RT Journal Article SR Electronic T1 Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP e000687 DO 10.1136/jitc-2020-000687 VO 8 IS 1 A1 Ramona Dadu A1 Theresa E Rodgers A1 Van A Trinh A1 Elizabeth Helen Kemp A1 Trisha D Cubb A1 Sapna Patel A1 Julie M Simon A1 Elizabeth M Burton A1 Hussein Tawbi YR 2020 UL http://jitc.bmj.com/content/8/1/e000687.abstract AB Background Immune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented.Case and methods A 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively.Results The patient’s symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient’s hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient’s clinical course of hypoparathyroidism. CaSR antibodies purified from the patient’s serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1.Conclusion The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid.