小剂量甲状腺素治疗能减少Graves病的复发吗?

观察单用抗甲状腺药物 (ATD)治疗组与ATD联合小剂量甲状腺素治疗组之间Graves病(GD)复发率。结果显示两组治疗结束时临床表现、甲状腺功能、TSH受体抗体 (TRAb)阳性率均相似 ,停药 1年GD复发率差异无显著性 ,但复发者甲状腺肿较严重、突眼率较高以及TRAb阳性率较高 (均P <0 .0 1)。     

妊娠期间甲状腺疾病的诊断和处理

正确处理妊娠期间甲状腺疾病是优生优育的重要内容之一。本文结合2011年颁布的“妊娠和产后甲状腺疾病诊治指南”,对妊娠期间甲状腺功能的生理变化,妊娠期甲状腺功能评定,控制存在的甲状腺功能异常避免给胎儿和妊娠过程造成的不良影响做一概述。对于妊娠期Graves病的诊断,要特别强调与妊娠甲状腺功能亢进综合征相鉴别,抗甲状腺药物的选择早期为丙硫氧嘧啶,中晚期改为甲巯咪唑。妊娠期一旦确诊甲状腺功能减退,应立即选择左甲状腺素（L—T4）治疗,并尽早使得血清促甲状腺激素（TSH）水平达标,即孕早期0．1～2．5mU／L,孕中期0．2～3．0mU／L,孕晚期0-3～3．0mU／L。由于妊娠期分化型甲状腺癌的预后和非妊娠期相似,因此手术可推迟至产后施行,并给予L-T4抑制治疗,将血清TSH控制在0．1～1．5mU／L。对于孕期的良性甲状腺结节,不建议补充L-T4治疗。     

Graves病患者甲状腺激素水平正常后sTSH长期抑制机制的探讨

目的 探讨临床上部分Graves病(GD)患者经抗甲状腺药物(ATD)治疗后甲状腺激素水平达到正常,但促甲状腺素(TSH)仍长期处于被抑制状态的机制.方法 入选初发122例GD甲亢患者,予以初始等效剂量的ATD治疗,每月随访时根据甲状腺功能测定的结果酌情减量,并适时添加左旋甲状腺素(L-T4).当甲状腺激素(FT3、FT4)水平持续正常3个月即达随访标准,复查FT3、FT4、sTSH、TSH受体抗体(TRAb),并根据TRAb是否阳性分组比较.结果 122例GD甲亢患者经(7.1±1.1)个月的ATD治疗后,甲状腺激素水平均已经达到正常3个月.随访时,58例TRAb转为阴性,64例TRAb持续阳性.两组甲状腺激素水平无差异, TRAb阳性组的sTSH水平明显低于阴性组[0.044 mIU/L(0.001～4.163 mIU/L) vs 1.749 mIU/L(0.079～4.646 mIU/L),P＜0.01];血清sTSH水平与TRAb呈明显负相关(r=-0.539,P＜0.01),与FT3、FT4、年龄、病程、治疗时间、L-T4剂量、L-T4添加时间等均无相关性.结论 药物治疗过程中,甲状腺激素水平正常的GD患者,其TSH水平长期受抑制的原因与高水平TRAb相关,可能由于TRAb直接与垂体内TSH受体结合,通过超短环反馈抑制TSH的分泌所致.     

妊娠期甲状腺功能减退症的研究进展

妊娠期间由于血清甲状腺素结合球蛋白、人绒毛膜促性腺激素水平增加以及肾脏对碘的清除率增加等,致使妊娠期甲状腺激素的产生、循环、代谢和调节会随妊娠的不同阶段而改变.这为妊娠期间甲状腺疾病的诊断和治疗带来困难.因此,建立妊娠特异性血清甲状腺激素的正常参考范围非常必要,这将降低妊娠期甲状腺疾病的漏诊率和误诊率.妊娠期母体甲状腺功能不足包括临床甲状腺功能减退症(甲减)、亚临床甲减和低甲状腺素血症,可以对后代的神经智力发育造成损伤.妊娠期甲减妇女应该接受左甲状腺素(L-T4)替代治疗,治疗目标为血清促甲状腺激素(TSH)水平在妊娠早期不超过2.5 mIU/L;妊娠中期和妊娠晚期不超过3.0 mIU/L或者不超过妊娠期特异性血清TSH的正常参考范围.     

