Keitaro Kanie 1 , Genzo Iguchi 2 , 3 , Megumi Inuzuka 4 , Kentaro Sakaki 5 , Hironori Bando 1 , Shin Urai 1 , Hiroki Shichi 1 , Yasunori Fujita 1 , Ryusaku Matsumoto 1 , Kentaro Suda 1 , Masaaki Yamamoto 6 , Hidenori Fukuoka 6 , Takao Taniguchi 5 , Wataru Ogawa 1 , Yutaka Takahashi 1 , 7
31 December 2020
Anti–pituitary-specific transcription factor 1 (PIT-1) hypophysitis (anti–PIT-1 antibody syndrome) is a thymoma-associated autoimmune disease characterized by acquired growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) deficiencies due to autoimmunity against PIT-1. Ectopic expression of PIT-1 in the thymoma plays a causal role in development of the disease. Here, we report 2 cases of anti–PIT-1 hypophysitis exhibiting as a form of paraneoplastic syndrome with conditions other than thymoma. A 79-year-old woman (case 1) and an 86-year-old man (case 2) were referred with a suspicion of anti–PIT-1 hypophysitis because of acquired GH, PRL, and TSH deficiencies. Case 1 was complicated by diffuse large B-cell lymphoma (DLBCL) of the bladder and case 2 was diagnosed with malignancy with multiple metastases of unknown origin. Because circulating anti–PIT-1 antibody was detected, both patients were diagnosed with anti–PIT-1 hypophysitis. Circulating PIT-1–reactive T cells were detected in case 1 via enzyme-linked immunospot (ELISPOT) assay. Interestingly, the PIT-1 protein was ectopically expressed in the DLBCL cells of case 1, whereas DLBCL tissues derived from patients without anti–PIT-1 hypophysitis were negative for PIT-1. In case 2, the materials were not available because of best supportive care was under way. These data show that anti–PIT-1 hypophysitis is associated not only with thymoma but also with other malignancies. Additionally, the ectopic expression of PIT-1 in the DLBCL tissues and presence of PIT-1–reactive T cells suggested that the underlying mechanisms were similar to those observed in thymoma. Thus, anti–PIT-1 hypophysitis is defined as a form of paraneoplastic syndrome.