title: Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy.
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.
  
  
  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.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Le
authors.initials: L
authors.lastname: Min
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
authors.forename: Carolyn
authors.initials: C
authors.lastname: Becker
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D049970:Graves Ophthalmopathy / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab