ArticleCancer immunology, immunotherapy : CII2021
Mechanistic insights into immune checkpoint inhibitor-related hypophysitis: a form of paraneoplastic syndrome.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Ectopic rabphilin-3A expression in lung adenocarcinoma associated with paraneoplastic arginine vasopressin deficiency during anti-PD-L1 therapy: a case report.Journal for immunotherapy of cancer · 2026Article
- Endocrine late-effects in survivors of childhood and adolescence cancer: clinical management.Journal of endocrinological investigation · 2026Review
- Immune-Mediated Hypophysitis: An Updated Review.Journal of clinical medicine · 2026Review
- Clinical characteristics, management, and prognosis of pembrolizumab-induced hypophysitis: retrospective analysis based on case reports.Frontiers in immunology · 2026Article
- Pharmacovigilance Insights Into Immune Checkpoint Inhibitor-Induced Risk of Paraneoplastic Syndrome: A Large-Scale Real World Study.CNS neuroscience & therapeutics · 2026Article
- Multiple or Single Endocrine Abnormalities Associated With Immune Checkpoint Inhibitors.The Journal of clinical endocrinology and metabolism · 2025Article
- Review
- Beyond Tumor Immunity: The Disruption of Endocrine and Infectious Homeostasis by Immune Checkpoint Inhibitors.International journal of molecular sciences · 2025Review
- Clinical characteristics and comparative analysis of PD-1/PD-L1 inhibitor-induced pituitary dysfunction versus other pituitary disorders.Scientific reports · 2025Article
- Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.Endocrine journal · 2025Review
- Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors.Nature reviews. Endocrinology · 2025Review
- Immune checkpoint inhibitor-related type 1 diabetes incidence, risk, and survival association.Journal of diabetes investigation · 2025Article
- Immunotherapy-Related Hypophysitis: A Narrative Review.Cancers · 2025Review
- An overview of hypopituitarism's causes.Frontiers in endocrinology · 2025Review
- Normal adrenocorticotropic hormone levels do not exclude adrenal insufficiency during immune checkpoint inhibitor therapy: evidence from clinical, steroid, and structural analyses.Frontiers in endocrinology · 2025Article
- Patterns of hormonal changes in hypophysitis by immune checkpoint inhibitor.The Korean journal of internal medicine · 2024Article
- Fertility Preservation in the Era of Immuno-Oncology: Lights and Shadows.Journal of personalized medicine · 2024Review
- Fluctuations in plasma adrenocorticotropic hormone concentration may predict the onset of immune checkpoint inhibitor-related hypophysitis.Journal for immunotherapy of cancer · 2024Article
- Pembrolizumab-induced secondary adrenal insufficiency due to adrenocorticotrophic hormone deficiency in a patient with non-small-cell lung carcinoma: a case report.Journal of pharmaceutical health care and sciences · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundImmune checkpoint inhibitors (ICIs) as a cancer immunotherapy have emerged as a treatment for multiple advanced cancer types. Because of enhanced immune responses, immune-related adverse events (irAEs), including endocrinopathies such as hypophysitis, have been associated with the use of ICIs. Most underlying mechanisms of ICI-related hypophysitis remain unclear, especially for programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) inhibitors. We hypothesized that ICI-related hypophysitis is associated with paraneoplastic syndrome caused by ectopic expression of pituitary-specific antigens.
methodsTwenty consecutive patients with ICI-related hypophysitis between 2017 and 2019 at Kobe University Hospital were retrospectively analyzed. Circulating anti-pituitary antibodies were detected using immunofluorescence staining and immunoblotting. Ectopic expression of pituitary autoantigens in tumor specimens was also examined.
resultsEighteen patients were treated with PD-1/PD-L1 inhibitors, and two were treated with a combination of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and PD-1 inhibitors. All patients showed adrenocorticotropic hormone (ACTH) deficiency and additionally, three showed thyroid-stimulating hormone (TSH) deficiency, and one showed gonadotropin-releasing hormone (GnRH) deficiency. Among these patients, three exhibited anti-pituitary antibodies, two with anti-corticotroph antibody and one with anti-somatotroph antibody. Interestingly, the anti-corticotroph antibody recognized proopiomelanocortin (POMC) and those two patients exhibited ectopic ACTH expression in the tumor, while the patients without anti-corticotroph antibody did not.
conclusionsWe demonstrated 10% of PD-1/PD-L1 inhibitors-related hypophysitis were associated with the autoimmunity against corticotrophs and maybe caused as a form of paraneoplastic syndrome, in which ectopic expression of ACTH in the tumor was observed. It is also suggested that the pathophysiology is heterogenous in ICI-related hypophysitis.
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