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      Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects

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          Abstract

          Purpose

          This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis.

          Methods

          The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences.

          Results

          Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining.

          Conclusion

          Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.

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          Most cited references 127

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          Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.

          Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.
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            Defining criteria for autoimmune diseases (Witebsky's postulates revisited)

            With new knowledge gained from molecular biology and hybridoma technology, as well as the original Witebsky postulates, we propose that three types of evidence can be marshalled to establish that a human disease is autoimmune in origin. They include direct evidence from transfer of pathogenic antibody or pathogenic T cells; indirect evidence based on reproduction of the autoimmune disease in experimental animals; and circumstantial evidence from clinical clues.
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              Autoimmune hypophysitis.

              Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum. We have analyzed 370 articles published from January 1962 to October 2004 and identified a total of 379 patients with primary lymphocytic hypophysitis. The present review synthesizes the clinical and research data reported in this body of scientific literature.
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                Author and article information

                Contributors
                +39 0815665289 , antonio.bellastella@unina2.it
                Journal
                Pituitary
                Pituitary
                Pituitary
                Springer US (New York )
                1386-341X
                1573-7403
                8 August 2016
                2016
                : 19
                : 6
                : 625-642
                Affiliations
                [1 ]GRID grid.9841.4, ISNI 0000000122008888, Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, , Second University of Naples, ; Naples, Italy
                [2 ]GRID grid.9841.4, ISNI 0000000122008888, Endocrinology and Metabolic Diseases Unit, Department of Cardiothoracic and Respiratory Sciences, , Second University of Naples, ; Piazza L. Miraglia 2, 80138 Naples, Italy
                [3 ]GRID grid.9841.4, ISNI 0000000122008888, Department of Clinical and Experimental Medicine, , Second University of Naples, ; Naples, Italy
                Article
                736
                10.1007/s11102-016-0736-z
                7088540
                27503372
                © Springer Science+Business Media New York 2016

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                © Springer Science+Business Media New York 2016

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