SAT-116 An Affair of the Heart - First Case Report of Immune Checkpoint Inhibitor Associated Cardiac Sarcoidosis Presenting with Non-PTH Medicated Hypercalcemia

Background: Immune checkpoint inhibitors (ICI) are an effective new tool in the treatment of malignancy by rescuing exhausted T-cells and enhancing anti-tumor immunity. The offset of immune self-tolerance can result in autoimmune adverse effects involving gastrointestinal, pulmonary and endocrine systems. Lung and skin sarcoidosis have been described in association with ICI use. We present the first case of non-PTH medicated hypercalcemia due to cardiac sarcoidosis in the setting of immunotherapy. Case Presentation: A 71-year-old man was referred to endocrinology for hypercalcemia. He had a fourteen-year history of scalp melanoma in remission until February 2019, when routine surveillance scans suggested metastatic disease. Computer tomography of the chest showed mediastinal and hilar lymphadenopathy (largest node 5.2 cm) and numerous pulmonary nodules (largest 1.7 cm). Biopsy of the largest pulmonary nodule and mediastinal lymph node (LN) confirmed BRAF wild-type metastatic melanoma. Ipilimumab/nivolumab (antiCTLA4/antiPD-1) combination therapy was started. After two cycles, hypercalcemia was noted on routine laboratory surveillance. He was asymptomatic and physical exam was unremarkable. Initial workup revealed: calcium 10.6 mg/dL (8.6-10.2), albumin 4 g/dL (3.5 - 5.2), phosphorus 3.8 mg/dL (2.7 - 4.5), PTH <0.6 pg/mL (15.0 - 65.0), PTHrP <2.0 pmol/L (0.0 - 2.3), 25 hydroxyvitamin D 22. 9 ng/mL (30 - 60), vitamin A 0.59 mg/L (0.30 - 1.20). He denied taking calcium-containing supplements. He was treated with hydration and immunotherapy was continued for two cycles, followed by single agent nivolumab. After three months on ICI, the metastatic lesions were reduced in size by 30%. His calcium peaked at 12.5 mg/dL and was treated with 4mg of intravenous Zoledronic acid without resolution. He developed worsening functional status, symptomatic hypotension, and elevated troponins. Cardiac MRI demonstrated myocarditis and nivolumab-induced myocarditis was suspected. Surprisingly, endomyocardial biopsy revealed multiple granulomas suggestive of sarcoidosis. AFB, PAS and Congo red stains were negative. He was treated with supportive care and glucocorticoids with resolution of hypercalcemia and improved cardiac function. Unfortunately, serum 1,25 dihydroxy vitamin D was not successfully measured until after the first dose of prednisone and was found at the upper limit of our reference range 62.0 pg/mL (19.9-79.3). Conclusion: Immune checkpoint inhibitors are effective agents in treating various cancers. Adverse effects due to autoimmunity are common and early recognition of life-threatening complications is critical. Although cutaneous and pulmonary sarcoidosis have been described with ICI, to our knowledge, this is the first case report of ICI-related cardiac sarcoidosis presenting with PTH-independent hypercalcemia.