Two Cases of Anti-PIT-1 Hypophysitis Exhibited as a Form of Paraneoplastic Syndrome

Abstract

Abstract Background: Anti-pituitary-specific transcription factor 1 (PIT-1) hypophysitis (anti-PIT-1 antibody syndrome) is a newly defined clinical entity, demonstrating an adult-onset hypopituitarism, and is a thymoma-associated autoimmune disease characterized by acquired GH, PRL, and TSH deficiencies due to autoimmunity against PIT-1 (1, 2). This disease is defined by an acquired specific GH, PRL, and TSH deficiencies and the presence of circulating anti-PIT-1 antibody and/or PIT-1-specific T cells (2). As the etiology, ectopic expression of PIT-1 in thymoma plays a causal role in the development of the disease (3); however, it is unknown whether this disease is involved in other conditions. Here, we report two PIT-1 hypophysitis cases, exhibiting as a form of paraneoplastic syndrome with malignancies other than thymoma. Clinical Case: A 79-year-old woman (case 1) and an 86-year-old man (case 2) were referred to us on suspicion of anti-PIT-1 hypophysitis because of acquired GH, PRL, and TSH deficiencies. In both patients, the endocrinological evaluation revealed extremely low basal levels and blunted responses of GH, PRL, and TSH to the provocative stimuli. In contrast, the secretion of HPA and HPG axis were preserved in both patients. Magnetic resonance imaging of the pituitary gland showed slight atrophy in case 1 and normal size in case 2. Interestingly, computed tomography imaging revealed no evidence for thymomas in both patients. On the other hand, case 1 was complicated with diffuse large B-cell lymphoma (DLBCL) of the bladder with multiple bilateral cervicals, axillary, para-aorta, and internal and external peri iliac lymphadenopathies. Case 2 was diagnosed with malignancy with multiple metastases of unknown origin with para-aortic and para-gastric lymphadenopathies, and vertebral body infiltrates. 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 using Enzyme-Linked Immunospot assay. Interestingly, the PIT-1 protein was ectopically expressed in the DLBCL tissue of case 1, while DLBCL tissues derived from control patients without anti-PIT-1 hypophysitis were negative for PIT-1. In case 2, the materials were not available because of the situation of the best supportive care. Conclusion: 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 (3). Thus, anti-PIT-1 hypophysitis is defined as a form of paraneoplastic syndrome. Reference: (1) J Clin Invest. 2011;121(1):113-119., (2) Endocr Rev. 2020;41(2)., (3) Sci Rep. 2017;7:43060.