What is the best approach for treating hyperparathyroidism?

From the Guidelines

The most effective approach for treating hyperparathyroidism, particularly in patients with chronic kidney disease, is total parathyroidectomy (TPTX) as it has been shown to reduce the recurrence of secondary hyperparathyroidism and improve outcomes. This recommendation is based on the most recent and highest quality study available, which suggests that TPTX has advantages over subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX + AT) in reducing the relapse of secondary hyperparathyroidism 1.

Key Considerations for Treatment

• For primary hyperparathyroidism, surgical removal of the affected parathyroid gland(s) is generally the definitive treatment, with minimally invasive parathyroidectomy being the preferred approach when a single adenoma is identified.
• For patients who are poor surgical candidates or have mild disease, medical management may include bisphosphonates like alendronate or cinacalcet to control calcium levels.
• Secondary hyperparathyroidism, often seen in kidney disease, requires treating the underlying cause with vitamin D supplements, phosphate binders, and sometimes cinacalcet.
• The choice between medical management and surgical intervention should be based on the severity of the disease, the presence of complications, and the patient's overall health status.

Surgical Options

• Total parathyroidectomy (TPTX) is recommended for patients with severe secondary hyperparathyroidism who do not respond to medical therapy.
• Subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX + AT) are alternative surgical options, but TPTX has been shown to have advantages in reducing the recurrence of secondary hyperparathyroidism.
• The choice of surgical approach should be individualized based on the patient's specific needs and the surgeon's expertise.

Medical Management

• Medical management of hyperparathyroidism includes the use of bisphosphonates, cinacalcet, vitamin D supplements, and phosphate binders to control calcium and phosphate levels.
• The goal of medical management is to reduce the levels of parathyroid hormone (PTH) and alleviate symptoms, but it may not be effective in all patients.
• Regular monitoring of calcium, phosphate, and PTH levels is necessary to adjust medical therapy and prevent complications.

Recent Guidelines and Recommendations

• The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline update recommends treating patients with PTH values that are progressively increasing or persistently above the upper limit of normal, and not basing treatment on a single elevated value 1.
• The guideline also recommends avoiding inappropriate calcium loading in adults with chronic kidney disease and restricting the use of calcium-based phosphate binders in patients with hyperphosphatemia.
• Future research should address the gaps in knowledge for the treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD), including the comparison of calcium-containing and calcium-free phosphate binders and the effect of dietary phosphate intake on bone health 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 Parathyroid Carcinoma [see Clinical Studies(14.2)]. 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 best approach for treating hyperparathyroidism with cinacalcet tablets depends on the type of hyperparathyroidism and the patient's condition.

• For secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, the recommended starting oral dose is 30 mg once daily, with titration every 2 to 4 weeks to target iPTH levels of 150 to 300 pg/mL.
• For parathyroid carcinoma and primary hyperparathyroidism, the recommended starting oral dose is 30 mg twice daily, with titration every 2 to 4 weeks to normalize serum calcium levels. It is essential to monitor serum calcium and phosphorus levels and intact parathyroid hormone (iPTH) levels during treatment with cinacalcet tablets to adjust the dose accordingly and prevent hypocalcemia 2.

From the Research

Treatment Approaches for Hyperparathyroidism

The treatment of hyperparathyroidism can vary depending on the type and severity of the condition. The following are some of the approaches that have been studied:

• Parathyroidectomy (PTX) is currently the only curative treatment for primary hyperparathyroidism (HPT) and is recommended for patients with moderate-to-severe disease 3.
• For patients with primary HPT who cannot or do not want to undergo surgery, medical management may be considered. This can include calcium and vitamin D supplementation, as well as pharmacological approaches such as cinacalcet and bisphosphonates 4.
• Cinacalcet is a calcimimetic that can reduce serum levels of parathyroid hormone (PTH) and calcium, and is a potential alternative for patients contraindicated for PTX or who have failed previous PTX and have recurrent primary HPT 3.
• In patients with secondary hyperparathyroidism (SHPT), calcimimetics such as cinacalcet have been shown to be effective in reducing PTH levels and improving calcium-phosphorus homeostasis 5, 6.
• Bisphosphonates, such as alendronate, can improve bone mineral density (BMD) in patients with primary HPT, but may not have a significant effect on serum calcium levels 4, 7.

Medical Management of Hyperparathyroidism

Medical management of hyperparathyroidism can include:

• Calcium supplementation: patients with primary HPT should follow guidelines established for all individuals, and calcium intake should not be limited in patients who do not undergo surgery 4.
• Vitamin D supplementation: patients with low serum 25-hydroxyvitamin D should be repleted with doses of vitamin D aiming to bring serum 25-hydroxyvitamin D levels to ≥ 50 nmol/L (20 ng/mL) at a minimum 4.
• Pharmacological approaches: cinacalcet and bisphosphonates can be used to control hypercalcemia and improve BMD in patients with primary HPT 4, 7.
• Combination therapy: combining resorptive agents with calcimimetics may be a promising approach, but more studies are needed to confirm its efficacy 7.