Burtis W J, Brady T G, Orloff J J, Ersbak J B, Warrell R P, Olson B R, Wu T L, Mitnick M E, Broadus A E, Stewart A F
Department of Medicine, West Haven Veterans Affairs Medical Center, Conn 06516.
N Engl J Med. 1990 Apr 19;322(16):1106-12. doi: 10.1056/NEJM199004193221603.
Tumors from patients with humoral hypercalcemia of cancer produce a parathyroid hormone-related protein (PTHRP). We have developed two region-specific immunoassays capable of measuring PTHRP in plasma: an immunoradiometric assay directed toward PTHRP amino acid sequence 1 to 74 and a radioimmunoassay directed toward PTHRP amino acid sequence 109 to 138. Sixty normal subjects had low or undetectable plasma PTHRP (1 to 74) concentrations (mean, 1.9 pmol per liter) and undetectable PTHRP (109 to 138) concentrations (less than 2.0 pmol per liter). Patients with humoral hypercalcemia of cancer (n = 30) had elevated levels of both PTHRP (1 to 74) (mean, 20.9 pmol per liter) and PTHRP (109 to 138) (mean, 23.9 pmol per liter). The plasma concentrations of immunoreactive PTHRP correlated with the levels of urinary cyclic AMP excreted; in some patients, the concentrations decreased after the tumors were resected. Patients with chronic renal failure (n = 15) had plasma PTHRP (1 to 74) concentrations similar to those in the normal subjects, but their plasma PTHRP (109 to 138) concentrations were elevated (mean, 29.6 pmol per liter). The levels of both peptides were normal in patients with hyperparathyroidism and those with hypercalcemia due to various other causes. Breast milk contained high concentrations of PTHRP. An anti-PTHRP (1 to 36) immunoaffinity column failed to extract PTHRP (109 to 138) immunoactivity from plasma, suggesting that the C-terminal region circulates as a separate peptide. We conclude that plasma PTHRP concentrations are high in the majority of patients with cancer-associated hypercalcemia and that the circulating forms of PTHRP in such patients include both a large N-terminal (1 to 74) peptide and a C-terminal (109 to 138) peptide. Measuring the concentrations of PTHRPs may be useful in the differential diagnosis of hypercalcemia.
患有癌症相关性体液性高钙血症患者的肿瘤会产生甲状旁腺激素相关蛋白（PTHRP）。我们开发了两种能够测定血浆中PTHRP的区域特异性免疫测定法：一种是针对PTHRP氨基酸序列1至74的免疫放射测定法，另一种是针对PTHRP氨基酸序列109至138的放射免疫测定法。60名正常受试者的血浆PTHRP（1至74）浓度较低或检测不到（平均为1.9 pmol/升），PTHRP（109至138）浓度检测不到（低于2.0 pmol/升）。患有癌症相关性体液性高钙血症的患者（n = 30），其PTHRP（1至74）水平（平均为20.9 pmol/升）和PTHRP（109至138）水平（平均为23.9 pmol/升）均升高。免疫反应性PTHRP的血浆浓度与尿中环磷酸腺苷（cAMP）的排泄水平相关；在一些患者中，肿瘤切除后浓度降低。慢性肾衰竭患者（n = 15）的血浆PTHRP（1至74）浓度与正常受试者相似，但其血浆PTHRP（109至138）浓度升高（平均为29.6 pmol/升）。甲状旁腺功能亢进患者以及因其他各种原因导致高钙血症的患者，这两种肽的水平均正常。母乳中含有高浓度的PTHRP。抗PTHRP（1至36）免疫亲和柱无法从血浆中提取PTHRP（109至138）的免疫活性，这表明C末端区域以单独的肽形式循环。我们得出结论，大多数癌症相关性高钙血症患者的血浆PTHRP浓度较高，并且此类患者中循环形式的PTHRP包括一个大的N末端（1至74）肽和一个C末端（109至138）肽。测定PTHRPs的浓度可能有助于高钙血症的鉴别诊断。
