CARBOXYL-TERMINAL FRAGMENTS OF PARATHYROID-HORMONE ARE NOT SECRETED PREFERENTIALLY IN PRIMARY HYPERPARATHYROIDISM AS THEY ARE IN OTHER HYPERCALCEMIC CONDITIONS

Calcium infusion in normal men decreases immunoreactive PTH (iPTH). In tact iPTH (1) shows the greatest decline, and there is a greater decre ase in carboxyl-terminal iPTH (C) than in midcarboxyl-terminal iPTH (M ); thus, C/I, M/1, and M/C ratios are increased. To verify whether thi s adaptive mechanism to hypercalcemia was present in patients with pri mary hyperparathyroidism (PHP), we measured total serum calcium (Ca), 1, C, and M as well as C/I, M/I, and M/C ratios in 32 normocalcemic no rmal subjects (NN), in the same normal subjects made hypercalcemic (HN ), in 31 patients with PHP, and in 12 patients with nonparathyroid hyp ercalcemia (NPHN). Eight patients with PHP and the 32 NN were submitte d to CaCl2 and Na2 EDTA infusions to evaluate their parathyroid functi on. Ca was lower (P < 0.005) in NN (2.21 +/- 0.06 mmol/L) than in PHP (2.80 +/- 0.25 mmol/L) or NPHN (2.83 +/- 0.20 mmol/L). The HN Ca value (2.80 +/- 0.18 mmol/L) was similar to those in PHP and NPHN subjects. C, M, and I were increased in PHP compared to the other groups (P < 0 .005). PHP had C/I and M/I ratios of 2.03 +/- 0.72 and 9.04 +/- 7.69, values similar to NN (2.29 +/- 0.55 and 8.70 +/- 3.0), but lower than HN (5.36 +/- 2.48 and 25.93 +/- 13.86; P < 0.005) and NPHN (11.91 +/- 13.06 and 18.69 +/- 10.81; P < 0.005). NPHN also had a lower M/C ratio than HN (2.76 +/- 2.02 vs. 4.99 +/- 1.81; P < 0.05). PHP and NN could increase their C/I ratio to the same maximum (4.71 +/- 1.26 vs. 5.70 +/- 2.94), but PHP did so at a much higher set-point (2.67 +/- 0.19 vs . 2.24 +/- 0.10 mmol/L; P < 0.005). PHP also had higher set-points for M/1, and M/C ratios even if they failed to increase the ratios to the high values in NN [M/I 11.6 +/- 6.4 vs. 29.3 +/- 18.3 (P < 0.005); M/ C, 2.16 +/- 1.20 vs. 5.0 +/- 1.93 (P < 0.005)]. Thus, carboxyl-termina l fragments are not secreted preferentially in PHP as they are in othe r hypercalcemic conditions. This relates to a higher set-point for the regulation of C/I and M/I ratios, permitting the secretion of more in tact hormone relative to C or M fragments. The lower M/C ratio in NPHN and in PHP made more hypercalcemic compared to HN suggests a lower pr oduction or a higher clearance of midcarboxyl-terminal fragments in ch ronic hypercalcemia.