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      Ipilimumab-induced autoimmune hypophysitis: a differential for sellar mass lesions

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          Summary

          Autoimmune hypophysitis (AH) has been previously described in a typical demographic population, primarily women in the reproductive age group and perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte-associated antigen 4 biological therapy (ipilimumab) against advanced cancers like metastatic melanomas has now resulted in a new form of hypophysitis being increasingly recognised under a spectrum of immune-related adverse events. Drug-related AH often presents with subtle symptoms and a pituitary mass, with the potential for fatality necessitating wide awareness and a high index of clinical suspicion given that it is usually treatable. We describe below two cases of AH within the last three months at our centre, which were treated with different regimens and produced good endocrine outcomes.

          Learning points

          • AH is a new and defined clinical entity occurring as a side effect of ipilimumab, which enhances immune-mediated destruction of metastatic melanoma.

          • It can present insidiously and have life-threatening complications related to hypocortisolism, hence a high index of clinical suspicion must be exerted by treating physicians, and seems to result in resolution of pituitary masses and variable improvements of pituitary function.

          • Clinical improvement, radiological resolution of pituitary masses and variable normalisation of pituitary function are possible with early treatment with high-dose oral or i.v. steroids and hormone replacement therapy, although duration and dosing protocols are unclear at this stage.

          • Ipilimumab should continue to be prescribed as treatment for metastatic melanoma; however, close clinical observation of patient's progress must be maintained while they are on this drug.

          • Predictive factors for onset of AH remain unclear and it is imperative that AH is distinguished from pituitary metastases.

          • Further studies are required to determine the safety of continuing therapy with ipilimumab in patients who have developed AH while on treatment.

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          Most cited references2

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          Ipilimumab-induced hypophysitis: MR imaging findings.

          Ipilimumab is a promising new immunotherapeutic antineoplastic agent with clinical activity in the treatment of metastatic melanoma and renal cell carcinoma. With advances in immunotherapy, however, a host of new side effects related to the mechanism of action of these drugs has appeared. At our institution, 3 patients presented with hypophysitis, which was attributed to an autoimmune process based on the documented relationship of the drug to other autoimmune phenomena and significant and rapid improvement with discontinuation of the drug and addition of steroids. We present the imaging findings in 3 patients with presumed ipilimumab-induced hypophysitis.
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            Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4: challenges from a new cause of a rare disease.

            Specific human monoclonal antibodies antagonize cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4 mAbs), a negative regulator of the immune system, inducing unrestrained T-cell activation. In patients with advanced or metastatic melanoma, one of these agents, ipilimumab, produced considerable disease control rates and, for the first time, a clear improvement in overall survival outcomes. However, accumulating clinical experience with anti-CTLA-4 mAbs identified a novel syndrome of autoimmune and autoinflammatory side effects, designated as "immune-related adverse events," including mainly rash, colitis, and hepatitis. Autoimmune hypophysitis has emerged as a distinctive side effect induced by anti-CTLA-4 mAbs. This condition may be life threatening because of adrenal insufficiency if not promptly recognized, but it may easily be diagnosed and treated if clinically suspected. Hypopituitarism caused by these agents is rarely reversible and prolonged or life-long substitutive hormonal treatment is often required. The precise mechanism of injury to the pituitary triggered by anti-CTLA-4 mAbs is yet to be fully elucidated.

              Author and article information

              Journal
              Endocrinol Diabetes Metab Case Rep
              Endocrinol Diabetes Metab Case Rep
              edm
              EDM Case Reports
              Endocrinology, Diabetes & Metabolism Case Reports
              Bioscientifica Ltd (Bristol )
              2052-0573
              1 December 2014
              2014
              : 2014
              : 140098
              Affiliations
              [1 ]Department of Diabetes and Endocrinology, The Townsville Hospital , Townsville, Queensland, Australia
              [2 ]Department of Oncology, The Townsville Hospital , Townsville, Queensland, Australia
              [3 ]School of Medicine and Dentistry, James Cook University , Douglas, Queensland, Australia
              Author notes
              Correspondence should be addressed to B T Rodrigues Email: beverly.rodrigues@ 123456my.jcu.edu.au
              Article
              EDM140098
              10.1530/EDM-14-0098
              4276072
              e416048c-eb49-4c9c-8766-cf0efde7da25
              © 2014 The authors

              This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

              History
              : 16 November 2014
              : 21 November 2014
              Categories
              Unique/Unexpected Symptoms or Presentations of a Disease

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