- Last Update On : 2016-08-15
Hypercalcemia of malignancy is a common cause of hypercalcemia in hospitalized patients. Hypercalcemia of malignancy is typically not due to excess parathyroid hormone (PTH). In these disorders, PTH is usually suppressed due to elevated serum calcium concentrations. Approximately 50-70% of these patients have increased secretion of parathyroid hormone-related peptide (PTHrP) by a primary tumor or its metastases. Ectopic PTHrP production is most commonly seen in breast carcinoma, squamous cell carcinoma of the lung or, head and neck, kidney, bladder, cervix, uterus, and ovary. Occasionally, neuroendocrine tumors and T-cell lymphoma may produce PTHrP. This syndrome is often referred to as humoral hypercalcemia of malignancy (HHM).
The N-terminus of PTHrP resembles PTH, allowing it to bind to PTH and mobilize calcium. Besides hypercalcemia, patients with HHM also demonstrate hypophosphatemia, hypercalcuria, hyperphosphaturia and elevated serum alkaline phosphatase. PTH levels are typically suppressed below 30 pg/mL.PTHrP is not detected by intact parathyroid hormone assays.
PTHrP is secreted by nearly all tissues in low concentration, but its physiological role is unknown. Elevated levels can be seen in pregnant and lactating women and in newborn infants. Some nonmalignant diseases such as systemic lupus erythematosus, HIV-associated lymphadenopathy, lymphedema and benign tumors of the ovary, kidney and the neuroendocrine system have also been associated with elevated levels of PTHrP.
PTHrP is cleaved into N-terminal and C-terminal peptides. Some immunoassays detect the C-terminal peptide, while others detect the N-terminal peptide. C-terminal peptide is more stable, but is elevated in renal failure, resulting in more false positive results. Reference range for the C-terminal PTHrP immunoassay performed by Quest Diagnostics is 14-27 pg/mL. Immunoassays that detect the N-terminal peptide are less affected by renal function. Mayo Medical Laboratories offer a commercially available N-terminal immunoassay. Reference range is 0 - 2.0 pmol/L
Specimen requirement is a lavender top tube of blood (EDTA). Specimen should be transported to the laboratory in ice. Plasma should be separated using a refrigerated centrifuge.