Hypercalcemia of malignancy: A study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide

Abstract

Objective: Examine the clinical and biochemical features including serum intact PTH (iPTH) and plasma PTH-related peptide (PTHrP) levels in patients with malignancy-associated hypercalcemia (MAHC). Material and Method: Forty-eight patients with histopathological or cytological proven malignancies and MAHC who were admitted to Siriraj Hospital were studied. Results: The malignancies that caused MAHC were squamous cell carcinoma (45.8%), non-squamous cell solid tumors (31.3%), and hematological malignancies (22.9%). Most patients (93.8%) had advanced stage malignancies. Corrected serum total calcium (cTCa) levels were 10.8-19.1 mg/dL (13.6 ± 2.4) and severe hypercalcemia was observed in 17 cases (40.5%). Serum iPTH levels were 0.95-17.1 pg/mL (3.9 ± 3.6). Most patients had suppressed serum iPTH levels of < 10 pg/mL. Plasma PTHrP levels were 0.2-44.0 pmol/L (3.8 ± 6.8). There were 27 cases (56.3%) that had humoral hypercalcemia of malignancy (HHM) with plasma PTHrP levels of > 1.5 pmol/L, and 22 cases had squamous cell carcinoma. There was no difference in serum cTCa, phosphorus, alkaline phosphatase, and iPTH levels between patients with HHM and non-HHM. In 48 MAHC patients, serum cTCa correlated to plasma PTHrP (r = 0.35, p = 0.029) and to serum iPTH (r = 0.49, p = 0.003). In 25 patients with HHM, a stronger correlation between serum cTCa and serum iPTH (r = 0.55, p = 0.005) but not between serum cTCa and plasma PTHrP levels (r = 0.41, p = 0.05) was observed. Stepwise multiple regression analyses showed that serum iPTH but not plasma PTHrP levels independently correlated to serum cTCa levels (r = 0.39, p = 0.04). Conclusion: The clinical manifestations of MAHC observed in the present study were similar to those previously reported. Serum calcium correlated to serum iPTH more strongly than to plasma PTHrP levels. The low but detectable serum iPTH level might play a role in the development of severe MAHC particularly in HHM.