Increased serum immunoreactive parathyroid hormone-related protein levels in chronic hypocalcemia

To elucidate possible negative feedback regulation of circulating PTH-related protein (PTHrP) by serum calcium levels, we measured serum immunoreactive PTHrP (iPTHrP) by a specific RIA for PTHrP-(1-34) in patients with hypocalcemia due to PTH deficiency or resistance. Serum iPTHrP levels were not detectable (< 4 pmol/L) in 9 of 11 patients with postoperative hypocalcemia who presented with transient tetany, in 1 patient with hypocalcemia due to hypomagnesemia induced by cisplatin treatment, in normal subjects (n = 60), or in 1 normocalcemic patient with pseudopseudohypoparathyroidism. In contrast, the other 2 patients with postoperative hypocalcemia who had had hypocalcemic symptoms for longer periods (6 months and 3 yr, respectively) showed increased iPTHrP levels (6.3 and 5.3 pmol/L). All 6 patients with idiopathic hypoparathyroidism showed undetectable or low PTH, but increased iPTHrP, ranging from 6.5-19.5 pmol/L (mean +/- SD, 10.8 +/- 4.8 pmol/L). Elevated serum iPTHrP levels (7.4 and 8.1 pmol/L) were also found in both patients with pseudohypoparathyroidism type I. When chronic and profound hypocalcemia in these patients was normalized by treatment with 1 alpha-hydroxyvitamin D3, the elevated serum iPTHrP levels were normalized (undetectable, < 4 pmol/L) in all 6 patients examined. These results suggest that chronic and profound hypocalcemia and/or vitamin D deficiency can stimulate endogenous PTHrP secretion via a negative feedback mechanism, although elevated iPTHrP does not normalize the decreased serum calcium levels.