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Test Code 5081 Parathyroid Hormone-Related Peptide (PTHrP), Plasma

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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: Centrifuge specimen down in a refrigerated centrifuge or in chilled centrifuge cups.


Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time
Plasma EDTA Frozen 30 days

Reference Values

≤4.2 pmol/L

Day(s) and Time(s) Performed

Monday through Thursday; 2 p.m. 

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 U.S. Food and Drug Administration.

CPT Code Information

82397

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

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 post-translational 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 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; and 5) as an indispensable component of successful pregnancy and fetal development (embryonic gene deletion is lethal in mammals).

 

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 hematolymphatic malignancies only sporadically produce PTHrP, with the exception of T-cell lymphomas and myeloma. In HHM, the typical laboratory presentation includes elevated calcium (Ca) 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.

Interpretation

Depending on the patient population, up to 80% of patients 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 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.

Clinical Reference

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

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

3. Goltzman D: Nonparathyroid Hypercalcemia. Front Horm Res 2019;51:77-90

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

Method Name

Immunochemiluminometric Assay (ICMA)