Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis
Recovery from secondary adrenal insufficiency in a patient with immune checkpoint inhibitor therapy induced hypophysitis
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DOI：
10.1186/s40425-019-0729-3
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发表时间：
2019-09-12
影响因子：
10.9
通讯作者：
Gallagher, Emily J.
中科院分区：
文献类型：
--
作者：
Thapi, Sahityasri;Leiter, Amanda;Gallagher, Emily J.
背景垂体炎是接受免疫检查点抑制剂治疗的癌症患者中公认的免疫相关不良事件。一名26岁的男性转移性透明细胞肾细胞癌患者开始接受抗程序性细胞死亡-1单克隆抗体（抗PD-1 mAb）纳武单抗治疗，随后接受纳武单抗和抗细胞毒性T淋巴细胞相关蛋白4（CTLA-4）mAb伊匹单抗联合治疗。在开始纳武单抗单药治疗后，患者发生甲状腺炎，无需治疗即可消退。在开始联合ICI治疗之前，在下午1：30抽取随机血清皮质醇，结果为15.0 μ g/dL（414 nmol/L）。开始ICI联合治疗后3周，患者突然出现严重疲劳，下午1点血清皮质醇为2.0 μ g/dL（55.2nmol/L），促肾上腺皮质激素（ACTH）为16 pg/mL（3.52pmol/L）。诊断为垂体炎，立即给予泼尼松1 mg/kg。他的症状迅速消退，并继续免疫检查点抑制剂治疗。他还发现促性腺激素和睾酮水平较低（睾酮最低值为81.19 ng/dL）。在接下来的六周内，泼尼松逐渐减少到每天5 mg的维持剂量。初次就诊后4个月，他的皮质醇仍然很低，但他的睾丸激素水平增加到973.43ng/dL。5个月后，他的随机血清皮质醇（下午1点）增加到11.0微克/分升（303.6纳摩尔/升）。在密切监测下谨慎停用泼尼松。两个月的糖皮质激素替代治疗，他仍然无症状的促肾上腺皮质激素为24.1pg/mL（5.3pmol/L），皮质醇为13.0 μ g/dL（358.8nmol/L）。ConclusionsThis case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypothyritis from immune checkpoint inhibitor therapy.在垂体炎发生后的第一年，每三个月重复一次垂体激素检测，可能会发现更多的患者下丘脑-垂体-肾上腺轴恢复。
BackgroundHypophysitis is a well-recognized immune-related adverse event in patients treated with immune checkpoint inhibitors for cancer. Some anterior pituitary hormones may recover; however, secondary adrenal insufficiency is usually permanent.Case presentationA 26-year old male with metastatic clear cell renal cell carcinoma was started on treatment with the anti-programmed cell death-1 monoclonal antibody (anti-PD-1 mAb) nivolumab, followed by combined nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb, ipilimumab. After starting nivolumab monotherapy the patient developed thyroiditis, which resolved without treatment. Prior to commencing combined ICI therapy, a random serum cortisol drawn at 1:30pm and was 15.0 mu g/dL (414nmol/L). Three weeks after starting combined ICI therapy he developed sudden onset of severe fatigue and 1pm serum cortisol was 2.0 mu g/dL (55.2nmol/L), adrenocorticotropic hormone (ACTH) was 16pg/mL (3.52pmol/L). A diagnosis of hypophysitis was made, and he was immediately started on prednisone 1mg/kg. His symptoms resolved rapidly, and he continued immune checkpoint inhibitor therapy. He was noted to also have low gonadotropic hormones and testosterone (nadir testosterone 81.19ng/dL). The prednisone was tapered slowly over the next six weeks to a maintenance dose of 5mg daily. Four months after the initial presentation his cortisol remained low, but his testosterone level had increased to 973.43ng/dL. After five months his random serum cortisol (1pm) increased to 11.0 mu g/dL (303.6nmol/L). The prednisone was cautiously discontinued with close monitoring. Two months off glucocorticoid replacement he remained asymptomatic with an ACTH of 24.1pg/mL (5.3pmol/L), and cortisol of 13.0 mu g/dL (358.8nmol/L).ConclusionsThis case documents the unusual recovery from secondary adrenal insufficiency in a patient who developed hypophysitis from immune checkpoint inhibitor therapy. Repeated pituitary hormone testing every three months for the first year after the development of hypophysitis may identify more patients with hypothalamic-pituitary-adrenal axis recovery.