温肾方药对甲状腺功能减退症大鼠甲状腺素代谢和性激素水平的调节

目的:观察温肾方药对甲状腺功能减退症大鼠甲状腺功能及血清性激素水平的影响,并分析该影响是否有剂量依赖性,该方药与西药甲状腺片合用是否效果更好。方法:实验于2005-04/05在上海中医药大学附属龙华医院科技实验中心完成。①选用清洁级健康成年Wistar大鼠60只,雌雄各半。②取10只为正常对照组:正常饲养。给予其余50只大鼠每天灌胃0.4g/L他巴唑混悬液1.35mL(2.7mg/kg),持续45d。第46天,将造模后大鼠50只随机分为5组:模型组、甲状腺片组、温肾方小剂量组、温肾方大剂量组、温肾方合甲状腺片组,每组10只。③模型组:灌胃9.0mL/kg生理盐水;甲状腺片组:灌胃9.0mL/kg甲状腺片混悬液穴上海市实业联合集团长城药业有限公司生产,批号20051001,40mg/片;用生理盐水配成0.4g/L混悬液雪;温肾方小剂量组:灌胃9.0mL/kg半硫丸悬液(半硫丸,主要成分为硫磺;将硫磺和豆腐以1∶1.5的比例进行炮制;由上海中医药大学附属龙华医院药剂科制为胶囊,用生理盐水配成30g/L混悬液);温肾方大剂量组:18.0mL/kg半硫丸胶囊混悬液;温肾方 甲状腺片组:灌胃9.0mL/kg甲状腺片混悬液和9.0mL/kg半硫丸悬液,1次/d,共15d。④15d后取大鼠颈部血液,采用放射免疫法测定血清游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺激素、促卵泡激素、促黄体生成素、雌二醇、孕酮水平。⑤各组计量结果差异比较采用方差分析和q检验。结果:大鼠60只均进入结果分析。①温肾方对甲状腺功能减退症大鼠甲状腺功能的影响:各治疗组血清游离三碘甲状腺原氨酸、游离甲状腺素水平明显高于模型组(P<0.05～0.01),血清促甲状腺激素水平明显低于模型组(P<0.05～0.01)。温肾方大剂量组、甲状腺片组、温肾方 甲状腺片组血清游离三碘甲状腺原氨酸、游离甲状腺素水平明显高于温肾方小剂量组(P<0.01),血清促甲状腺激素水平明显低于温肾方小剂量组(P<0.05～0.01)。温肾方 甲状腺片组血清游离三碘甲状腺原氨酸、游离甲状腺素水平明显高于其他治疗组及模型组(P<0.01),血清促甲状腺激素水平明显低于其他治疗组及模型组(P<0.05～0.01)。②温肾方对甲状腺功能减退症大鼠血清性激素水平的影响:除温肾方小剂量组对雄性大鼠促黄体生成素、雌性大鼠促卵泡激素外,各治疗组大鼠血清性激素水平明显高于模型组(P<0.01);除温肾方大剂量组雌性大鼠促黄体生成素、孕酮外,温肾方大剂量组、甲状腺片组、温肾方 甲状腺片组大鼠血清促卵泡激素、促黄体生成素、雌二醇、孕酮水平均明显高于温肾方小剂量组(P<0.05～0.01);其中温肾方 甲状腺片组与其他治疗组比较,均差异明显(P<0.05～0.01)。结论:温肾方可调节甲状腺功能减退症血清性激素水平,改善甲状腺功能,且该作用存在剂量依赖性,温肾方与甲状腺片合用效果更好。     

