Updated: 8/5/2021

Parathyroid Hormone (PTH)

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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)

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