Zeng Mei Fang, Chen Li Li, Ye Hong Ying, Gong Wei, Zhou Li Nuo, Li Yi Ming, Zhao Xiao Long
Department of Endocrinology, Huashan Hospital North Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China.
Medicine (Baltimore). 2017 Nov;96(44):e8426. doi: 10.1097/MD.0000000000008426.
Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system.
A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland.
Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively.
Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval.
The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time.
The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.
纳武单抗是一种单克隆IgG抗体，可阻断程序性死亡受体-1（PD1），从而恢复天然T细胞介导的针对癌细胞的免疫反应。然而，它也会引发大量与自身免疫相关的不良事件，这些事件常累及内分泌系统。
一名54岁的肾透明细胞癌男性接受了纳武单抗静脉治疗。常规监测显示，在第6次注射纳武单抗后促甲状腺激素升高，游离甲状腺素降低。第12次注射后，他出现全身乏力、反复低血糖和相对性低血压。实验室检查显示血钠降低，清晨皮质醇水平低，促肾上腺皮质激素（ACTH）无相应升高。其他垂体激素正常。磁共振成像（MRI）显示无占位性病变，但垂体呈不均匀强化。
原发性甲状腺功能减退和孤立性ACTH缺乏。病因分别被认为是纳武单抗诱导的自身免疫性淋巴细胞性甲状腺炎和垂体炎。
口服左甲状腺素和醋酸可的松进行激素替代治疗。将纳武单抗调整为较低剂量和较长间隔时间。
经过充分替代治疗后患者感觉良好。6个月后纳武单抗恢复至常规剂量和间隔时间。在此期间转移灶未明显进展。
本报告首次详细介绍了纳武单抗诱导的甲状腺功能减退和孤立性ACTH缺乏合并症。肾上腺功能不全往往隐匿发生。我们建议在使用纳武单抗及其他癌症免疫疗法期间，常规监测空腹血糖、血压、血钠以及甲状腺功能。当出现意外的乏力、低血糖、低血压或低钠血症时，应考虑肾上腺功能不全。
