What are the potential solutions for a patient with primary hyperparathyroidism (PHPT)?

From the Guidelines

The primary treatment for primary hyperparathyroidism is surgical removal of the abnormal parathyroid gland(s), known as parathyroidectomy, which is recommended for all symptomatic patients and many asymptomatic patients who meet specific criteria. This is based on the most recent evidence from the Journal of the American College of Radiology, which states that treatment of primary hyperparathyroidism is surgical excision of the abnormally functioning parathyroid tissue and is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia 1.

There are two accepted curative operative strategies for primary hyperparathyroidism: bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP). BNE refers to a bilateral operation in which all parathyroid glands are identified and examined by the surgeon, who resects the diseased glands. MIP is defined as a unilateral operation utilizing limited dissection for targeted removal of only the affected gland. MIP is therefore less invasive than BNE and is often performed as it conveys the benefits of shorter operating times, faster recovery, and decreased perioperative costs 1.

Some key points to consider in the management of primary hyperparathyroidism include:

• Surgical removal of the abnormal parathyroid gland(s) is the only definitive cure
• MIP is often preferred over BNE due to its less invasive nature and faster recovery time
• Preoperative localization of the abnormal parathyroid gland(s) is essential for targeted curative surgery
• Regular monitoring of serum calcium, PTH, vitamin D, and bone density is essential for non-surgical patients
• Medical management options, such as bisphosphonates and calcimimetics, can be used to manage symptoms in patients who cannot or choose not to undergo surgery 1.

It is essential to note that parathyroid reoperations are surgically challenging, with lower cure rates than first-time surgery and higher complication rates. As such, recent international guidelines state that preoperative imaging is essential in the reoperative setting to localize a target parathyroid lesion (or lesions) and to identify postoperative changes from previous parathyroid explorations that can impact a subsequent surgery 1.

In terms of medical management, options include:

• Bisphosphonates, such as alendronate, to improve bone density
• Calcimimetics, such as cinacalcet, to lower calcium levels by reducing PTH secretion
• Estrogen therapy in postmenopausal women
• Maintaining adequate hydration and avoiding thiazide diuretics, which can worsen hypercalcemia
• Limiting calcium intake to 800-1000 mg daily and ensuring sufficient vitamin D levels without supplementing excessively 1.

Overall, the goal of treatment for primary hyperparathyroidism is to alleviate symptoms, prevent long-term complications, and improve quality of life. Surgical removal of the abnormal parathyroid gland(s) is the most effective way to achieve this goal, and medical management options should be used in conjunction with or in place of surgery as needed.

From the FDA Drug Label

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 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 The potential solutions for a patient with primary hyperparathyroidism include:

• Cinacalcet tablets: 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 2
• Parathyroidectomy: although the drug label does not provide information on how to perform the surgery, it is mentioned as an option for patients with primary HPT who meet certain criteria 2
• Dose titration: the dose of cinacalcet tablets should be titrated every 2 to 4 weeks to normalize serum calcium levels 2
• Monitoring for hypocalcemia: serum calcium should be measured every 2 months for patients with primary hyperparathyroidism 2

From the Research

Potential Solutions for Primary Hyperparathyroidism

• Parathyroidectomy is currently the only curative treatment for primary hyperparathyroidism (PHPT) 3, 4, 5
• Medical management options are available for patients who are ineligible for, or unwilling to undergo, surgery and those in whom parathyroidectomy has failed 3, 4, 6, 7
• Cinacalcet, an allosteric modulator of the calcium-sensing receptor, has been found to be effective in reducing or normalizing serum calcium levels in several groups of PHPT patients 3, 6, 7
• Other medical treatment options include:
  • Estrogen therapy for postmenopausal women without contraindications to hormone replacement 4
  • Calcitonin to decrease serum calcium levels on a short-term basis 4
  • Bisphosphonates, which require further study 4, 7
• Cinacalcet may be considered to reduce serum calcium and parathyroid hormone serum levels in patients with PHPT who cannot or will not undergo surgery and those with refractory PHPT after parathyroidectomy 7

Patient Selection for Medical Management

• Patients with mild disease may have a benign natural history and may not have progression to severe disease, and may be managed medically 4
• Asymptomatic individuals with mild hypercalcemia and close to normal bone mass and renal function may be managed medically, particularly those who are over the age of 50 years 4
• Patients with hyperplasia in all glands rather than an isolated adenoma, patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms may be considered for medical therapy 6

Considerations for Cinacalcet Treatment

• Cinacalcet is well tolerated when used at low doses, but side effects are not uncommon when relatively high doses are needed to control hypercalcemia 3
• The effects of cinacalcet on bone mineral density are uncertain, and more frequent monitoring of bone mineral density may be required along with a medication proven to improve bone mineral density 7
• Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation 6