诊断学理论与实践 ›› 2022, Vol. 21 ›› Issue (06): 741-745.doi: 10.16150/j.1671-2870.2022.06.13
张美玲1, 朱潇邦1, 宋爱玲1(), 周剑平1,2,3, 李庆云1,2,3
收稿日期:
2022-07-26
出版日期:
2022-12-25
发布日期:
2023-04-23
通讯作者:
宋爱玲
E-mail:e_sail@163.com
基金资助:
ZHANG Meiling1, ZHU Xiaobang1, SHONG Ailing1(), ZHOU Jianping1,2,3, LI Qingyun1,2,3
Received:
2022-07-26
Online:
2022-12-25
Published:
2023-04-23
Contact:
SHONG Ailing
E-mail:e_sail@163.com
摘要:
本文报道1例经细胞程序性死亡配体1(Programmed cell death-ligand 1,PD-L1)抑制剂治疗7个周期后导致免疫相关垂体炎(immune-related hypophysitis, irH)病例。患者表现为乏力、纳差、低血压,血清促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、促甲状腺激素水平较PD-L1抑制剂治疗前明显降低(分别由治疗前的正常值48 ng/L、4.64 μIU/mL降至3.8 ng/L、0.266 μIU/mL),予氢化可的松替代治疗20 d后,患者的临床症状及激素水平逐步好转。回顾近10年PubMed、万方及中国知网数据库收录的由免疫检查点抑制剂导致的300余例垂体炎病例,其中84例肺癌患者,由PD-L1抑制剂引起irH的肺癌患者为10例,患者主要表现为乏力、厌食、体重下降、低血压。与细胞毒性T淋巴细胞相关蛋白4抗体阻断剂相比, PD-1/PD-L1引起的irH发病率低,且发病相对较迟,且垂体MRI检查多无明显异常,但病情危重,甚至可危及生命,临床需引起重视。
中图分类号:
张美玲, 朱潇邦, 宋爱玲, 周剑平, 李庆云. 小细胞肺癌患者采用PD-L1抑制剂治疗致垂体炎1例报道并文献复习[J]. 诊断学理论与实践, 2022, 21(06): 741-745.
ZHANG Meiling, ZHU Xiaobang, SHONG Ailing, ZHOU Jianping, LI Qingyun. PD-L1 inhibitors-induced hypophysitis in a patient with small cell lung cancer: a case report and literatures review[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(06): 741-745.
表1
垂体靶腺轴激素水平变化
检测项目 | ICI治疗前 | irH确诊时 | 糖皮质激素治疗irH 20 d | 糖皮质激素停药15 d | 参考值 |
---|---|---|---|---|---|
垂体-肾上腺轴激素皮质醇(nmol/L) | |||||
8 AM | 406.0 | 39a) | 148.5 | 224.5 | 133~537 |
4 PM | 402.1 | 37.8a) | / | 68.2~327 | |
0 AM | 400.6 | 39.6a) | / | 258.4 | / |
促肾上腺皮质激素(ACTH)(ng/L) | |||||
8 AM | 48 | 3.8a) | 2.89a) | <1.0a) | 7.2~63.3 |
4 PM | / | 1.72a) | / | 2.46a) | 5.0~40.0 |
0 AM | / | 1.52a) | / | 1.19a) | 5.0~10.0 |
垂体-甲状腺轴激素 | |||||
促甲状腺激素(TSH)(μIU/mL) | 4.64 | 0.266a) | 3.71 | 0.948 | 0.27~4.2 |
总甲状腺素(TT4)(nmol/L) | 78.29 | 59.48a) | 80.44 | 53.16a) | 66~181 |
三碘甲状腺原氨酸(TT3)(nmol/L) | 1.38 | 0.632a) | 1.01a) | 1.00a) | 1.3~3.1 |
游离甲状腺素(FT4)(pmol/L) | 13.56 | 10.68a) | 16.79 | 13.41 | 12.0~22.0 |
游离三碘甲状腺原氨酸(FT3)(pmol/L) | 14.92 | 2.44a) | 2.99a) | 2.61a) | 3.1~6.8 |
垂体-性腺轴激素 | |||||
黄体生成素(LH)(mIU/mL) | / | 19.31a) | / | 5.05 | 1.24~8.62 |
卵泡刺激素(FSH)(mIU/mL) | 39.19a) | 22.45 | 2.64~13.13 | ||
泌乳素(PRL)(ng/mL) | 0.55a) | 11.23 | 2.64~13.13 | ||
孕酮(P)(ng/mL) | 0.03a) | 0.05a) | 0.14~2.06 | ||
睾酮(T)(ng/mL) | 2.29 | 0.61a) | 1.75~7.81 | ||
雌二醇(S)(pg/mL) | 17.91 | 22.36 | 15~38.95 |
表2
PD-1/PD-L1在肺癌治疗中致irH的病例报道
参考 文献 | 年龄 (岁) | 性别 | 诊断 | 使用 药物 | 发生 时间 | 临床 症状 | MRI 表现 | 激素及电解质水平 | 激素恢 复情况 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ACTH | F | TSH | FT4 | FSH/LH | GH | PRL | 钠 | 钾 | |||||||||
[ | 69 | 女 | ADE | Nivolumb | 16周 | 乏力、纳差 | 前叶萎缩,垂体 高度2.2 mm | ↓ | ↓ | ↓ | ↑ | - | - | - | - | - | NA |
[ | 75 | 男 | ADE | Nivolumb | 26周 | 乏力、纳 差、低血压 | 垂体无明显异常 | ↓ | ↓ | ↑ | - | - | - | ↓ | - | - | TSH、PRA 恢复,ACTH 未恢复 |
[ | 63 | 男 | ADE | Nivolumb | 15周 | 纳差、乏 力、低血压、发热 | 垂体无明显异常 | ↓ | ↓ | - | - | - | - | - | ↓ | - | NA |
[ | 58 | 女 | SCLC | Nivolumb+ ipilimab | 6周 | 头痛、恶心 呕吐、纳差 | 垂体增大1.5 cm, 垂体柄增粗4 mm | ↓ | ↓ | ↓ | - | ↓ | - | ↑ | - | - | NA |
[ | 65 | 男 | NSCLC | Atezolizumab | 56周 | 乏力、纳差 | 垂体前叶萎缩 | ↓ | ↓ | - | - | - | - | - | - | - | 24个月后 ACTH 未恢复 |
[ | 70 | 男 | NSCLC | Atezolizumab | 54周 | 乏力、纳差 | 垂体无明显异常 | ↓ | ↓ | - | - | ↑ | - | - | - | 13个月后 ACTH 未恢复 | |
[ | 55 | 男 | NSCLC | Nivolumab | 66周 | 乏力、体重 下降 | 垂体无明显异常 | ↓ | ↓ | ↓ | ↑ | - | - | - | - | - | TSH恢复 |
[ | 59 | 男 | NSCLC | Pembrolizumab | 16周 | 乏力、纳 差、发热 | 垂体无明显异常 | ↓ | ↓ | ↑ | ↓ | - | - | - | ↓ | - | NA |
[ | 79 | 男 | SCC | Nivolumab | 20周 | 乏力、纳 差、低血压 | 垂体无明显异常 | ↓ | ↓ | - | - | - | - | - | ↓ | - | ACTH恢复 |
[ | 61 | 男 | SCLC | Nivolumab | 13周 | 乏力、纳 差、低血压 | 垂体无明显异常 | ↓ | ↓ | - | - | ↑ | - | ↑ | - | - | 10个月 ACTH未恢复 |
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