SUN-416 Ipilimumab Associated Hypophysitis and Thyroiditis

Abstract

INTRODUCTION Ipilimumab, an anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody, is approved for use in advanced melanoma based upon survival benefit. Anti CTLA 4 antibodies are associated with a myriad of side effects. CLINICAL CASE A 65 year old male with stage 3A malignant melanoma s/p excision on Ipilimumab for 6 months, HTN, aortic stenosis, DM type II and recent c.diff infection presented with generalized weakness, imbalance, lightheadedness and 60 lbs weight loss over 4 weeks. On admission, patient was hemodynamically stable. Initial lab work revealed thyrotoxicosis with suppressed TSH (0.012mcunit/mL), elevated FT4 (2.8pg/mL) and FT3 (9.7pg/mL); low random cortisol (1.7mcg/dL) and hypercalcemia (11.8mg/dl). TRAb was negative. Further evaluation revealed low ACTH level (6.1pg/mL) consistent with secondary adrenal insufficiency and mildly elevated prolactin (18ng/mL). He was started on low dose hydrocortisone and methimazole (MMI). MRI brain showed no pituitary abnormality or metastasis. U/S thyroid showed a multinodular goiter. Of note, patient’s TFTs two months ago showed secondary hypothyroidism (TSH:0.064ng/dL, FT4:0.4ng/dL) but his current presentation was consistent with thyrotoxicosis suspected secondary to thyroiditis. For his non-PTH related hypercalcemia, multiple myeloma workup was negative. Hypercalcemia was thought to be secondary to hyperthyroidism. During his admission, patient developed acute encephalopathy. Infectious and neurological workup was negative. Suspecting Ipilumumab induced hypophysitis, treatment with high dose prednisone (1mg/kg/day) was initiated which resulted in significant improvement in his condition. MMI was discontinued following improvement in TFTs. DISCUSSION Following Ipilimumab immunotherapy, the reported incidence of hypophysitis is 8% and that of thyroiditis 6%. One study showed 80% of patients initially present with thyrotoxicosis and subsequently develop hypothyroidism suggesting thyroiditis is a more common cause of thyrotoxicosis. Interestingly, our patient initially had hypophysitis causing central hypothyroidism but later developed thyroiditis and adrenal insufficiency. Clinically, concerning features with hypophysitis include adrenal crisis with hemodynamic instability, hypernatremia or mass effect from enlarged pituitary. Typical imaging shows pituitary enlargement, stalk thickening, or delayed enhancement but absence of these findings does not rule out hypophysitis. In cases of mild to moderate toxicity where endocrinopathies can be managed easily, Ipilimumab may be resumed once steroids are tapered. If higher toxicities develop, recommendation is to discontinue therapy. CONCLUSION Our patient presented with moderate hypophysitis along with primary thyroiditis as a side effect of Ipilimumab. He was treated with high dose steroids. Ipilimumab was discontinued.