MON-338 1-25 Vitamin D-Mediated Hypercalcemia of Malignancy

Introduction: Hypercalcemia of malignancy may be due to several pathogenic mechanisms. Here we present a previously undescribed situation of a vitamin D-mediated hypercalcemia due to uterine adenocarcinoma. Case: 65 year-old woman with type 2 diabetes, OSA, obesity (class III), HTN, hypothyroidism, recurrent cholecystitis, who came to the ED with a 2-week history of abdominal pain. Her initial symptoms were malaise, polydipsia, abdominal pain, back pain, constipation, and poor concentration. She was not taking any medications or supplements that may cause hypercalcemia. Exam was notable for obesity, altered mentation, peripheral edema, and elevated JVP. Labs: Calcium 15.5 mg/dL (8.1-10.5 mg/dL), albumin 2.7 g/dL (3.0-5.3 g/dL), blood gas consistent with chronic hypercapnic respiratory failure, and urine culture positive for ESBL E. coli. Imaging/Path: CT abdomen/pelvis revealed a new large pelvic mass arising from the uterus with associated retroperitoneal adenopathy. Biopsy was consistent with metastatic uterine adenocarcinoma. Hospital course: She was treated with pamidronate 90 mg IV x1, calcitonin 400 units IM TID for 2 days, and IV fluids. Hospital course was complicated by severe sepsis and ICU admission. Calcium normalized over 2 days, but began to uptrend about 1 week after her first dose of pamidronate. Calcium levels remained between 12 - 14 mg/dL despite repeated doses of pamidronate and calcitonin. Denosumab was added. Further workup revealed PTH 2 pg/mL (9-55 pg/mL), PTHrP <2.0 pmol/L (0.0-3.4 pmol/L), 1,25- vitamin D 181 pg/mL (19.9-79.3 pg/mL), and 25-vitamin D 21 ng/mL (30-80 ng/mL). IV hydrocortisone was started, and calcium level dropped to within the normal range after about 1 day. Given her poor prognosis, functional status, and her expressed wishes, she transitioned to comfort care and passed away. Pathophysiology: Hypercalcemia of malignancy is mediated through 3 main mechanisms: (1) PTHrP is released from tumor cells, mimicking PTH’s effect on the bones and kidneys, (2) osteolysis due to local cytokine release or multiple myeloma cells directly causing osteoclast activation, and (3) vitamin D-mediated due to overexpression of 1α-hydroxylase by lymphoma cells or macrophages. Ectopic production of PTH by tumor cells is also possible, but very rare. Nearly 80% of hypercalcemia of malignancy is mediated by PTHrP, about 20% is mediated by the lytic mechanism, and the remainder is vitamin D-mediated. Conclusion: There are case reports of vitamin D-mediated hypercalcemia in ovarian dysgerminoma, and PTHrP-mediated hypercalcemia in uterine cancers, however this is the first case report of vitamin D-mediated hypercalcemia due to uterine adenocarcinoma. Our experience highlights the importance of further workup when a patient fails to respond to usual therapy.