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Test ID: PTHRP
Parathyroid Hormone-Related Peptide (PTHrP), Plasma

Secondary ID A test code used for billing and in test definitions created prior to November 2011

81774

NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnostic work-up of patients with suspected hypercalcemia of malignancy

 

Diagnostic work-up of patients with hypercalcemia of unknown origin

Method Name A short description of the method used to perform the test

Immunochemiluminometric Assay (ICMA)

Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name

PTH-Related Peptide

Aliases Lists additional common names for a test, as an aid in searching

Humoral Hypercalcemia of Malignancy Factor
Parathyroid Hormone Related Peptid
Parathyroid Related Polypeptide
Parathyroid Related Protein
PRP
PTH Related Peptide
PTHRP, Plasma
PTH Related Protein

Specimen Type Describes the specimen type needed for testing

Plasma EDTA

Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.

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

Submission Container/Tube: Plastic vial

Specimen Volume: 0.7 mL

Collection Instructions:

1. Fasting

2. Spin specimen down in a refrigerated centrifuge or in chilled centrifuge cups.

Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.

Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.

0.25 mL

Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected

Hemolysis

Mild OK; Gross OK

Lipemia

Mild OK; Gross OK

Icterus

Mild OK; Gross OK

Other

NA

 

Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.

Specimen TypeTemperatureTime
Plasma EDTAFrozen90 days

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hypercalcemia of malignancy is a common cause of hypercalcemia in hospitalized patients. Hypercalcemia of malignancy is typically not due to excess parathyroid hormone (PTH). In these disorders, PTH is usually suppressed due to elevated serum calcium concentrations. A variety of other mechanisms lead to inappropriate hypercalcemia in hypercalcemia of malignancy. These include:

-Impaired renal function due to a tumor or its treatment

-Osteolytic activity within bony metastases

-Release of calcemic cytokines by non-osteolytic bony metastases

-Eectopic 1-alpha hydroxylase activity in tumor tissues

-Secretion of humoral factors mimicking PTH action (humoral hypercalcemia of malignancy [HHM]), usually associated with secretion of parathyroid hormone-related peptide (PTHrP) by the primary tumor (or more commonly its metastases)

-Other, as yet unknown factors

 

Frequently, a single cause can not be pinpointed. Amongst the defined causes of the condition, PTHrP secretion is believed to be the most common culprit.

 

PTHrP is a single monomeric peptide that exists in several isoforms, ranging from approximately 60 amino acids to 173 amino acids in size, which are created by differential splicing and post-translational processing by prohormone convertases. PTHrP is produced in low concentrations by virtually all tissues. The physiological role of PTHrP remains incompletely understood. Its functions can be broadly divided into 4 categories, not all of which are present in all PTHrP isoforms or in all tissues:

-Transepithelial calcium transport, particularly in the kidney and mammary gland

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

-Regulation of cellular proliferation

-Cellular differentiation and apoptosis of multiple tissues

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

 

PTHrP's diverse functions are mediated through a range of different receptors, which are activated by different portions of PTHrP. Among the many receptors that respond to PTHrP is the PTH receptor, courtesy of the fact that 8 of the 13 N-terminal amino acids of PTH and of 3 common PTHrP isoforms are identical. Since most of PTHrP's actions in normal physiology are autocrine or paracrine, with circulating levels being very low, this receptor cross-talk only becomes relevant when there is extreme and sustained over-production of PTHrP. This is seen occasionally in pregnancy, lactation and, rarely, in a variety of non-malignant diseases. However, most commonly it is observed when tumors secrete PTHrP ectopically. In rough correlation with physiological production levels of PTHrP in the corresponding healthy tissues, ectopic 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 hemato-lymphatic malignancies only sporadically produce PTHrP, with the notable exceptions of T-cell lymphomas and myeloma.

 

Patients with HHM may have increased PTHrP values before treatment. PTHrP level decreases and PTH level increases, accompanied by decreased serum calcium values, with successful treatment.

 

See "Diagnostic Use of Parathyroid Hormone Assays" in Publications.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

<2.0 pmol/L

Interpretation Provides information to assist in interpretation of the test results

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, the 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), HMM 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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The test should not be used to exclude cancer or screen tumor patients for humoral hypercalcemia of malignancy.

 

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, lymphedema of chest or pleural cavities, and with benign tumors of the ovary, kidney and the neuroendocrine system.

 

Because of the complexity of PTHrP isoforms, the differences between various PTHrP assays and the lack of a common calibration standard, PTHrP measurements performed with different assays can not be compared easily.

 

The complex isoform mixture of PTHrP can occasionally lead to pronounced nonlinearity on dilution of patient specimens. In these situations an accurate measurement of PTHrP concentrations might be impossible.

 

Like all immunometric assays, PTHrP assays are susceptible to false low results at extremely high analyte concentrations ("hooking") and to rare false positive results due to heterophile antibody interference. Therefore, if test results are incongruent with the clinical picture, the laboratory should be contacted.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Burtis WJ: Parathyroid hormone-related protein: structure, function and measurement. Clin Chem 1992;38(11):2171-2183

2. Wysolmerski JJ, Stewart AF: The physiology of parathyroid hormone-related protein: an emerging role as a developmental factor. Annu Rev Physiol 1998;60:431-460

3. Guise TA, Mundy GR: Cancer and bone. Endocr Rev, 1998;19(1):18-54

4. Clemens TL, Cormier S, Eichinger A, et al: Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets. Br J Pharmacol 2001;134(6):1113-1136

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

6. Wu TJ, Lin CL, Taylor RL, et al: Increased parathyroid hormone-related peptide in patients with hypercalcemia associated with islet cell carcinoma. Mayo Clin Proc 1997;72(12):1111-1115

Method Description Describes how the test is performed and provides a method-specific reference

The test is performed by an immunochemiluminometric assay by using 2 affinity-purified antibodies from a goat immunized with (1-86) parathyroid hormone-related peptide (PTHrP). One batch of the purified antibody is labeled with acridinium ester as tracer antibodies; a second batch of purified antibody is immobilized onto the bead. When the plasma specimen has PTHrP, the tracer antibodies are linked to the bead via PTHrP and the immobilized antibody.(Wu TJ, Taylor RL, Kao PC: Parathyroid hormone-related peptide immunochemiluminometric assay. Developed with polyclonal antisera produced from a single animal. Ann Clin Lab Sci 1997;27:384-390)

Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.

Monday through Thursday; 1:30 p.m.

Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.

2 days

Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result

5 days

Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location The location of the laboratory that performs the test

Rochester

Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.

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 Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

82397

LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.

Result IDReporting NameLOINC Code
81774PTH-Related Peptide15087-0