Hypercalcemia in poorly differentiated endometrial cancer: a report of two cases

Hypercalcemia as a paraneoplastic syndrome is associated with poor prognosis. It is most commonly caused by parathyroid hormone-related protein (PTHrP) production, less commonly by bony metastases, and very rarely by ectopic parathyroid hormone (PTH) secretion. Hypercalcemia in endometrial cancer is relatively rare.

We present two cases of hypercalcemia in patients with poorly differentiated endometrial cancer, both of whom had elevated PTH levels and no evidence of parathyroid disease or bone metastases at baseline. In the first case, hypercalcemia rapidly progressed in parallel with metastatic disease, leading to clinical deterioration and death within one month. In the second case, calcium and PTH levels improved with systemic chemotherapy and cinacalcet but recurred with disease progression, supporting a tumor-driven mechanism. Both cases demonstrated aggressive histology and mismatch repair deficiency. Notably, hypercalcemia and PTH levels closely tracked tumor burden and clinical course.

Ectopic PTH secretion should be considered in patients with endometrial cancer presenting with hypercalcemia and elevated PTH in the absence of parathyroid pathology. Recognition of this rare entity is important to avoid misdiagnosis and to guide appropriate oncologic management.