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Test ID: PTHRP Parathyroid Hormone-Related Peptide, Plasma

Reporting Name

PTH-Related Peptide

Useful For

Aiding in the evaluation of individuals with hypercalcemia of unknown origin


Aiding in the evaluation of individuals with suspected humoral hypercalcemia of malignancy


The test should not be used to exclude cancer or screen individuals with tumors for humoral hypercalcemia of malignancy.

Clinical Information

Parathyroid hormone-related peptide (PTHrP) exists in several isoforms, ranging in size from 60 to 173 amino acids, which are created by differential splicing and posttranslational processing by prohormone convertases. PTHrP is produced in low concentrations by virtually all tissues. The N-terminus and the secondary structure of multiple isoforms of PTHrP resemble parathyroid hormone (PTH), allowing PTHrP to bind to the same receptor as PTH.


The physiological role of PTHrP can be divided into 5 categories:

1) Transepithelial calcium transport, particularly in the kidney and mammary gland

2) Smooth muscle relaxation in the uterus, bladder, gastrointestinal tract, and arterial wall

3) Regulation of cellular proliferation

4) Cellular differentiation and apoptosis of multiple tissues

5) As an indispensable component of successful pregnancy and fetal development (embryonic gene deletion is lethal in mammals)


Humoral hypercalcemia of malignancy (HHM) is a common complication of cancer. Elevations of PTHrP are the most common cause of malignancy-associated hypercalcemia. PTHrP leads to hypercalcemia by stimulating calcium resorption from bone and reabsorption in the kidneys. 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 induction of orexigenic peptides.


Various malignancies secrete PTHrP resulting in HHM. PTHrP production is most commonly seen in carcinomas of breast, lung (squamous), head and neck (squamous), kidney, bladder, cervix, uterus, and ovary. Neuroendocrine tumors may also occasionally produce PTHrP. Most other carcinomas, sarcomas, and hematolymphoid malignancies only sporadically produce PTHrP, with the exception of T-cell lymphomas and myeloma. In HHM, the typical laboratory presentation includes elevated calcium and PTHrP, decreased PTH, and suppressed serum 1,25 dihydroxyvitamin D3 levels. Patients with HHM may have increased PTHrP values before treatment. PTHrP level decreases and PTH level increases, accompanied by decreased serum calcium values, are observed with successful treatment.


Depending on the patient population, up to 80% of individuals with malignant tumors and hypercalcemia will be suffering from humoral hypercalcemia of malignancy (HHM). Of these, 50% to 70% might have an elevated parathyroid hormone-related peptide (PTHrP) level. These patients will also usually show typical biochemical changes of excess parathyroid hormone (PTH)-receptor activation, namely, besides the hypercalcemia, they 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), HHM should be considered as a diagnostic possibility, particularly if the patient is an older adult, has a history of malignancy, or has risk factors for malignancy. An elevated PTHrP level in such a patient is highly suggestive of HHM as the cause for the hypercalcemia.

Report Available

2 to 5 days

Day(s) Performed

Monday through Thursday

Clinical Reference

1. Donovan PJ, Achong N, Griffin K, Galligan J, Pretorius CJ, McLeod DS. PTHrP-mediated hypercalcemia: causes and survival in 138 patients. J Clin Endocrinol Metab. 2015;100(5):2024-2029

2. Goltzman D: Nonparathyroid hypercalcemia. Front Horm Res. 2019;51:77-90

3. Jacobs TP, Bilezikian JP. Clinical Review: Rare causes of hypercalcemia. J Clin Endocrinol Metab. 2005;90(11):6316-6322

4. Mundy GR, Edwards JR. PTH-related peptide (PTHrP) in hypercalcemia. J Am Soc Nephrol. 2008;19(4):672-675

Method Name

Immunochemiluminometric Assay (ICMA)

Specimen Type

Plasma EDTA

Specimen Required

Collection Container/Tube: Ice-cooled, lavender top (EDTA)

Submission Container/Tube: Plastic vial

Specimen Volume: 0.7 mL

Collection Instructions:

1. Centrifuge specimen in a refrigerated centrifuge or in chilled centrifuge cups.

2. Aliquot plasma into plastic vial and freeze.

Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Plasma EDTA Frozen 30 days

Reference Values

≤4.2 pmol/L

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
PTHRP PTH-Related Peptide 15087-0


Result ID Test Result Name Result LOINC Value
81774 PTH-Related Peptide 15087-0


If not ordering electronically, complete, print, and send a General Request (T239) with the specimen.

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