3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Two Cases of anti–PIT-1 Hypophysitis Exhibited as a Form of Paraneoplastic Syndrome not Associated With Thymoma

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references 16

          • Record: found
          • Abstract: found
          • Article: not found

          Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis.

          Classical paraneoplastic encephalitis syndromes with 'onconeural' antibodies directed to intracellular antigens, and the recently described paraneoplastic or non-paraneoplastic encephalitides and antibodies against both neural surface antigens (voltage-gated potassium channel-complexes, N-methyl-d-aspartate receptors) and intracellular antigens (glutamic acid decarboxylase-65), constitute an increasingly recognized group of immune-mediated brain diseases. Evidence for specific immune mechanisms, however, is scarce. Here, we report qualitative and quantitative immunopathology in brain tissue (biopsy or autopsy material) of 17 cases with encephalitis and antibodies to either intracellular (Hu, Ma2, glutamic acid decarboxylase) or surface antigenic targets (voltage-gated potassium channel-complex or N-methyl-d-aspartate receptors). We hypothesized that the encephalitides with antibodies against intracellular antigens (intracellular antigen-onconeural and intracellular antigen-glutamic acid decarboxylase groups) would show neurodegeneration mediated by T cell cytotoxicity and the encephalitides with antibodies against surface antigens would be antibody-mediated and would show less T cell involvement. We found a higher CD8/CD3 ratio and more frequent appositions of granzyme-B(+) cytotoxic T cells to neurons, with associated neuronal loss, in the intracellular antigen-onconeural group (anti-Hu and anti-Ma2 cases) compared to the patients with surface antigens (anti-N-methyl-d-aspartate receptors and anti-voltage-gated potassium channel complex cases). One of the glutamic acid decarboxylase antibody encephalitis cases (intracellular antigen-glutamic acid decarboxylase group) showed multiple appositions of GrB-positive T cells to neurons. Generally, however, the glutamic acid decarboxylase antibody cases showed less intense inflammation and also had relatively low CD8/CD3 ratios compared with the intracellular antigen-onconeural cases. Conversely, we found complement C9neo deposition on neurons associated with acute neuronal cell death in the surface antigen group only, specifically in the voltage-gated potassium channel-complex antibody patients. N-methyl-d-aspartate receptors-antibody cases showed no evidence of antibody and complement-mediated tissue injury and were distinguished from all other encephalitides by the absence of clear neuronal pathology and a low density of inflammatory cells. Although tissue samples varied in location and in the stage of disease, our findings strongly support a central role for T cell-mediated neuronal cytotoxicity in encephalitides with antibodies against intracellular antigens. In voltage-gated potassium channel-complex encephalitis, a subset of the surface antigen antibody encephalitides, an antibody- and complement-mediated immune response appears to be responsible for neuronal loss and cerebral atrophy; the apparent absence of these mechanisms in N-methyl-d-aspartate receptors antibody encephalitis is intriguing and requires further study.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Hypopituitarism.

            Incidence and prevalence of hypopituitarism are estimated to be 4.2 per 100,000 per year and 45.5 per 100,000, respectively. Although the clinical symptoms of this disorder are usually unspecific, it can cause life-threatening events and lead to increased mortality. Current research has refined the diagnosis of hypopituitarism. Identification of growth hormone and corticotropin deficiency generally requires a stimulation test, whereas other deficiencies can be detected by basal hormones in combination with clinical judgment. Newly developed formulations of replacement hormones are convenient and physiological. Work has shown that many patients with brain damage--such as traumatic brain injury or aneurysmal subarachnoid haemorrhage--are at high risk of (sometimes unrecognised) hypopituitarism. Thus, a much increased true prevalence of this disorder needs to be assumed. As a result, hypopituitarism is not a rare disease and should be recognised by the general practitioner.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

              To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults.
                Bookmark

                Author and article information

                Contributors
                Journal
                J Endocr Soc
                J Endocr Soc
                jes
                Journal of the Endocrine Society
                Oxford University Press (US )
                2472-1972
                01 March 2021
                31 December 2020
                31 December 2020
                : 5
                : 3
                Affiliations
                [1 ] Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe, Japan
                [2 ] Medical Center for Student Health, Kobe University , Kobe, Japan
                [3 ] Department of Bio-signal Pathophysiology, Kobe University Graduate School of Medicine , Kobe, Japan
                [4 ] Department of Diabetes and Endocrinology, Saiseikai Shiga Hospital , Shiga, Japan
                [5 ] Department of Diabetes and Endocrinology, Red Cross Otsu Hospital , Shiga, Japan
                [6 ] Division of Diabetes and Endocrinology, Kobe University Hospital , Kobe, Japan
                [7 ] Department of Diabetes and Endocrinology, Nara Medical University , Nara, Japan
                Author notes
                Correspondence: Yutaka Takahashi, MD, PhD, Department of Diabetes and Endocrinology, Nara Medical University, 840 Shijou-cho Kashihara, Nara, 634-8521, Japan. Email: takahash@ 123456naramed-u.ac.jp .
                Article
                bvaa194
                10.1210/jendso/bvaa194
                7814384
                © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                Page count
                Pages: 8
                Product
                Funding
                Funded by: Japan Society for the Promotion of Science, DOI 10.13039/501100001691;
                Award ID: 23659477
                Award ID: 26670459
                Award ID: 15K09431
                Award ID: 18K08514
                Award ID: 17K16165
                Funded by: Foundation for Growth Science;
                Funded by: Japan Agency for Medical Research and Development, DOI 10.13039/100009619;
                Award ID: 17bm0804012h0001
                Funded by: Uehara Memorial Foundation, DOI 10.13039/100008732;
                Funded by: Naito Foundation, DOI 10.13039/100007428;
                Categories
                Case Reports
                AcademicSubjects/MED00250

                Comments

                Comment on this article