PTHrP-mediated hypercalcemia: causes and survival in 138 patients.

Context: Hypercalcemia is a common complication of cancer with PTHrP an important mediator. Literature on the underlying causes of PTHrP-mediated hypercalcemia, in both malignant and benign conditions, is limited to small case series and case reports.

Objective: The purpose of this study was to systematically identify a large series of cases of PTHrP-mediated hypercalcemia and to document differences in demographics and the clinical course between malignant and benign etiologies.

Design, Setting, And Patients: This was a hospital-based, retrospective case series that identified subjects from 1999 to 2010 from the public hospital system in Queensland, Australia. Included subjects were 18 years and older and had persistent hypercalcemia with simultaneously elevated PTHrP.

Results: A total of 138 cases were identified. Solid organ malignancies made up 82.6% (n = 114) of cases, with squamous cell carcinoma (28.2% of total) and adenocarcinomas (27.5%) almost equally as common. Hematological malignancy and benign conditions made up 8.7% (n = 12) each. Squamous cell carcinoma of the lung was the single most commonly identified etiology (10.9%). Causes not previously identified included myxoid sarcoma, plasma cell leukemia, duodenal adenocarcinoma, metastatic Merkel cell carcinoma, and epithelioid hemangioendothelioma. Median survival was different among the groups (52 days [interquartile range, 21-132 days] for solid organ malignancy, 362 days [18-652 days] for hematological malignancy, and 906 days [16 days to undefined] for the apparently benign group; P < .0001). There were no differences in PTHrP among the groups. Although the mean corrected calcium level was lower in the benign group (3.03 mmol/L [2.80-3.29 mmol/L]) compared with that in the solid organ (3.11 mmol/L [2.89-3.46 mmol/L]) and hematological malignancy groups (3.60 mmol/L [3.01-3.79 mmol/L]) groups (P = .046), it was not a useful discriminator of etiology.

Conclusion: PTHrP-mediated hypercalcemia is most frequently caused by solid organ malignancy, and it portends a poor prognosis. Although the solid organ malignancy group had the shortest survival, the hematological malignancy and apparently benign causes groups still had relatively short overall survival.