Parathyroid Hormone Physiology and Function

Parathyroid hormone is a polypeptide hormone which plays a vital role in calcium metabolism along with vitamin D and calcitonin.

Secretion of Parathyroid and Anatomy of Parathyroid Gland

Parathyroid hormone contains 84 amino acids secreted by the parathyroid glands. It is formed by cleavage of proparathyroid hormone which is formed from cleavage of preproparathyroid hormone (115 amino acids)

Its target organs are kidneys, skeletal system, and intestine.

The parathyroid glands are approximately four very small brownish red structures, about 5 mm x 3 mm x 1 mm that are flattened and ovoid and lie in the posterior aspect of the thyroid gland. Occasionally, the inferior pair may be situated in the mediastinum. As many as 12 glands may be present.

PTH half-life is approximately 4 minutes. It has a molecular mass of approximately 9500 Daltons.

Functions of Parathyroid Hormone

Main function of parathyroid hormone is to increase calcium levels in the blood. It causes the following effects

• It maintains the serum calcium level by decreasing secretion of calcium, increasing resorption of calcium from bone and increasing absorption of dietary calcium from intestine
• Inhibits the calcifying effect of vitamin D.
• Increases the solubility of calcium and phosphorus, maintaining these substances in an ionic form beyond their expected solubility.

It achieves these functions by affecting kidneys, bones, and intestines.

Kidneys

Parathyroid causes

• Increase in renal calcium reabsorption by promoting calcium reabsorption in the ascending loop of Henle, distal tubule, and collecting tubule
• Increases renal phosphate excretion by blocking reabsorption of phosphate in the proximal tubule.
• Conversion of 25-hydroxyvitamin D to, 1,25-dihydroxyvitamin D-3 [most active form of vit D3]. This is carried by activation of the enzyme 1-hydroxylase in the proximal tubules of the kidney.
• Parathyroid reduces the reabsorption of phosphate from the proximal tubule of the kidney leading to greater phosphate excretion. [In contrast, parathyroid enhances the uptake of phosphate from the intestine and bones into the blood]

Bone

It facilitates the absorption of calcium from the bone to increase calcium levels in the blood. This happens in two ways

Rapid phase

This leads to rise in serum calcium within minutes and appears to occur at the level of the osteoblasts and osteocytes

When the parathyroid hormone binds to receptors on these cells, the osteocytic membrane pumps calcium ions from the bone fluid into the extracellular fluid.

Slow Phase

This phase of bone resorption occurs over several days. It has two components

• Activation of osteoclasts to digest bone
• Increase in number of osteoclasts

[Mature osteoclasts lack parathyroid hormone membrane receptors. Therefore activation and proliferation of osteoclasts appear to be stimulated by cytokine release by activated osteoblasts and osteocytes or by differentiation of immature osteoclast precursors that possess parathyroid hormone and vitamin D receptors.]

Intestine

Parathyroid hormone stimulates calcium and phosphorous absorption from intestine via active vitamin D. It does not directly affect intestine. Calcium binding proteins in the intestine are also enhanced.

Control of Parathyroid Hormone Secretion

Parathyroid hormone is released in response to low extracellular concentrations of free calcium. Phosphate per se is not a significant regulator of this hormone.

So when calcium falls below normal range, there is an increase in secretion of parathyroid hormone. When calcium levels become high, the level of secretion falls.

Extracellular calcium concentration is sensed by calcium-sensing receptor which is a membrane protein.

There is a probable role of vitamin D3 causing an inhibitory effect on parathyroid gland as well.

Magnesium plays a role in stimulus-secretion coupling. A mild decrease in magnesium causes stimulatory effect whereas severe hypomagnesemia inhibits parathyroid hormone secretion.

Clinical significance and Disease States

Normal parathyroid levels are necessary for optimal calcium homeostasis. A state of lower than normal parathyroid is called hypoparathyroidism whereas the high parathyroid state is called hyperparathyroidism.

The average hormone level is 8–51 pg/mL. Normal total plasma calcium level ranges from 8.5 to 10.2 mg/ dL.

Hyperparathyroidism

There are two kinds of hyperparathyroid states – primary and secondary.

Primary hyperparathyroidism is due to abnormal unregulated hypersecretion of parathyroid mostly due to an adenoma of the gland.

Secondary hyperparathyroidism refers to inappropriately high levels of parathyroid levels due to low calcium states as in renal failure.

Hypoparathyroidism

Hypoparathyroidism is state of insufficient hormone levels and most commonly due to damage to or removal of parathyroid glands during thyroid surgery.

Others

Pseudohypoparathyroidism, familial hypocalciuric hypercalcemia, and autosomal dominant hypercalciuric hypocalcemia are some genetic disorders affecting parathyroid metabolism.