程序性细胞死亡蛋白1抑制剂相关性垂体炎临床特征分析

Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis

目的探讨程序性死亡蛋白1(PD-1)抑制剂相关性垂体炎的临床特征。方法回顾性病例系列研究。收集2020年1月至2023年5月于河北大学附属医院及河北医科大学第三医院治疗的PD-1抑制剂相关性垂体炎患者的临床及随访资料,分析其临床表现及预后。结果共纳入15例PD-1抑制剂相关性垂体炎患者,其中男性13例,女性2例,发病年龄(62.1±7.5)岁,发病时PD-1治疗周期6.5(4.7,11.6)个。临床症状表现为消化道症状14例、疲乏12例、低血钠12例、低血钾1例、低血糖1例、低血压5例、发热1例。15例患者均表现为继发性肾上腺皮质功能减退,4例继发性甲状腺功能减退,2例继发性性腺功能减退,未见垂体后叶功能减退。垂体MRI表现为空泡蝶鞍1例,垂体小囊性病变1例,垂体柄略向左偏移1例,蝶鞍部高代谢、垂体异常信号1例,11例未见异常。随访时间(47.66±11.93)周,末次随访时,1例血清促肾上腺皮质激素及皮质醇恢复正常。结论PD-1抑制剂相关性垂体炎发病时间较晚,临床表现以消化道症状及疲乏多见,以肾上腺皮质功能减退为主要表现,甲状腺及性腺功能减退次之,垂体影像学改变不明显。

Objective To explore the clinical features of programmed cell death-1(PD-1)inhibitor-associated hypophysitis and improve the understanding of the disease.Methods For the present retrospective case series study,the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis.Results Fifteen cases of PD-1 inhibitor-induced hypophysitis were included,with 13 males and 2 females.The mean age of onset was(62.1±7.5)years,and the median time of onset was 6.5(4.7,11.6)cycles of PD-1 inhibitor.At diagnosis,14 patients complained of gastrointestinal symptoms,and 12 patients complained of fatigue.There were 12,1,1,5,and 1 cases of hyponatremia,hypokalemia,hypoglycemia,hypotension,and fever,respectively.Secondary adrenocortical insufficiency occurred in all cases.Moreover,four patients had secondary hypothyroidism,and two patients had secondary hypogonadism.Posterior pituitary hypofunction was not found.Pituitary MRI showed one case each of vacuolar sella turcica,pituitary cystic lesion,pituitary stalk slightly shifted to the left,high metabolism in the sella turcica,and pituitary abnormal signal,while no abnormalities were found in 11 cases.The follow-up time was(47.66±11.93)weeks.At the last follow-up,one patient′s serum levels of adrenocorticotropic hormone and cortisol returned to normal.Conclusions Hypophysitis associated with PD-1 inhibitors occurs later,and gastrointestinal symptoms and fatigue are the most common clinical manifestations.PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction,and some cases manifest as hypothyroidism and hypogonadism.In addition,patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.