How to manage a patient with suspected primary hyperparathyroidism (PHPT) and hypercalcemia?

From the Guidelines

Management of suspected primary hyperparathyroidism (PHPT) with hypercalcemia requires a systematic approach beginning with confirmation of the diagnosis, and definitive treatment is parathyroidectomy, particularly indicated for patients with significant hypercalcemia, reduced bone density, kidney stones, or age <50 years, as stated in the most recent guidelines 1. To manage a patient with suspected PHPT and hypercalcemia, first, obtain serum calcium, intact parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D, and 24-hour urinary calcium levels. Diagnosis is confirmed with elevated or inappropriately normal PTH in the setting of hypercalcemia. For asymptomatic patients with mild hypercalcemia (<12 mg/dL), adequate hydration and avoidance of thiazide diuretics and calcium supplements are recommended while awaiting definitive treatment. For symptomatic or severe hypercalcemia (>12 mg/dL), initiate aggressive IV normal saline at 200-300 mL/hour to promote calcium excretion, followed by IV bisphosphonates such as zoledronic acid 4 mg or pamidronate 60-90 mg as a single dose. Some key points to consider in the management of PHPT include:

• 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, as stated in the guidelines 1.
• Parathyroidectomy is the definitive treatment for PHPT, and it is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia 1.
• For non-surgical candidates, cinacalcet (starting at 30 mg twice daily) can be used for medical management, as it can help reduce PTH levels and alleviate symptoms 1.
• Regular monitoring of calcium, PTH, renal function, and bone density is essential for all patients, as it can help identify potential complications and guide treatment decisions 1. The patient's PTH level is 30 and ionized calcium is 6.0, which suggests hyperparathyroidism, and the patient should be managed accordingly, with a focus on definitive treatment with parathyroidectomy, as well as medical management to control symptoms and prevent complications.

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)]. Seventeen patients with severe hypercalcemia due to primary HPT, who had failed or had contraindications to parathyroidectomy, participated in an open-label, single-arm study. At baseline the mean (SE) serum calcium was 12.7 (0.2) mg/dL. At the end of the titration phase the mean (SE) serum calcium was 10.4 (0.3) mg/dL, which is a mean reduction of 2. 3 (0. 3) mg/dL from baseline.

The patient has hypercalcemia with an ionized calcium level of 6.0 and a PTH of 30, suggesting primary hyperparathyroidism (PHPT).

• The patient's serum calcium level is elevated, which is consistent with PHPT.
• Cinacalcet may be considered for the treatment of hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy.
• The dosage of cinacalcet should be titrated to maintain a corrected total serum calcium concentration within the normal range, starting with a dose of 30 mg twice daily and titrating as needed 2.
• In a study of patients with severe hypercalcemia due to primary HPT, cinacalcet reduced the mean serum calcium level from 12.7 mg/dL to 10.4 mg/dL at the end of the titration phase 2.

From the Research

Management of Primary Hyperparathyroidism (PHPT)

• The management of PHPT involves surgical and medical approaches, depending on the severity of the disease and the presence of symptoms or complications 3, 4.
• Parathyroidectomy is recommended for patients with symptomatic PHPT, significant hypercalcemia, impaired renal function, renal stones, or osteoporosis, as well as for those younger than 50 years old 3.
• Medical management may be considered for patients with mild asymptomatic disease, contraindications to surgery, or failed previous surgical intervention 3.

Biochemical Evaluation

• Serum calcium level is an appropriate first-line biochemical test for the diagnosis of PHPT, but ionized calcium measurements may provide additional benefit in certain cases 5.
• Ionized calcium level is a more sensitive indicator of PHPT and is correlated with parathyroid hormone (PTH) level and adenoma size 5.
• A study found that 91.3% of patients with PHPT had a positive technetium-99 sestamibi (Tc) parathyroid scan with an ionized calcium level above 6.0 mg/dL 6.

Treatment Options

• Calcium and vitamin D intake should be optimized in patients with PHPT 3.
• Antiresorptive therapy may be used for skeletal protection in patients with an increased fracture risk 3.
• Cinacalcet, a calcimimetic agent, has been shown to effectively lower serum calcium and PTH levels 3.
• Various medical therapies can increase bone mineral density (BMD) or reduce serum levels of calcium, but no single drug can do both 7.