被“豆浆”改写的一例TSH异常增高案例分析

2022-08-06 刘涛 铜川市人民医院 “检验医学”公众号

病史:患者女,33岁,2022年3月正常孕检检测甲功三项(FT3、FT4、TSH),TSH为4.75mlU/L,后诊断为亚临床甲减,规律服用优甲乐(四碘甲状腺原氨酸),定期检查TSH。

前 言

亚临床甲减作为常见内分泌异常疾病,妊娠期机体激素水平改变或分泌异常,导致免疫功能发生相应改变,进而导致甲状腺激素代谢紊乱而引发[1]。适量的甲状腺激素有利于维持女性生殖内分泌轴的功能稳定,亚临床甲减可增加自然流产、早产、子代神经智力发育异常等风险,因此,妊娠期合并亚临床甲减一经确诊,及时有效的处理尤为重要。

临床上常以左甲状腺素钠片(优甲乐)作为替代治疗药物,可有效降低TSH水平。优甲乐是一种甲状腺激素类药物,左甲状腺素钠为该药物的主要成分,与机体甲状腺合成的四碘甲状腺原氨酸完全相同[2]。口服后于体内转化为三碘甲状腺原氨酸以实现维持材体正常发育、促进代谢、增加产热、提高交感一肾上腺系统感受性等效果[3]。

案例经过

病史:患者女,33岁,2022年3月正常孕检检测甲功三项(FT3、FT4、TSH),TSH为4.75mlU/L,后诊断为亚临床甲减,规律服用优甲乐(四碘甲状腺原氨酸),定期检查TSH。2022年6月14日检测TSH为6.93mlU/L,因患者定期服药且既往TSH检测结果平稳(图1),2022年6月20日到检验科对本次结果提出疑问。

图1 患者TSH近期检测结果

案例分析

1、检查患者样本,样本离心彻底,条码清楚,检测为双向通道,不存在样本张冠李戴的情况。

2、对当天质控结果进行分析,质控图延续性良好,两个水平质控结果均在控。

3、其他患者检测结果与临床相符,未提出质疑。

4、对该患者样本再次进行检测,检测结果为6.98mIU/L,本实验室检测平台为西门子Atellica生化免疫一体机,TSH两次检测结果一致。

操作过程没有错误,是什么原因导致本次TSH异常增高呢?

联系该孕妇,孕妇叙述自己当晚没有熬夜,睡眠正常,没有使用其他药物,与临床医生联系未发现其他干扰TSH的相关疾病。对该患者样本进行甲功七项目检测,进一步产找原因。

检测结果(图2)T3:1.04nmol/L、T4:52.30nmol/,由于该孕妇既往没有检查过T3、T4结果,无法比对此两项,从此结果看,T3、T4降低,TSH升高,为下丘脑-垂体-甲状腺轴的反馈正常调节,从检验结果来讲,检测结果无误。由于患者规律服用优甲乐(四碘甲状腺原氨酸),因此阅读优甲乐说明书。

图2 复检甲功七项检测结果

图3 停止服用豆浆后检测结果

优甲乐[药理作用]:优甲乐含有25~300μg与甲状腺产生的T4完全相同的合成甲状腺素T4。左旋甲状腺素(四碘甲状腺原氨酸,T4)由人体甲状腺合成和分泌。当甲状腺激素缺乏(甲状腺功能减退症)时,垂体前叶分泌促甲状腺素(TSH)增多,进而促使甲状腺合成和分泌T4。

目前血液TSH浓度已经被认为是反映依赖甲状腺激素代谢状况的首要指标。优甲乐通过人体内分泌的反馈作用机制,抑制TSH的分泌,进而达到减少甲状腺TSH受体和血液中TSH受体抗体,起到预防甲亢复发的作用。优甲乐还能够有效地抑制脑垂体TSH的过度分泌,从而达到预防术后甲状腺肿复发的作用。

从说明书中可以发现,优甲乐主要作用即为补充T4,通过反馈作用,抑制TSH的分泌,因此可以推断,是否该孕妇某种方式影响优甲乐的吸收,导致T4含量降低,从而致使TSH浓度升高。

在说明书中并没有给出具体影响优甲乐吸收的原因,查找相关文献,一项由加州大学洛杉矶分校大卫·格芬医学院DeborahA.Chon等的研究表明,牛奶、豆类、浓咖啡、饮料[4]等,会影响优甲乐的吸收。

患者是否存在饮用以上食物,导致优甲乐吸收不足呢?再次联系患者,询问患者是否食用以上食物,患者告诉我们,最近新购买了一台豆浆机,早上会喝一杯豆浆,但是是在服药后半小时之后饮用。听到这个答案,让我们也松了一口气,于是向患者说明相关影响因素,并告知患者,近期早上不要喝豆浆,或者在服药4小时候再喝豆浆。7月2日检测TSH结果为2.51mIU/L,检测结果与之前一致。得到患者的高赞,原来是一杯豆浆改变了TSH结果。

豆浆、牛奶等影响优甲乐吸收的原因可能为乳钙成分高,均匀化、吸收率都较好,会在胃肠道内与左旋甲状腺素发生非特异性吸附,干扰优甲乐的吸收[4]。

总 结

除了饮食,以下因素也会影响优甲乐吸收:

