Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France.
Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l'hypophyse HYPO, Marseille, France.
Eur J Endocrinol. 2019 Sep 1;181(3):R107-R118. doi: 10.1530/EJE-19-0169.
In recent years, the development of immunotherapy has constituted a revolution in the therapy for many cancers, with a specific toxicity profile including endocrine immune-related adverse events. Immune check point inhibitors (ICI)-induced hypophysitis is a common endocrine side effect, particularly with CTLA-4 antibodies and combination therapy, with frequent hormonal deficiencies at diagnosis. It can be difficult to evoke such diagnosis as the initial clinical symptoms are not specific (headache, asthenia…); thus, patients receiving such immunomodulatory therapies should be closely monitored by systematic hormone measurements, especially in the first weeks of treatment. Usually, hormonal deficiencies improve, except for corticotroph function. Despite a lack of large prospective studies on ICI-induced hypophysitis, some detailed longitudinal cohort studies have focused on such cases of hypophysitis and allow for optimal monitoring, follow-up and management of patients with this immune-related adverse event. In the case of ICI-induced hypophysitis, patients need long-term multidisciplinary follow-up, with specific education for those patients with corticotropin deficiency to allow them to be autonomous with their treatment. In this review, based on a clinical case, we detail the most relevant and novel aspects related to the incidence, diagnosis, treatment, evolution and management of hypophysitis induced by immunotherapy, with a focus on possible mechanisms and current recommendations and guidelines. Lastly, we emphasize several key points, such as the absence of indication to systematically treat with high-dose glucocorticoid and the pursuit of immunotherapy in such hypophysitis. These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.
近年来，免疫疗法的发展在许多癌症的治疗中构成了一场革命，具有特定的毒性特征，包括内分泌免疫相关的不良反应。免疫检查点抑制剂（ICI）引起的垂体炎是一种常见的内分泌副作用，特别是与 CTLA-4 抗体和联合治疗有关，诊断时经常出现激素缺乏。由于最初的临床症状不具有特异性（头痛、乏力等），因此很难引起这种诊断，因此接受这种免疫调节治疗的患者应通过系统的激素测量进行密切监测，尤其是在治疗的最初几周。通常，除了促肾上腺皮质激素功能外，激素缺乏会得到改善。尽管缺乏关于 ICI 诱导的垂体炎的大型前瞻性研究，但一些详细的纵向队列研究集中在这种垂体炎病例上，从而能够对患者进行最佳的监测、随访和管理。对于 ICI 诱导的垂体炎，患者需要长期的多学科随访，并对那些促肾上腺皮质激素缺乏的患者进行特定的教育，以使他们能够自主治疗。在这篇综述中，我们基于一个临床病例，详细介绍了与免疫疗法引起的垂体炎的发病率、诊断、治疗、演变和管理相关的最相关和最新的方面，重点介绍了可能的机制以及当前的建议和指南。最后，我们强调了几个关键点，例如没有指征系统地用大剂量糖皮质激素治疗，以及在这种垂体炎中继续进行免疫治疗。接受免疫治疗的患者的肿瘤学家和内分泌学家应牢记这些要点。
