SAT-493 A Case of Endometrial Adenocarcinoma Presenting with PTHrP-Mediated Hypercalcemia

Background Hypercalcemia of malignancy mediated by PTHrP is the most common cause of hypercalcemia in non-metastatic solid tumors, but its association with endometrial adenocarcinoma is rare(1). Clinical Case A 50 year old woman with endometrial hyperplasia and an enlarging uterine mass presented with pelvic pain and fatigue and was found to have new onset hypercalcemia. On presentation, her labs were as follows: calcium 13.1 mg/dl (8.7-10.2 mg/dl), albumin 4.2 g/dl (3.5-4.8 g/dl), creatinine 1.0 mg/dl (0.4-1.0 mg/dl), 25-OH Vitamin D 35 ng/ml (30-100 ng/ml), and PTH 4 pg/ml (14-72 pg/ml). SPEP, UPEP and 1,25-OH Vitamin D were normal. Given her PTH-independent hypercalcemia and known uterine mass, hypercalcemia of malignancy was high on the differential diagnosis. Her PTHrP did return elevated at 5.5 pmol/L (<2.0 pmol/L). Imaging showed a large 11.2 cm mass in the uterine fundus with retroperitoneal lymphadenopathy and pulmonary nodules concerning for metastatic disease. Pathology of the mass revealed endometrial adenocarcinoma. She was treated with IV fluids, calcitonin, and pamidronate with normalization of her calcium. She later received chemotherapy, and initially her calcium remained stable. However, she later had progression of her malignancy with rising calcium levels, requiring additional bisphosphonate therapy. This had limited effect on her calcium, and her PTHrP had climbed to 30 pmol/L. Given her refractory hypercalcemia to bisphosphonate therapy, consideration was given to start denosumab. However, she had declined clinically with further progression of her malignancy, and she transitioned to hospice care. She died 5 months after her initial presentation. Conclusion This case is a rare instance of PTHrP-mediated hypercalcemia seen in endometrial carcinoma. Treatment of the underlying malignancy is the main therapy for hypercalcemia of malignancy, and PTHrP is a useful tumor marker for assessing treatment response. Denosumab is an emerging treatment option for hypercalcemia of malignancy that is refractory to bisphosphonate therapy(2). References 1. Andrew F. Stewart. Hypercalcemia Associated with Cancer., N Engl J Med 2005; 352:373-379. 2. Sonail Thosani, Mimi L Hu. Denosumab: a new agent in the management of hypercalcemia of malignancy. Future Oncol 2015 Nov; 11(21): 2865-2871.