药物:消胆胺、考来替泊、胃黏膜保护剂硫糖铝、抗酸药氢氧化铝、钙片、H2 受体阻滞剂以及质子泵抑制剂等通过各种形式妨碍其吸收。因此,这些药物最好间隔4h后服用。

优甲乐储存温度:优甲乐药物说明书建议储藏温度为25℃以下,尤其夏季,会发现患者甲状腺功能的指标会出现异常波动情况,或许与高温影响优甲乐药效有关。

服药时间:优甲乐主要在小肠被吸收,容易受胃内PH影响,进食后胃酸分泌量增加,因此建议用清水空腹服药,30min后进食,豆制品、牛奶等服药后4小时再食用,检测甲功项目尽量选用空腹采血检测,减少检验前对检测结果的影响因素。

购药途径:遇一患者,通过其他方式购买优甲乐,用量增加后TSH还是无法降到要求值,在我院购买优甲乐服用后TSH很快降下来。

专家点评

随着检验技术的不断发展,临床医师、患者对检验人员解读报告能力的要求不断提升,本文从药理方面入手,剥丝抽茧,查找出导致TSH的影响因素。作为检验人员,除了做好基础检验工作,更应该关注检验结果的影响因素,做好临床报告解读工作。面对每一次患者对结果的质疑,都是一种挑战和进步,从检验中的质量控制查找可能存在的操作失误,到检验前的药物、饮食、采血时间等的影响因素,逐一寻找到影响检测结果的正真原因,不仅能提高检验人员对检验以外知识的学习,还能提升检验人员解决问题的能力,更能得到患者对检验人员的认可,提升患者就医体验感。检验人路漫漫其修远兮,吾将上下而求索!

点评专家:王剑锋主任技师

参考文献

[1]朱静静,徐琳.优甲乐对妊娠甲状腺功能减退症患者甲状腺功能及母婴妊娠结局的影响分析[J].海峡药学,201931(6):179-181.

[2]陈霞,谷雪梅,方明.左旋甲状腺激素片替代治疗冠心病合并亚临床甲减患者TSH、血脂及MPO、hs-CRP水平变化及意义[J].浙江医学,2016,38(11):822-825.

[3]ZdraveskaNikolina,Zdravkovska Maja,AnastasovskaVioleta, et al. Diagnostic reevaluation of congenital hypothyroidismin Macedonia: predictors for transient opermanent hypothyroid-ism[J].Endocrine connections,2018,7(2):278-285.

[4]Chon, Deborah A.,Reisman, Tamar,Weinreb, Jane E.,Hershman, Jerome M.,Leung, Angela M..Concurrent Milk Ingestion Decreases Absorption of Levothyroxine[J].Thyroid: official journal of the American Thyroid Association,2018,28(4):454-457.

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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-09 ms1000002107032646

    真棒

    0

  3. 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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-09 远方的寻梦者

    亚临床甲减作为常见内分泌异常疾病,妊娠期机体激素水平改变或分泌异常,导致免疫功能发生相应改变,进而导致甲状腺激素代谢紊乱而引发

    0

  4. 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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-08 仁心济世
  5. 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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-08 gostraight
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createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Mon Aug 08 06:55:00 CST 2022, time=2022-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1559940, encodeId=c35a15599405e, content=<a href='/topic/show?id=468192183fb' target=_blank style='color:#2F92EE;'>#豆浆#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92183, encryptionId=468192183fb, topicName=豆浆)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f83d15047337, createdName=gostraight, createdTime=Mon Aug 08 06:55:00 CST 2022, time=2022-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1561665, encodeId=bd2415616657a, content=<a href='/topic/show?id=118142341b1' target=_blank style='color:#2F92EE;'>#增高#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42341, encryptionId=118142341b1, topicName=增高)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=af9415191444, createdName=liuxiaona, createdTime=Mon Aug 08 06:55:00 CST 2022, time=2022-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1565949, encodeId=5d741565949c6, content=<a href='/topic/show?id=468192183fb' target=_blank style='color:#2F92EE;'>#豆浆#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92183, encryptionId=468192183fb, topicName=豆浆)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Mon Aug 08 06:55:00 CST 2022, time=2022-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1567674, 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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-08 liuxiaona
  7. [GetPortalCommentsPageByObjectIdResponse(id=2056381, encodeId=69b5205638139, content=<a href='/topic/show?id=9205623394a' target=_blank style='color:#2F92EE;'>#案例分析#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62339, encryptionId=9205623394a, topicName=案例分析)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Sat Apr 15 05:55:00 CST 2023, time=2023-04-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1237663, encodeId=e953123e6633f, content=真棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0e548268336, createdName=ms1000002107032646, createdTime=Tue Aug 09 18:55:57 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1237473, encodeId=9020123e473d1, content=亚临床甲减作为常见内分泌异常疾病,妊娠期机体激素水平改变或分泌异常,导致免疫功能发生相应改变,进而导致甲状腺激素代谢紊乱而引发, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/10/13/09a1c6a3b0a40a39c37ae02a36a89024.jpg, createdBy=40f12506927, createdName=远方的寻梦者, createdTime=Tue Aug 09 00:41:57 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407812, encodeId=7de6140e812fc, content=<a href='/topic/show?id=e0731e891b9' target=_blank style='color:#2F92EE;'>#TSH#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17891, encryptionId=e0731e891b9, topicName=TSH)], attachment=null, authenticateStatus=null, 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  8. 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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-08 liuxiaona
  9. 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encodeId=3b72123e00322, content=签到学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Aug 06 22:34:13 CST 2022, time=2022-08-06, status=1, ipAttribution=)]
    2022-08-07 ms4000001617073333

    0

  10. 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    2022-08-06 屋顶瞄爱赏月

    签到学习

    0