不同甲状腺功能状态下人体血清脂联素水平的变化

目的：观察甲状腺功能不同状态下人体血清脂联素水平差异，分析影响脂联素水平的因素。方法：①选择2005—03／2006—02解放军第二军医大学长海医院内分泌门诊就诊的甲状腺功能亢进症患者69例，男26例，女43例。均有高代谢症状和体征、甲状腺肿伴或不伴血管杂音、血清游离甲状腺素升高、促甲状腺素减低。选择同期本院内分泌门诊就诊的甲状腺功能减退症患者32例，男12例，女20例。血清促甲状腺素均增高、游离甲状腺素水平减低。选择同期本院体检中心健康体检者30名，男15名，女15名。以上纳入对象均对检测项目知情同意。②测量纳入对象身高、体质量，计算体质量指数和腰臀比及体脂百分比（女性=1.2&;#215;体质量指数＋0．23&;#215;年龄-5．4；男性：1.2&;#215;体质量指数＋0.23&;#215;年龄-16．2）。采用放射免疫法测定血清脂联素水平。用自动生化发光分析系统及配套试剂检测血清甲状腺激素及促甲状腺素水平。③用协方差分析对两个样本均数做显著性检验，用直线回归方程做两因素间直线相关分析，用多元逐步回归做最显著性因素分析。结果：甲状腺功能亢进症患者69例、甲状腺功能减退症患者32例、健康者30名均进入结果分析。①血清脂联素水平：甲状腺功能亢进症患者明显高于同性别的健康者（女性P〈0．01，男性P〈0．01）；甲状腺功能减退症女性患者明显低于健康男性，男性则与健康男性相近（女性P〈0．01，男性P〉0．05）；男性均明显低于女性（P〈0.01）。②相关分析及多元逐步回归分析结果：健康人血清脂联素水平与体质量指数、腰臀比呈显著负相关（r=-0．42，-0．47，P〈0．01）。甲状腺功能亢进症、甲状腺功能减退症患者血浆脂联素水平与游离三碘甲状腺原氨酸、游离甲状腺素呈显著正相关（r=-0．417，0．324，P〈0．01，0.05），与促甲状腺素呈显著负相关（r=-0．22，P〈0．05）。多元逐步分析结果显示，甲状腺功能亢进症和甲状腺功能减退症患者内调整了体质量指数和腰臀比的影响后，游离甲状腺素是血清脂联素水平最显著的影响因素。结论：①甲状腺不同功能状态下血清脂联素水平存在性别差异。甲状腺功能亢进状态可促进脂联素的产生。②游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺素可影响到体内脂联素的水平，且以游离甲状腺素影响最为明显。     

甲状腺素对原发性甲状腺功能减退症认知功能损害的治疗效果

目的研究甲状腺素对成人原发性甲状腺功能减退症(甲减)患者认知损害的治疗效果。方法运用修订韦氏记忆量表和正背倒背任务检测26例初发成人原发性甲减患者治疗前、后及28例健康对照组的记忆功能。结果修订韦氏记忆量表检测显示,原发性甲减患者记忆商显著低于健康对照组,治疗后记忆商较治疗前明显提高(P<0.05),但仍低于健康对照组(P<0.05)。数字正背倒背任务检测,原发性甲减患者4位倒背数字任务正确率显著低于对照组(P<0.05),治疗后4位倒背数字任务正确率显著提高,与健康对照组未见明显差异(P>0.05)。结论原发性甲减患者存在记忆功能损害,甲状腺素替代治疗能够改善甲减患者的记忆功能。     

甲状腺功能减退症误诊2例分析

对我院所遇甲状腺功能减退症误诊2例分析如下。     

左旋甲状腺素对甲状腺功能减退症患者骨量的影响

目的探讨甲状腺素替代治疗对甲状腺功能减退症（甲减）患者骨量的影响。方法选取2012年1月到11月甲状腺素替代治疗的患者51例,其血清激素水平恢复正常,另选取同一时间段体检的54例为健康组,对每个患者采用双能X线骨密度仪分别测定其腰椎（L1-4）、两侧股骨骨密度,比较两组间骨密度值是否存在差异。结果甲减组患者双侧股骨头的骨密度显著低于健康组;女性患者腰椎及右侧股骨骨密度减低更显著。结论甲状腺素替代治疗后的甲减患者骨密度仍然比健康者低,需要定期测定骨密度。     

原发性甲状腺功能减退症误诊21例分析

现将我院1996-06～2005-06门诊或住院部收治的原发性甲状腺功能减退症（甲减）院外误诊21例分析如下.     

原发性甲状腺功能减退症误诊9例分析

对我院1998—10～2006—08收治的原发性甲状腺功能减退症（以下简称甲减）误诊9例分析如下。     

左旋甲状腺素治疗甲状腺功能减退症的疗效与安全性

目的观察左旋甲状腺素(L-T4)治疗甲状腺功能减退症的疗效与安全性。方法将216例甲状腺功能减退患者按随机数字表法分为研究组和对照组各108例,研究组给予左甲状腺素钠片口服,对照组给予甲状腺片口服。治疗6个月后评估疗效,观察不良反应发生情况,于治疗前及治疗6个月后检测2组患者甲状腺功能指标[促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)]水平。结果治疗6个月后,研究组总有效率高于对照组,总不良反应发生率则低于对照组(P<0.05);2组TSH水平均较治疗前降低,FT3、FT4水平则均较治疗前上升,且研究组变化幅度大于对照组(P<0.05或P<0.01)。结论 L-T4治疗甲状腺功能减退可显著增强疗效,改善患者甲状腺功能,且安全性良好,于患者疾病转归有利。     

