PTH lec

• Parathyroid Gland


  Regulation and Distribution of Calcium
• Calcium


  • For muscle contraction and blood coagulation
  • 99% in bone & teeth and 1% in blood & ECF
• Parathyroid glands


  • 2, 4 or 8 found near the posterior aspect or within the thyroid gland
  • Smallest (20-40 mg) endocrine gland with a beanlike shape
• Parathyroid gland function


  Maintain the body's calcium level
• Calcium in the blood

  • Ionized Ca²+
  • Protein bound Ca²+
  • Complex Ca²+
• Ionized Ca²+


  • Unbound or free, 45% (around 50%)
  • Physiologically active
• Protein bound Ca²+


  • Bound to protein (albumin), 40%
  • More Ca2+ binds at alkaline pH (arterial)
  • Less Ca²+ binds at acidic pH (venous)
• Complex Ca²+


  Bound to anions, 15% (E.g. HCO3 & PO4)
• Hormonal Control of Calcium Metabolism

  1. 7-dehydrocholesterol in skin

  2. Dietary vitamin D, or D, 290 to 315 nm of ultraviolet B radiation

  3. Pre-vitamin D

  4. Liver adds OH to 25-hydroxyvitamin D

  5. Kidneys adds OH to 25-hydroxyvitamin D to form 1,25 dihydroxyvitamin D (activated)

  6. Promotes calcium absorption via intestines & kidneys
• Low serum calcium


  Activates parathyroid hormone
• Parathyroid hormone


  • Stimulates osteoclastic activity, which releases Ca2+ and HPO4
  • Promotes reabsorption of Ca+2, excretion of HPO4, and activation of renal 1-a-hydroxylase
• High serum calcium


  Activates secretion of calcitonin
• Calcitonin


  Inhibits PTH and Vitamin D, causing Ca+2 in blood
• Vitamin D


  Promotes calcium (re)absorption
• Hypercalcemia


  Caused by bone resorption, increased intestinal and renal absorption of calcium
• Hypocalcemia


  Caused by bone deposition, decreased intestinal and renal absorption of calcium
• Endocrine causes of Hypercalcemia


  • Primary Hyperparathyroidism
  • Genetic Syndromes
• Primary Hyperparathyroidism


  Adenoma or hyperplasia of parathyroid gland, leading to ↑ PTH, ↑ Ca+, Hypercalciuria
• Multiple Endocrine Neoplasia Type 1 (MEN-1)


  Loss in tumor suppressor gene in C11, leading to tumors of parathyroids, pituitary & pancreas
• Multiple Endocrine Neoplasia Type 2A (MEN-2A)


  Activating mutation in ret proto oncogene in C10, leading to tumors of parathyroids, medullary thyroid, and pheochromocytoma
• Primary Hyperparathyroidism


  • Adenoma of Parathyroid gland
  • Hyperplasia of Parathyroid gland
• Primary Hyperparathyroidism


  • ↑ PTH, ↑ Ca+, Hypercalciuria
• Parathyroid Gland


  Endocrine Cause of Hypercalcemia
• Endocrine Causes of Hypercalcemia


  • Primary Hyperparathyroidism
  • Genetic Syndromes
• Multiple endocrine neoplasia, type 1 (MEN-1)


  • Loss in tumor suppressor gene in C11
  • Tumor of parathyroids, pituitary & pancreas
• Multiple endocrine neoplasia, type 2a (MEN-2A)


  • Activating mutation in ret proto oncogene in C10
  • Tumor of parathyroids, medullary thyroid; pheochromocytoma
• Genetic Syndromes


  • Multiple endocrine neoplasia, type 1 (MEN-1)
  • Multiple endocrine neoplasia, type 2a (MEN-2A)
  • Familial hyperparathyroidism
  • Familial hypocalciuric hypercalcemia (FHH)
• Familial hypocalciuric hypercalcemia (FHH)


  • Mutation in the calcium sensing receptor of Parathyroids
  • ↑ PTH, ↑ Ca in blood but ↓ urinary Ca excretion
• Endocrine Causes of Hypercalcemia


  • Primary Hyperparathyroidism
  • Genetic Syndromes
  • Hypervitaminosis D
  • Multiple myeloma
  • Parathyroid hormone-related protein (PTHrP)
• Hypervitaminosis D


  • ↑ Vitamin D intake
  • Extrarenal 1a - hydroxylation
  • E.g. Granulomatous disease (sarcoidosis, tuberculosis)
  • ↑ 1,25 (OH)₂D, ↑ Ca*, ↓ PTH
• Multiple myeloma


  Secretion of cytokines that activate osteoclasts
• Parathyroid hormone-related protein (PTHrP)


  • Humoral hypercalcemia of malignancy
  • Produced by benign and malignant tumors
• Organ System Causes of Hypercalcemia

  • Milk-alkali syndrome (Burnett's syndrome)
  • Renal failure
• Milk-alkali syndrome (Burnett's syndrome)


  • Ingestion of calcium with alkali (carbonate or barcarbonate)
  • Treatment of peptic ulcer (1920's)
• Renal failure


  • Renal excretion of Cat and HPO
  • Hydroxylation of 25-hydroxy Vitamin D, stimulating PTH secretion
• Signs and Symptoms of Hypercalcemia

  • Neuromascular (Tetany, Chvosteck's sign, Trousseau's sign)
  • CNS (e.g. Seizures, personality changes, etc.)
  • Cardiovascular (e.g. Congestive heart failure, etc.)
• Endocrine Causes of Hypocalcemia


  • Neck surgery (thyroidectomy, lymph node dissection. Etc.)
  • Autoimmune destruction of Parathyroid tissue
  • Mutation of PTH gene
  • Deposition of copper and aluminum in Parathyroid gland
  • Magnesium deficiency
  • Pseudohypoparathyroidism
  • Hypovitaminosis D
• Autoimmune destruction of Parathyroid tissue

  Type 1 diabetes, Hashimoto's thyroiditis & Addison's disease
• Magnesium deficiency


  Inhibits PTH secretion and action on target tissue
• Pseudohypoparathyroidism


  Heritable, lack of responsiveness of target tissue to PTH