Production and secretion of parathyroid hormone-related protein in pheochromocytoma: participation of an alpha-adrenergic mechanism.

We studied the relation between calcium metabolism and serum PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) in 12 patients with benign pheochromocytoma, 10 of whom had not received any medication before admission. Basal serum PRP-LI levels were elevated in 7 of these 10 untreated patients. After tumor resection, serum PRP-LI became undetectable in all 10 patients examined. Serum calcium decreased (P < 0.01), and serum phosphorus increased significantly (P < 0.05) after tumor resection. Serum PTH increased in 5 of 7 patients postoperatively. alpha-Adrenoceptor-blocking agents given as preoperative treatment (n = 6) decreased elevated PRP-LI levels in 5 patients, had no effect in the remaining patient with undetectable levels, and tended to decrease serum calcium levels that were normal in 5 of 6 patients and elevated in 1, while serum phosphorus levels showed reciprocal changes. In the remaining 2 patients who had received alpha-adrenoceptor-blocking agents before admission, serum PRP-LI was undetectable. Tissue PRP-LI concentrations were high in all resected tumors (n = 8). Western blot analysis of tumor extracts showed multiple bands at about 14, 16, 21, 27, and 34 kilodaltons, which differed among tumors. Northern blot analysis of PTHrP mRNA (n = 5) and immunohistochemistry (n = 5) showed positive findings. These findings suggest that PTHrP is synthesized in pheochromocytoma and released into the general circulation, probably via an alpha-adrenergic mechanism, and that changes in serum PRP-LI levels are fairly positively associated with those in serum calcium levels in patients with pheochromocytoma.