Patel Nishchil, Hirwa Kagabo, Gardner Gemma, Pearce Kirsten, Jeffery Jinny, Iqbal Fizzah, Flanagan Daniel
Department of Endocrinology, University Hospital Plymouth, UK.
Endocr Connect. 2024 Oct 29;13(11). doi: 10.1530/EC-24-0223. Print 2024 Nov 1.
The aim of this study was to define functional and anatomical pituitary disease at the time of presentation following immune checkpoint inhibitor (ICI) therapy and to describe any changes in pituitary function over time.
We conducted a retrospective observational audit of patients on ICI therapy at our centre between January 2013 and September 2023. We reviewed all patients on ICI therapy under the care of the oncology department at University Hospital Plymouth, a 1000-bedded hospital serving a population of 500,000 people. From this group, we identified all individuals referred to the endocrinology department with a suspected diagnosis of adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. People were included if they had pituitary disease, as evidenced by low ACTH, other pituitary dysfunction and/or abnormalities on pituitary imaging.
Nine hundred and fifty-four patients received ICI therapy during the study period, and 37 (a prevalence of 3.9%) developed hypothalamic-pituitary-adrenal axis dysfunction. Their mean age was 65 years, and 70% were male. About 86.5% of the total patients affected were treated for metastatic malignancies. Ten of the 37 patients died during follow-up as a direct consequence or complication of their primary cancer diagnosis. The median interval for the onset of symptoms was 4 months. Following repeated testing, there was no recovery in cortisol or ACTH levels for any individual. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target the corticotrophs, with no evidence of recovery over time. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, which appeared to be a particular feature of immune-mediated hypophysitis. These were confined to the anterior aspect of the pituitary gland, appearing as striations, and were not visible on any of the scans performed more than 3 months after the likely onset of the disease.
These data show that immune-related hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary that are richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and, therefore, cortisol production.
本研究的目的是在免疫检查点抑制剂（ICI）治疗后的就诊时明确功能性和解剖学垂体疾病，并描述垂体功能随时间的任何变化。
我们对2013年1月至2023年9月期间在我们中心接受ICI治疗的患者进行了一项回顾性观察性审计。我们回顾了普利茅斯大学医院肿瘤科护理下所有接受ICI治疗的患者，该医院有1000张床位，服务于50万人口。从这个群体中，我们确定了所有因疑似肾上腺功能不全而转诊至内分泌科的个体。患者开始接受肾上腺类固醇替代治疗，随后接受正式的垂体检测。如果患者患有垂体疾病，如促肾上腺皮质激素（ACTH）水平低、其他垂体功能障碍和/或垂体影像学异常所证明，则纳入研究。
在研究期间，954名患者接受了ICI治疗，37名（患病率为3.9%）出现下丘脑-垂体-肾上腺轴功能障碍。他们的平均年龄为65岁，70%为男性。受影响的患者中约86.5%接受了转移性恶性肿瘤治疗。37名患者中有10名在随访期间因原发性癌症诊断的直接后果或并发症死亡。症状出现的中位间隔时间为4个月。经过反复检测，任何个体的皮质醇或ACTH水平均未恢复。其他永久性垂体前叶激素缺陷并不常见。与免疫治疗相关的垂体炎似乎特别针对促肾上腺皮质激素细胞，没有随时间恢复的证据。在进行扫描的27名患者中，有7名的MRI扫描出现了特定异常，这似乎是免疫介导的垂体炎的一个特殊特征。这些异常局限于垂体前叶，表现为条纹状，在疾病可能发作后3个月以上进行的任何扫描中均不可见。
这些数据表明，免疫相关性垂体炎是免疫检查点抑制剂治疗的常见并发症。这可能导致垂体中促肾上腺皮质激素细胞最丰富区域出现影像学异常。其内分泌后果是ACTH永久性缺陷，进而导致皮质醇分泌缺陷。
