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

Department of Endocrine Neoplasia and Hormonal Disorders (S.A.S., S.G.W.), Phase I Program (L.H.C.), and Department of Neurosurgery (I.E.M.), The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Address all correspondence and requests for reprints to: Steven G. Waguespack, M.D., FAAP, FACE, Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 435, Houston, Texas 77030. E-mail: swagues{at}mdanderson.org.

CYTOTOXIC 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).

View larger version (67K): [in this window] [in a new window]   FIG. 1. Coronal post contrast T1 weighted magnetic resonance images through the sella turcica showing: a normal pituitary gland 2 wk before CP-675,206 therapy (A), an enlarged pituitary (arrow) 3 months after CP-675,206 infusion at the time of presentation with headaches and multiple anterior pituitary hormone deficiencies (B), and complete resolution of the pituitary enlargement with a return to baseline appearance 3 months after initial presentation and 6 months after CP-675,206 therapy (C).

	Footnotes

 
Disclosure Statement: The authors have nothing to disclose.

Abbreviation: CTLA4, Cytotoxic T lymphocyte-associated antigen 4.

Received November 13, 2006.

Accepted January 3, 2007.

	References

Top References

 

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2. Kapadia D, Fong L 2005 CTLA-4 blockade: autoimmunity as treatment. J Clin Oncol 23:8926–8928[Free Full Text]
3. Blansfield JA, Beck KE, Tran K, Yang JC, Hughes MS, Kammula US, Royal RE, Topalian SL, Haworth LR, Levy C, Rosenberg SA, Sherry RM 2005 Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother 28:593–598[CrossRef][Medline]
4. Maker AV, Yang JC, Sherry RM, Topalian SL, Kammula US, Royal RE, Hughes M, Yellin MJ, Haworth LR, Levy C, Allen T, Mavroukakis SA, Attia P, Rosenberg SA 2006 Intrapatient dose escalation of anti-CTLA-4 antibody in patients with metastatic melanoma. J Immunother 29:455–463[CrossRef][Medline]

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This Article Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shaw, S. A. Articles by Waguespack, S. G. Search for Related Content PubMed PubMed Citation Articles by Shaw, S. A. Articles by Waguespack, S. G. Related Collections Autoimmunity Neuroendocrinology and Pituitary