Parathyroid Glands

Original article by Tom Leach | Last updated on 3/1/2016
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Introduction 

The parathyroid glands control the level of calcium and phosphates in the blood.

  • Phosphate levels can vary up to 2-3x the normal level without causing major problems
  • Calcium levels have to be much more tightly controlled
 
There are many other things that are involved and interlinked with this!
Calcium is involved with:
  • Contraction of skeletal, cardiac and smooth muscle
  • Blood clotting
  • Control of nerve impulses
  • Increases in the level of calcium cause depression of the nervous system
  • Decreases in the level of calcium causes excitation of the nervous system
 

Background Info

  • There are 4 parathyroid glands in humans – one behind each of the poles of the two lobes of the thyroid gland.
  • The glands are about 6x3x3mm
  • They have the appearance of dark brown fat. They can often be hard to distinguish from just another lobule of the thyroid gland – and in the past in total thyroidectomies, they were often removed by mistake.
  • You can lose the function of half of the parathyroid glands before there will be any physiological degradation. Even if you lose more than this, the remaining tissue is often able to hypertrophy, so that over time you may regain normal parathyroid function.
 

Anatomy

The parathyroid glands are made up mostly of chief cells and it is these that secrete the parathyroid hormone (PTH).
There are a very small number of oxyphil cells, and it is not certain exactly what these are for. Some believe that they are modified or depleted chief cells that no longer have a secretory function. These cells are absent in children.
 

Physiology

PTH – this is a very large amino acid, that as it travels will gradually lose small fragments of itself. The main molecule is removed very quickly by the kidneys, but the fragments remain in the blood for a long time and continue to exhibit PTH actions.
 
PTH will cause a rise in serum concentrations of calcium and a fall in serum concentrations of phosphate - but the effects on phosphate are complicated.
Note that the level of phosphate falls more quickly than the level of calcium rises.
 
The mechanisms by which calcium ion concentration is altered is:
  1. PTH causes an decreased excretion of calcium by the kidneys. 
  2. PTH causes an increase in the rate of calcium and phosphate absorption from bone. This effect is caused by PTH action on osteocytes. Osteocytes are osteoblasts that have become trapped in the matrix they secrete and are found throughout the bone. Generally osteoblasts are found on the surface and osteoclasts are found in the bone matrix. Osteoclast activity is not altered by PTH

The osteoblasts and osteocytes are all connected to one another by thin filmy extensions. These extensions cover the whole bone, and are known as the osteocytic membrane system. This membrane separates the bone surface from the extracellular fluid. The cells that make up this membrane, pump calcium ions out of the bone side and into the extracellular fluid, meaning that the concentration of calcium ions in the fluid surrounding the bone is only 1/3 of that in the extracellular fluid. So, when stimulated by PTH, these cells increase the rate at which they pump calcium, and thus increase the concentration of calcium in the serum. When the pumps reduce their activity, levels of calcium increase in the bone fluid, and these extra ions are deposited in the bone matrix.

  • If PTH is raised for long enough, then it will also cause proliferation of osteoclasts and greater activation of the osteoclasts already present. This will increase the amount of breakdown of bone, and increase serum concentrations of calcium and phosphates. It is thought that his mechanism is not directly mediated by PTH, but that osteoblasts and osteocytes release a second, unknown messenger that acts on osteoclasts.

Levels of calcium in the blood will begin to rise within minutes of PTH being secreted.

 

Extended activation of the parathyroid glands can thus lead to weakened bones, and this will cause secondary stimulation of osteoblasts. However, this is not great enough to prevent the increased action of osteoclasts, and overall bone degradation will still occur.

 

PTH also has one other effect: increasing calcium and phosphate absorption from the gut.

 
PTH and phosphate
  • Phosphate excretion from the kidney is ↑
  • Phosphate absorption from the gut and from bone is also ↑
  • The net effect is a fall in serum phosphate concentration
 
Mechanism
Phosphate
Excretion by kidneys
Absorption from gut
Absorption from bone
Net Serum concentration
 
The parathyroid glands will become enlarged in pregnancy and lactation due to depletion of calcium by the child and in milk.
Conversely, conditions that increase calcium concentration in the blood will cause atrophy and reduction in size of the glands. These conditions might include excess calcium in the diet, increased vitamin D in the diet, bone absorption due to another reason (e.g. due to inactivity – i.e. not using your bones!)
 

Calcitonin

This is a hormone released by the thyroid gland in response to high levels of calcium in the blood. It basically causes the reverse of the effects caused by PTH – however, it’s effects are much weaker. It is produced and secreted by the parafollicular or C cells of the thyroid gland. These are found between follicles, and make up less than 0.1% of thyroid tissue.
Effects
  • Decreased absorption of bone by osteoclasts
  •  Decreased formation of new osteoclasts – however, a longer-term result of this will be a decrease in the number of osteoblasts and so long-term there will be little effect on calcium concentrations.
When the thyroid is removed, there is not a measurable difference in serum calcium levels, and thus we can deduce that PTH is by far the most important controller of calcium levels in the serum. The effect of calcitonin is greater in children due the amount of bone remodelling that goes on at this stage.
 
 

Conditions involving the parathyroid gland

Hyperparathyroidism

Type
PTH
Causes
Primary
Normal
High
Tumour of the parathyroid gland
Secondary
High
Low
A low level of Ca2+ induces the parathyroid gland to produce large amounts of PTH. Low levels of Ca2+ are commonly due to renal failure. Can also be caused by insufficient vit D, insufficient Ca2+ in the diet, excessive Mg2+ in the diet
Tertiary
High
High
Basically occurs after years of secondary hyperparathyroidism, but then the secondary cause is resolved. The parathyroid gland has been used to procuring such high levels of PTH for so long, it basically just broken, and secretes high levels of PTH even though levels of Ca2+ are now responsive to PTH. There is hyperplasia of the glands, and loss of response to ca2+.
 

Hypoparathyroidism

Less common
 

Medullary thyroid carcinoma

This is associated with parathyroidism (often tertiary) as a result of hyperadrenalism. Together, these are all classed as multiple endocrine neoplasia syndrome (MEN) type I