Clinical features of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis: a new aspect of paraneoplastic autoimmune condition
Shin Urai, Genzo Iguchi, Keitaro Kanie, Hironori Bando, Masaaki Yamamoto, Yuka Oi, Yuya Kashitani, Keiji Iida, Maki Kanzawa, Hidenori Fukuoka, Michiko Takahashi, Yasushi Shintani, Wataru Ogawa, Yutaka Takahashi
Abstract
The pathogenesis of anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis was gradually revealed as cases emerged. Our comprehensive analysis, including all reported cases, identified a new instance of anti-PIT-1 hypophysitis postimmune checkpoint inhibitor therapy. All 9 patients exhibited extremely low growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels; 2 had a slightly atrophic pituitary gland; 4 had thymoma, and 5 had malignant neoplasms of diffuse large B-cell lymphoma (DLBCL) and other origins. Patients with thymoma showed multiple autoimmune diseases. HLA-A*24:02 and/or A*02:06 were present in six and DR53 in 5 cases analyzed. High anti-PIT-1 antibody titers and ectopic PIT-1 expression in the cytosol and nucleus of the tumor tissues were observed in patients with thymoma or DLBCL, whereas it was exclusively observed in the nuclei of a bladder cancer patient. These findings provide new insights into the pathophysiology of paraneoplastic autoimmune hypophysitis.