Recurrent hypercalcemia due to ectopic production of parathyroid hormone-related protein and intact parathyroid hormone in a single patient with multiple malignancies

Objective: To report a case of recurrent hypercalcemia due to ectopic production of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) from transitional cell carcinoma of the urinary bladder. Methods: We present clinical, laboratory, and pathologic findings in a 73-year-old man with recurrent hypercalcemia. Results of serum calcium, PTH, PTH-rP and immunostaining of tumors for PTH and PTH-rP over 9 years are presented. Results: In 1990 this patient was diagnosed with primary hyperparathyroidism, which was cured by resection of a parathyroid adenoma in the neck. Hypercalcemia recurred in 1992, and he was found to have squamous cell carcinoma of the right lung. PTH-rP levels were not measured, but the resected tumor immunostained positive for the presence of PTH-rP. The patient subsequently remained normocalcemic until 1996, when the plasma calcium and PTH levels increased again. Surgical exploration of the neck revealed no parathyroid adenoma. Elevated plasma levels of calcium and PTH persisted after surgery. In 1998 the patient was diagnosed with stage IV invasive transitional cell carcinoma (TCC) of the urinary bladder and underwent radical cystectomy. The tumor tissue was not immunoreactive to PTH-rP. A year later, plasma levels of PTH and PTH-rP increased, but surgical re-exploration of the neck again revealed no parathyroid adenoma. CT scanning identified a large retroperitoneal mass, and a CT-guided biopsy of the mass showed metastatic, poorly differentiated TCC immunopositive for PTH and PTH-rP. Conclusion: This is the first report of ectopic production of PTH from metastatic TCC of the urinary bladder coexisting with PTH-rP mediated hypercalcemia.