CALCIUM-SENSING BY PARATHYROID-GLANDS IN SECONDARY HYPERPARATHYROIDISM

Calcium-sensing by the parathyroids is abnormal in familial benign hyp ocalciuric hypercalcemia and in primary hyperparathyroidism (1 degrees HPT), but the role of a calcium-sensing defect in uremic secondary hy perparathyroidism (2 degrees HPT) remains controversial. To study the regulation of PTH release by calcium, set point estimates were obtaine d using the four parameter model during in, vivo dynamic tests of para thyroid gland function in 31 patients with 2 degrees HPT, 8 patients w ith advanced 2 degrees HPT studied shortly before undergoing parathyro idectomy (Pre-PTX), 3 patients with 1 degrees HPT, and 20 subjects wit h normal renal function (NL); the response to 2-h iv calcium infusions was also evaluated. Neither blood ionized calcium (iCa(+2)) levels no r the set point for calcium-regulated PTH release differed between 2 d egrees HPT and NL; iCa(+2) levels and set point values were moderately elevated in Pre-PTX and markedly elevated in 1 degrees HPT. Compared with values obtained in NL, the lowest serum PTH levels achieved durin g calcium infusions, expressed as a percentage of preinfusion values, were incrementally greater in 2 degrees HPT, Pre-PTX, and 1 degrees HP T, whereas the slope of the relationship between iCa+2 and PTH, expres sed as the natural logarithm (In) of percent preinfusion values, decre ased incrementally in 2 degrees HPT, Pre-PTX, and 1 degrees HPT. The i nhibitory effect of calcium on PTH release is blunted both in 2 degree s HPT and 1 degrees HPT because of increases in parathyroid gland mass , but a calcium-sensing defect is a late, rather than early, consequen ce of renal 2 degrees HPT.