TSH受体基因突变与先天性非自身免性甲状腺功能亢进症

先天性甲状腺功能亢进是一组综合征。较少见。其中:1)患Graves病母亲的婴儿,这是最常见的新生儿甲亢,是因母体内的甲状腺刺激性抗体(TSAb),通过胎盘进入胎儿血内引起的,随着胎儿的出生,TSAb被清除,新生儿甲亢也消失,故是暂时的;2) Graves病,研究认为TSH受体基因突变,使体内产生能与TSH受体结合的刺激性抗体所致;3)自体免疫性甲状腺疾病:TSH受体基因突变.     

甲状腺疾病与妊娠

妊娠期甲状腺激素的产生、循环、代谢、调节以及甲状腺免疫均会随妊娠的不同阶段而改变。相关的改变包括:(1)雌激素刺激的血清甲状腺素结合球蛋白水平升高。(2)由于人绒毛膜促性腺激素与促甲状腺激素(TSH)的同源性导致的甲状腺激素产生增加。(3)碘在胎盘的降解加快和在肾脏的排除增加。母体甲状腺这些生理性的变化为妊娠期甲状腺疾病的诊断和治疗带来困惑,因此,需要建立孕期特异的TSH、总T4和游离T4正常参考范围。遗憾的是,目前尚无这样的标准。如非妊娠状态一样,TSH也可以作为诊断妊娠期甲状腺疾病首选的指标,TSH检测不受方法学的限制,下限介于0.2~0.4 mIU/L之间,2.5 mIU/L可以作为TSH在妊娠早期正常范围保守的上限。TT4结果稳定,可以通过非妊娠状态的正常值乘以系数1.5来推断妊娠期的参考范围。妊娠期甲状腺功能减退的患者应该接受左旋T4(L-T4)替代治疗,并尽快使TSH低于2.5 mIU/L,L-T4的剂量在妊娠期要较妊娠前增加30%~50%。对于妊娠期甲状腺功能亢进的患者,丙硫氧嘧啶是首选的治疗药物。甲状腺功能正常的自身免疫性甲状腺炎的孕妇在妊娠期发生甲状腺功能减退、分娩后发生产后甲状腺炎的危险性提高,应该注意监测甲状腺功能。     

促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.     

促甲状腺激素受体抗体的检测及其在Graves病诊疗中的价值

血清促甲状腺激素受体抗体(TRAb)是Graves病的特征性抗体,伴随生物检验技术的进步,TSAb的检测方法历经了三代发展.目前的多数研究证实,检测TRAb不仅有助于判断甲状腺毒症发生的原因、评估甲状腺功能、制定诊疗方案,同时对Graves病的相关疾病如Graves眼病、胫前黏液性水肿、肝功能损害病情的评估有重要意义,通过监测TRAb可以一定程度上控制Graves病及其并发症的加重或者复发.检测有Graves病病史的孕妇血清TRAb对安全妊娠也有意义.将目前TRAb的检测方法及其临床意义的研究进展作一综述,有助于临床医师通过TRAb做出决策并提高临床疗效.     

促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.     

甲巯咪唑与丙硫氧嘧啶治疗Graves甲状腺机能亢进症疗效比较

目的探讨甲巯咪唑与丙硫氧嘧啶治疗Graves甲状腺机能亢进症（简称甲亢）的临床疗效差异,为Graves甲亢的临床用药提供理论依据。方法选择100例Graves甲亢初诊患者随机分成两组各50例,分别采用剂量相当的甲巯咪唑与丙硫氧嘧啶治疗。于治疗前、治疗第45天、第90天采血检测血清促甲状腺素（TSH）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素受体抗体（TRAb）、甲状腺过氧化物酶抗体（TPOAb）,比较两组各时间点TSH、FT3、FT4、TRAb、TPOAb水平的差异。结果治疗前两组TSH、FT3、FT4、TRAb、TPOAb水平无统计学差异（P均〉0.05）。治疗后与治疗前比较,两组TSH、FT3、FT4、TRAb、TPOAb水平均降低（P均〈0.05）。治疗第45天、第90天后丙硫氧嘧啶组FT3、FT4水平均高于甲巯咪唑组（P均〈0.01）。治疗后TRAb、TPOAb水平两组间差异无统计学意义（P均〉0.05）。结论甲巯咪唑治疗Graves甲亢疗效显著性优于丙硫氧嘧啶。     

