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Calcium-Sensing by Parathyroid Glands in Secondary Hyperparathyroidism¹

Departments of Medicine, Pediatrics, and Biomathematics (W.G.G., T.R.B., A.J.V.H., I.B.S.), University of California at Los Angeles School of Medicine, Los Angeles, California 90095; Division of Endocrinology, Department of Internal Medicine (J.D.V.), University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; and Endocrine Unit (H.J.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: William G. Goodman, Division of Nephrology, 7–155 Factor Building, University of California at Los Angeles Medical Center, 10833 Le Conte Avenue, Los Angeles, California 90095 E-mail: wgoodman{at}ucla.edu

Calcium-sensing by the parathyroids is abnormal in familial benign hypocalciuric hypercalcemia and in primary hyperparathyroidism (1°HPT), but the role of a calcium-sensing defect in uremic secondary hyperparathyroidism (2°HPT) remains controversial. To study the regulation of PTH release by calcium, set point estimates were obtained using the four parameter model during in vivo dynamic tests of parathyroid gland function in 31 patients with 2°HPT, 8 patients with advanced 2°HPT studied shortly before undergoing parathyroidectomy (Pre-PTX), 3 patients with 1°HPT, and 20 subjects with normal renal function (NL); the response to 2-h iv calcium infusions was also evaluated. Neither blood ionized calcium (iCa⁺²) levels nor the set point for calcium-regulated PTH release differed between 2°HPT and NL; iCa⁺² levels and set point values were moderately elevated in Pre-PTX and markedly elevated in 1°HPT. Compared with values obtained in NL, the lowest serum PTH levels achieved during calcium infusions, expressed as a percentage of preinfusion values, were incrementally greater in 2°HPT, Pre-PTX, and 1°HPT, whereas the slope of the relationship between iCa⁺² and PTH, expressed as the natural logarithm (ln) of percent preinfusion values, decreased incrementally in 2°HPT, Pre-PTX, and 1°HPT. The inhibitory effect of calcium on PTH release is blunted both in 2°HPT and 1°HPT because of increases in parathyroid gland mass, but a calcium-sensing defect is a late, rather than early, consequence of renal 2°HPT.

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