Does Amlodipine Raise PTH?
Yes, amlodipine and other dihydropyridine calcium channel blockers are independently associated with higher PTH levels.
Evidence for PTH Elevation
The most robust evidence comes from a large community-based study demonstrating that dihydropyridine calcium channel blockers (which includes amlodipine) are independently associated with elevated PTH levels 1. Specifically:
- Dihydropyridine CCB users had significantly higher PTH levels compared to non-users (49.5 vs 44.4 pg/mL, p < 0.0001) in adjusted analyses 1
- The association remained significant after controlling for confounders, with dihydropyridine use independently associated with a +5.0 pg/mL increase in PTH (p < 0.0001) 1
- Non-dihydropyridine calcium channel blockers showed no significant PTH elevation (β = +0.58 pg/mL, p = 0.68), indicating this effect is specific to the dihydropyridine class 1
Proposed Mechanism
The mechanism likely involves dihydropyridine-sensitive calcium channels on parathyroid cells 1:
- Dihydropyridine CCBs may interfere with calcium sensing by parathyroid cells, leading to inappropriate PTH secretion despite normal calcium levels 1
- This represents a pharmacologic disruption of normal calcium-PTH homeostasis, rather than a compensatory response to hypocalcemia 1
Contradictory Animal Data
One animal study in hypertensive rats showed amlodipine actually reduced PTH levels 2. However:
- This animal model (stroke-prone spontaneously hypertensive rats) may not reflect human physiology 2
- The human observational data from a large, well-controlled cohort is more clinically relevant than animal studies for predicting effects in patients 1
- The human study specifically controlled for kidney function, hypertension severity, and other confounders that could not be adequately controlled in the animal model 1
Clinical Significance
The PTH elevation associated with amlodipine is modest but statistically significant 1:
- The magnitude of PTH increase (+5.0 pg/mL) is smaller than that seen with loop diuretics (+12.0 pg/mL) but larger than measurement variability 1
- This may contribute to long-term skeletal effects, as PTH influences bone turnover and mineral metabolism 1
- The clinical relevance for fracture risk or bone density requires further study, though the association provides a potential mechanistic link 1
Important Caveats
- This effect appears specific to dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) and does not occur with non-dihydropyridines (diltiazem, verapamil) 1
- The PTH elevation occurs in patients with normal kidney function, so this is not simply a consequence of renal impairment 1
- Patients taking amlodipine who have elevated PTH should still be evaluated for other causes of secondary hyperparathyroidism, including vitamin D deficiency, chronic kidney disease, and inadequate calcium intake 3, 4