Parathyroid Hormone (PTH)

Introduction

• Calcium homeostasis controlled by a combination of  vitamin D and PTH 

PTH Pathway

• Synthesis 
  • secreted by the chief cells of parathyroid
  • responds to ionized calcium levels (physiologically-active), not total calcium levels (which includes physiologically-inactive calcium bound to protein)
    • in low pH settings, an excess of hydrogen ions bind to protein, displacing calcium ions leading to an increase in ionized calcium and vice versa in high pH settings 
• Function 
  • ↑ serum free Ca²⁺ and ↓ serum phosphate in response to hypocalcemia/hypomagnesemia via
    • ↑ bone resorption of calcium and phosphate (bone is destroyed)
      • PTH receptor is on the osteoblasts secretes IL-1 to activate osteoclasts via production of M-CSF and RANK-L
      • PTH decreases osteoprotegrin (OPG), decoy receptor for RANKL, thereby resulting in an increased interaction between RANKL and osteoclasts
    • ↑ kidney resorption of calcium in distal convoluted tubule
    • ↓ kidney resorption of phosphate (increasing urine phosphate)
• ↑ 1,25-(OH)₂ vitamin D production (via 1 alpha-hydroxylase)

Clinical Conditions

• Hypoparathyroidism 
• Hyperparathyroidism 
• Familial hypocalciuric hypercalcemia
  • defective calcium receptor that can not detect elevated calcium level
    • loss of negative feedback causes hypercalcemia (via increased PTH, 1-alpha OH)