What are the treatment approaches for primary vs secondary hyperparathyroidism?

From the Guidelines

Treatment approaches for primary and secondary hyperparathyroidism differ based on their distinct underlying causes. For primary hyperparathyroidism, parathyroidectomy (surgical removal of the affected parathyroid gland) is the definitive treatment, especially for symptomatic patients, those under 50 years old, with significantly elevated calcium levels (>1 mg/dL above normal), reduced bone density, or kidney complications 1. Patients who are poor surgical candidates may be managed with medications including cinacalcet (30-90 mg daily), which reduces PTH secretion, or bisphosphonates like alendronate (70 mg weekly) to protect bone density. For asymptomatic patients with mild disease, watchful waiting with regular monitoring of calcium levels and bone density may be appropriate.

Secondary hyperparathyroidism treatment focuses on addressing the underlying cause, typically chronic kidney disease. Management includes:

• Correcting vitamin D deficiency with calcitriol (0.25-1 mcg daily) or paricalcitol (1-4 mcg daily)
• Controlling phosphate levels with phosphate binders such as sevelamer (800-1600 mg with meals) or calcium acetate
• Using calcimimetics like cinacalcet (30-180 mg daily) to reduce PTH secretion Dietary phosphate restriction and adequate dialysis are also essential components of treatment. In severe cases unresponsive to medical therapy, subtotal parathyroidectomy may be necessary 1. Regular monitoring of calcium, phosphate, PTH, and vitamin D levels is crucial for both conditions to guide treatment adjustments. According to the most recent study 1, total parathyroidectomy (TPTX) is superior to total parathyroidectomy with autotransplantation (TPTX + AT) in reducing the recurrence of secondary hyperparathyroidism. However, this conclusion needs to be tested in large-scale confirmatory trials. TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of refractory secondary hyperparathyroidism.

Some key points to consider:

• The choice of surgical approach for secondary hyperparathyroidism is controversial, and the optimal surgical strategy has not been definitively established 1.
• Medical therapy is often effective for controlling secondary hyperparathyroidism, but surgical therapy can provide effective reductions in PTH levels and improve clinical outcomes 1.
• The use of calcimimetics, such as cinacalcet, can reduce PTH secretion and is a useful adjunct to medical therapy 1.
• Regular monitoring of calcium, phosphate, PTH, and vitamin D levels is essential to guide treatment adjustments and prevent complications 1.

From the FDA Drug Label

Cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis [see Clinical Studies (14. 1)]. Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy [see Clinical Studies (14.3)].

The treatment approaches for primary and secondary hyperparathyroidism differ:

• Secondary hyperparathyroidism: The recommended starting oral dose of cinacalcet tablets is 30 mg once daily. Cinacalcet tablets should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH levels of 150 to 300 pg/mL 2.
• Primary hyperparathyroidism: The recommended starting oral dose of cinacalcet tablets is 30 mg twice daily. The dose of cinacalcet tablets should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, and 90 mg twice daily, and 90 mg 3 or 4 times daily as necessary to normalize serum calcium levels 2.

From the Research

Treatment Approaches for Primary and Secondary Hyperparathyroidism

The treatment approaches for primary and secondary hyperparathyroidism differ due to the distinct causes and manifestations of these conditions.

• Primary Hyperparathyroidism: This condition is typically treated with surgical removal of the hyperfunctional parathyroid tissue 3. In some cases, especially during the COVID-19 pandemic, pharmacologic management may be used as a temporary measure until surgery can be safely performed 4. Medications such as cinacalcet, bisphosphonates, and denosumab can help control hypercalcemia and improve bone mineral density.
• Secondary Hyperparathyroidism: The treatment of secondary hyperparathyroidism often involves the use of active vitamin D or vitamin D analogs to suppress parathyroid hormone (PTH) secretion 5. However, this therapy can be limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus product. Alternative treatments include paricalcitol, which has been shown to reduce PTH concentrations without causing significant hypercalcemia or hyperphosphatemia 5, and cinacalcet, a calcimimetic agent that lowers PTH levels without increasing calcium and phosphorus levels 6. In severe and refractory cases, surgical parathyroidectomy may be required 7.

Comparison of Treatment Outcomes

Studies have compared the outcomes of different treatment approaches for primary and secondary hyperparathyroidism.

• A study comparing paricalcitol and calcitriol in the treatment of secondary hyperparathyroidism found that paricalcitol reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased calcium-phosphorus product 5.
• A study on parathyroidectomy for secondary hyperparathyroidism in patients with chronic kidney disease found that the procedure was associated with significant fluctuations in serum calcium levels, but long-term morbidity and mortality were lower than previously reported 7.
• A study on the operative treatment of primary hyperparathyroidism in daycare surgery found that parathyroidectomy in the daycare setting was feasible and safe, but many patients returned to the emergency department due to symptoms related to decreased calcium levels 3.

Pharmacologic Management

Pharmacologic management plays a crucial role in the treatment of both primary and secondary hyperparathyroidism.

• Cinacalcet is a commonly used medication for controlling hypercalcemia in primary hyperparathyroidism 4 and secondary hyperparathyroidism 6.
• Bisphosphonates and denosumab are used to improve bone mineral density in patients with primary hyperparathyroidism 4.
• Paricalcitol is an effective treatment for secondary hyperparathyroidism, reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia 5.