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临床甲状腺病学

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临床甲状腺病学

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《临床甲状腺病学》介绍了甲状腺疾病表现。甲状腺密度减低见于囊肿和囊性变、桥本甲状腺炎、囊腺瘤、囊腺癌、甲状舌管囊肿等。甲状腺密度增高常见于甲状腺内钙化、病灶内出血等。甲状腺肿大常见于甲状腺内肿块性病变、弥漫性甲状腺肿及桥本甲状腺炎等。
Author Description

向光大,广州军区武汉总医院内分泌科主任,教授,主任医师,医学博士,硕士生导师。毕业于中南大学湘雅医学院,2010—2011年在美国得克萨斯大学留学。担任中华医学会内分泌学分会委员,中华医学会性腺组副组长,全军内分泌专业常委,广州军区内分泌专业主任委员、湖北省医学会内分泌专业副主任委员,湖北省医学会糖尿病专业常委,武汉医学会内分泌专业副主任委员。同时担任中华糖尿病杂志、中国糖尿病杂志和临床内科杂志及中华医学遗传学杂志编委。此外,还担任Clin Endocrinology,Diabetic Med,Metabolism等国外期刊的特约审稿专家。先后发表学术论文150多篇,其中以第一作者在Diabetes、Diabetes Care、Diabetologia、J Clin Endocrinol Metab、European J of Endocrinology、Metabolism等国外刊物上发表SCI学术论文25篇。以第一完成人获得湖北省科技进步一等奖2项,军队医疗成果二等奖2项。
Catalogue

第一章 正常甲状腺轴
第一节 甲状腺的解剖与组织胚胎学
第二节 甲状腺激素
第三节 甲状腺功能调控
第四节 促甲状腺激素释放激素
第五节 促甲状腺激素和促甲状腺激素受体

第二章 甲状腺功能相关实验室检查
第一节 血液循环中甲状腺激素测定
一、血清总甲状腺素测定
二、血清三碘甲状腺原氨酸测定
三、血清游离T3、游离T4测定
四、血清反T3测定
五、甲状腺素结合球蛋白测定
第二节 甲状腺激素合成功能测定
一、甲状腺吸131I试验
二、甲状腺浓聚99m Tc测定
三、过氯酸钾排泄试验
第三节 甲状腺激素在机体组织中效应评价
一、基础代谢率测定
二、跟腱反射松弛时间测定
三、无创伤性心功能检查
四、其他相关指标测定
第四节 下丘脑-垂体-甲状腺轴评价
一、促甲状腺激素兴奋试验
二、促甲状腺激素释放激素兴奋试验
三、促甲状腺激素测定
四、甲状腺激素抑制试验
五、卡比马唑试验
第五节 尿碘测定
第六节 甲状腺相关自身抗体测定
一、甲状腺过氧化物酶抗体
二、促甲状腺激素受体抗体
三、甲状腺球蛋白抗体
第七节 甲状腺细针穿刺活检

第三章 甲状腺影像学检查
第一节 甲状腺核素显像检查
第二节 甲状腺超声检查
第三节 甲状腺CT检查
第四节 甲状腺磁共振成像检查

第四章 甲状腺功能亢进症
第一节 成人Graves病
第二节 甲状腺相关性眼病
第三节 妊娠期甲状腺功能亢进症
第四节 儿童甲状腺功能亢进症
第五节 老年甲状腺功能亢进症
第六节 亚临床甲状腺功能亢进症

第五章 甲状腺功能减退症
第六章 甲状腺炎症
第七章 特殊类型甲状腺病
第八章 甲状腺结节与肿瘤
第九章 甲状腺相关综合征
第十章 甲状旁腺疾病
索引
Book Abstract

