What are the guidelines for managing elevated Parathyroid Hormone (PTH) levels?

From the Guidelines

Elevated Parathyroid Hormone (PTH) levels should be managed with a comprehensive approach targeting the underlying cause, prioritizing surgical removal of the affected parathyroid gland(s) for primary hyperparathyroidism and addressing the underlying cause for secondary hyperparathyroidism, as supported by the most recent study 1.

Managing Elevated PTH Levels

To manage elevated PTH levels, it is essential to first determine if the elevated PTH is primary (due to parathyroid gland issues) or secondary (due to low calcium or vitamin D).

• For primary hyperparathyroidism, surgical removal of the affected parathyroid gland(s) is typically recommended when patients are symptomatic or meet specific criteria.
• For secondary hyperparathyroidism, address the underlying cause by:
  • Correcting vitamin D deficiency with supplements (typically 1,000-2,000 IU daily of vitamin D3) 1
  • Increasing dietary calcium (1,000-1,200 mg daily)
  • Treating kidney dysfunction if present

Medications and Lifestyle Modifications

Medications like cinacalcet (starting at 30 mg daily) may be used for patients who cannot undergo surgery or have renal causes 1. Regular monitoring of calcium, phosphorus, and PTH levels is essential, with frequency depending on severity. Lifestyle modifications include:

• Adequate hydration
• Weight-bearing exercise
• Limiting phosphate-rich processed foods This approach works because it either removes the source of excess PTH production or corrects the metabolic imbalances triggering the elevated PTH, restoring normal calcium homeostasis.

Surgical Intervention

For patients with refractory or progressive secondary hyperparathyroidism, surgical parathyroidectomy, specifically total parathyroidectomy (TPTX), is recommended as it has been shown to reduce the incidence of various complications of CKD, such as stroke and cardiovascular and all-cause mortality 1. TPTX has great advantages over subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX + AT) in reducing the relapse of secondary hyperparathyroidism. The choice of surgical approach should be based on the individual patient's needs and the surgeon's expertise.

From the FDA Drug Label

The recommended starting oral dose of cinacalcet tablets is 30 mg once daily. Serum calcium and serum phosphorus should be measured within 1 week and intact parathyroid hormone (iPTH) should be measured 1 to 4 weeks after initiation or dose adjustment of cinacalcet tablets. Cinacalcet tablets should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH levels of 150 to 300 pg/mL.

For secondary hyperparathyroidism patients with CKD on dialysis, if serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, calcium-containing phosphate binders and/or vitamin D sterols can be used to raise serum calcium. If serum calcium falls below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be increased, withhold administration of cinacalcet tablets until serum calcium levels reach 8 mg/dL and/or symptoms of hypocalcemia have resolved.

The guidelines for managing elevated Parathyroid Hormone (PTH) levels are to:

• Start with a dose of 30 mg once daily of cinacalcet tablets
• Titrate the dose every 2 to 4 weeks to target iPTH levels of 150 to 300 pg/mL
• Monitor serum calcium levels frequently and adjust the dose as needed to avoid hypocalcemia
• Use calcium-containing phosphate binders and/or vitamin D sterols to raise serum calcium if it falls below 8.4 mg/dL
• Withhold administration of cinacalcet tablets if serum calcium falls below 7.5 mg/dL or if symptoms of hypocalcemia persist 2.

From the Research

Guidelines for Managing Elevated Parathyroid Hormone (PTH) Levels

• The management of elevated PTH levels involves reducing PTH levels to a range that supports normal bone turnover and minimizes ectopic calcification 3.
• Treatment of secondary hyperparathyroidism (SHPT) with vitamin D analogs, such as paricalcitol and doxercalciferol, can provide a greater safety margin for the treatment of SHPT and enhance the survival of chronic kidney disease (CKD) patients 3.
• High-dose ergocalciferol has been shown to be safe and effective in decreasing PTH levels in patients with stage III-IV CKD 4, 5.
• Vitamin D treatment can also decrease PTH levels in patients with primary hyperparathyroidism (PHPT) 6.
• Paricalcitol has been shown to be more effective than ergocalciferol in decreasing PTH levels in patients with CKD stages 3 or 4 with vitamin D deficiency and SHPT 7.

Treatment Options

• Vitamin D analogs, such as paricalcitol and doxercalciferol, can be used to treat SHPT in CKD patients 3, 7.
• Ergocalciferol can be used to treat vitamin D deficiency and decrease PTH levels in CKD patients 4, 5.
• Cholecalciferol can be used to treat vitamin D deficiency and decrease PTH levels in PHPT patients 6.
• Non-calcium-based phosphate binders, such as sevelamer and lanthanum carbonate, and cinacalcet, an allosteric activator of the calcium receptor, can be used to reduce the risk of hypercalcemia with vitamin D therapy 3.

Monitoring and Adjustment

• Serum PTH, 25-hydroxyvitamin D, calcium, and phosphorus levels should be monitored regularly to adjust treatment doses and minimize the risk of hypercalcemia and hyperphosphatemia 3, 4, 5, 6, 7.
• Treatment doses should be adjusted based on the patient's response to therapy and the presence of any adverse effects 3, 4, 5, 6, 7.