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JCEM：Tildacerfont对成人典型先天性肾上腺增生症患者的疗效与安全性研究

2021-08-17 MedSci原创 MedSci原创

先天性肾上腺增生症
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最近发表在Journal of clinical Endocrinology&Metabolism上的两项2期临床研究的结果，21-羟化酶缺乏(21OHD)导致的典型先天性肾上腺皮质增生症(C

最近发表在Journal of clinical Endocrinology&Metabolism上的两项2期临床研究的结果，21-羟化酶缺乏(21OHD)导致的典型先天性肾上腺皮质增生症(CAH)患者可能从药物tildacerfont中获益。 Spruce Biosciences的Chris N. Barnes博士指出，目前治疗CAH的方法是通过给予超生理水平的糖皮质激素(GC)来下调过量雄激素的产生。然而，这种方法可能会导致明显的副作用，如生长发育不良、肥胖，以及发生2型糖尿病、心血管疾病、骨质疏松、皮肤毒性、胃肠道紊乱和寿命缩短的风险增加。 “Tildacerfont(SPR001；LY2371712)是一种强效、选择性、非甾体类、口服、第二代CRF 1型(CRF1)受体拮抗剂，可与垂体中的CRF1受体高亲和力结合，并减少ACTH分泌，当对 CAH 患者给药时，ACTH分泌的减少有望减少肾上腺皮质醇前体和雄激素的过度产生。通过独立的机制控制肾上腺雄激素过多，tildacerfont可以减轻与高雄激素暴露相关的临床症状，使GC减少到接近生理水平的给药，从而减少超生理GC的不

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    2022-02-03 xuyong523

    #肾上腺#

    0

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    2021-10-26 1179102698_36768935

    #疗效与安全性#

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    2021-09-19 仁者大医

    #JCEM#

    0

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encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2022-04-05 ms2186806800017884

    #先天性肾上腺增生#

    0

  5. 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encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2021-10-11 jml2009

    #ACER#

    0

  6. 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encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2022-05-18 ms3994565386320060

    #ILD#

    0

  7. 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createdBy=e656479, createdName=achengzhao, createdTime=Thu Jun 30 06:44:45 CST 2022, time=2022-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1778971, encodeId=93ba1e78971f3, content=<a href='/topic/show?id=58421840ab' target=_blank style='color:#2F92EE;'>#ACER#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1840, encryptionId=58421840ab, topicName=ACER)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Fri Apr 08 06:44:45 CST 2022, time=2022-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656067, encodeId=2cdc165606e71, content=<a href='/topic/show?id=2a011829d7' target=_blank style='color:#2F92EE;'>#ACE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1829, encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2022-06-30 achengzhao

    #JCE#

    0

  8. 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createdBy=e656479, createdName=achengzhao, createdTime=Thu Jun 30 06:44:45 CST 2022, time=2022-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1778971, encodeId=93ba1e78971f3, content=<a href='/topic/show?id=58421840ab' target=_blank style='color:#2F92EE;'>#ACER#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1840, encryptionId=58421840ab, topicName=ACER)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Fri Apr 08 06:44:45 CST 2022, time=2022-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656067, encodeId=2cdc165606e71, content=<a href='/topic/show?id=2a011829d7' target=_blank style='color:#2F92EE;'>#ACE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1829, encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2022-04-08 jml2009

    #ACER#

    0

  9. 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createdBy=e656479, createdName=achengzhao, createdTime=Thu Jun 30 06:44:45 CST 2022, time=2022-06-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1778971, encodeId=93ba1e78971f3, content=<a href='/topic/show?id=58421840ab' target=_blank style='color:#2F92EE;'>#ACER#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1840, encryptionId=58421840ab, topicName=ACER)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Fri Apr 08 06:44:45 CST 2022, time=2022-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1656067, encodeId=2cdc165606e71, content=<a href='/topic/show?id=2a011829d7' target=_blank style='color:#2F92EE;'>#ACE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1829, encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2022-01-11 shanyongle

    #ACE#

    0

  10. 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encryptionId=2a011829d7, topicName=ACE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=635024767990, createdName=shanyongle, createdTime=Tue Jan 11 06:44:45 CST 2022, time=2022-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369556, encodeId=96a61369556a5, content=<a href='/topic/show?id=bc9f28589d0' target=_blank style='color:#2F92EE;'>#先天性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28589, encryptionId=bc9f28589d0, topicName=先天性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a435298, createdName=huirong, createdTime=Thu Aug 19 00:44:45 CST 2021, time=2021-08-19, status=1, ipAttribution=)]
    2021-08-19 huirong

    #先天性#

    0

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JCEM：先天性肾上腺增生症雄激素的排泄的调节——改良的糖皮质激素vs.常规糖皮质激素

替代路径介导的雄激素合成在先天性肾上腺增生症(CAH)中显着增加了雄激素的过剩。改良的氢化可的松通过替代途径弱化主要底物——17OHP来控制雄激素的合成，它比传统的糖皮质激素（GC）治疗要优越。

2018 TES临床实践指南：类固醇21-羟化酶缺乏导致的先天性肾上腺皮质增生症

2018年9月，美国内分泌学会(TES)更新发布了类固醇21-羟化酶缺乏导致的先天性肾上腺皮质增生症的管理指南，是对2010年版指南的更新，专家小组基于当前证据以及专家观点针对类固醇21-羟化酶缺乏导致的先天性肾上腺皮质增生症管理提出实践指导。

JCEM：先天性肾上腺增生症患者的心血管和代谢结局

由此可见，CAH患者表现出心血管和代谢危险因素的高患病率。目前的证据依赖于替代结局。有必要进行长期前瞻性研究来评估降低CAH患者心血管风险的策略。