(二)脱碘酶与不同疾病
1.甲状腺功能亢进症甲状腺功能正常的个体,D2是产生T3主要的脱碘酶,而在甲状腺毒症个体,D1是主要产生T,的脱碘酶。在甲亢的个体,与T4相比,T3产生的比例和外周循环中T3浓度增加了2倍。在这样的患者中,fT3比fT4增加更多。因为,人Diol启动子为T3应答的,进而引起甲亢患者D1活性或mRNA明显增加。这在Grave病患者的甲状腺组织和单核白细胞中得到证实。
PTU可以阻断D1的活性,其具有抗甲状腺毒症作用,而且与正常甲状腺功能者相比,甲状腺毒症患者PTU作用更明显。在一项甲状腺毒症或者正常人同时给予PTU及甲巯咪唑干预,之后检测血清T3的生成量研究中,发现在甲状腺毒症患者中D1是主要产生T3的脱碘酶。此外,只有用PTU的最大剂量或者其他抑制T4向T3转变的方法,如加入药物碘番酸或者吉非贝齐(博利脂)才可以抑制严重甲状腺毒症患者D1活性:而正常个体,适当剂量PTU则可抑制其D1活性。
2.胺碘酮胺碘酮是一种含有大量碘的抗心律失常药物,而且它与甲状腺激素有某些相同的结构。给予胺碘酮治疗期间,甲状腺激素代谢改变,导致血清T4浓度(大约40%)和血清r—T3浓度(约170%)增加,血清T3浓度(10%~25%)降低,fT3和fT4也有类似的改变,因此甲状腺功能检测可能是异常的。对甲状腺功能的影响主要由于碘占胺碘酮重量的37%,此外,该药物对脱碘酶也有影响。
胺碘酮药物治疗期间,患者的T3向T3转换率从26%~43%降到10%~17%,但是由于T4产生是增加的,所以,净T3的量和fT3浓度是正常的。动物实验已经证实上述效应是由胺碘酮对脱碘酶作用引起。例如,给予大鼠胺碘酮干预,发现其D1mRNA水平是正常的,但是在肝脏、心脏和肾脏组织匀浆发现其活性明显受到抑制,而且呈剂量依赖性。胺碘酮对D1活性的抑制作用机制主要是通过药物本身或者药物代谢产物竞争D1的底物。
3.脱碘酶在非甲状腺疾病任何病危情况、危害生命的创伤或者外科手术能引起典型的(stereotypie)垂体—甲状腺功能的改变,有时候甚至引起低T3综合征或者正常甲状腺病态综合征。这些患者出现低血清T3浓度,且与疾病严重性呈现负相关,此外,这类患者T4和TSH浓度可能降低,而r—T3浓度可能增加。
要弄清楚上述疾病出现低T3综合征的原因存在困难,这是因为甲状腺轴对于疾病的反应存在种间差异,另外存在脱碘酶和T3清除率改变导致外周T3浓度的变化。此外,有研究发现这些患者血清TSH水平没有受到明显影响,提示外周T3浓度降低不是由于上游的中枢性抑制作用,而是由于外周T4脱碘酶活性降低或外周T3清除率升高。有研究证实给予上述疾病出现甲状腺功能减退症患者左甲状腺激素治疗后,发现其血清T3和T4浓度仍然是降低的,这提示是外周T4脱碘酶活性降低或T3清除率升高起作用。
近年来对病危患者低T3综合征发病机制研究中发现D3在其发病机制中起重要的作用。D3广泛表达于胎儿的很多组织器官,但是,它只高度表达于成人的子宫内膜和胎盘。以前认为D3主要调节子宫和胎盘等处的母源—胎儿甲状腺激素转运。但是对于好转的病危患者的肝脏和骨骼肌进行研究发现其肝脏的D1表达下调,而D3活性增强,而D1和D3mRNA水平与其在肝脏和骨骼肌的脱碘酶活性相一致,提示对D1和D3活性的调节可能出现在翻译前。上述出现的不同组织的D1和D3活性提示在上述疾病中,甲状腺激素生物活度的改变存在组织特异性。D3活性增加可以增加r—T3的合成,而D1活性降低,降低r—T3的清除率。
上述疾病患者中的三种脱碘酶的表达改变引起的非甲状腺病态综合征并非疾病的病理过程,而是对疾病的生理反应。总之,虽然外周组织中的脱碘酶的变化可能与上述疾病引起的非甲状腺病态综合征的病理生理改变有关,但是脱碘作用不足以引起上述变化。因为下丘脑—垂体—甲状腺轴对于外周组织T3生成减少有强大的代偿能力,因此中枢性甲减可能也参与上述综合征的发生。在病危的个体,TSH分泌是减少的,而持续输注TRH,可明显增加血清T4和T3浓度。而在这些危急患者中往往出现中枢性甲减,引起这一现象的分子机制至今仍不很清楚,在节制饮食的大鼠和人类中发现多巴胺和糖皮质激素对TSH的分泌具有抑制作用,而瘦素可以增加血清TSH、T4和T3浓度。给予大鼠脂多糖注射后,发现其海马组织核因子(NF—kB)信号通路活性增高,D2表达增高,但目前还不清楚是否这种诱导的D2活性是否引起局部甲状腺毒症。
……

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