The PTH-calcium curve and the set point of calcium in primary and secondary hyperparathyroidism

Malberti, Fabio; Farina, Marco; Imbasciati, E

doi:10.1093/ndt/14.10.2398

Cited by 68 publications

(51 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In clinical disorders such as CKD, vitamin D deficiency, and primary hyperparathyroidism, an increase in parathyroid gland mass from hyperplasia in the former two disorders or an adenoma in most cases of primary hyperparathyroidism is associated with increases in the maximal PTH response to hypocalcemia (18,19,30,33,67). In CKD, calcitriol and its analogs decrease PTH transcription and upregulate vitamin D receptors (68); therefore, it is not surprising that prolonged calcitriol treatment in CKD often results in a reduction in maximal PTH values (69,70).…”

Section: Maximal Pthmentioning

confidence: 99%

“…Similarly, the infusion of parathyroid hormone related peptide (PTHrP) more than doubled the maximal PTH response in both normal and azotemic rats (80,81). In patients who had primary hyperparathyroidism and in whom several days of bisphosphonate treatment corrected the hypercalcemia, the maximal PTH response to hypocalcemia increased by more than twofold (67). Similarly, a single dose of a bisphosphonate given to hemodialysis patients induced a modest but significant increase in the maximal PTH response (82).…”

Section: Maximal Pthmentioning

confidence: 99%

“…Such a mechanism was shown to contribute to the increase in PTH values in rats that were maintained on a low-calcium diet (85). Although it was possible that the regulatory protein AUF1 could be a factor in the bisphosphonate study in which 5 to 10 d elapsed before restudy (67), it would seem less likely to be a factor in short-term studies such as acute metabolic acidosis or PTHrP infusion.…”

Section: Maximal Pthmentioning

confidence: 99%

“…Such a concept originated from the relationship shown in curve 1 of Figure 1, which shows PTH to be the primary modifier of the serum calcium concentration. The calcemic effect of high PTH values is readily appreciated when hypercalcemia is present in hemodialysis patients with severe hyperparathyroidism ( Figure 7A) (67,143,144) At the time our hypothesis was advanced, such a concept was in agreement with published in vitro data that had shown that parathyroid glands that were obtained from patients with primary and secondary hyperparathyroidism had a higher set point of calcium than did normal parathyroid glands (145,146); however, as a result of subsequent studies of hyperparathyroidism in hemodialysis patients in whom the set point of calcium increased even though calcitriol treatment decreased PTH values, it became apparent that besides the magnitude of hyperparathyroidism, the adaptation of PTH secretion to the existing serum calcium concentration affected the set point of calcium for PTH secretion.…”

