课件：单忠艳妊娠甲状腺.ppt

,妊娠甲状腺疾病的诊治 解读妊娠和产后甲状腺疾病诊治指南,中国医科大学附属第一医院 单忠艳,一、指南简介,J Clin Endocrinol Metab 92: S1-S47,2007,美国 TES 指南,Thyroid 21: 1-45, 2011,美国 ATA 指南,中华医学会内分泌学分会和中华医学会围产医学分会 合作，遵循“立足国情，循证为本，求新求实，资源共享” 的原则，以ATA2011年的妊娠和产后甲状腺疾病诊断和 处理指南为蓝本，加入我国学者的研究内容，结合我国 临床工作和妇幼保健工作的实际情况编撰本指南。,指南编撰原则,一、 妊娠期甲状腺相关指标正常值 二、 临床甲状腺功能减退症 三、 亚临床甲状腺功能减退症 四、 单纯低甲状腺素血症 五、 甲状腺自身抗体阳性 六、 产后甲状腺炎 七、 妊娠期甲状腺毒症 八、 碘缺乏 九、 甲状腺结节和甲状腺癌 十、 先天性甲状腺功能减退症 十一、妊娠期甲状腺疾病筛查,指南目录,11个章节 68项问题条款 57项推荐条款,推荐条款根据循证医学的强度分为5级,推荐条款,二、妊娠亚临床甲减诊断和治疗,亚临床甲减诊断（本指南 vs ATA）,ATA Thyroid 21: 1-45,2011,SCH is dened as a serum TSH between 2.5 and 10 mIU/L with a normal FT4 concentration,血清TSH正常范围的确定,美国国家临床生化研究院(NACB),我国学者获得的TSH参考值,中国妊娠妇女血清TSH、FT4参考值（2.5th 97.5th ）,李佳、滕卫平、单忠艳等，中华内分泌代谢杂志 2008，24：605-608 罗 军、韩 密、范建霞等，中华围产医学杂志，2012，待发表 Yan Y, Dong Z, Dong L et al: Clinical Endocrinology 2011, 74: 262-269,我国学者获得的TSH参考值,亚临床甲减：干预,SCH has been associated with adverse maternal and fetal outcomes. However, due to the lack of randomized controlled trials there is insufcient evidence to recommend for or against universal LT4 treatment in TAb negative pregnant women with SCH. Level I-USPSTF,亚临床甲减：干预,Women who are positive for TPOAb and have SCH should be treated with LT4. Level B-USPSTF,亚临床甲减：调查,妊娠期亚临床甲减与产科并发症,薛海波、单忠艳、滕卫平等 ：中华内分泌代谢杂志，2010，26：4-7,亚临床甲减：调查,注：亚临床甲减A组TSH2.53.93mIU/L；亚临床甲减B组TSH3.93mIU/L组。 a P0.05, b P0.01。 DPC试剂测定,妊娠T1期亚临床甲减对后代神经智力发育的影响,薛海波、单忠艳、滕卫平等：中华内分泌代谢杂志，2010，26：4-7,测定方法：DPC试剂,妊娠妇女血清TSH升高程度与后代MDI/PDI的相关关系,亚临床甲减：调查,PDI,MDI,薛海波、单忠艳、滕卫平等：中华内分泌代谢杂志，2010，26：4-7,测定方法：DPC试剂。,血清 TSH升高程度与后代MDI、PDI降低相关关系,亚临床甲减：调查,Lazarus JH ; New Engl J Med 366：493-501 2012,亚临床甲减：干预,CATS 研究 N=22,000,Lazarus JH ; New Engl J Med 366：493-501 2012,亚临床甲减：干预,The previous observational study included women with a mean thyrotropin level of 13.2 mIU per liter, 9 significantly higher than in the treatment groups in the current study, in which the median thyrotropin levels were 3.8 mIU per liter (range, 1.5 to 4.7) in the United Kingdom and 3.1 mIU per liter (range, 1.3 to 4.0) in Italy. Only about half the women in the trial were included on the basis of an elevated thyrotropin level; about half had hypothyroxinemia, and a small fraction (5%) had both. The absence of a clinically significant effect of levothyroxine treatment in the current study may be explained at least in part by the inclusion of women with milder hypothyroidism,Brent GA ; New Engl J Med 366:52, 2012,亚临床甲减：干预,CATS研究中L-T4干预亚临床甲减得到的阴性结果至少部分 可以用治疗的妊娠妇女亚临床甲减程度较轻解释,亚临床甲减：干预,Abalovich M：Thyroid 12：63-68，2002,足量L-T4治疗（N=27）,非足量L-T4治疗（N=24）,三、妊娠低甲状腺素血症,推荐条款,Isolated hypothyroxinemia is dened as a normal maternal TSH concentration in conjunction with FT4 concentrations in the lower 5th or 10th percentile of the reference range.,中国妊娠妇女FT4参考值的5th和10th切点值（pmol/L）,推荐条款,Isolated hypothyroxinemia should not be treated in preg- nancy. Level C-USPSTF,推荐条款,低T4血症：调查,低T4血症：调查,妊娠期低T4血症导致后代神经智力发育损害,*,#,Compared to control group* p=0.004；# p=0.007,Yuanbin LI,Zhongyan SHAN：Clin Endocrino;(oxf),2010. 