Therapy insight: management of Graves' disease during pregnancy

The diagnosis of Graves' disease in pregnancy can be complex because of normal gravid physiologic changes in thyroid hormone metabolism. Mothers with active Graves' disease should be treated with antithyroid drugs, which impact both maternal and fetal thyroid function. Optimally, the lowest possible dose should be used to maintain maternal free thyroxine levels at or just above the upper limit of the normal nonpregnant reference range. Fetal thyroid function depends on the balance between the transplacental passage of thyroid-stimulating maternal antibodies and thyroid-inhibiting antithyroid drugs. Elevated levels of serum maternal anti-TSH-receptor antibodies early in the third trimester are a risk factor for fetal hyperthyroidism and should prompt evaluation of the fetal thyroid by ultrasound, even in women with previously ablated Graves' disease. Maternal antithyroid medication can be modulated to treat fetal hyperthyroidism. Serum TSH and either total or free thyroxine levels should be measured in fetal cord blood at delivery in women with active Graves' disease, and those with a history of (131)I-mediated thyroid ablation or thyroidectomy who have anti-TSH-receptor antibodies. Neonatal thyrotoxicosis can occur in the first few days of life after clearance of maternal antithyroid drug, and can last for several months, until maternal antibodies are also cleared.     

Management of thyrotoxicosis and pregnancy: Review of the current literature and an update of the care pathway

Pregnancy can be complicated by hyperthyroidism or thyrotoxicosis. Diagnosis is founded on an increase in free thyroid hormones and low TSH. The most frequent etiologies are Graves’ disease, an autoimmune disease linked to stimulatory anti-TSH receptor antibodies, and non-autoimmune gestational hyperthyroidism linked to the TSH-like activity of the chorionic growth hormone (hCG). During pregnancy, thyrotoxicosis can entail maternal, obstetrical and fetal or neonatal complications. Graves’ hyperthyroidism may be responsible for fetal and neonatal hyperthyroidism due to placental transfer of stimulatory anti-TSH receptor antibodies. During pregnancy, treatment of thyrotoxicosis must restore normal thyroid function in the mother without affecting fetal thyroid function. The recent reassessment of the prevalence of teratogenic effects in children of women treated with antithyroid drugs in the first weeks of gestation should orient the care pathway before and during pregnancy for women of child-bearing age with hyperthyroidism linked to Graves’ disease.     

Graves病患者甲状腺功能改变与细胞免疫相关分析

目的探讨Graves病患者甲状腺功能与机体的细胞免疫间的关系。方法（1）采用流式细胞仪检测20例高功能Graves病患者和20例健康对照组的T淋巴细胞亚群和CD8-／IFN-γT（Th1）细胞和CD8-／IL-4＋T（Th2）细胞的百分含量。（2）化学发光法检测FT3、FT4、s-TSH,放射免疫法检测TRAb、TGAb、TMAb。（3）应用逐步回归分析,以FT3、FT4、8-TSH为因变量,CD4T细胞、CD8T细胞、CD4＋／CD8＋T细胞比值、Th2细胞百分含量、Th1细胞百分含量、Th1／Th2比值、TRAb、TGAb、TMAb滴度为自变量进行分析。结果（1）Graves病患者的FT3,s—TSH、TRAb、TGAb、TMAb滴度均较正常对照组明显增高（P〈0．01）。（2）Graves病患者较正常人群CD4＋T细胞和CD4＋／CD8＋T细胞比值增高;Th2百分含量增高;而CD8＋T细胞、Th1细胞及Th1／Th2细胞比值下降（P均〈0．05）。（3）CD4／CD8＋T细胞比值、Th1／Th2细胞比值以及TRAb、TGAb、TMAb成为影响FT3、FT4、TSH变化的重要因素。结论Graves病患者机体的T细胞免疫调节失衡不仅参与疾病的发生和发展,还影响了甲状腺激素功能。CD4＋／CD8＋T细胞比值、Th1／Th2比值可作为临床治疗的监测高功能Graves病活动及疗效的指标。     

甲状腺功能亢进症的药物治疗

甲状腺功能亢进症（甲亢）病因较复杂,在临床上以弥漫性毒性甲状腺肿伴甲亢（Graves病）最常见。甲亢的药物治疗包括抗甲状腺药（ATD）、碘剂、B受体阻滞剂、糖皮质激素、碳酸锂等。ATD是治疗甲亢的主要手段,常用药物为丙基硫氧嘧啶（PTU）和甲巯咪唑（MMI）。总的来说,ATD治疗安全且有效,但其临床不良反应亦较常见,一般程度较轻,及时停药能自行恢复,但亦可出现少见、严重的副作用。MMI与PTUI：L较,其不良反应显著低于PTU,且前者大多具有剂量依赖性。因此轻中度甲亢及甲亢维持治疗首选MMI。复方碘溶液用于术前准备及甲亢危象等;糖皮质激素主要用于甲状腺相关性眼病、甲亢危象等;B受体阻滞剂多用于控制甲亢初治期的症状;碳酸锂一般不作为常规使用,仅适合短期治疗。临床医师根据患者的病情及个体差异综合考虑,选用合适的治疗方案,密切监测疗效及不良反应。     

