SUN-751 - Extreme Hypercalcemia in Two Cases of Ectopic PTH Production by Diffusely Metastatic Poorly Differentiated Carcinoma Portends Poor Prognosis

Introduction:
Hypercalcemia caused by ectopic production of parathyroid hormone (PTH) in the setting of malignancy that is not parathyroid carcinoma is exceedingly rare. We highlight two patients with diffusely metastatic poorly differentiated carcinoma presenting with maximum PTH levels of 3,593 pg/mL and 830 pg/mL, respectively, causing elevated serum calcium levels of 18.4 mg/dL and 19.3 mg/dL, and no evidence of a parathyroid tumor.
Case Reports:
Case 1 is a 61-year-old female who presented with pelvic mass, vaginal discharge, polyuria, polydipsia, and dizziness. Initial lab evaluation showed calcium of 14.1 mg/dL, PTH of 188 pg/mL, and PTH-rp of 3 pmol/L. CT scan showed a large uterine mass, a colo-uterine fistula, metastatic lung nodules, a pancreatic head mass, and multiple renal stones. Biopsy of the uterine mass showed endometrioid adenocarcinoma. Sestamibi scan did not show parathyroid adenoma, and calcium was treated with fluids and pamidronate. One month later, cancer was widely metastatic with biopsy of lung nodule revealing poorly differentiated carcinoma. Calcium rose to 15.2 mg/dL with PTH of 1500 pg/mL and maxed out at 3593 pg/mL. Despite maximal calcium lowering therapy, comfort measures were advised and patient passed away within 2 months of initial hypercalcemia.
Case 2 is a 70-year-old female presenting with abdominal pain, fatigue, confusion, polydipsia, and polyuria. She was treated for endometrial carcinoma 8 years prior. Initial labs revealed an elevated serum calcium of 19.3 mg/dL, PTH of 352 pg/mL, and PTH-RP of 1.1 pmol/L for which she received IV fluids, zoledronic acid, calcitonin, cinacalcet, and later denosumab. PET CT revealed several lesions in the lung, liver, and bone with abdominal and mediastinal lymph node adenopathy. Liver biopsy showed poorly differentiated adenocarcinoma of uncertain primary site. A 4D-CT of the neck showed no cervical mass or parathyroid gland enlargement. Hypercalcemia remained difficult to control and PTH rose rapidly to 830 within 15 days, so comfort measures were advised and patient passed away within 2 months of initial hypercalcemia.

Discussion:
Both patients were diagnosed with ectopic PTH in the setting of diffusely metastatic, poorly differentiated carcinoma. Ectopic PTH secretion is a rare, accounting for less than 1% (roughly 60) of cases. These have been documented with various primary malignancies all after parathyroid tumors were ruled out, and therefore, provide the ectopic source of PTH. The severity and recurrence of hypercalcemia is often extreme, and these two cases highlight the very rapid PTH elevation within 2 months.

Conclusion:
Non-parathyroid malignancies should also be considered as a possibility for hypercalcemia with significantly elevated PTH, once parathyroid adenoma and carcinoma is ruled out, but often has rapid, poor prognosis as reported by these two case studies.

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