Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancy.
BACKGROUND
Increased serum parathyroid hormone-related peptide (PTHrP) concentration is used to diagnose humoral hypercalcemia of malignancy (HHM) in humans and animals. A commercially available assay for human PTHrP has diagnostic utility in the dog, but has not been assessed in cats.


OBJECTIVE
The goals of this study were to determine serum or plasma levels of PTHrP in a population of hypercalcemic cats and to determine whether increased PTHrP concentration was associated with malignancy. In addition, we validated immunoradiometric assays (IRMAs) for intact parathormone (iPTH) and PTHrP for use with feline samples.


METHODS
A retrospective analysis of iPTH and PTHrP results from 322 hypercalcemic cats (ionized calcium concentration > 1.4 mmol/L) was performed. Immunoassays for human iPTH and PTHrP (residues 1-84) were validated using standard methods, and reference intervals were calculated using values from 31 healthy adult cats. Hypercalcemic cats were classified as parathyroid-independent (iPTH < 2.3 pmol/L), equivocal (iPTH 2.3-4.6 pmol/L), or parathyroid-dependent (iPTH > 4.6 pmol/L). Seven cats with detectable or increased PTHrP concentrations were evaluated further for underlying disease. Formalin-fixed neoplastic tissues were immunohistochemically stained using rabbit antibody to human midregion PTHrP.


RESULTS
Assays for iPTH and PTHrP showed acceptable precision for feline samples. The reference interval for iPTH was 0.8-4.6 pmol/L and for PTHrP was < 1.5 pmol/L. The majority of hypercalcemic cats (263/322, 81.7%) were parathyroid-independent, with fewer cats in the equivocal (32/322, 9.9%) and parathyroid-dependent (27/322, 8.4%) groups. In 31 (9.6%) cats, PTHrP concentration was > 1.5 pmol/L (range 1.5-26.6 pmol/L). All 7 cats for which follow-up information was available had HHM; 6 had carcinomas (4 lung carcinomas, 1 undifferentiated carcinoma, 1 thyroid carcinoma) and 1 had lymphoma. All tumors had mild to moderate positive staining for PTHrP; however, lung carcinomas from normocalcemic cats also stained positive.


CONCLUSIONS
Human IRMA for PTHrP (1-84) can be used to measure PTHrP in cats. Malignancies, particularly carcinomas, appear to secrete PTHrP and induce HHM in this species. Immunohistochemistry alone cannot predict the occurrence of HHM in cats.
Bolliger
Anne Provencher
AP
Endocrine Diagnostic Section, Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824, USA. acbolliger@bluewin.ch
Graham
Peter A
PA
Richard
Virgile
V
Rosol
Thomas J
TJ
Nachreiner
Raymond F
RF
Refsal
Kent R
KR
D000818:Animals; D002277:Carcinoma / Q000097:blood / Q000503:physiopathology / Q000662:veterinary*; D002371:Cat Diseases / Q000097:blood / Q000175:diagnosis*; D002415:Cats; D005260:Female; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology / Q000662:veterinary*; D007150:Immunohistochemistry / Q000662:veterinary; D015592:Immunoradiometric Assay / Q000379:methods / Q000662:veterinary*; D008297:Male; D010281:Parathyroid Hormone / Q000032:analysis / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D015203:Reproducibility of Results; D012189:Retrospective Studies
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins