From the Guidelines
The best initial treatment for elevated PTH and hypercalcemia is surgical parathyroidectomy, as it is the definitive treatment for primary hyperparathyroidism, which is the most common cause of PTH-dependent hypercalcemia, as stated in the 2021 study by the Journal of the American College of Radiology 1.
Initial Management
While awaiting surgery or in non-surgical candidates, initial management includes:
- Intravenous normal saline hydration, typically administered at 200-300 mL/hour depending on the patient's cardiovascular status
- Bisphosphonate therapy, such as zoledronic acid 4 mg IV or pamidronate 60-90 mg IV, to inhibit osteoclast-mediated bone resorption
- Cinacalcet (starting at 30 mg twice daily and titrating as needed) to reduce PTH secretion
- Furosemide 20-40 mg IV may be added after adequate hydration to enhance calcium excretion
Rationale
The 2021 study by the Journal of the American College of Radiology 1 provides the most recent and highest quality evidence for the treatment of primary hyperparathyroidism. Surgical parathyroidectomy is the definitive treatment, and medical management is used to control symptoms and prevent complications while awaiting surgery. The use of cinacalcet, bisphosphonates, and furosemide is supported by earlier studies, such as the 2018 study by the Annals of Internal Medicine 1 and the 2017 study by Kidney International 1.
Key Points
- Primary hyperparathyroidism is the most common cause of PTH-dependent hypercalcemia
- Surgical parathyroidectomy is the definitive treatment
- Medical management includes cinacalcet, bisphosphonates, and furosemide
- Severe hypercalcemia (>14 mg/dL) should be treated as a medical emergency due to risks of cardiac arrhythmias, altered mental status, and renal failure
- Patients should be advised to maintain adequate hydration and avoid calcium-rich foods and supplements until definitive treatment is established.
From the FDA Drug Label
1.1 Secondary Hyperparathyroidism Cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis 1.2 Parathyroid Carcinoma Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma 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 2.2 Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis The recommended starting oral dose of cinacalcet tablets is 30 mg once daily. 2.3 Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism The recommended starting oral dose of cinacalcet tablets is 30 mg twice daily.
The best initial treatment for elevated PTH and hypercalcemia is cinacalcet.
- The recommended starting dose for secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis is 30 mg once daily 2.
- The recommended starting dose for parathyroid carcinoma and primary hyperparathyroidism is 30 mg twice daily 2. Key considerations:
- Monitor serum calcium and phosphorus levels within 1 week and intact parathyroid hormone (iPTH) levels 1 to 4 weeks after initiation or dose adjustment of cinacalcet tablets.
- Titrate the dose no more frequently than every 2 to 4 weeks to target iPTH levels of 150 to 300 pg/mL.
- Monitor for signs of hypocalcemia and adjust the dose or provide supplemental calcium as needed.
From the Research
Initial Treatment for Elevated PTH and Hypercalcemia
The initial treatment for elevated parathyroid hormone (PTH) and hypercalcemia depends on the severity of the condition and the underlying cause.
- For mild hypercalcemia, treatment may not be necessary, and the condition can be managed with observation and monitoring 3.
- For symptomatic or severe hypercalcemia, initial therapy consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 3, 4.
- In patients with primary hyperparathyroidism (PHPT), parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement 3.
- Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas) 3.
Treatment Options
- Hydration: Normal saline hydration can help decrease calcium levels in patients with severe hypercalcemia secondary to PHPT 5.
- Bisphosphonates: Zoledronic acid has been shown to be effective in reducing serum calcium levels in patients with severe hypercalcemia secondary to PHPT 5, 6.
- Furosemide: However, furosemide may not have a significant additional effect on calcium levels in patients with severe hypercalcemia secondary to PHPT when compared to saline hydration alone 5.
- Denosumab: May be used in patients with kidney failure or in refractory cases 4.