Felis ISSN 2398-2950

PTHrP assay

Synonym(s): parathyroid hormone related protein, parathyroid hormone related peptide

Contributor(s): Peter Graham, Anne Provencher-Bolliger

Overview

  • Parathyroid hormone related protein (PTHrP) is released by certain tumors to cause humoral hypercalcemia of malignancy.
  • Several isoforms (139 to 173 AA's in man) are produced by a gene separate from the parathyroid  hormone (PTH) gene and subjected to post-translational modification. Multiple metabolic fragments of PTHrP may exist in circulation including carboxyl fragments. The biological action of these C-terminal fragments, if any, is not known.
  • Normal physiological role appears to be in calcium homeostasis in the fetus and during lactation in addition to other local autocrine/paracrine properties in adults. Its role in most adult tissues is unknown.
  • Amino (N-) terminal homology with PTH. 8 of first 13 amino-acids identical between human PTH and PTHrP. The N-terminal (AA's 1-34) confers biological activity that mimics most functions of PTH. Remainder of molecule shows little homology with PTH.

Sampling

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Tests

Methodologies

  • Immunoradiometric assay (IRMA).
  • Assay is a specific 2-site intact PTHrP assay:
    • Most assays use one set of antibodies directed against the N-terminal (AA's 1-40) and another set directed against the mid-molecule (~AA's 60-70).
    • Two sites ensure that PTHrP measured independently of PTH and that only intact molecule and not cross-reacting fragments are measured.

Availability

  • Limited to veterinary endocrine reference laboratories and regional human laboratories.
  • Veterinary labs use assay kits developed for use in humans and validate for use with animal plasma (dog, cat, horse).

Validity

Sensitivity

  • PTHrP is the mechanism by which only a proportion of cancers cause hypercalcemia. Some neoplasms use different mechanisms including direct osteolysis (eg osteosarcoma Osteosarcoma, myeloma, metastatic carcinoma, the secretion of cytokines and the production of calcitriol.
  • The PTHrP test is can only be described as sensitive for PTHrP mediated hypercalcemia. Its diagnostic sensitivity for hypercalcemia of malignancy in general is quite poor.
  • For example, only about 30-40% of hypercalcemic canine lymphoma Lymphoma patients have detectable plasma PTHrP. A negative PTHrP result, therefore, does not rule out lymphoma as a cause of the hypercalcemia.

Specificity

  • Generaly considered to be highly specific. Yields few false positive results.
  • Rare positive PTHrP in the face of lab evidence for primary hyperparathyroidism Primary hyperparathyroidism might suggest parathyroid carcinoma.

Predictive value

  • Depends on prevalence of PTHrP-mediated-hypercalcemia in population being tested.

Technique (intrinsic) limitations

  • Strict sample handling requirements.

Result Data

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Further Reading

Publications

Refereed papers

  • Recent references from VetMed Resource and PubMed.
  • Provencher-Bolliger A L, Graham P A, Richard V, Rosol T J, Nachreiner R F & Refsal K R (2002) Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancyVet Clin Path 31, 3-8.
  • Rosol T J, Nagode L A, Couto C G, Hammer A S, Chew D J, Peterson J L, Ayl R D, Steinmeyer C L & Capen CC (1992) Parathyroid hormone (PTH)-related protein, PTH and 1,25 dihydroxyvitamin D in dogs with cancer-associated neoplasia. Endocrinol 131, 1157 - 1164 (uses N-terminal assays only not modern intact molecule assays).

Other sources of information

  • Refsal K R, Provencher-Bolliger A L, Graham P A & Nachreiner R F (2001) Update on the diagnosis and treatment of disorders of calcium regulationVet Clin N Amer 5, 1043-1062.


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