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Case Reports
. 2011 Feb;164(2):303-7.
doi: 10.1530/EJE-10-0833. Epub 2010 Nov 18.

Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy

Le Min  1 , Anand Vaidya, Carolyn Becker
Affiliations
Case Reports

Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy

Le Min et al. Eur J Endocrinol. 2011 Feb.

Abstract

Objective: Ipilimumab is a fully human MAB against cytotoxic T-lymphocyte antigen 4 (CTLA4). CTLA4 negatively regulates immune cell activation. In patients with metastatic melanoma, ipilimumab increases survival time and induces complete remission in some patients. However, immune-related adverse events including endocrinopathies have been reported. Bevacizumab, an angiogenesis inhibitor, has been used in combination with ipilimumab in patients with advanced melanoma.

Patients and methods: In this study, we report three patients who received ipilimumab alone or combined with bevacizumab therapy and developed thyroiditis, and the first report of euthyroid Graves' ophthalmopathy.

Results: Case 1 is a 51-year-old female who presented with severe eye pain, proptosis, and periorbital edema. Laboratory results revealed normal TSH, elevated thyroid antibodies but low titer of anti-TSH receptor antibody. Imaging was consistent with Graves' ophthalmopathy. Cases 2 and 3 were referred for hyperthyroidism, and workup revealed thyroiditis. These three cases suggest that patients with advanced melanoma treated with ipilimumab +/- bevacizumab may be susceptible to a variety of thyroid disorders.

Conclusions: Anti-CTLA4 therapy has shown promising results in treating advanced malignancy such as melanoma and renal carcinoma. A number of endocrinopathies, including thyroid disorders, may develop during ipilimumab therapy. The association of bevacizumab with endocrinopathies is not clear, although a few reports suggest a link to hypothyroidism. All patients on ipilimumab and/or bevacizumab therapy should be monitored for signs or symptoms of thyroiditis.

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Figures

Figure 1
Figure 1
Change in TSH in cases 2 and 3 prior to and after ipilimumab therapy
See this image and copyright information in PMC

References

    1. Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–594. - PubMed
    1. Blansfield JA, Beck KE, Tran K, Yang JC, Hughes MS, Kammula US, Royal RE, Topalian SL, Haworth LR, Levy C, Rosenberg SA, Sherry RM. Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother. 2005;28:593–598. - PMC - PubMed
    1. Dillard T, Yedinak CG, Alumkal J, Fleseriu M. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary. 2010;13:29–38. - PubMed
    1. Boehm S, Rothermundt C, Hess D, Joerger M. Antiangiogenic drugs in oncology: a focus on drug safety and the elderly - a mini-review. Gerontology. 2010;56:303–309. - PubMed
    1. Karantanis D, Bogsrud TV, Wiseman GA, Mullan BP, Subramaniam RM, Nathan MA, Peller PJ, Bahn RS, Lowe VJ. Clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland. J Nucl Med. 2007;48:896–901. - PubMed

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