Bisphosphonate-resistant hypercalcemia in a rare case of paraneoplastic PTH secretion

Abstract

Background/objective

To report a rare case of ectopic parathyroid hormone (PTH) secretion from poorly-differentiated adenocarcinoma and the lessons learned in management.

Case report

A 54-year-old woman presented with fatigue, hip pain, and confusion. Workup revealed calcium of 16.9 mg/dl (N: 8.5–10.3 mg/dl), PTH of 981 pg/ml (N: 15–65 pg/ml), and parathyroid hormone-related peptide (PTHrP) of 20 pmol/L (N: 14–27 pmol/L). Parathyroid four-dimensional computed tomography was unrevealing. Magnetic resonance cholangiopancreatography demonstrated innumerable hepatic lesions. Biopsy of the liver and pubic ramus revealed poorly differentiated adenocarcinoma of unknown origin with acinar cell differentiation and focal PTH positivity.

Initial treatment with intravenous bisphosphonates and cinacalcet showed a poor response. Calcitonin had a short-lived response. Although chemotherapy significantly improved calcium levels, she was unable to tolerate chemotherapy. Despite a rise in PTH from 196 to 674 pg/ml, denosumab improved calcium levels from 13 to 9.7 mg/dl. She expired due to a cardiac arrest.

Discussion

PTH secretion from tumors with acinar cell differentiation outside of the pancreas has not been described. Cinacalcet was ineffective and it is doubtful that the malignant cells had calcium-sensing receptors. Calcitonin was effective initially, but she eventually developed tachyphylaxis. Use of denosumab later in the treatment course has resulted in significant improvement in calcium despite worsening PTH levels.

Conclusion

Denosumab is effective in the treatment of paraneoplastic PTH-mediated hypercalcemia and should be considered in patients who have resistance to bisphosphonate therapy.