Paraneoplastic autoimmune hypophysitis: An emerging concept

Hironori Bando; Keitaro Kanie; Yutaka Takahashi

doi:10.1016/j.beem.2021.101601

Paraneoplastic autoimmune hypophysitis: An emerging concept

Best Pract Res Clin Endocrinol Metab. 2022 May;36(3):101601. doi: 10.1016/j.beem.2021.101601. Epub 2021 Nov 25.

Authors

Hironori Bando¹, Keitaro Kanie², Yutaka Takahashi³

Affiliations

¹ Division of Development of Advanced Therapy for Metabolic Diseases, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: hbando@med.kobe-u.ac.jp.
² Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: dmaf9714@med.kobe-u.ac.jp.
³ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Japan. Electronic address: takahash@naramed-u.ac.jp.

PMID: 34876362
DOI: 10.1016/j.beem.2021.101601

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.

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

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adrenocorticotropic Hormone / deficiency
Autoantibodies
Autoimmune Diseases*
Autoimmune Hypophysitis*
Endocrine System Diseases
Genetic Diseases, Inborn
Humans
Hypoglycemia
Hypophysitis* / etiology
Pituitary Diseases* / etiology

Substances

Autoantibodies
Adrenocorticotropic Hormone

Supplementary concepts

ACTH Deficiency, Isolated