Aix-Marseille université, institut national de la santé et de la recherche médicale (Inserm), U1251, Marseille Medical Genetics (MMG), Assistance publique-Hôpitaux de Marseille (AP-HM), service d'endocrinologie, hôpital de la conception, centre de référence des maladies rares de l'hypophyse HYPO, 13005 Marseille, France.
Aix-Marseille université, institut national de la santé et de la recherche médicale (Inserm), U1251, Marseille Medical Genetics (MMG), Assistance publique-Hôpitaux de Marseille (AP-HM), service d'endocrinologie, hôpital de la conception, centre de référence des maladies rares de l'hypophyse HYPO, 13005 Marseille, France.
Ann Endocrinol (Paris). 2023 May;84(3):339-345. doi: 10.1016/j.ando.2023.03.014. Epub 2023 Mar 23.
Over the past decade, the development of ICI (immune checkpoint inhibitors) has constituted a revolution in the treatment of many cancers, but with a specific toxicity profile including endocrine IRAEs (immune-related adverse events). As the indications for these molecules are constantly increasing due to their efficacy, it is important that endocrinologists and oncologists know how to detect, manage and monitor this type of toxicity. Many guidelines and recommendations have been proposed in the last few years for the management of endocrinopathies. French guidelines on immunotherapy-related endocrine IRAEs were published in 2018, with a specific algorithm for hypophysitis and primary adrenal insufficiency (PAI), based on clinical suspicion followed by biochemical and imaging evaluation, and are still relevant today. Here we present the general pathophysiological mechanisms of these toxicities, and discuss the incidence, diagnosis, treatment, progression, management and monitoring of pituitary and adrenal disorders in patients treated by immunotherapy, with emphasis on hypophysitis, which is much more frequent than PAI with this type of molecule. We also highlight several key points, such as the need for emergency treatment by hydrocortisone with the possibility of continuing immunotherapy in these endocrinopathies, and the long-term persistence of corticotropin or adrenal deficiency in most cases, requiring specific "hydrocortisone education". These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.
在过去的十年中,ICI(免疫检查点抑制剂)的发展在许多癌症的治疗中构成了一场革命,但具有特定的毒性特征,包括内分泌 IRAEs(免疫相关不良事件)。由于这些分子的疗效不断增加,因此内分泌学家和肿瘤学家了解如何检测、管理和监测这种毒性非常重要。在过去的几年中,已经提出了许多关于内分泌疾病管理的指南和建议。2018 年发表了关于免疫治疗相关内分泌 IRAEs 的法国指南,针对垂体炎和原发性肾上腺功能不全 (PAI) 提出了具体的算法,基于临床怀疑,然后进行生化和影像学评估,这些指南至今仍然适用。在这里,我们介绍了这些毒性的一般病理生理学机制,并讨论了接受免疫治疗的患者垂体和肾上腺疾病的发生率、诊断、治疗、进展、管理和监测,重点介绍了垂体炎,与这种类型的分子相比,垂体炎更为常见。我们还强调了一些关键点,例如在这些内分泌疾病中需要用氢化可的松进行紧急治疗,并有可能继续进行免疫治疗,以及在大多数情况下,促肾上腺皮质激素或肾上腺功能不全的长期持续存在,需要特定的“氢化可的松教育”。这些要点应该被治疗和监测接受免疫治疗的患者的肿瘤学家和内分泌学家牢记在心。