From the Guidelines
Primary hyperparathyroidism is directly associated with elevated calcium levels, as the overproduction of parathyroid hormone (PTH) leads to an increase in calcium absorption, reduced excretion, and bone resorption, resulting in hypercalcemia. This condition is typically characterized by the autonomous overproduction of PTH by one or more parathyroid glands, leading to an elevation in serum calcium levels 1. The primary function of PTH is to regulate calcium levels, and when it is overproduced, it can cause a range of complications, including kidney stones, osteoporosis, cognitive impairment, and cardiovascular disease.
Pathophysiology
The relationship between PTH and calcium is normally regulated by a negative feedback loop, where high calcium levels inhibit PTH secretion and low calcium levels stimulate it 1. However, in primary hyperparathyroidism, this regulatory mechanism fails, resulting in persistent hypercalcemia. The diagnosis of primary hyperparathyroidism is confirmed by finding elevated or inappropriately normal PTH levels in the presence of hypercalcemia.
Treatment and Complications
Treatment of primary hyperparathyroidism usually involves surgical removal of the affected parathyroid gland(s), which normalizes calcium levels in most patients 1. Without treatment, chronic hypercalcemia can lead to a range of complications, including kidney stones, osteoporosis, cognitive impairment, and cardiovascular disease. It is essential to diagnose and treat primary hyperparathyroidism promptly to prevent these complications and improve patient outcomes.
Key Points
- Primary hyperparathyroidism is a condition characterized by the overproduction of PTH, leading to hypercalcemia.
- The diagnosis is confirmed by finding elevated or inappropriately normal PTH levels in the presence of hypercalcemia.
- Treatment usually involves surgical removal of the affected parathyroid gland(s).
- Chronic hypercalcemia can lead to complications, including kidney stones, osteoporosis, cognitive impairment, and cardiovascular disease.
- Prompt diagnosis and treatment are essential to prevent these complications and improve patient outcomes 1.
From the FDA Drug Label
At baseline the mean (SE) serum calcium was 12.7 (0.2) mg/dL. At the end of the titration phase the mean (SE) serum calcium was 10.4 (0.3) mg/dL, which is a mean reduction of 2. 3 (0. 3) mg/dL from baseline.
A total of 33 patients were randomized to cinacalcet and 34 patients randomized to placebo. ... During the efficacy period a significantly higher percentage of cinacalcet-treated patients compared with the placebo-treated patients achieved mean corrected total serum calcium concentration (≤ 10.3 mg/dL [2.57 mmol/L], 75.8% vs 0%, p < 0.001) and ≥ 1 mg/dL [0.25 mmol/L] decrease from baseline in mean corrected total serum calcium concentration (84.8% vs 5.9%, p < 0. 001).
Primary Hyperparathyroidism is associated with elevated calcium levels. The use of cinacalcet in patients with primary hyperparathyroidism has been shown to reduce serum calcium levels. In one study, the mean serum calcium level decreased from 12.7 mg/dL at baseline to 10.4 mg/dL at the end of the titration phase 2. In another study, 75.8% of cinacalcet-treated patients achieved a mean corrected total serum calcium concentration of ≤ 10.3 mg/dL, compared to 0% of placebo-treated patients 2.
- Key findings:
- Cinacalcet reduces serum calcium levels in patients with primary hyperparathyroidism.
- Significant decrease in mean corrected total serum calcium concentration in cinacalcet-treated patients compared to placebo-treated patients.
- Clinical implications: Cinacalcet may be used to treat hypercalcemia in adult patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy 2.
From the Research
Relationship Between Primary Hyperparathyroidism and Elevated Calcium Levels
- Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and elevated or inappropriately normal serum levels of parathyroid hormone 3.
- The condition is the most common cause of hypercalcemia in the outpatient setting, often presenting with non-specific signs and symptoms of hypercalcemia, skeletal fragility, nephrolithiasis, and nephrocalcinosis 4.
- Hypercalcemia in PHPT can lead to various clinical manifestations, including osteoporosis, hypercalciuria, vertebral fractures, and nephrolithiasis, which can be asymptomatic in some cases 3, 5.
Diagnosis and Management
- Diagnosis of PHPT typically occurs through routine calcium measurement, with corrected high total calcium associated with high or inappropriately abnormal parathyroid hormone (PTH) levels 5.
- Parathyroidectomy is considered the gold standard treatment for PHPT, recommended in patients with symptoms, asymptomatic disease with risk of progression, or subclinical evidence of end-organ sequelae 3, 5.
- Medical management may be considered in patients with mild asymptomatic disease, contraindications to surgery, or failed previous surgical intervention, with options including calcium and vitamin D optimization, antiresorptive therapy, and cinacalcet 4, 6.
Treatment Options
- Cinacalcet, a calcimimetic agent, has been shown to effectively lower serum calcium and PTH levels, maintaining its effect over time 6.
- Bisphosphonates, such as pamidronate, alendronate, and clodronate, can improve bone mineral density (BMD) but may have a decreasing effect on serum calcium levels over time 6.
- Combining resorptive agents with calcimimetics may be a promising approach, but more studies are needed to determine its effectiveness 6.