Calcium-sensing by parathyroid glands in secondary hyperparathyroidism.

Calcium-sensing by the parathyroids is abnormal in familial benign hypocalciuric hypercalcemia and in primary hyperparathyroidism (primary HPT), but the role of a calcium-sensing defect in uremic secondary hyperparathyroidism (secondary 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 secondary HPT, 8 patients with advanced secondary HPT studied shortly before undergoing parathyroidectomy (Pre-PTX), 3 patients with primary HPT, and 20 subjects with normal renal function (NL); the response to 2-h i.v. calcium infusions was also evaluated. Neither blood ionized calcium (iCa+2) levels nor the set point for calcium-regulated PTH release differed between secondary HPT and NL; iCa+2 levels and set point values were moderately elevated in Pre-PTX and markedly elevated in primary HPT. Compared with values obtained in NL, the lowest serum PTH levels achieved during calcium infusions, expressed as a percentage of pre-infusion values, were incrementally greater in secondary HPT, Pre-PTX, and primary 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 secondary HPT, Pre-PTX, and primary HPT. The inhibitory effect of calcium on PTH release is blunted both in secondary HPT and primary HPT because of increases in parathyroid gland mass, but a calcium-sensing defect is a late, rather than early, consequence of renal secondary HPT.

[1]  W. Goodman,et al.  In vivo assessments of calcium-regulated parathyroid hormone release in secondary hyperparathyroidism. , 1996, Kidney international.

[2]  L. Quarles,et al.  Non-suppressible parathyroid hormone secretion is related to gland size in uremic secondary hyperparathyroidism. , 1996, Kidney international.

[3]  R. Lepage,et al.  Accumulation of a non-(1-84) molecular form of parathyroid hormone (PTH) detected by intact PTH assay in renal failure: importance in the interpretation of PTH values. , 1996, The Journal of clinical endocrinology and metabolism.

[4]  A. Felsenfeld,et al.  The set point of calcium--another view. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  P. D'amour,et al.  Influence of Ca2+ concentration on the clearance and circulating levels of intact and carboxy‐terminal iPTH in pentobarbital‐anesthetized dogs , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  E. Brown,et al.  Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. , 1996, The Journal of clinical endocrinology and metabolism.

[7]  W. Goodman,et al.  Parathyroid gland function and the set point for PTH release: understanding the available data. , 1996, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  G. Segre,et al.  Calcium-regulated parathyroid hormone release in patients with mild or advanced secondary hyperparathyroidism. , 1995, Kidney international.

[9]  A. Arnold,et al.  Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia. , 1995, The Journal of clinical investigation.

[10]  P. Messa,et al.  Direct in vivo assessment of parathyroid hormone-calcium relationship curve in renal patients. , 1994, Kidney international.

[11]  Heath H rd.  Familial benign hypercalcemia--from clinical description to molecular genetics. , 1994 .

[12]  E. Brown,et al.  Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype. , 1994, The Journal of clinical investigation.

[13]  M. Straume,et al.  Model-independent quantification of measurement error: empirical estimation of discrete variance function profiles based on standard curves. , 1994, Methods in enzymology.

[14]  H. Heath.  Familial benign hypercalcemia--from clinical description to molecular genetics. , 1994, The Western journal of medicine.

[15]  K. Kurokawa,et al.  Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. , 1993, The Journal of clinical investigation.

[16]  J. Gornbein,et al.  Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism. , 1993, The Journal of clinical endocrinology and metabolism.

[17]  F. Malberti,et al.  Improvement of secondary hyperparathyroidism and reduction of the set point of calcium after intravenous calcitriol. , 1993, Kidney international. Supplement.

[18]  F. Llach,et al.  Parathyroid gland function in chronic renal failure. , 1993, Kidney international.

[19]  S. Khosla,et al.  Calcium infusion suggests a "set-point" abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism. , 1993, The Journal of clinical endocrinology and metabolism.

[20]  R. Dunlay,et al.  A comparison of parathyroid-gland function in haemodialysis patients with different forms of renal osteodystrophy. , 1991, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  R. Dunlay,et al.  Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis. , 1989, Kidney international.

[22]  E. Brown,et al.  Hysteresis in the relationship between serum ionized calcium and intact parathyroid hormone during recovery from induced hyper- and hypocalcemia in normal humans. , 1989, The Journal of clinical endocrinology and metabolism.

[23]  J. Delmez,et al.  Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium. , 1989, The Journal of clinical investigation.

[24]  W. Goodman,et al.  Bone disease in pediatric patients undergoing dialysis with CAPD or CCPD. , 1988, Kidney international.

[25]  J. Rastad,et al.  Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism. , 1988, The Journal of endocrinology.

[26]  M. Paillard,et al.  Maximal PTH secretory rate and set point for calcium in normal subjects and patients with primary hyperparathyroidism. In vivo studies. , 1988, Mineral and electrolyte metabolism.

[27]  Brennan,et al.  Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. , 1987, Clinical chemistry.

[28]  J. Auwerx,et al.  Altered parathyroid set point to calcium in familial hypocalciuric hypercalcaemia. , 1984, Acta endocrinologica.

[29]  R. Horst,et al.  A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies. , 1984, The Journal of clinical endocrinology and metabolism.

[30]  F. Llach,et al.  The Effects of Calciferol and its Metabolites on Patients With Chronic Renal Failure , 1983 .

[31]  A. Moss,et al.  Parathyroid imaging: comparison of high-resolution CT and high-resolution sonography. , 1983, AJR. American journal of roentgenology.

[32]  F. Llach,et al.  The effects of calciferol and its metabolites on patients with chronic renal failure. II. Calcitriol, 1 alpha-hydroxyvitamin D3, and 24,25-dihydroxyvitamin D3. , 1983, Archives of internal medicine.

[33]  E. Brown,et al.  Four-parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue. , 1983, The Journal of clinical endocrinology and metabolism.

[34]  G. Åkerström,et al.  Regulation of parathyroid hormone release in primary and secondary hyperparathyroidism - studies in vivo and in vitro. , 1982, Acta endocrinologica.

[35]  E. Brown,et al.  Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure. , 1982, The Journal of clinical endocrinology and metabolism.

[36]  E. Brown,et al.  Abnormal calcium-regulated PTH release in normal parathyroid tissue from patients with adenoma. , 1981, The American journal of medicine.

[37]  J. Doppman,et al.  Calcium-regulated parathyroid hormone release in primary hyperparathyroidism: studies in vitro with dispersed parathyroid cells. , 1979, The American journal of medicine.

[38]  S. Klahr,et al.  Impaired parathyroid hormone metabolism in patients with chronic renal failure. , 1978, The New England journal of medicine.