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Parathyroid Hormone-related Peptide (PTHrP)

Parathyroid hormone-related peptide (PTHrP) may be evaluated in patients with hypercalcemia associated with malignancy and in patients with hypercalcemia of unknown origin. It may also be monitored as a tumor marker during the treatment phase of the disease. 

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Parathyroid hormone-related peptide (PTHrP) is produced in low concentrations by virtually all tissues. PTHrP exists in several isoforms, ranging in size from 60 to 173 amino acids.

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.

Various malignancies secrete PTHrP resulting in hypercalcemia, 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.  It also plays a significant function in osteolysis in bony metastases, particularly in breast cancer, and has been postulated to play a role in malignancy-associated cachexia through the induction of orexigenic peptides.

 Parathyroid hormone-related peptide (PTHrP) can be elevated in pregnant and lactating women and in newborn infants. Nonmalignant conditions that have been described in association with elevated plasma PTHrP levels include systemic lupus erythematosus, HIV-associated lymphadenopathy, and with benign tumors of the ovary, kidney, and neuroendocrine system.

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