Section: Shift Of the Pth-calcium Curve In Hemodialysis Patientsmentioning

confidence: 99%

See 3 more Smart Citations

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Felsenfeld

Rodríguez

Aguilera–Tejero

2007

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

This review examines the dynamics of parathyroid hormone secretion in health and in various causes of secondary hyperparathyroidism. Although most studies of parathyroid hormone and calcium have focused on the modification of parathyroid hormone secretion by serum calcium, the relationship between parathyroid hormone and serum calcium is bifunctional because parathyroid hormone also modifies serum calcium. In normal animals and humans, factors such as phosphorus and vitamin D modify the basal parathyroid hormone level and the maximal parathyroid hormone response to hypocalcemia. Certain medications, such as lithium and estrogen, in normal individuals and sustained changes in the serum calcium concentration in hemodialysis patients change the set point of calcium, which reflects the serum calcium concentration at which parathyroid hormone secretion responds. Hypocalcemia increases the basal/maximal parathyroid hormone ratio, a measure of the relative degree of parathyroid hormone stimulation. The phenomenon of hysteresis, defined as a different parathyroid hormone value for the same serum calcium concentration during the induction of and recovery from hypo-and hypercalcemia, is discussed because it provides important insights into factors that affect parathyroid hormone secretion. In three causes of secondary hyperparathyroidism-chronic kidney disease, vitamin D deficiency, and aging-factors that affect the dynamics of parathyroid hormone secretion are evaluated in detail. During recovery from vitamin D deficiency, the maximal parathyroid hormone remains elevated while the basal parathyroid hormone value rapidly becomes normal because of a shift in the set point of calcium. Much remains to be learned about the dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism. T his review examines the dynamics of parathyroid hormone (PTH) secretion in health and in various causes of secondary hyperparathyroidism with an emphasis on chronic kidney disease (CKD). For better understanding of factors that affect PTH secretion, the PTH-calcium relationship is evaluated with respect to (1) PTH secretion in the baseline state (basal PTH) and its sensitivity to the serum calcium concentration; (2) the maximal PTH response to hypocalcemia and factors that have been reported to modify the maximal PTH response to hypocalcemia; (3) shifts in the set point of calcium for PTH secretion in normal individuals as a result of treatment with medications such as lithium and estrogen and in hemodialysis patients during sustained changes in the serum calcium concentration; (4) the dynamics of PTH secretion in the secondary hyperparathyroidism of CKD, vitamin D deficiency, and aging; and (5) the phenomenon of hysteresis, defined as a different PTH value for the same serum calcium concentration during the induction of and recovery from both hypo-and hypercalcemia. A focus on hysteresis is justified because it provides important insights into how PTH secretion is modified by rate and directional changes in the serum c...

show abstract

Section: Maximal Pthmentioning

confidence: 99%

Section: Maximal Pthmentioning

confidence: 99%

Section: Maximal Pthmentioning

confidence: 99%

Section: Shift Of the Pth-calcium Curve In Hemodialysis Patientsmentioning

confidence: 99%

See 2 more Smart Citations

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Felsenfeld

Rodríguez

Aguilera–Tejero

2007

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…decreases with hypocalcemia and increases with hypercalcemia (Pahl et al 1996, HardyYverneau et al 1998, Malberti et al 1999.…”

Section: Introductionmentioning

confidence: 99%

The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve

Bas

Aguilera–Tejero

Bas³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

The influence of secondary hyperparathyroidism (2 HPT) on the set point of the parathyroid hormone (PTH)-Ca 2+ curve is controversial. In vitro experiments have shown an increase in the set point. However, clinical studies with hemodialysis patients have provided a variety of results (increases, decreases and no changes in the set point have been reported). The present study was designed to investigate the influence of the progression of 2 HPT on the set point of the PTH-Ca 2+ curve. The PTH-Ca 2+ curve and the expression of parathyroid calcium receptor (CaR mRNA) and vitamin D receptor (VDR mRNA) have been studied in normal rabbits (group I, n=9) and in nephrectomized rabbits (group II, n=18) at two stages after inducing 2 HPT: 2-3 weeks (group IIA) and 5-6 weeks (group IIB). In group I, the set point of the PTH-Ca 2+ curve was 1·63 0·03 mM. A progressive hypocalcemia was detected during the evolution of 2 HPT (groups IIA and IIB). Rabbits from group IIA had a significant (P<0·001) decrease in the set point to values of 1·45 0·02 mM. However, the set point increased significantly in group IIB (P<0·001) to 1·56 0·03 mM. CaR mRNA was similarly decreased in groups IIA (39 12%) and IIB (48 7%). No changes were detected in VDR mRNA. In conclusion, a reduction in the set point of the PTH-Ca 2+ curve in response to decreased extracellular Ca 2+ was detected in the early phases of 2 HPT. However, with the progression of 2 HPT the set point tended to increase even though extracellular Ca 2+ was markedly decreased. The increase in the set point in the course of 2 HPT seems to be a complex process that cannot be fully explained by changes in parathyroid CaR mRNA or VDR mRNA.

show abstract

The Calcium‐Sensing Receptor ( CaSR ) in Disease

Keller¹,

Josephs²,

Gregory³

et al. 2022

GPCRs as Therapeutic Targets

View full text Add to dashboard Cite

The PTH-calcium curve and the set point of calcium in primary and secondary hyperparathyroidism

Cited by 68 publications

References 21 publications

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve

The Calcium‐Sensing Receptor ( CaSR ) in Disease

Contact Info

Product

Resources

About