What medications can increase parathyroid hormone (PTH) levels?

Medications That Increase Parathyroid Hormone (PTH) Levels

Several medications can increase parathyroid hormone levels, with oral phosphate supplements being the most significant and commonly used medication that directly elevates PTH. 1

Medications That Directly Increase PTH

• Oral phosphate supplements: High doses of oral phosphate (>80mg/kg daily) can cause secondary hyperparathyroidism by stimulating PTH secretion 1
• Teriparatide (recombinant human PTH 1-34): This medication is a direct parathyroid hormone analog that increases PTH levels and is used for treatment of osteoporosis 2
• TransCon PTH (palopegteriparatide): A long-acting PTH replacement therapy used in hypoparathyroidism 3
• Recombinant human PTH (1-84): Used in hypoparathyroidism treatment to directly increase PTH levels 4

Medications That Indirectly Increase PTH

• Phosphate binders: When used in chronic kidney disease, they can lead to hypocalcemia which stimulates PTH secretion 1
• Calcimimetics (when discontinued): Abrupt discontinuation of cinacalcet can cause rebound increase in PTH levels 1
• Medications causing hypocalcemia:
  • Bisphosphonates (can transiently lower calcium, triggering PTH increase) 5
  • Denosumab (can cause hypocalcemia leading to secondary hyperparathyroidism) 1

Mechanism of PTH Elevation

PTH secretion increases in response to:

• Hypocalcemia: Low serum calcium directly stimulates PTH secretion 1, 6
• Hyperphosphatemia: High serum phosphate levels stimulate PTH production 1
• Vitamin D deficiency: Low vitamin D levels lead to decreased intestinal calcium absorption, causing secondary hyperparathyroidism 1, 6

Clinical Considerations

In Chronic Kidney Disease (CKD)

• Progressive CKD leads to secondary hyperparathyroidism due to phosphate retention, hypocalcemia, and decreased vitamin D activation 1
• In CKD patients, the following can increase PTH:
  • Phosphate-containing medications 1
  • High dietary phosphate intake (even without frank hyperphosphatemia) 1
  • Inadequate vitamin D supplementation 1

In X-Linked Hypophosphatemia (XLH)

• Oral phosphate supplements must be carefully balanced with active vitamin D to prevent secondary hyperparathyroidism 1
• Phosphate doses >80mg/kg daily significantly increase risk of hyperparathyroidism 1

Management Considerations

• When using phosphate supplements, always combine with active vitamin D to prevent secondary hyperparathyroidism 1
• Monitor PTH levels regularly in patients receiving medications that can affect calcium-phosphate metabolism 1
• For patients with elevated PTH due to phosphate supplements:
  • Decrease phosphate dose and/or increase frequency of administration 1
  • Increase active vitamin D dose 1
• In cases of persistent secondary hyperparathyroidism despite above measures, calcimimetics (cinacalcet) may be considered, though with caution due to risk of hypocalcemia 1

Cautions and Monitoring

• Monitor serum calcium, phosphate, and PTH levels regularly in patients taking medications that can affect PTH 1
• For patients on teriparatide, monitor for transient hypercalcemia which typically peaks 4-6 hours after administration 2
• In patients with CKD, avoid routine use of activated vitamin D in early stages (G3a-G5 not on dialysis) as it may worsen hypercalcemia without improving outcomes 1

Remember that medication-induced PTH elevation should be managed based on the underlying cause, with the goal of maintaining normal calcium and phosphate homeostasis to prevent complications related to bone metabolism disorders 1, 6.