SUN-415 Panhypopituitarism: A Wake-Up Call in Patients Taking Anti-CTLA-4 Treatment

Background: Novel immune checkpoint proteins inhibitors, such cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) like ipilimumab could produce hypophysitis as a side effect with a prevalence between 0 to 10%. There are no guidelines in how to monitor patients receiving similar agents. We present a case that was follow up hormonally and developed hypophysitis. Clinical Case:A 63-year-old male presented in 2015 with severe frontal headache that lasted 4 days with no improvement with Ibuprofen and fatigue 5 days after receiving third dose of ipilimumab for metastatic malignant melanoma. He denied nausea, vomiting, visual symptoms. Magnetic resonance (MRI) demonstrated a diffuse pituitary enlargement. Laboratory results showed decreased hormones like: cortisol (0.5mcg/dl, n:4-22mcg/dl), freeT4 (0.36 ng/dl, n:0.8-1.8ng/dl), TSH (0.36 mIU/L, n:0.40-4.5mIU/L) prolactin (<1ng/ml, n 2-18 ng/ml), free testosterone (33.6 pg/ml, n:35-155pg/ml) and normal IGF-1 (62 ng/ml, n:41-279) consistent with panhypopituitarism in the setting of hypophysitis secondary to ipilimumab. Cortisol and thyroid hormones levels where checked before beginning ipilimumab and after receiving first dose and were within normal limits. After patient received the second dose, patient had an episode of colitis which lasted 10 days, which required prednisone 40 mg for 1 week and then it was tapered for another 2 weeks. At that point cortisol was checked which was normal (9.9 mcg/l n:4-22mcg/dl), however patient was on steroids. Patient received third dose of ipilimumab and then he developed severe headache and was diagnosed with hypophysitis. Patient was started on dexamethasone high doses, which was tapper down and switched to hydrocortisone 20 mg am and 10 at pm and was started on levothyroxine 137 mcg daily. Two months after diagnosis an MRI was repeat which did not show any pituitary enlargement, however patient had persistent panhypopituitarism on laboratory results. Four months after diagnosis was started on testosterone replacement therapy. Last visit was in 2018 patient was without fatigue, he is on hydrocortisone 15mg am, 10mg pm, levothyroxine 175 mcg, and testosterone gel every day. His cortisol is decreased (1 mcg/dl , n:4-22mcg/dl), IGF-1 now is low (37 ng/ml n:41-279), prolactin is decrease (1.3 ng/ml, n 2-18 ng/ml), free T4 normal on replacement (1.1 ng/dl, n:0.8-1.8ng/dl), normal free testosterone on replacement (57.6 pg/ml, n:35-155pg/ml). Conclusion: endocrinopathies are seen up to 10% in patients on CTLA-4, therefore awareness of more serious deficits like hypophysitis should need to be promptly recognized and follow up is recommended, like we are implementing this approach in our institution.