SAT-494 A Very Rare Case: Hypercalcemia Caused by Ectopic PTH Secretion in Endometrial Cancer

Up to 40% of cancer patients develop hypercalcemia due to malignancy. Parathyroid hormone related peptide (PTHrP) secretion accounts for >80% of the cases. Here, we describe an unusual case of hypercalcemia due to PTH secretion by endometrial cancer. A 46-year old female presented with nausea, vomiting and right lower quadrant pain. She was noted to be tachycardic, with a pulse of 110 bpm; physical exam was significant only for mild abdominal distention. Laboratory analysis showed a serum calcium of 12.8 mg/dl (8.5-10.5), albumin of 3.8 g/dl (3.5-5), mild transaminitis and normal renal function. A contrasted CT of the abdomen and pelvis revealed a 26 cm right ovarian mass, hypodense lesions throughout the liver, moderate ascites and omental fat nodularity worrisome for ovarian malignancy and peritoneal carcinomatosis. Total abdominal hysterectomy with bilateral salpingo-oophorectomy with biopsy of small bowel mesentery and liver were performed. Pathology showed dedifferentiated endometroid adenocarcinoma with metastasis to the ovaries, liver and small bowel mesentery. Post-operatively, the calcium normalized but then gradually climbed to 12.6 mg/dl despite adequate intravenous hydration. Workup showed a PTH of 135 pg/ml (10-65), PTHrP was undetectable, 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D were normal. Neck ultrasound was negative for an obvious parathyroid adenoma. However, immunohistochemical staining of the surgical pathology was strongly positive for PTH. Pamidronate 30 mg IV was administered. Serum calcium normalized , and the patient was discharged for outpatient neo-adjuvant chemotherapy. Unfortunately, she passed away from septic shock and multi-organ failure a few weeks after diagnosis. Hypercalcemia in malignancy may arise via three distinct mechanisms: (1) humoral hypercalcemia arising from tumor secretion of PTHrP or PTH; (2) osteolytic hypercalcemia from direct skeletal involvement, and (3) over secretion of 1,2 dihydroxyvitamin D. Very rarely, ectopic PTH production has been described in the literature as the cause of humoral hypercalcemia. By 2018, there were only 26 cases in the reported literature. Three were from gynecological cancer, with two related to ovarian cancer. Only one reported case was related to endometroid adenocarcinoma. To our knowledge, this is the second reported case. The presence of hypercalcemia in malignancy has been associated with increased mortality; the survival was two years in patients with mild hypercalcemia versus 1-2 months with more severe hypercalcemia. Though unusual, this case highlights the importance of considering ectopic PTH secretion rather than the default assumption of primary hyperparathyroidism in cancer patients with high calcium and PTH levels.