Hypercalcemia of Malignancy: A Study of Clinical Features and Relationships among Circulating Levels of Calcium, Parathyroid Hormone and Parathyroid Hormone-Related Peptide
Sutin Sriussadaporn MD*, Meta Phoojaroenchanachai MD*, Sirirat Ploybutr MSc*, Nattachet Plengvidhya MD*, Thavatchai Peerapatdit MD*, Wannee Nitiyanant MD*, Sathit Vannasaeng MD*, Apichati Vichayanrat MD*
Affiliation : * Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University
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).
Materials and Methods : 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 previ-
ously 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.
Keywords : Hypercalcemia, Malignancy, Intact PTH, PTH-related peptide
