Abstract
We evaluated the circulating forms of immunoreactive PTHrP in 115 healthy subjects and 122 patients with malignant diseases by using radioassay systems (RAS) specific for the C-terminal (109–141) fragment of PTHrP (C-RAS) and for the N-terminal(l–86) (N-RAS). PTHrP levels in healthy controls ranged from 1.5 to 38.2 (mean: 24.5) pmol/L with the C-RAS and from 0.9 to 2.5 (mean: 1.7) pmol/L with the N-RAS. The ratio of circulating N-terminal fragment (N) to C-terminal fragment (C)of PTHrP was calculated to be about 1:14.4 in the healthy subjects. Of the 122 patients with malignant diseases, 40 (32.8%) had circulating PTHrP levels undetectable with the N-RAS, but only 11 (9.0%) patients had levels undetectable with the C-RAS. Of the former 122 patients, 41 (33.6%) had high PTHrP as determined with the C-RAS, and 10 (8.2%) had high PTHrP as determined with the N-RAS. The former of these included only 8 (19.5%) HHM patients, while the latter included 8 (80.0%) HHM patients. The circulating N to C ratio was about 1:70.7 in the HHM patients. The N and C obtained with the different RASs showed a close correlation (r = 0.86). The values also showed a close correlation with serum Ca; r = 0.75 for C-RAS and r = 0.81 for N-RAS. In addition, the correlations between the PTHrP reading obtained with the different RAS s and serum Cr were: r = 0.42 with C-RAS and r = 0.26 with N-RAS. The circulating form of immunoreactive PTHrP fragments is therefore comprised mainly of PTHrP(109–141). In contrast, circulating concentrations of the PTHrP(l-86) fragment are very low, but detection of the PTHrP(l-86) fragment with the N-RAS is a more useful indicator of HHM with fewer false positive results and is less likely to be influenced by renal function than the detection of the PTHrP(109–141) fragment with C-RAS.
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References
Bilezikian JP. Parathyroid hormone-related peptide in sickness and in health (editorial).N Engl J Med 322: 1151–1153, 1990.
Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups.N Engl J Med 303: 1377–1383, 1980.
Goltzman D, Stewart AF, Broadus AE. Malignancy-associated hypercalcemia: evaluation with a cytochemical bioassay for paiaihyroidhormone.J Clin Endocrinol Metab 53: 899–904, 1981.
Stewart AF, Insogna KL, Goltzman D, Broadus AE. Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy.Proc Natl Acad Sci USA 80: 1454–1458, 1983.
Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF. Humoral hypercalcemia of cancer. Identification of a novel parathyroid-like peptide.N Engl J Med 319: 556–563, 1988.
Budayr AA, Nissenson RA, Klein RF, Pun KK, Clark OH, Diep D, et al. Increased serum levels of a parathyroid hormone-like protein in malignancy-associated hyper-calcemia.Ann Int Med 111: 807–812, 1989.
Suva LJ, Winslow GA, Wettenhall REH, Hammonds RG, Mosely JM, Diefenbach-Jagger H, et al. A parathyroid hormone-related protein implicated in malignant hyper-calcemia: Cloning and expression.Science 237: 893–896, 1987.
Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RJ, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF: Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hyper-calcemia of cancer.N Engl J Med 322: 1106–1112, 1990.
Ratcliffe WA, Hughes S, Gilian MG, Heath DA, Ratcliffe JG. Production and characterization of monoclonal antibodies to parathyroid hormone-related protein.J Immunol Methods 127: 109–116, 1990.
Ratcliffe WA, Norbury S, Stott RA, Heath DA, Ratcliffe JG. Immunoreactivity of plasma parathyrin-related peptide: three region-specific radioassays and a two-site immuno-radiometric assay compared.Clin Chem 37: 1781–1787, 1991.
Blind E, Raue F, Meinel T, Bucher M, Manegold C, Ebert W, et al. Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay.Clin Investig 71: 31–36, 1993.
Ratcliffe WA, Norbury S, Heath DA, Ratcliffe JG. Development and validation of an immunoradiometric assay of parathyrin-related protein in unextracted plasma.Clin Chem 37: 678–685, 1991.
Gaich G, Burtis W J. Measurement of circulating parathyroid hormone-related protein in rats with humoral hypercalcemia of malignancy using a two-site immunoradiometric assay.Endocrinology 127: 1444–1449, 1990.
Burtis WJ, Brady TG, Orloff JJ, Ersback JB, Warrell RP, Olson BR, et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer.N Engl J Med 322: 1106–1112, 1990.
Imamura H, Sato K, Shizume K, Satoh T, Kasono K, Ozawa M, et al. Urinary excretion of parathyroid hormone-related protein fragments in patients with humoral hypercalcemia of malignancy and hypercalcemic tumor-bearing nude mice.J Bone mineral Res 6: 77–84, 1991.
Kasahara H, Tsuchiya M, Adachi R, Horikawa S, Tanaka S, Tachibana S. Development of a C-terminal-region-specific radioimmunoassay of parathyroid hormone-related protein.Biomed Res 13: 155–161, 1992.
Pandian MR, Morgan CH, Carton E, Segre GV. Modified immunoradiometric assay of parathyroid hormone-related protein: clinical application in the differential diagnosis of hypercalcemia.Clin Chem 38: 282–288, 1992.
Fraser WD, Robinson J, Lawton R, Durham B, Gallacher ST, Boyle IT, et al. Clinical and laboratory studies of a new immunoradiometric assay of parathyroid hormone-related protein.Clin Chem 39: 414–419, 1993.
Mitlak BH, Hutchinson JS, Kaufman SD, Nussbaum SR. Parathyroid hormone-related peptide mediates hyper-calcemia in an islet tumor of the pancreas.Horm Metab Res 23: 344–346, 1991.
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Suehiro, M., Murakami, M. & Fukuchi, M. Circulating forms of immunoreactive parathyroid hormone-related protein for identifying patients with humoral hypercalcemia of malignancy: A comparative study with C-terminal(109–141)- and N-terminal(1–86)-region-specific PTHrP radioassay. Ann Nucl Med 8, 231–237 (1994). https://doi.org/10.1007/BF03165025
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DOI: https://doi.org/10.1007/BF03165025