Pituitary and adrenal disorders induced by immune checkpoint inhibitors - 29/04/23
Atteintes hypophysaires et surrénaliennes secondaires au traitement par immunothérapie/IPCI (inhibiteurs des points de contrôle immunitaires)
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Highlights |
• | Hypophysitis is a common IRAE in patients undergoing anti-CTLA-4 and combination treatment and appears to be dose-dependent. |
• | PAI is a rare IRAE, which occurs especially in patients with nivolumab or ipilimumab in monotherapy or combination treatment. |
• | Clinical and hormonal monitoring before and during immunotherapy is necessary for early diagnosis of hypophysitis or PAI, especially in the first months of treatment, with special attention paid to TSH level in hypophysitis (TSH decrease may precede hypophysitis). |
• | If hypophysitis or PAI is suspected, the corticotropin replacement is an emergency. |
• | ACTH assay is useful to distinguish PAI from SAI, and thus add mineralocorticoid therapy in PAI, and examine the other endocrine axes in cases of SAI. |
• | Imaging must be performed if hypophysitis (MRI) or a PAI (adrenal CT) is suspected, with monitoring for the first 3 months for hypophysitis, especially to rule out differential diagnosis of cerebral or bilateral adrenal metastasis. |
• | Diabetes insipidus and visual disorder are rare in immunotherapy-induced hypophysitis. |
• | In case of hypophysitis or PAI, high-dose GCs should not be administered systematically, but only in case of major tumour syndrome (severe resistant headache or visual disorder) in hypophysitis. |
• | Immunotherapy should not be stopped (can sometimes be delayed) in case of ICI-induced hypophysitis or PAI. |
• | Adrenal insufficiency in PAI and corticotropin deficiency in hypophysitis are usually definitive and require education of patients and oncologists on adaptation and injection of hydrocortisone. |
• | Multidisciplinary long-term follow-up with an endocrinologist and an oncologist is needed in such endocrine IRAEs. |
Abstract |
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.
El texto completo de este artículo está disponible en PDF.Résumé |
Au cours de la dernière décennie, le développement des IPCI (inhibiteurs des points de contrôles immunitaires) a constitué une révolution dans la thérapie de nombreux cancers, avec un profil de toxicité spécifique dont des effets 2aires endocriniens immuno-induits. Du fait de leur efficacité, les indications de ces molécules sont en constante augmentation, il est donc important que les endocrinologues et les oncologues sachent comment détecter, gérer et surveiller ce type de toxicité. De nombreux consensus et recommandations ont été proposés ces dernières années pour la gestion de ces endocrinopathies. Des recommandations françaises sur les toxicités endocriniennes de l’immunothérapie publiées en 2018, toujours d’actualité, proposent un algorithme détaillé de la prise en charge de l’hypophysite et de l’insuffisance surrénale primaire (ISP), basées sur la clinique, une évaluation biologique et d’imagerie. Après l’exposition des données générales sur les mécanismes physiopathologiques de ces toxicités, nous aborderons l’incidence, le diagnostic, le traitement, l’évolution et la surveillance des atteintes hypophysaires et surrénaliennes de l’immunothérapie, en insistant sur l’hypophysite, beaucoup plus fréquente que l’ISP avec ce type de molécule. Nous soulignerons également quelques points clés, comme la nécessité d’un traitement d’urgence par hydrocortisone avec la possibilité de poursuivre l’immunothérapie dans ces endocrinopathies ainsi que la fréquente persistance à long terme d’une insuffisance corticotrope ou surrénalienne avec la nécessité d’une « éducation à l’hydrocortisone » spécifique chez ces patients. Ces données doivent être gardées à l’esprit par les oncologues et les endocrinologues qui traitent et suivent les patients traités par immunothérapie.
El texto completo de este artículo está disponible en PDF.Keywords : Hypophysitis, Primary adrenal insufficiency, Immune-related adverse events, Immune checkpoint inhibitors, Hypopituitarism, Immunotherapy
Mots clés : Hypophysite, Insuffisance surrénale, Effets indésirables immuno-induits, Inhibiteurs des points de contrôle immunitaires, Hypopituitarisme, Immunothérapie
Esquema
Vol 84 - N° 3
P. 339-345 - mai 2023 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.