du Payrat Juliette Abeillon, Cugnet-Anceau Christine, Maillet Denis, Levy Manon, Raverot Gérald, Disse Emmanuel, Borson-Chazot Françoise
Hospices civils de Lyon, fédération d'endocrinologie, 28, avenue Doyen-Lépine, 69677 Bron cedex, France; ImmuCare, institut de cancérologie des hospices civils de Lyon (IDCRC-HCL), Lyon, France.
Hospices civils de Lyon, hôpital Lyon-Sud, service d'endocrinologie diabétologie et nutrition, 165, Chemin-du-Grand-Revoyet, 69310 Pierre-Bénite, France; ImmuCare, institut de cancérologie des hospices civils de Lyon (IDCRC-HCL), Lyon, France.
Bull Cancer. 2020 Apr;107(4):490-498. doi: 10.1016/j.bulcan.2020.01.012. Epub 2020 Mar 19.
Checkpoint inhibitors immunotherapy is more and more prescribed in oncology, causing new immune related endocrine adverse events. Hypophysitis occurs in approximately 10 % of patients treated with anti-CTLA4. It occurs two to three months after initiation of the immunotherapy. The initial presentation is characterized, in typical forms, by the association of headache, asthenia and hyponatremia. Hormonal exploration usually shows ACTH, gonadotropic and thyrotropic deficiencies. ACTH deficiency may be life-threatening and requires urgent supplementation, without awaiting for biological results. MRI is warranted in order to exclude differential diagnoses, such as pituitary metastases. Hypophysitis induced by anti-PD1/PDL1 seems to be a different nosologic entity characterized by a later onset and a less symptomatic presentation. Biologically ACTH deficiency seems to be constant and permanent, and often isolated. Treatment requires high-dose steroids only in case of severe tumor syndrome (resistant headache, visual disturbance) or acute decompensation of ACTH deficiency. Patients always need lifelong hormonal supplementation of pituitary deficits and must be followed and educated specifically. Immunotherapy can be delayed during the acute phase, but can be secondarily continued if there is an oncological benefit. As it is a pauci-symptomatic but potentially life-threatening complication, biological screening must be systematic in patients treated with checkpoint inhibitors.
免疫检查点抑制剂免疫疗法在肿瘤学领域的应用越来越广泛,这引发了新的免疫相关内分泌不良事件。垂体炎发生在约10%接受抗CTLA4治疗的患者中。它在免疫疗法开始后的两到三个月出现。典型表现为头痛、乏力和低钠血症同时出现。激素检查通常显示促肾上腺皮质激素、促性腺激素和促甲状腺激素缺乏。促肾上腺皮质激素缺乏可能危及生命,需要紧急补充,无需等待生物学检查结果。有必要进行MRI检查以排除鉴别诊断,如垂体转移瘤。抗PD1/PDL1诱导的垂体炎似乎是一种不同的疾病实体,其特点是发病较晚且症状较轻。从生物学角度看,促肾上腺皮质激素缺乏似乎持续且永久,且常为孤立性。仅在出现严重肿瘤综合征(顽固性头痛、视力障碍)或促肾上腺皮质激素缺乏急性失代偿时才需要高剂量类固醇治疗。患者始终需要终身补充垂体功能减退的激素,并且必须进行专门的随访和教育。急性期可延迟免疫治疗,但如果有肿瘤学获益,随后可继续治疗。由于这是一种症状轻微但可能危及生命的并发症,接受免疫检查点抑制剂治疗的患者必须进行系统的生物学筛查。