PTH Intact

Order Code

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5046

Preferred Specimen

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Collect 1 mL of EDTA plasma, ensuring that tubes are chilled before collection. Immediately centrifuge the sample and separate the plasma from the cellular components. Transfer the plasma into a plastic transport tube and clearly label it as EDTA plasma. Freeze the specimen promptly—this is critical and should be marked as Frozen (CFZ). The patient must be fasting before sample collection. When multiple tests are requested, provide a separate tube specifically for this assay.

ContainerType

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SEDTA (lavender top) tube

Minimum Volume

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0.7 mL frozen plasma

Transport Temperature

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Critical Frozen (cfz)

Expected Turnaround Time

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4-7 days

Specimen Stability

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Unacceptable room temperature; unacceptable refrigerated; 30 days frozen

Methodology

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Immunochemiluminometric assay (icma)

Rejection Criteria

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• Thawed samples

Overview

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Parathyroid hormone-related protein (PTHrP) belongs to the PTH gene family and is produced by a wide range of tissues, including neuroendocrine, epithelial, and mesoderm-derived cells such as connective tissue, muscle, and blood cells (Horwitz, 2021). PTHrP plays several physiological roles: it facilitates calcium transport across cell membranes, acts as a smooth muscle relaxant, influences cellular differentiation, regulates proliferation, and is critical for fetal development (Mayo, 2021).

Due to its strong homology with the amino-terminal region of parathyroid hormone (PTH)—a key regulator of calcium balance—PTHrP binds to and activates the same Type I PTH receptor responsible for calcium metabolism (Wysolmerski, 2012). Through this interaction, PTHrP elevates blood calcium by promoting bone resorption and reducing urinary calcium excretion (Horwitz, 2021). Elevated PTHrP levels are frequently observed in tumors linked to hypercalcemia, including breast, kidney, and lung cancers, as well as multiple myeloma. It is the primary mediator of hypercalcemia of malignancy (HHM), a common complication in cancer patients (Vakiti, 2021).

Clinical Significance

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• Part of the evaluation of hypercalcemia, especially in the clinical setting of known or suspected cancer (ie, humoral hypercalcemia of malignancy)
• Not indicated for screening of humoral hypercalcemia of malignancy

Additional Information

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• Greater that 90% of instances of hypercalcemia are caused by either primary hyperparathyroidism or humoral hypercalcemia of malignancy (HHM) (Shane 2021).
• HHM is the most common cause of hypercalcemia in the inpatient setting (Horwitz 2021).
• Serum calcium levels greater than 13 mg/dL on initial presentation raises suspicion for malignancy as cause for markedly elevated calcium (Vakiti 2021).
• HHM is found in approximately 20% to 30% of patients with cancer and occurs in both solid and hematologic malignancies. Cancers most often associated with HHM include breast, lung, head and neck, kidney, bladder, cervix, uterus, ovarian, T-cell lymphomas, and myeloma. HHM is associated with a poor prognosis (Horwitz 2021).

Interpretative Information

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Elevated:

• Humoral hypercalcemia of malignancy
• Pregnancy, lactating women, newborn infants
• Systemic lupus erythematosus
• HIV-associated lymphadenopathy
• Benign tumors of the ovary, kidney, neuroendocrine system (Mayo 2021)

Limitations

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• PTHrP results from different assays cannot be readily compared due to the multiple PTHrP isoforms tested for and and the lack of a common calibration standard.
• False positive results may occur due to heterophile antibody interference.
• False negatives results (due to hook effect) may occur in immunometric assays at extremely high analyte (ie, PTHrP) concentrations (Mayo 2021).

References

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Diagnostic Role

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Parathyroid hormone related protein (PTHrP) levels are most often ordered as part of the workup of an elevated blood calcium level found during routine screening blood work or incidentally during an evaluation for an unrelated condition. Once primary hyperparathyroidism has been ruled-out (ie, increased blood PTH level concurrent with high calcium and low phosphate blood levels), a PTHrP level is appropriate, especially if there is underlying known or suspected malignancy. In particular, humoral hypercalcemia of malignancy (HHM) should be considered in the presence of hypercalcemia, a PTH level that is within the population reference range but above 30 pg/mL, and normal or near-normal serum phosphate level. Up to 80% of patients with malignant tumors and hypercalcemia will have HHM (Mayo 2021; Vakiti 2021).

Alias

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• Parathyroid hormone related peptide
• Pth related protein

Test Setup Days

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Monday through Thursday AM shift

CPT

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82397 LOINC: 15087-0

Reference Range

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<=4.2 PMOL/L

UNIT CODE	UNIT CODE NAME	ANALYTE	GENDER	AGE	REFERENCE RANGE	Units of Measure
5046	CFZ PTH REL PEP				<=4.2 PMOL/L