Transient Hypophysitis after Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA4) Blockade

Abstract

C T LYMPHOCYTE-associated antigen 4 (CTLA4) blockade using the human anti-CTLA4 monoclonal antibody CP-675,206 has antitumor activity in melanoma (1). Blockade of CTLA4 binding to its B7 ligands results in disruption of peripheral immune tolerance and enhanced T cell activation (2), which can cause secondary autoimmune endocrinopathies, including hypophysitis and thyroiditis (1, 3, 4). We herein present a more detailed clinical history of a patient who developed transient hypophysitis after receiving CP-675,206 (1). A 44-yr-old male with stage IV melanoma developed extreme fatigue, headache, and decreased libido 3 months after a single 15-mg/kg infusion of CP-675,206. Magnetic resonance imaging (Fig. 1) demonstrated new diffuse enlargement of the pituitary gland, and laboratory analyses revealed TSH, prolactin, and gonadotropin deficiencies; GH and ACTH production were normal (Table 1). Previous thyroid function studies obtained 1 wk before drug infusion had been normal: free T4 1.2 ng/dl (range 0.7–1.9) and TSH 0.72 mU/liter (range 0.3–5.5). Although a biopsy was not performed to confirm the diagnosis, the patient’s clinical presentation was felt to be consistent with hypophysitis. Appropriate hormone replacement was initiated, and the patient was monitored while receiving no immunosuppressant therapy. Follow-up imaging performed 6 months after the CP-675,206 infusion revealed resolution of the pituitary gland abnormality (Fig. 1). Twelve months after the CP-675,206 infusion, the patient required no hormone replacement and had no biochemical evidence of hypopituitarism, except for a persistently undetectable prolactin level (Table 1). Abbreviation: CTLA4, Cytotoxic T lymphocyte-associated antigen 4.