Hormones Regulating Plasma Calcium Levels – PTH, Calcitonin, Vitamin D

• Hormones Regulating Plasma Calcium Levels – PTH, Calcitonin, Vitamin D maintain calcium homeostasis.
• Hormones Regulating Plasma Calcium Levels – PTH, Calcitonin, Vitamin DPTH, Calcitonin, and Vitamin D regulate calcium absorption, reabsorption, and bone resorption.
• Calcium homeostasis is maintained by the interplay of PTH, calcitonin, and vitamin D, each of which can be targeted pharmacologically.

Parathyroid Hormone (PTH)/ Parathormone

Physiology:

• Secreted by parathyroid chief cells in response to low calcium.
• Increases serum calcium by:
  • Stimulating osteoclast activity via osteoblast signaling.
  • Increasing renal calcium reabsorption.
  • Activating vitamin D to enhance intestinal calcium absorption.

Pharmacology:

1. PTH Analogues:
   • Teriparatide (PTH 1–34):
     • Uses: Osteoporosis (stimulates bone formation).
     • Adverse Effects: Hypercalcemia, potential osteosarcoma (animal studies).

2. PTH Inhibitors:
   • Calcimimetics (e.g., Cinacalcet):
     • Uses: Secondary hyperparathyroidism in CKD, parathyroid carcinoma.
     • Mechanism: Increases calcium receptor sensitivity, reducing PTH secretion.

Calcitonin

Physiology:

• Secreted by thyroid parafollicular (C) cells in response to high calcium.
• Lowers calcium by inhibiting osteoclast-mediated bone resorption and reducing renal calcium reabsorption.

Pharmacology:

• Salmon Calcitonin:
  • Uses: Hypercalcemia, Paget’s disease, osteoporosis (less common).
  • Adverse Effects: Hypersensitivity, nausea, flushing.

Vitamin D

Physiology:

• Obtained as cholecalciferol (D3) from skin or ergocalciferol (D2) from diet.
• Hydroxylated in liver (25-OH D) and kidney (1,25-(OH)2 D or calcitriol).
• Enhances calcium and phosphate absorption and promotes bone mineralization.

Pharmacology:

1. Vitamin D Analogues:
   • Calcitriol (active form):
     • Uses: Hypocalcemia, osteoporosis, rickets, osteomalacia.
     • Adverse Effects: Hypercalcemia, hypercalciuria.

2. Synthetic Analogues (e.g., Paricalcitol, Alfacalcidol):
   • Uses: Secondary hyperparathyroidism in CKD.
   • Mechanism: Similar to calcitriol, with variations in potency and kinetics.

Clinical Applications

• Osteoporosis: Treated with teriparatide or calcitriol.
• Hypercalcemia: Managed with calcitonin.
• Hypocalcemia/Rickets: Corrected with vitamin D analogues.
• Secondary Hyperparathyroidism: Controlled with calcimimetics or synthetic vitamin D analogues.

Side Effects

• Teriparatide: Hypercalcemia, leg cramps, nausea.
• Salmon Calcitonin: Nausea, flushing, allergic reactions.
• Calcitriol: Hypercalcemia, hypercalciuria, kidney stones.

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