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.