Parathyroid Gland

• Pre-pro-PTH is 115 amino acids long and consists of a biologically active sequence, a C terminal fragment sequence, a pro sequence and a signal sequence.
• Stages of PTH synthesis:

  1. Pre-pro-PTH is synthesized in the RER
  2. Signal sequence is cleaved within the lumen of the endoplasmic reticulum, leaving pro-PTH.
  3. After transfer to the Golgi apparatus the pro sequence is also cleaved, resulting in the production of mature PTH, which can then be stored in secretory granules for release.
• How does PTH act to increase calcium in the body?

  • Increases bone resorption
  • Increases reabsorption in the kidney
  • Stimulates Vitamin D synthesis
• PTH regulation:

  1. Chief cells have a unique G-protein calcium receptor (CaR) on their surface.
  2. Calcium in the blood binds to CaR leading to production of phosphoinositide
  3. Phosphoinositide inhibits PTH secretion
• Hyperparathyroidism can be classified as either primary, secondary or tertiary
• Primary hyperparathyroidism is a pathological increase in PTH as a result of direct alterations to the parathyroid gland such as a benign tumor or hyperplasia. The negative feedback system is ineffective as the growth does not respond to elevated calcium levels.
• Clinical features of primary hyperparathyroidism:

  • Hypercalcemia
  • Hypophosphatemia
  • Osteoporosis
  • Kidney stones
• Secondary hyperparathyroidism is a physiologically elevated PTH due to reduced calcium levels. It occurs most commonly in advanced chronic kidney disease when decreased formation of active vitamin D in the kidneys and other factors lead to hypocalcemia and chronic stimulation of PTH secretion. It can also occur due to prolonged vitamin D deficiency
• Diagnosis of hyperparathyroidism is made by measuring serum calcium, phosphate and PTH;

  • In primary and tertiary hyperparathyroidism, calcium levels will be high
  • In secondary hyperparathyroidism, calcium may be low or normal.
• Primary and tertiary hyperparathyroidism has to be treated with surgery. Secondary hyperparathyroidism may have to be treated with vitamin D supplementation or a kidney transplant, depending on the cause.
• The synthesis of calcitriol is completed in the kidneys, parathyroid hormone(PTH) is secreted by the parathyroid glands, and calcitonin is secreted by the thyroid glands.
• PTH mechanism of action in the bone:

  • PTH binds to osteoblasts and upregulates the expression of a protein called RANKL.
  • RANKL stimulates pre-osteoclasts to differentiate into osteoclasts.
  •  Osteoclasts resorb bone and release calcium into the bloodstream
• PTH mechanism of action in the kidney:

  • PTH upregulates the expression of specific channels in the distal convoluted tubule
  • This leads to increased reabsorption of calcium into the blood, and also increases excretion of phosphate.
• The role of the chief cell in the parathyroid gland is to secrete parathyroid hormone (PTH). They contain prominent Golgi apparatus and endoplasmic reticulum to allow for the synthesis and secretion of PTH. The chief cells are the smaller of the two cell types, however, they are more abundant.
• PTH increases calcium in the body
• • Tertiary hyperparathyroidism results when PTH secretion becomes autonomous of serum calcium concentration.
  • Tertiary hyperparathyroidism generally occurs in patients with long-standing secondary hyperparathyroidism, as in patients with end-stage renal disease of several years’ duration.
• Parathyroid gland histology

  A) Oxyphil Cells

  B) Blood Vessel

  C) Chief cell