Clinical heterogeneity of hypophysitis secondary to PD-1/PD-L1 blockade: insights from four cases
| Autor: | Alessandro Brancatella, Giulia Di Dalmazi, Daniele Sgrò, Nicola Viola, Patrizio Caturegli, Mirco Cosottini, Isabella Lupi, Claudio Marcocci, Giulia Lanzolla, Francesco Latrofa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
LH
Male Hydrocortisone Endocrinology Diabetes and Metabolism Hypergonadotropic hypogonadism Levothyroxine White Pembrolizumab lcsh:Diseases of the endocrine glands. Clinical endocrinology Gastroenterology Cortisol 0302 clinical medicine Diabetes mellitus type 1 Diabetic ketoacidosis FSH Hyperglycaemia Insulin Medicine HLA genotyping Testosterone Myasthaenia Fatigue TSH Hyponatraemia Headache Nausea Autoimmune disorders Pituitary function Nivolumab Thyrotoxicosis Italy October Oncology Thyroid antibodies Fludrocortisone 030220 oncology & carcinogenesis Renin (blood) Autoimmune hypophysitis Female Atezolizumab Hyponatremia Immune checkpoint inhibitors Pyrexia medicine.drug Adult CT scan medicine.medical_specialty Vomiting Hypophysitis Immunology Vitiligo 030209 endocrinology & metabolism Ipilimumab Adenocarcinoma Glucose (blood) Metastatic melanoma ACTH Asthenia Glucocorticoids Gonadotrophins Gonadotropins Hyperkalaemia Hypoadrenalism Hypogonadism Hypothyroidism Indirect immunofluorescence Insight into disease pathogenesis or mechanism of therapy Mineralocorticoids Non-small cell lung cancer Oestradiol (E2) Pituitary Potassium Sodium 03 medical and health sciences Internal medicine Internal Medicine Insight into Disease Pathogenesis or Mechanism of Therapy lcsh:RC648-665 business.industry medicine.disease business |
| Zdroj: | Endocrinology, Diabetes & Metabolism Case Reports Endocrinology, Diabetes & Metabolism Case Reports, Vol 1, Iss 1, Pp 1-6 (2019) |
| ISSN: | 2052-0573 |
| Popis: | Summary Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy. Learning points: PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade. Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities. Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease. PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|