The Calcimimetic Cinacalcet Normalizes Serum Calcium in Subjects with Primary Hyperparathyroidism

Shoback, Dolores; Bilezikian, John P.; Turner, Stewart A.; McCary, Laura C.; Guo, Matthew; Peacock, Munro

doi:10.1210/jc.2002-021597

Cited by 231 publications

(154 citation statements)

References 15 publications

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“…However, longitudinal intervention studies are needed in order to investigate this issue. One potential approach could be to evaluate the metabolic effects of pharmacological treatment with calcimimetics, specific parathyroid calcium receptor agonists, which decrease PTH and calcium levels, apparently without having adverse effects on other tissues [36,37].…”

Section: Discussionmentioning

confidence: 99%

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

et al. 2006

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Aims/hypothesis Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretionin the normocalcaemic general population. Materials and methods We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n=961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT.Results In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg −1 min −1 (mU/l) −1 × 100 (0.024 mg kg −1 min −1 [pmol/l] −1 ×100) decrease in M/I (p=0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n=413, regression coefficient for 1 SD increase −0.45, p=0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. Conclusion/interpretation Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.

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Section: Discussionmentioning

confidence: 99%

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

et al. 2006

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“…Cinacalcet HCl, the agonist of the calcium-sensing receptor (CASR) currently available for the control of hypercalcaemia in PHPT patients with a wide range of disease severity, reduces circulating PTH levels, normalizes serum calcium, and reduces fasting urine calcium excretion though 24-h urine calcium levels are unaffected (16,17). CASR molecules are expressed throughout the different segments of the nephron (18): CASR is mainly expressed in the thick ascending loop of Henle, where it functions as a major determinant of urinary calcium excretion.…”

Section: Effects Of Cinacalcet On Hypercalciuriamentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

Verdelli

Corbetta

2017

European Journal of Endocrinology

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Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed.

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“…In patients with primary parathyroid adenomas and normal renal function (40) or in chronic hemodialysis patients with end-stage kidney disease (41), the acute effects of cinacalcet administration consist of a rapid decrease of serum PTH within 2 to 4 h, closely followed by a decrease of serum calcium within 4 to 8 h in patients with renal disease, but not in patients with parathyroid adenoma. Long-term administration of cinacalcet to patients with primary hyperparathyroidism induces a progressive decrease in serum calcium toward the normal range and an increase in serum phosphorus, despite only minor changes in serum PTH (42).…”

Section: Clinical Use Of Cinacalcetmentioning

confidence: 99%

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

Drüeke¹,

Ritz²

2009

Clinical Journal of the American Society of Nephrology

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The discovery of the calcium-sensing receptor (CaR) 15 yr ago was rapidly followed by the development of drugs modulating its activity, the so-called calcimimetics (increasing the CaR signal) and calcilytics (decreasing the CaR signal). The indication for calcimimetics is treatment of primary and secondary hyperparathyroidism, whereas calcilytics have potential for treatment of osteoporosis. A large number of clinical studies has shown that cinacalcet, the only presently available calcimimetic, effectively reduces serum parathyroid hormone in dialysis patients with secondary hyperparathyroidism. In contrast to the effect of active vitamin D derivatives, it simultaneously decreases serum calcium and phosphorus. Experimental studies showed a concomitant decrease in parathyroid hyperplasia. In the treatment of secondary hyperparathyroidism of dialysis patients, important questions remain unresolved, for example, whether there are reasons to prefer calcimimetics to active vitamin D derivatives and whether combined administration offers advantages compared with calcimimetics or active vitamin D given in isolation. For lowering parathyroid hormone, available evidence from recent studies suggests that combination therapy should be preferred to single drug treatment because of less side-effects and greater efficacy in controlling parathyroid overfunction. Future randomized controlled trial must answer whether calcimimetics impact on cardiovascular events or survival and whether in this respect there are differences between vitamin D sterols and calcimimetics.

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The Calcimimetic Cinacalcet Normalizes Serum Calcium in Subjects with Primary Hyperparathyroidism

Cited by 231 publications

References 15 publications

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

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