What are the clinical manifestations of Primary Hyperparathyroidism (PHPT)?

From the Guidelines

Parathyroidectomy is the recommended treatment for primary hyperparathyroidism, even in asymptomatic patients, due to the potential negative effects of long-term hypercalcemia. The treatment of primary hyperparathyroidism (PHPT) involves surgical excision of the abnormally functioning parathyroid tissue, which is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia 1. There are two accepted curative operative strategies for PHPT: bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP).

Key Considerations

• 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 a unilateral operation utilizing limited dissection for targeted removal of only the affected gland, which is less invasive than BNE and often performed when a single adenoma is present.
• The role of imaging in PHPT is to localize the abnormally functioning gland or glands with high accuracy and high confidence to facilitate targeted curative surgery, with no utility in confirming or excluding the diagnosis of PHPT 1.

Treatment Approaches

• Surgical excision of the affected parathyroid gland(s) is the primary treatment for PHPT, with BNE and MIP being the two accepted curative operative strategies.
• Medical management may include medications such as cinacalcet to lower calcium levels, bisphosphonates like alendronate to improve bone mineral density, and maintaining normal vitamin D levels.
• Regular monitoring includes serum calcium, PTH, vitamin D, renal function, and bone density scans every 1-2 years.

Important Factors

• PHPT is more common in women, with an incidence of 66 per 100,000 person-years, and 25 per 100,000 person-years in men 1.
• Most cases are sporadic, although hereditary causes exist, including multiple endocrine neoplasia types 1 and 2A as well as familial hyperparathyroidism.
• The prevalence of PHPT appears to be increasing significantly, with most cases presenting as an asymptomatic disorder in countries where biochemical screening is routine 1.

From the Research

Treatment Options for Primary Hyperparathyroidism

• The only curative treatment for primary hyperparathyroidism (pHPT) is surgery, specifically parathyroidectomy 2, 3, 4, 5.
• There are two main surgical options: bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP) 2.
• MIP is the standard treatment option in selected patients with positive imaging, but BNE remains the gold standard procedure in parathyroid surgery 2.
• Cinacalcet is a medical treatment option that can be used to control hypercalcemia in patients who are not able to undergo parathyroidectomy or have failed surgery 3, 5, 6.

Surgical Techniques

• Directed parathyroidectomy is currently the standard technique for treatment of primary hyperparathyroidism worldwide 4.
• The most appropriate type of surgical procedure depends on the number and localization of the hyperactive parathyroid glands, availability of modern imaging techniques, limitation of each type of procedure, and expertise 4.
• Possible ectopic locations of parathyroid glands should be investigated if the intended gland is not found in its normal anatomical site 2.

Medical Treatment with Cinacalcet

• Cinacalcet has been shown to decrease serum calcium and parathyroid hormone serum levels in patients with PHPT 3, 5, 6.
• 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 6.
• 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 6.