72(6):825-829.,低T4血症：调查,妊娠16-20周孕妇低T4血症与后代PDI和MDI,Lazarus JH ; New Engl J Med 366：493-501 2012,低T4血症：干预,CATS 研究 N=22,000,Lazarus JH ; New Engl J Med 366：493-501 2012,低T4血症：干预,The previous observational study included women with a mean thyrotropin level of 13.2 mIU per liter, 9 significantly higher than in the treatment groups in the current study, in which the median thyrotropin levels were 3.8 mIU per liter (range, 1.5 to 4.7) in the United Kingdom and 3.1 mIU per liter (range, 1.3 to 4.0) in Italy. Only about half the women in the trial were included on the basis of an elevated thyrotropin level; about half had hypothyroxinemia, and a small fraction (5%) had both. The absence of a clinically significant effect of levothyroxine treatment in the current study may be explained at least in part by the inclusion of women with milder hypothyroidism,Brent GA ; New Engl J Med 366:52, 2012,CATS研究中L-T4干预亚临床甲减得到的阴性结果至少部分 可以用治疗的妊娠妇女亚临床甲减程度较轻解释,低T4血症：干预,四、妊娠甲状腺抗体阳性,推荐条款,Euthyroid women (not receiving LT4) who are TAb require monitoring for hypothyroidism during pregnancy. Serum TSH should be evaluated every 4 weeks during the rst half of pregnancy and at least once between 26 and 32 weeks gestation. Level B-USPSTF,推荐条款,There is insufcient evidence to recommend for or against LT4 therapy in TAb euthyroid women during pregnancy.,Thangaratinam S , etal: Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence 英国伦敦女王玛丽大学，健康科学中心,甲状腺自身抗体与流产、早产：荟萃分析,原始资料： 抗体与流产：31项研究（19项队列研究， 12项病例对照），N=12,126； 抗体与早产：5项研究，N=12,566,妊娠甲状腺抗体阳性,Thangaratinam S, et. BMJ. 2011, 9;342：d2616.,甲状腺自身抗体（甲功正常）与流产、早产关系-meta分析,Thangaratinam S, et. BMJ. 2011, 9;342：d2616.,妊娠妇女TAA阳性流产发生危险升高3倍,妊娠妇女TAA阳性早产发生危险升高2倍,Thangaratinam S, et. BMJ. 2011, 9;342：d2616.,妊娠妇女TAA阳性IVF流产发生危险升高2倍,Konstantinos A Toulis1, et al. Eur J Endocrin, 2010, 162 643652,妊娠期TPOAb阳性与后代智力发育,回顾性调查：16-20周孕妇，后代25-30月MDI和PDI,李元宾、单忠艳等：Clin Endocrino;(oxf),2010, 72（6）：825-829.,前瞻性研究：妊娠8周妇女，后代14-30月MDI和PDI；2组： TPOAb300 IU/mL,Negro R, et al. JCEM 2006， 91：2587-2591,妊娠甲状腺抗体阳性：L-T4干预,治疗组 N=57 非治疗组 N=58,妊娠甲状腺抗体阳性：L-T4 干预,Negro R, et al. JCEM 2006， 91：2587-2591,治疗组 N=57 非治疗组 N=58,S1 TPOAb（+）77 cases： Selenium intervention S0 TPOAb（+）74 cases： placebo,Negro R：JCEM, 92: 1263, 2007,妊娠甲状腺抗体阳性：硒干预,Negro R. et al. JCEM 2007,妊娠甲状腺抗体阳性：硒干预,硒干预TPOAb阳性孕妇减少PPTD和永久性甲减发生率,安徽医科大学妇幼保健教研室 陶芳标小组,N=1017，妊娠前20周标本,Tao FB：JCEM， 2011，96：3234-3241,妊娠亚甲减、低T4血症：出生缺陷,Tao FB：JCEM， 2011，96：3234-3241,妊娠亚甲减、低T4血症：出生缺陷,Tao FB：JCEM， 2011，96：3234-3241,流程,五、妊娠甲状腺疾病筛查,推荐条款,There is insufcient evidence to recommend for or against universal TSH screening at the rst trimester visit. Level I-USPSTF,推荐条款,Because no studies to date have demonstrated a benet to treatment of isolated maternal hypothyroximenia, universal FT4 screening of pregnant women is not recommended. Level D-USPSTF,妊娠期进行甲状腺疾病筛查的高危人群,有甲亢、甲减、产后甲状腺炎或甲状腺手术史 有甲状腺疾病家族史 患有甲状腺肿 甲状腺自身抗体阳性 (已知) 提示存在甲状腺低功或高功症状或体征（包括贫血、 高胆固醇水平和低钠血症） 患有1型糖尿病 患有其他自身免疫性疾病 不孕 具有头颈部放射史 具有早产史,Abalovich M et al.J Clin Endocrinol Metab,2007,92:S1-S47.,10. 肥胖症的妇女 BMI40Kg/m2 11. 30岁以上妇女 12. 曾用胺碘酮的妇女 13. 用过锂治疗的妇女 14. 6周内碘造影剂暴露的妇女,对高危人群进行筛查的局限,Bijay Vaidya JCEM 92: 203-207, 2007,仅在高危妇女中筛查甲状腺功能，1/3 TSH升高的患者被漏诊,高危人群筛查策略的局限性,Wang W, Teng W, Shan Z et al. Euro J Endocrinol, 2011, 164: 263268,结果：仅对高风险妊娠妇女实施筛查会漏掉80.4%甲亢 和81.6%的甲减妇女,2899名妊娠早期妇女,成本效益（Cost-effectiveness）分析,用Markov状态转移模型对不筛查、筛查TSH、筛查TPOAb三个模式做成本效益分析 结果发现，对妊娠早期妇女进行TSH和TPOAb的筛查，在治疗花费及预防可能存在的不良结局方面都具有较高的成本效益,