Parathyroid hormone-related peptide in plasma of patients with hypercalcemia and malignant lesions.
We developed and validated a radioimmunoassay for circulating human parathyroid hormone-related peptide (PTHrP), based on a commercial antiserum to the synthetic 1-34 fragment of PTHrP, 125I-Tyr degrees-PTHrP(1-34) as radioligand, and prior extraction of the native peptide from plasma with C-2 cartridges. We determined immunoreactive PTHrP concentrations in plasma samples from 48 healthy persons (mean +/- SD, 3.1 +/- 1.0 pmol/liter; range, less than 2 to 5 pmol/liter), 8 patients with primary hyperparathyroidism, 36 patients with hypercalcemia and a concurrent malignant lesion, and 9 normocalcemic patients with cancer and increased serum levels of carcinoembryonic antigen or prostate-specific antigen. PTHrP was normal in samples from patients with primary hyperparathyroidism (3.2 +/- 1.1 pmol/liter), secondary hyperparathyroidism (2.5 +/- 1.3 pmol/liter), and cancer without hypercalcemia (2.4 +/- 1.0 pmol/liter). In contrast, plasma immunoreactive PTHrP levels were increased (6.0 to 85.0 pmol/liter) in 47% of patients with hypercalcemia and cancer of various types, with or without bone metastatic lesions. Large amounts of PTHrP were also found in conditioned medium from cultured human prostatic carcinoma cells. Thus, PTHrP may be a causative factor for hypercalcemia associated with a malignant lesion in at least half of the cases. Measurement of circulating PTHrP may be of differential diagnostic help in hypercalcemic states.
Section of Clinical Chemistry, Mayo Clinic, Rochester, MN 55905.
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D007516:Adenoma, Islet Cell / Q000097:blood; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000097:blood / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood* / Q000209:etiology; D006961:Hyperparathyroidism / Q000097:blood / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications; D007680:Kidney Neoplasms / Q000097:blood; D008223:Lymphoma / Q000097:blood; D009101:Multiple Myeloma / Q000097:blood; D009363:Neoplasm Proteins / Q000097:blood*; D009369:Neoplasms / Q000097:blood* / Q000150:complications; D010190:Pancreatic Neoplasms / Q000097:blood; D044162:Parathyroid Hormone-Related Protein; D017430:Prostate-Specific Antigen; D011506:Proteins / Q000032:analysis*; D011863:Radioimmunoassay; D012016:Reference Values; D001749:Urinary Bladder Neoplasms / Q000097:blood
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D017430:Prostate-Specific Antigen