What is the management of primary hyperparathyroidism (PHPT)?

From the Guidelines

Surgical removal of the abnormal parathyroid gland(s) through parathyroidectomy is the definitive treatment for primary hyperparathyroidism, particularly for symptomatic patients or those meeting surgical criteria, as it offers the only curative approach by addressing the underlying pathophysiology of autonomous PTH secretion. The management of primary hyperparathyroidism involves a comprehensive approach, considering the patient's disease severity, surgical risk, and overall health status.

Key Considerations

• Surgical criteria include serum calcium >1 mg/dL above normal range, osteoporosis (T-score <-2.5), kidney stones, reduced creatinine clearance (<60 mL/min), or age under 50 years 1.
• Minimally invasive parathyroidectomy (MIP) is preferred when a single adenoma is identified preoperatively, as it conveys the benefits of shorter operating times, faster recovery, and decreased perioperative costs 1.
• For patients who are poor surgical candidates or have mild asymptomatic disease, medical management includes regular monitoring with serum calcium and PTH measurements every 6-12 months, bone density testing every 1-2 years, and renal imaging if indicated.

Medical Management

• Pharmacologic options include cinacalcet to lower calcium levels by increasing calcium-sensing receptor sensitivity, bisphosphonates like alendronate for bone protection, and adequate hydration 1.
• Patients should maintain normal calcium intake rather than restricting it, avoid thiazide diuretics which can worsen hypercalcemia, and ensure adequate vitamin D levels to prevent secondary hyperparathyroidism.

Surgical Approach

• Bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP) are the two accepted curative operative strategies for primary hyperparathyroidism, with BNE being the traditional standard method and MIP being less invasive and preferred for single adenoma cases 1.
• The choice between BNE and MIP depends on the patient's specific condition, including the presence of multigland disease or discordant preoperative imaging results.
• In cases of persistent or recurrent primary hyperparathyroidism, parathyroid reoperations are surgically challenging, with lower cure rates and higher complication rates, emphasizing the importance of accurate preoperative localization and careful surgical planning 1.

From the FDA Drug Label

1.3 Primary Hyperparathyroidism 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 management of primary hyperparathyroidism involves the use of cinacalcet for the treatment of hypercalcemia in adult patients who are unable to undergo parathyroidectomy.

• The recommended starting oral dose of cinacalcet is 30 mg twice daily.
• The dose of cinacalcet 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.
• Serum calcium should be measured within 1 week after initiation or dose adjustment of cinacalcet.
• Cinacalcet can be used alone or in combination with vitamin D sterols and/or phosphate binders.
• Patients should be monitored for hypocalcemia, and dose adjustment may be necessary to prevent hypocalcemia 2.

From the Research

Medical Management of Primary Hyperparathyroidism

• Cinacalcet has been shown to be a reasonable alternative to surgery for certain patient subgroups, including those with hyperplasia in all glands, patients with persisting HPT following unsuccessful surgery, and patients with comorbidities that make surgery inadvisable 3.
• Cinacalcet can effectively control hypercalcemia and hypophosphatemia, lower PTH levels, and improve cognitive parameters 3, 4.
• The medication has been found to normalize serum calcium in most patients, although it only modestly reduces serum PTH levels 4.

Patient Selection for Medical Management

• Patients who are not surgical candidates, who refuse surgery, or those with refractory PHPT after parathyroidectomy may be considered for cinacalcet treatment 5.
• Cinacalcet may be particularly beneficial for patients with mild disease who do not meet the guidelines for surgery 6.
• However, the effects of cinacalcet on bone mineral density and other complications of PHPT are uncertain, and more frequent monitoring may be required 5.

Surgical Management of Primary Hyperparathyroidism

• Parathyroidectomy is the definitive cure for primary hyperparathyroidism, and most patients with pHPT should be considered for surgery 7.
• The reviewed literature suggests that there were improved outcomes among patients with asymptomatic pHPT who underwent curative surgery 7.
• However, more randomized clinical trials are needed to strongly support a surgical recommendation for all asymptomatic patients with pHPT 7.