What is the pathophysiology of hyperparathyroidism (Primary Hyperparathyroidism)?

From the Guidelines

Hyperparathyroidism is defined as excessive parathyroid hormone (PTH) production, typically resulting in hypercalcemia, and is most commonly caused by a single parathyroid adenoma (80%). The condition can be primary, where the parathyroid glands autonomously overproduce PTH, or secondary, developing as a compensatory response to low calcium levels, commonly in kidney disease 1. Primary hyperparathyroidism (PHPT) is diagnosed by biochemical testing, specifically serum calcium and serum PTH, and can be asymptomatic or present with symptoms related to target organ involvement, including bone demineralization, fractures, nephrolithiasis, nephrocalcinosis, muscle weakness, or neurocognitive disorders.

Key Aspects of Hyperparathyroidism

• The most common form of hyperparathyroidism is primary hyperparathyroidism (PHPT), which occurs when parathyroid glands autonomously overproduce PTH.
• PHPT can be caused by a single parathyroid adenoma, multiple adenomas, parathyroid hyperplasia, or, rarely, parathyroid carcinoma.
• The condition is more common in women, with an incidence of 66 per 100,000 person-years, and 25 per 100,000 person-years in men.
• Treatment of PHPT 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.

Diagnosis and Treatment

• Diagnosis is through blood tests showing elevated PTH and calcium levels, along with imaging studies to locate abnormal glands.
• Surgical excision of the affected gland(s) is the primary treatment for PHPT, with two accepted curative operative strategies being bilateral neck exploration (BNE) and minimally invasive parathyroidectomy (MIP) 1.
• BNE is a bilateral operation where all parathyroid glands are identified and examined, while MIP is a unilateral operation utilizing limited dissection for targeted removal of only the affected gland.
• The choice between BNE and MIP depends on the presence of a single adenoma, the accuracy of preoperative localization, and the suspicion of multigland disease.

Complications and Recurrence

• Persistent PHPT is defined as failure to achieve normocalcemia within 6 months of initial parathyroidectomy, whereas recurrent PHPT is defined as hypercalcemia occurring after a normocalcemic interval of 6 months or more after parathyroidectomy 1.
• Parathyroid reoperations are surgically challenging, with lower cure rates than first-time surgery and higher complication rates, emphasizing the importance of accurate preoperative imaging in the reoperative setting.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Hyperparathyroidism Overview

• Hyperparathyroidism is a common endocrine disorder characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone 2, 3.
• The disorder can manifest with osteoporosis, hypercalciuria, vertebral fractures, and nephrolithiasis, and can be asymptomatic in many cases 2, 3.

Pathogenesis and Diagnosis

• Primary hyperparathyroidism is almost always due to a benign overgrowth of parathyroid tissue, either as a single gland or as a multiple gland disorder 3.
• The disease is generally discovered when asymptomatic, but has the potential to become symptomatic, resulting in bone loss and kidney stones 3.

Treatment Options

• Parathyroidectomy is the only curative treatment for primary hyperparathyroidism, and is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae 2.
• Medical therapies, such as cinacalcet, can increase bone mineral density or reduce serum levels of calcium, but no single drug can do both 4, 5, 6.
• Cinacalcet has been shown to decrease serum calcium and parathyroid hormone serum levels in patients with primary hyperparathyroidism, and may be considered for patients who cannot or will not undergo surgery 5, 6.

Management and Monitoring

• Management of primary hyperparathyroidism should rely on an individual evaluation when counseling patients, taking into account the great variation in how the disease is manifested 4.
• Patients who do not undergo parathyroid surgery should be monitored for serum calcium concentrations and bone density 3.
• Combining resorptive agents with calcimimetics, such as cinacalcet, may be a useful approach, but more studies are needed to evaluate the effectiveness of this strategy 4.