Paraneoplastic autoimmune hypophysitis: An emerging concept - 23/05/22

Doi : 10.1016/j.beem.2021.101601

Hironori Bando ^a,^b,^⁎ : Assistant Professor, Keitaro Kanie ^b : Clinical Fellow, Yutaka Takahashi ^b,^c : Professor
^a Division of Development of Advanced Therapy for Metabolic Diseases, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
^b Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
^c Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Japan

^∗Corresponding author. Division of Development of Advanced Therapy for Metabolic Diseases, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki, Chuo, Kobe, Hyogo 650-0017, Japan. Fax: +81 78 382 2080.Division of Development of Advanced Therapy for Metabolic DiseasesDepartment of Internal MedicineKobe University Graduate School of Medicine7-5-1 Kusunoki, ChuoKobeHyogo650-0017Japan

Abstract

Pituitary autoimmunity is one of the principal causes of hypopituitarism. Additionally, hypophysitis is one of the immune-related adverse events associated with immunotherapy. Recent case-oriented research has revealed a novel type of autoimmune hypophysitis, anti-PIT-1 hypophysitis, related to isolated adrenocorticotropic hormone (ACTH) deficiency and immune checkpoint inhibitor-related hypophysitis, as a form of paraneoplastic syndrome. Under these conditions, the ectopic expression of pituitary antigens present in tumors evokes a breakdown of immune tolerance, resulting in the production of autoantibodies and autoreactive cytotoxic T cells that specifically harm pituitary cells. Consequently, an innovative clinical entity of paraneoplastic autoimmune hypophysitis has been purported. This novel concept and its underlying mechanisms provide clues for understanding the pathogenesis of autoimmune pituitary diseases and can be applied to other autoimmune diseases. This review discusses the etiology of paraneoplastic autoimmune hypophysitis and its future.

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Keywords : paraneoplastic syndrome, anti-PIT-1 hypophysitis, isolated ACTH deficiency, immune-checkpoint inhibitor-related hypophysitis