Primary Actions of Parathyroid Hormone
Parathyroid hormone (PTH) primarily functions to increase serum calcium levels through three coordinated mechanisms: stimulating renal calcium reabsorption while decreasing phosphate reabsorption, activating vitamin D to enhance intestinal calcium absorption, and mobilizing calcium from bone stores. 1
Core Physiological Mechanisms
PTH is released from the parathyroid glands in response to hypocalcemia detected by calcium-sensing receptors, and it acts on three primary target organs to restore calcium homeostasis 1:
Renal Actions
- PTH binds to PTH1R receptors in both the distal and proximal renal tubules, increasing calcium reabsorption while simultaneously decreasing phosphate reabsorption 1, 2
- This phosphaturic effect (increased urinary phosphate excretion) is critical for maintaining normal serum phosphate levels, particularly as kidney function declines 2
- The net result is increased serum calcium without elevating phosphate concentration 1
Vitamin D Activation
- PTH stimulates the enzyme 1-α-hydroxylase (CYP27B1) in the kidney to convert 25-hydroxyvitamin D into the active form 1,25-dihydroxyvitamin D 1
- This active vitamin D then increases intestinal calcium absorption, providing an indirect mechanism for PTH to raise serum calcium 3, 4
Bone Effects
- PTH binding to PTH1R in bone stimulates the release of both calcium and phosphate from bone into the circulation 1
- PTH increases bone turnover, mobilizing calcium primarily but not exclusively from cortical bone 4
- At physiologic levels, PTH can also augment bone formation, particularly in trabecular bone, which has therapeutic implications for osteoporosis treatment 4
Overall Homeostatic Result
The combined actions of PTH result in increased serum calcium concentration without affecting the overall phosphate concentration, as the phosphaturic renal effect counterbalances phosphate release from bone 1
Clinical Context and Measurement Considerations
Assay Complexity
- PTH is synthesized as a 115-amino acid precursor (pre-proPTH) that is cleaved to the biologically active 84-amino acid peptide 1
- The first 34 amino acids contain the biologically active portion of the molecule 1
- Different generation PTH assays measure varying amounts of PTH fragments in addition to full-length PTH, which can significantly impact clinical interpretation 1, 2
Pathophysiological Importance
- In chronic kidney disease, PTH elevation represents a compensatory response to maintain mineral homeostasis when phosphate excretion becomes impaired 2, 5
- When creatinine clearance falls below 20-30 mL/min/1.73 m² (CKD Stage 4), the maximum phosphaturic effect of PTH is reached, and serum phosphorus begins to rise despite elevated PTH 2
- Excessive PTH levels lead to high-turnover bone disease, vascular calcification, and increased cardiovascular mortality 2