系统性红斑狼疮合并甲状腺疾病的临床特征分析

目的 调查系统性红斑狼疮（SLE）合并免疫性甲状腺疾病的年患病数,并探讨分析其临床特点.方法 回顾性调查2008年度武汉同济医院风湿免疫科住院的172例SLE病例,分析其中49例检测了甲状腺功能患者的临床资料,并分组比较SLE合并甲状腺疾病的临床特征.结果 SLE合并甲状腺功能减退症（甲减）组,17例;SLE合并甲状腺功能亢进症（甲亢）组,10例;病例对照组,22例.SLE合并甲状腺疾病的总体患病率约为15.7%,合并甲减和甲亢的患病率分别为9.89%和5.81%.多关节炎和抗ds-DNA抗体阳性检出率低是SLE合并甲减的主要特征,发热则在SLE合并甲亢的病人多见（P均＜0.05）.结论 SLE合并甲状腺疾病临床并不少见,它具有独特的临床特征,应注意监测其甲状腺功能.     

Drug discontinuation after treatment with minimum maintenance dose of an antithyroid drug in Graves' disease: a retrospective study on effects of treatment duration with minimum maintenance dose on lasting remission

According to the guideline issued by the Japan Thyroid Association in 2006 for treatment of Graves' disease, discontinuing antithyroid drug (ATD) therapy is recommended when serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations have been maintained within the reference range for a certain period after treatment with one ATD tablet every other day (minimum maintenance dose therapy, MMDT). In this retrospective study, the relationship between MMDT duration and remission rate was investigated. The participants were 107 consecutive patients with Graves' disease whose ATD therapy was stopped according to the guideline. Serum FT4, TSH, and TSH receptor antibody (TRAb) levels were measured when ATD was discontinued and every 3 months thereafter. The percentage of patients in remission was 86.9% at 6 months, 73.8% at 1 year, and 68.2% at 2 years after ATD discontinuation. The remission rate increased with MMDT duration, being significantly higher in patients with MMDT durations of 19 months or more than those with MMDT durations of 6 months or less. In patients with MMDT durations of 6 months or less, the remission rate was significantly lower in TRAb-positive patients than in TRAb-negative patients at the time of withdrawal of ATD; however, this was not observed in patients with MMDT durations of 7 months or more. These findings suggest that in patients who discontinue ATD after a certain MMDT duration, the remission rate increases as the MMDT duration increases, and ATD should not be discontinued in TRAb-positive patients with MMDT durations of 6 months or less.     

Pericardial effusion associated with subclinical hypothyroidism

Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Subclinical hypothyroidism is defined by elevated serum levels of TSH with normal levels of free thyroid hormones. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. It has been reported that sub-clinical hypothyroidism is associated with both, a significant risk of coronary heart disease at baseline and at follow-up and that mortality from cardiovascular causes is significantly higher at follow-up. However subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications. Pericardial effusion can be present in systemic disorders including hypothyroidism. We present a case of subclinical hypothyroidism in a 41-year-old Italian woman with an ubiquitary pericardial effusion. Also this case focuses attention on subclinical hypothyroidism.     

Graves病患者131I治愈前后尿微量蛋白的变化观察

目的：探讨Graves病（简称GD）患者131 I治愈前后尿微量蛋白变化的影响因素。方法选择GD患者20例（GD组）,根据131I治愈前后分成治疗前的GD组、治愈3个月R3M组、治愈12个月R12M组,并设正常对照组20例。采用全自动化学免疫发光法检测血清游离甲功3项[包括游离三碘甲状腺原氨酸（ FT3）、游离甲状腺素（ FT4）、促甲状腺素（ TSH）]、促甲状腺受体抗体（ TRAb）、尿微量白蛋白（ Alb）、尿免疫球蛋白（IgG）、尿微球蛋白（β2-MG）含量。采用散射比浊法检测血清中超敏C反应蛋白（hs-CRP）。全自动血凝仪测定血清D-二聚体（ D-D）。 SPECT计算总肾小球滤过率（ TRGFR）。结果 GD组游离甲功3项与各组比较差异有统计学意义（ P＜0.01）。 GD组、R3M组的TRAb、Alb、IgG与其余组比较差异有统计学意义（ P＜0.01）。直线相关分析显示,FT3与Alb、IgG呈显著正相关（ r分别为0.64、0.72, P均＜0.01）, TRAb与Alb、IgG呈显著正相关（ r分别为0.66、0.56,P均＜0.01）。结论 GD肾损害的部位在肾小球,与免疫紊乱关系密切;GD相关抗体的消失可作为判断GD肾损害的恢复及治疗效果的参考指标。