原发性甲状腺功能减退症与血脂代谢的相关性研究

目的：探讨不同程度甲状腺功能减退症和病程对血脂的影响,并观察甲状腺功能减退症患者激素替代治疗后血脂谱的动态变化。方法收集甲状腺功能减退症患者97例,亚临床甲状腺功能减退症32例,中度甲状腺功能减退症28例,重度甲状腺功能减退症37例和31例健康体检者。分别在初诊和激素替代治疗1个月后检测各组血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A（ApoA）、载脂蛋白B（ApoB）、脂蛋白（a）[Lp（a）]。通过病史回顾对病程估计的方法确定病程时间。结果不同程度的甲状腺功能减退症对血脂影响不同,重度甲状腺功能减退症组血脂各项均升高,中度甲状腺功能减退症组除TG与HDL-C外均升高,亚甲状腺功能减退症组ApoA与Lp（a）升高。血脂各项与FT3和FT4呈负相关,与TSH呈正相关。甲状腺功能减退症患者激素替代治疗1个月后血脂各项除 Lp（a）外其余基本恢复正常。结论甲状腺功能减退症可引起血脂增高,随甲状腺功能减退症程度加重及病程延长,血脂升高越明显,经激素替代治疗后,甲状腺功能减退症病情好转血脂逐渐恢复,血脂可先于甲状腺功能恢复正常。     

125例女性甲状腺功能减退症患者血清性激素水平检测及分析

目的研究女性甲状腺功能减退症(简称甲减)患者是否存在性激素水平失衡,观察甲状腺激素变化和性激素变化之间的关系。方法采用放射免疫法测定研究对象的睾酮(T)、雌二醇(E2)、促卵泡生成激素(FSH)、促黄体生成激素(LH)、催乳素(PRL)水平,采用硫酸铵沉淀法测定血清性激素结合球蛋白结合容量(SH-BG-BC)。结果 T、E2、SHBG-BC改变差异有统计学意义(P0.01),而FSH、LH、PRL显著升高,差异有统计学意义(P0.01),女性甲减患者性激素E2下降明显,差异有统计学意义(P0.01)。结论女性甲减患者性激素水平紊乱。     

甲状腺激素对大鼠额叶乙酰胆碱的影响

目的研究成年期甲状腺功能减退症大鼠额叶内乙酰胆碱变化及甲状腺素替代治疗后的情况。方法 26只成年期雄性SD大鼠随机分为三组,用丙基硫氧嘧啶(PTU)建立成年期大鼠甲减模型,采用放射免疫法测定健康对照组、甲减组、甲状腺素替代治疗组(T4-6)大鼠的血清甲状腺激素水平;碱性羟胺比色法测定脑组织乙酰胆碱含量;用单因素方差分析比较三组之间各项指标差异。结果与健康对照组相比,甲减组大鼠血清T3、T4水平显著减低、TSH水平增加(P<0.05);替代治疗后,血清T3、T4、TSH恢复至正常水平;甲减组大鼠额叶内乙酰胆碱含量降低(P<0.05),替代治疗后乙酰胆碱含量与对照组相比差异无统计学意义(P>0.05)。结论成年期甲减大鼠额叶内乙酰胆碱含量减少,甲状腺素替代治疗后乙酰胆碱含量恢复正常。     

Nuclear binding of triiodothyronine and thyroxine in lymphocytes from subjects with hyperthyroidism, hypothyroidism and resistance to thyroid hormones

Binding of triiodothyronine (T3) and thyroxine (T4) to nuclei of intact human lymphocytes was studied. The binding characteristics were analysed by Scatchard's method. In lymphocytes from euthyroid healthy subjects there was a single set of saturable nuclear T3 and T4 binding sites with an apparent mean equilibrium association constant of 3.3 X 10(10) l/mol and 1.7 X 10(10) l/mol, respectively. The estimated mean maximal specific binding capacity for T3 was 50 fmol/mg DNA and for T4 was 55 fmol/mg DNA, indicating that these two hormones may have a common receptor. In hyperthyroid and hypothyroid patients nuclear affinity for T3 and T4 was very similar to that for euthyroid reference subjects. In hyperthyroidism, T3 and T4 binding capacity was unaltered, whereas in hypothyroidism it was nearly twice as high as in euthyroidism. Lymphocytes from three members of a family with hereditary peripheral resistance to thyroid hormone action were studied. One set of saturable T3 and T4 nuclear binding sites with affinity constants similar to those in the euthyroid group was found. However, in these subjects the estimated binding capacity for T3 and T4 was rather low, indicating that the biochemical defect in this family might be a mild deficiency of nuclear receptor protein. Incubation with diphenylhydantoin and salicylate added in vitro did not alter the binding of T3 and T4 to lymphocyte nuclei. Nuclear binding was also not affected in patients receiving therapeutic amounts of diphenylhydantoin.     

