Parathyroid Hormone-Related Peptide

No detectable (or minimal) parathyroid hormone–related protein (PTHrP) is normal.

Over the last 20-25 years, our understanding of PTHrP has magnified along with our ability to discern the role PTH in multiple physiologic and pathologic conditions. The production and action of PTHrP, along with the complex role it plays in cancer, are just beginning to be understood. PTHrP is widely distributed in the human body and has broad roles in the endocrine, paracrine, and intracrine systems, which affect a multitude of physiologic and pathologic conditions, along with playing a central role in organogenesis. ^{[1, 2]}

PTHrP resembles PTH in as much as they bind to the same type 1 PTH/PTHrP receptor and induce a similar response in the body. For this reason, hypercalcemia of malignancy resembles hyperparathyroidism and has been historically labeled a paraneoplastic syndrome. One of the many effects PTHrP may have on the body is the induction of hypercalcemia; thus, hypercalcemia of malignancy might warrant an evaluation of PTHrP levels.

Collection

See the list below:

• Specimen - Blood

• Container - Lavender (EDTA) or pink (K₂ EDTA); collect in chilled container

• Collection method - Routine venipuncture

Panels

PTHrP is not typically a part of a panel and should be ordered specifically.

Description

PTH-related peptide is produced by some cancers, including those of the lung, breast, head, neck, bladder, gastrointestinal tract, and ovaries, as well as leukemia and lymphoma. High levels of PTH-related protein may be the cause of elevated calcium levels in many cancer patients. This condition is referred to as humoral hypercalcemia of malignancy (HHM). Since PTHrP has the same N-terminal as PTH, it can bind to the same receptor and stimulate the action of PTH. This results in bone resorption and calcium resorption in the kidneys, but has minimal effect on calcium absorption in the intestines. Additionally, PTHrP has multiple proposed normal roles, including fetal calcium regulation during development, placental calcium transfer, lactation, dental eruption, smooth muscle relaxation, and epithelial cell growth. ^{[3, 4, 5, 6, 7, 1]}

Research suggests that in the early stages of cancer, PTHrP actually has an inhibitory effect, interfering with tumor progression. In advanced cancers, however, evidence indicates that it plays the opposite role, promoting tumor development and metastasis; the peptide is particularly prone to metastatic action in bone, with PTHrP-mediated osteolysis being important in the establishment of tumor cell colonies. Research has also been carried out into the possible role of PTHrP in regulating tumor dormancy. ^[8]

Indications/Applications

PTHrP may be evaluated in patients with hypercalcemia associated with malignancy. It may also be monitored as a tumor marker during the treatment phase of disease. Current research is exploring applications of the administration of PTHrP as treatment for several diseases, including breast cancer, diabetes, and osteoporosis. ^[1]