Ipilimumab-Induced Hypophysitis and Thyroiditis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 306-326-Neoplasia of Endocrine Tissues: Case Reports
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-312
Bithika Marie Thompson*1 and Rutwij Joshi2
1Washington Univ, St. Louis, MO, 2Washington University, St. Louis, MO
Background: Ipilimumab, a monoclonal antibody against the cytotoxic T lymphocyte 4 antigen (CTLA-4), is currently approved for the treatment of unresectable and advanced metastatic melanoma. Immune related adverse events (IRAEs) are a common side effect of treatment. The development of IRAEs is associated with a better drug response. Of the different types of IRAEs, endocrinopathies account for 7%. The decision to discontinue ipilimumab in patients who develop IRAEs is currently debated. We present a case of combined hypophysitis and thyroiditis in a patient receiving ipilimumab. Although individually both are well-described presentations, there are no cases in the literature describing this combination.

Clinical Case:  A 52 year old man with metastatic melanoma presented with progressive fatigue, headache, anorexia, and nausea. He had received his third dose of ipilimumab three weeks prior to the onset of symptoms. On examination, he was afebrile, normotensive, and tachycardic. Neurological exam revealed normal extraocular movements and intact visual fields. No evidence of goiter or thyroid tenderness was noted. Abdomen was soft without organomegaly and no lymphadenopathy was appreciated. Laboratory evaluation revealed a TSH of <0.02 mcIU/ml (n = 0.35- 5.5) and free T4 of 2.29 ng/dl (n= 0.9- 1.8). Thyroid stimulating Ig and thyroperoxidase Ab were negative. Prolactin was low at 1.7 ng/mL (n= 2.1-18.0). Morning cortisol was undetectable at <1.5 mcg/dL. 21-hydroxylase Ab was negative. He had low gonadotropins with LH of 1.3 IU/L (n= 1.5-9.3) and FSH of 1.7 IU/L (1.4-18.0) with a total testosterone level of <50 ng/dL (n= 24-827). Brain MRI was negative for metastases.

A diagnosis of combined autoimmune hypophysitis and thyroiditis was made. The ipilimumab was continued and the endocrinopathies treated medically. Stress dose steroids resulted in immediate resolution of his symptoms. Methimazole resulted in euthyroidism. Testosterone was withheld given a concern for tumor growth. He demonstrated decreased tumor size on follow-up imaging. The thyroiditis resolved following the completion of ipilimumab treatment. He has required long term maintenance steroids.

Conclusion: An increasing number of patients will receive anti-CTLA-4 therapies for metastatic melanoma. Endocrinologists should be aware of the potential endocrine derangements that may occur, screening recommendations, and the treatment considerations associated with these endocrinopathies.

Nothing to Disclose: BMT, RJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm