INTERRELATIONS BETWEEN THE CALCIUM SET-POINTS OF PARFITT AND BROWN INPRIMARY HYPERPARATHYROIDISM - A SEQUENTIAL CITRATE AND CALCIUM CLAMP STUDY

The objective of the present study was to compare the calcium set-poin ts of E. M. Brown and A. M. Parfitt obtained by sequential citrate and calcium clamp in patients with primary hyperparathyroidism and health y controls. Twenty-six patients with primary hyperparathyroidism were investigated and compared to 22 healthy volunteers. All participants w ere investigated by sequential calcium lowering and raising comprising the following four phases: Phase (1) blood ionized calcium lowering o f about 0.02 mmol1(-1); phase (2) steady-state (relative) hypocalcaemi a of blood ionized calcium 0.20 mmol1(-1) below baseline; phase (3) bl ood ionized calcium is raised to about 0.20 mmol1(-1) above baseline; and phase (4) (relative) hypercalcaemia of blood ionized calcium 0.20 mmol1(-1) above baseline. Serum parathyroid hormone (1-84) was measure d by an immunoradiometric assay. Blood ionized calcium was measured by a calcium selective electrode. We found the calcium set-points of Par fitt to be 1.42 mmol1(-1) (SD 0.12, n = 52) vs. 1.25 mmol1(-1) (SD 0.0 4, n=44) in patients and controls, respectively (P<0.001). The calcium set-points of Brown were 1.32 mmol1(-1) (SD 0.10, n = 26) vs. 1.13 mm oll(-1) (SD 0.04, n=22), respectively (P<0.001). By comparing the calc ium set-points of Parfitt and Brown, a strikingly good correlation was observed, in patients (r=0.91, P<0.001) and in controls (r=085, P<0.0 01). We demonstrate in this paper in vivo that Brown's and Parfitt's c alcium set-points are raised in primary hyperparathyroidism and return to normal following parathyroidectomy. The values for Brown's and Par fitt's calcium set-points are significantly different, but strikingly well correlated, supporting the view that Brown and Pariitt describe t wo different points on the same sigmoidal curve, corresponding to 50% and about 85% inhibition of PTH maximum, respectively. The mathematica l form of the sigmoidal curve between blood ionized calcium and parath yroid hormone is very similar in primary hyperparathyroidism and norma l humans.