Effect of epinephrine on the peripheral metabolism of thyroxine

10 normal young men received repository epinephrine repeatedly for 4 days during the course of a radiothyroxine (radio-T4) disappearance curve. During epinephrine administration, serum radio-T4 disappearance rate (k) slowed abruptly, fecal clearance decreased, urinary clearance was initially unchanged but later decreased slightly, volume of thyroxine distribution decreased, and external radioactivity over the liver remained unchanged. Beginning on day 2 of epinephrine and persisting at least 1 day after epinephrine was discontinued, serum thyroxine-binding globulin (TBG) maximal binding capacity increased, thyroxine-binding prealbumin (TBPA) maximal binding capacity decreased, and free T4 iodine decreased. Stable serum T4 iodine decreased during the experiment. Three indexes, namely the free T4 iodine, the reciprocal of TBG capacity, and the urinary radio-T4 "clearance" changed in parallel, suggesting that the increase in TBG capacity was responsible for a delayed decrease in radio-T4 metabolism. However, these changes were temporally dissociated from the decrease in k, which began and ended abruptly with initiation or discontinuing of epinephrine administration. This dissociation is unexplained, but may be caused by alterations in T4 binding in tissue sites.     

突触相关蛋白25在成年期甲状腺功能减退症大鼠额叶内表达变化及甲状腺素治疗效应

目的研究成年期甲状腺功能减退症(甲减)大鼠额叶内突触相关蛋白25(SNAP-25)的表达及甲状腺素替代治疗后的恢复状况,探讨甲减脑损伤及恢复的分子基础。方法用丙基硫氧嘧啶(PTU)建立成年期大鼠甲减模型,采用放射免疫法测定甲减组、常规剂量甲状腺素替代治疗组、大剂量甲状腺素替代治疗组、健康对照组大鼠的血清甲状腺素水平,免疫组织化学方法分析四组大鼠额叶内SNAP-25蛋白的表达情况。结果与健康对照组相比,甲减组大鼠血清T3、T4水平显著减低(P<0.02);常规剂量(5μg.kg-1.d-1)替代治疗后,血清T3、T4恢复至正常水平。甲减组额叶I、II、III、IV、V层SNAP-25蛋白的表达水平显著高于健康对照组(P<0.01);常规剂量替代治疗组SNAP-25表达水平与健康对照组比较未见明显差异;与甲减组相比,大剂量(20μg.kg-1.d-1)替代治疗组SNAP-25表达水平在额叶各层显著减低(P<0.05)。结论成年期甲减大鼠额叶SNAP-25蛋白表达增多,常规及大剂量甲状腺素替代治疗后均可降低该蛋白表达,大剂量替代治疗后SNAP-25表达水平更接近正常。     

Studies of peripheral thyroxine distribution in thyrotoxicosis and hypothyroidism

Compartmental analysis of the peripheral distribution of labeled thyroxine was applied to various groups of subjects with thyrotoxicosis and hypothyroidism. It was observed that the hepatic incorporation of thyroxine was augmented in subjects with Graves' disease when compared to non-Graves' disease control groups at all levels of thyroid function. Decreased values of hepatic incorporation occurred in primary hypothyroid subjects. These lowered values were not acutely corrected by elevation of the serum thyroxine level, but were observed to be rectified after several months' therapy with exogenous thyroid hormone. These alterations of the hepatic thyroxine-(131)I incorporation were independently verified by direct quantitative liver scintiscan determinations.Employing a dual thyroxine tracer system, we were able to demonstrate that during the early phases of equilibration of a tracer dose of thyroxine, alterations in the rate of deiodination were observed to be present in the various thyroid disease states. Increased deiodination rates were found in subjects with Graves' disease and the reverse was noted in patients with primary hypothyroidism. Kinetic analysis of thyroxine compartmental distribution during this early phase of equilibration of a labeled thyroxine tracer indicated that the primary tissue uptake occurred in the liver. These findings supported the contention that the amount of labeled thyroxine incorporated in the liver may be directly related to the deiodination rate of thyroxine by that organ. The pathogenetic basis of these alterations is presently unknown.