PD-1抑制剂相关垂体炎的诊断与治疗

Diagnosis and treatment of hypophysitis caused by PD-1 inhibitor

目的探讨程序性死亡受体1(PD-1)抑制剂导致垂体炎的诊治方法。方法分析1例PD-1抑制剂导致垂体炎患者的临床资料,并复习相关文献。结果本病例患者男性,80岁,因膀胱肿瘤接受PD-1抑制剂帕博利珠单抗治疗,用药后出现乏力、精神萎靡、纳差并自行停药。外院检查甲状腺功能提示甲状腺功能减退,甲状腺过氧化物酶抗体和甲状腺球蛋白抗体阴性,加用左甲状腺素钠治疗。后患者出现意识不清、深昏迷,转至本院。实验室检查提示重度低钠血症、继发性肾上腺皮质功能减退及原发性甲状腺功能减退症;垂体MR检查诊断为PD-1抑制剂导致的垂体炎。予以糖皮质激素及左甲状腺素钠替代治疗,患者临床症状明显改善。结论当接受免疫检查点抑制剂治疗的患者出现乏力、纳差等症状时,需警惕发生该药物相关垂体炎的可能,及时筛查肾上腺功能、甲状腺功能及血糖情况等,定期监测内分泌指标的变化,关注患者可能出现的相关症状、体征,及时发现免疫相关不良反应。

Objective To discusses the diagnosis and treatment of hypophysitis caused by programmed death-1(PD-1)inhibitor.Methods To analyze the clinical data of a patient with hypophysitis due to PD-1 inhibitor and to review the relevant literature.Results This case is a male,80 years old,treated with PD-1 inhibitor pablizumab for bladder tumor,who developed malaise,depression,poor appetite and discontinued the drug on his own.The thyroid function in the external hospital showed hypothyroidism,and the thyroid peroxidase antibody and thyroglobulin antibody were negative,and levothyroxine sodium was added for treatment.Later,the patient developed unconsciousness and in deep coma,and was transferred to our hospital.Laboratory tests suggested severe hyponatremia,secondary hypoadrenocorticism and primary hypothyroidism;pituitary MR examination diagnosed hypophysitis due to PD-1 inhibitor.Glucocorticoids and levothyroxine sodium replacement therapy were administered,and the patient's clinical symptoms improved significantly.Conclusions When the patients treated with immune checkpoint inhibitors have symptoms such as fatigue and anorexia,we should be vigilant against the possibility of hypophysitis associated with the drug,and screen the adrenal function,thyroid function and blood sugar in time.Regularly monitor the changes of endocrine indicators,pay attention to the possible symptoms and signs of patients,in order to detect immune-related adverse reactions in time.