Parathyroid Hormone-Related Peptide (PTHrP), Plasma

CPT CODE:

USEFUL FOR:

Diagnostic work-up of patients with suspected hypercalcemia of malignancy
Diagnostic work-up of patients with hypercalcemia of unknown origin 

SPECIMEN REQUIRED:

Draw blood in an ice-cooled, lavender-top (EDTA) tube(s) from afasting patient. Spin down in a refrigerated centrifuge or in chilled centrifuge cups and send 0.5 mL of EDTA plasma frozen in plastic vial.

TRANSPORT TEMPERATURE:

Frozen\Refrig NO\Ambient NO

CLINICAL INFORMATION:

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. A variety of other mechanisms lead to inappropriate hypercalcemia in hypercalcemia of malignancy. These include:-Impaired renal function due to a tumor or its treatment -Osteolytic activity within bony metastases -Release of calcemic cytokines by non-osteolytic bony metastases -Eectopic 1-alpha hydroxylase activity in tumor tissues -Secretion of humoral factors mimicking PTH action (humoral  hypercalcemia of malignancy [HHM]), usually associated with  secretion of PTHrP by the primary tumor (or more commonly  its metastases) -Other, as yet unknown factors
Frequently, a single cause can not be pinpointed. Amongst the defined causes of the condition, PTHrP secretion is believed to be the most common culprit.
PTHrP is a single monomeric peptide that exists in several isoforms, ranging from approximately 60 amino acids to 173 amino acids in size, which are created by differential splicing and post-translational processing by prohormone convertases. PTHrP is produced in low concentrations by virtually all tissues. The physiological role of PTHrP remains incompletely understood. Its functions can be broadly divided into 4 categories, not all of which are present in all PTHrP isoforms or in all tissues:-Transepithelial calcium transport, particularly in the kidney and  mammary gland-Smooth muscle relaxation in the uterus, bladder, gastrointestinal  tract, and arterial wall-Regulation of cellular proliferation-Cellular differentiation and apoptosis of multiple tissues-As an indispensable component of successful pregnancy and  fetal development (embryonic gene deletion is lethal in mammals).
PTHrP's diverse functions are mediated through a range of different receptors, which are activated by different portions of PTHrP. Among the many receptors that respond to PTHrP is the PTH receptor, courtesy of the fact that 8 of the 13 N-terminal amino acids of PTH and of 3 common PTHrP isoforms are identical. Since most of PTHrP's actions in normal physiology are autocrine or paracrine, with circulating levels being very low, this receptor cross-talk only becomes relevant when there is extreme and sustained over-production of PTHrP. This is seen occasionally in pregnancy, lactation and, rarely,

CLINICAL INTERPRETATION:

Depending on the patient population, up to 80% of patients with malignant tumors and hypercalcemia will be suffering from HHM. Of these, 50% to 70% might have an elevated PTHrP level. These patients will also usually show typical biochemical changes of excess PTH-receptor activation, namely, besides the hypercalcemia, the might have hypophosphatemia, hypercalcuria, hyperphosphaturia and elevated serum alkaline phosphatase. Their PTH levels will typically be less than 30 pg/mL or undetectable. 
In patients with biochemical findings that suggest but do not prove primary hyperparathyroidism (eg, hypercalcemia, but normal or near normal serum phosphate and a PTH level that is within the population reference range, but above 30 pg/mL), HMM should be considered as a diagnostic possibility, particularly if the patient is elderly, has a history of malignancy or risk factors for malignancy. An elevated PTHrP level in such a patient is highly suggestive of HHM as the cause for the hypercalcemia. 

REFERENCE VALUES:

<2.0 pmol/L