺自身免疫现象 碘充足地区甲减多源于自身免疫性疾病,1.碘使甲状腺组织成分的抗原性增强,2.碘与甲状腺球蛋白结合,增加甲状腺球 蛋白的免疫性,3.碘刺激B淋巴细胞产生免疫球蛋白.,碘引起甲状腺功能减退的原因,酸,硫酸盐,葡萄糖醛,丙氨酸脱羧脱胺,D1,D3,3,5,3,5,Extrathyroidal,Conversion Sites,(Liver, kidney, Others),T3,T4,-,I,-,T4,T3,T4,T3,Thyroid,TSH,Pituitary,Hypothalamus,T3,T4,TRH,+,-,-,-,+,TSH及TRH促进T3和T4的合成,肝肾等1型5脱碘酶使T4脱碘产生T3,不论甲状腺或外周形成的T3均可反馈抑制垂体,T4到达垂体后可被垂体中2型5脱碘酶几乎完全转换成T3抑制垂体分泌,D1,D2,There are few reports about nuclear uptake of T3,- Mori et al. 2002 showed a,cytoplasmic thyroid binding protein,(CTBP) regulating nuclear and total T3 uptake,T3发挥生理作用过先与血液中TBG分离，游离的T3通过细胞浆膜再与胞浆中的胞浆甲状腺结合,蛋白CTBP 结合，再解离出的T3及尚未结合的T3通过核膜进入细胞核与其受体结合发生效应,Whickham 甲减发生与基线TSH及抗体有关,N=912 随访20年,二 甲状腺功能减退症,基线时: TSH2mU/L,甲减,抗体阳性者发生率最高,并与滴度相关.,追踪20年观察结果显示:自发甲减的年发病率:,女性为3.50/00, 其中9%在10 开始治疗,TSH 5-10 每年筛查,分 类,根据病变发生部位,原发性甲减（甲状腺本身病变）,占全部甲减的95%以上；,常见原因：自身免疫、甲状腺手术或放射碘治疗后,中枢性甲减（下丘脑和垂体病变）,TSH或TRH分泌减少所致；,常见原因：肿瘤、颅咽管瘤 局部放射或手术 及分娩大出血,甲状腺激素抵抗综合征-,周围性甲减,根据甲状腺功能减低的程度分类,亚临床甲减（subclinical hypothyroidism）,临床甲减（overt hypothyroidism）,粘液性水肿,根据发病年龄分类,先天性甲减: 胎儿期或婴儿期发病 婴幼儿及儿童甲减,成人甲减,临床表现,女性中年以后发病多，起病隐袭。,.,缺乏特异症状易与衰老混淆,代谢率减低症状未老先衰 怕冷无汗，贪睡懒动, 食欲下降但体重增加, 腹胀, 便秘, ， 记忆力减退，反应迟钝, 月经量多, 不孕 关节疼痛,溢乳,甲状腺疾病家族史 及甲状腺手术史 放射碘治疗史、 Graves病 桥本甲状腺炎病史,反应迟钝、表情呆滞、声音嘶哑、听力障碍，毛发稀疏干燥,粘液性水肿面容:苍白、颜面和/或眼睑浮肿、唇厚舌大,、,有齿压痕，,皮厚干粗、脱屑、手脚掌皮肤可呈姜黄色，,甲状腺不大或轻中度肿大,较韧不均匀,无压痛,心率缓慢房室传导阻滞,低体温,跟腱反射时间延长，,浆膜腔积液 心包积液 心力衰竭,蝶鞍增大易误为垂体泌乳素瘤,体格检查,甲减的诊断思路,T4减低 TSH,原发和继发性甲减的鉴别,T,4,正常, TSH正常无甲减,T,4, TSH原发甲减,T,4, TSH正常或继发甲减,T,4, TSH 激素拮抗综合征,肿瘤,甲减的实验室检查,TSH,FT,4,T,3,代偿T,3,失代偿,亚临床甲减仅有TSH增高,原发性甲减血清TSH增高，增高的水平与病情程度相关,成人TSH分泌有昼夜节律， 23：0002：00最高,自身免疫指标: TGAb; TPOAb. 多呈强阳性,TBAb;TBII,阻断TSH作用,部分原发性甲减蝶鞍增大，血清泌乳素升高、需要与垂体泌乳素瘤鉴别,心肌酶,血脂异常,贫血,轻、中度正色素性贫血,蛋白尿,三甲减治疗,左甲状腺素钠（L-T4）替代治疗原则,1. 青、中年: 起始50ug/d, 每间隔一个月左右上调25ug/d,4.8 ）组,Goal TSH in Hypothyroidism,Young (age 26) vs. old (age 71),McDermott et al.Thyroid 2001,Survey of ATA members(n=162),1,2,3,4,Age 26,Age71,TSH,调查美国ATA会员治疗甲减年轻人（平均26岁）和,老年人（平均71岁）替代治疗达标范围分别是0-2及1-4,甲减治疗经验,Variations in L-T4 Replacement with Different Causesof Hypothyroidism,Gordon and Gordon,1999,Atrophic,Thyroiditis,(n=36),Hashimotos,Thyroiditis,(n=36),Gravess/p,131IRx,(n=37),Thyroid Cancer,(normal TSH),(n=36),Median Daily Dose,(mcg/d),P20,Hypothyroid,NTIS,14%,50%,50%,86%,T4,T3,TSH,DECREASED T3 PRODUCTION,DECREASED TSH AND T4,PRODUCTION,The Two Major Nonthyroidal-Illness syndromes,Time (days or weeks),Time (days or weeks),Decreased Serum Thyroxine-,the More Serious Change,Decreased Triiodothyronine Production in Nonthyroidal Illness:Is Treatment Indicated?,Patients need not be very ill.,This change may reduce,protein catabolism,which is,prevented by replacement of,triiodothyronine.,No evidence of other benefit,of replacement.,Time (days or weeks),Decreased Thyroxine and Triiodothyronine,Production in Nonthyroidal Illness:,Is Treatment Indicated?,Patients are usually very ill.,No benefit of thyroxine,therapy, and harm in one,study.,One study of high-dose,triiodothyronine-no benefit.,Time (days or weeks),Thyroxine Therapy in Patients,with Acute Renal Insufficiency,Thyroxine,Placebo,No. of patients,28,31,Serum creatinine(mg/dl),3.2,3.8,Base-line serum TSH(mU/L),0.9,1.1,Base-line serum free thyroxine(ng/dl),0.7,0.7,Base-line serum free triiodothyronine(ng/dl),0.1,0.1,Required dialysis,18(64%),15(48%),Recovery of normal renal function,15(54%),20(64%),Mortality,12(43%),4(13%),(Treatment was four doses of 150ug of thyroxine,given intravenously,at 12-hour intervals.),Acker CG.et al. Kidney international 2000.57,293,谢谢大家！,结 语,