Bolliger Anne Provencher, Graham Peter A, Richard Virgile, Rosol Thomas J, Nachreiner Raymond F, Refsal Kent R
Endocrine Diagnostic Section, Animal Health Diagnostic Laboratory, Michigan State University, East Lansing, MI 48824, USA.
Vet Clin Pathol. 2002;31(1):3-8. doi: 10.1111/j.1939-165x.2002.tb00268.x.
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.
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.
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.
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.
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.
血清甲状旁腺激素相关肽（PTHrP）浓度升高用于诊断人和动物的恶性肿瘤体液性高钙血症（HHM）。一种市售的人PTHrP检测方法在犬类中有诊断价值，但尚未在猫类中进行评估。
本研究的目的是确定高钙血症猫群体中的血清或血浆PTHrP水平，并确定PTHrP浓度升高是否与恶性肿瘤相关。此外，我们验证了用于猫样本的完整甲状旁腺激素（iPTH）和PTHrP的免疫放射分析（IRMA）。
对322只高钙血症猫（离子钙浓度>1.4 mmol/L）的iPTH和PTHrP结果进行回顾性分析。使用标准方法验证了人iPTH和PTHrP（第1-84位氨基酸残基）的免疫分析，并使用31只健康成年猫的值计算参考区间。高钙血症猫被分类为甲状旁腺非依赖性（iPTH<2.3 pmol/L）、不明确（iPTH 2.3-4.6 pmol/L）或甲状旁腺依赖性（iPTH>4.6 pmol/L）。对7只PTHrP浓度可检测到或升高的猫进一步评估潜在疾病。用抗人PTHrP中部区域的兔抗体对福尔马林固定的肿瘤组织进行免疫组织化学染色。
iPTH和PTHrP检测对猫样本显示出可接受的精密度。iPTH的参考区间为0.8-4.6 pmol/L，PTHrP的参考区间为<1.5 pmol/L。大多数高钙血症猫（263/322，81.7%）为甲状旁腺非依赖性，不明确组（32/322，9.9%）和甲状旁腺依赖性组（27/322，8.4%）的猫较少。在31只（9.6%）猫中，PTHrP浓度>1.5 pmol/L（范围1.5-26.6 pmol/L）。所有7只可获得随访信息的猫均患有HHM；6只患有癌（4只肺癌、1只未分化癌、1只甲状腺癌），1只患有淋巴瘤。所有肿瘤对PTHrP均有轻度至中度阳性染色；然而，正常血钙猫的肺癌也呈阳性染色。
人PTHrP（1-84）的IRMA可用于测量猫的PTHrP。恶性肿瘤，尤其是癌，似乎在该物种中分泌PTHrP并诱发HHM。仅免疫组织化学不能预测猫HHM的发生。
