Endocrine Reviews Journal Article

New Autoimmune Pituitary Disease

September 12, 2019
 

Masaaki Yamamoto, Genzo Iguchi, Hironori Bando, Keitaro Kanie, Ryoko Hidaka-Takeno, Hidenori Fukuoka, Yutaka Takahashi
Endocrine Reviews, Volume 41, Issue 2, April 2020, bnz003
https://doi.org/10.1210/endrev/bnz003

Abstract

Some endocrine disorders, including hypophysitis and isolated adrenocorticotropic hormone (ACTH) deficiency, are caused by an autoimmune response to endocrine organs. Although the pathogenesis of some autoimmune endocrine diseases has been elucidated, it remains obscure for most.

Anti–PIT-1 hypophysitis (anti–PIT-1 antibody syndrome) is a newly described pituitary autoimmune disease characterized by acquired and specific growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies. This disorder is associated with a thymoma or neoplasm that ectopically expresses pituitary-specific transcription factor 1 (PIT-1) protein. Circulating anti–PIT-1 antibody is a disease marker, and PIT-1–reactive cytotoxic T cells (CTLs) play a pivotal role in disease development.

In addition, isolated ACTH deficiency appears to be caused by autoimmunity to corticotrophs; however, the pathogenesis remains unclear. A recently described case of isolated ACTH deficiency with large cell neuroendocrine carcinoma (LCNEC) showed ectopically expressed proopiomelanocortin (POMC), and circulating anti-POMC antibody and POMC-reactive CTLs were also detected. As CTL infiltrations around corticotrophs were also observed, isolated ACTH deficiency may be associated at least in part with a paraneoplastic syndrome.

Although several underlying mechanisms for pituitary autoimmunity have been proposed, these observations highlight the importance of paraneoplastic syndrome as a cause of pituitary autoimmune disease. In this review, we focus on the pathophysiology and connection of anti–PIT-1 hypophysitis and isolated ACTH deficiency and discuss the state-of-art knowledge for understanding pituitary autoimmunity.

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