Superior Parathyroid Glands – Anatomy, Structure, Functions

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Superior Parathyroid Glands/Parathyroid glands are four small glands of the endocrine system which regulate the calcium in our bodies. Parathyroid glands are located in the neck behind the thyroid where they continuously monitor and regulate blood calcium levels.

Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.

Types

Superior parathyroid glands – These glands derive from the fourth pharyngeal pouch.  They are classically located near the posterolateral aspect of the superior pole of the thyroid, 1cm superior to the junction of the recurrent laryngeal nerve (RLN), and the inferior thyroid artery. They classically lie deep to the plane of the recurrent laryngeal nerve.

Inferior parathyroid glands – These glands derive from the third pharyngeal pouch. These glands are classically located near the inferior poles of the thyroid glands, within 1-2 cm of the insertion of the inferior thyroid artery into the inferior pole of the thyroid. They classically lie superficial to the plane of the RLN. Their location is much more variable than the superior parathyroids, and can be intra-thyroidal or within the thymus or other mediastinal structures, and can even be found along the aortic arch.

Overview of the Parathyroid Glands

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone.

Key Points

The parathyroid glands are four or more small glands, about the size of a grain of rice, located on the posterior surface of the thyroid gland.

The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so the nervous and muscular systems can function properly.

Key Terms

calcitonin: A hormone that is produced primarily by the parafollicular cells of the thyroid. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone.

parathyroid gland: One of four endocrine glands situated in the neck, usually on the posterior surface of the thyroid gland, that produce parathyroid hormone.

parathyroid hormone: A hormone produced by the parathyroid gland that acts to increase blood calcium levels by stimulating osteoclasts to release calcium from the bone.

The parathyroid glands are small endocrine glands —approximately the size of a grain of rice—in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the posterior surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest.

This is an illustration of the parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes. The two parathyroid glands on each side of the thryoid gland that are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands.

Parathyroid gland: The parathyroid gland in relation to the thyroid gland. They are located on the posterior surface of the lobes.

The two parathyroid glands on each side that are positioned higher are called the superior parathyroid glands, while the lower two are called the inferior parathyroid glands. Occasionally, some individuals may have six, eight, or even more parathyroid glands.

Parathyroid glands control the amount of calcium in the blood and within the bones. The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so that the nervous and muscular systems can function properly. When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated to release
parathyroid hormone (PTH) into the blood.

PTH modulates calcium and phosphate homeostasis, as well as bone physiology. PTH has effects antagonistic to those of calcitonin by increasing blood calcium levels by stimulating osteoclasts to break down bone and release calcium. PTH also increases gastrointestinal calcium absorption by activating vitamin D, and promotes calcium conservation by re-absorption in the kidneys.

Parathyroid Hormone

Parathyroid hormone maintains the body’s calcium levels by increasing the absorption of calcium from the bones, kidneys, and GI tract.

Key Points

The parathyroid hormone works in concert with another hormone, calcitonin, that is produced by the thyroid to maintain blood calcium levels.

Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

When blood calcium levels drop below a certain point, calcium-sensing receptors in the parathyroid gland are activated, and the parathyroid glands release a parathyroid hormone into the blood.

PTH acts on the bone to increase blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream; on the GI tract to increase the activity of the enzyme in the intestines that activates vitamin D; and on the kidneys to promote calcium reabsorption.

Key Terms

vitamin D: A fat-soluble vitamin required for normal bone development and that prevents rickets; it can be manufactured in the skin on exposure to sunlight.

osteoclast: A large multinuclear cell associated with the breakdown and resorption of bone.

bone remodeling: The resorption by osteoclasts and replacement by osteoblasts in bones.

Parathyroid Glands

The parathyroid glands are small, pea-sized endocrine glands located on the rear side of the thyroid gland. The major function of the parathyroid glands is to maintain the body’s calcium level within a very narrow range, so that the nervous and muscular systems, which depend on calcium to transmit action potentials, can function properly.

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When blood calcium levels drop below a certain point, the calcium-sensing receptors in the parathyroid gland are activated, and the parathyroid glands release parathyroid hormone (PTH) into the blood. PTH is a small protein hormone that is integral to the regulation of the level of calcium in the blood via the bone, kidneys, and intestines.

PTH works in concert with another hormone, calcitonin, that is produced by the thyroid to maintain calcium homoeostasis. Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

This interaction between parathyroid hormone and calcitonin is also an important part of bone remodeling. This is a lifelong process where mature bone tissue is removed from the skeleton and new bone tissue is formed.

This diagram shows the parathyroid glands in the neck sending parathyroid hormone into the bloodstream. This activates calcium reabsorption and vitamin D hydroxylation in the kidneys, calcium absorption from the intestines, and calcium reabsorption from bones. This increases calcium levels in the blood, which provides feedback to the parathyroid glands.

Calcium regulation: Parathyroid hormone regulates the levels of calcium in the blood. to the parathyroid glands.

Parathyroid Hormone Action

  • Parathyroid hormone acts on a bone to increase its blood calcium levels by stimulating osteoclasts to break down bone and release calcium into the bloodstream.
  • Parathyroid hormone acts on the gastrointestinal tract to increase blood calcium by increasing the activity of the enzyme in the intestines that activates vitamin D.
  • It acts on the kidneys to increase blood calcium levels by promoting calcium reabsorption in the nephrons.

The Role of Calcium in the Human Body… and how the Parathyroid Glands Control All Calcium Levels in our Bodies.

First a word about CALCIUM and what it does in our bodies. We use many elements in our bodies to perform all the different functions of life. Calcium is essential to life, and is used primarily for three things:

  • To provide the electrical energy for our nervous system.  The most important thing that calcium does in the human body provides the means for electrical impulses to travel along nerves. Calcium is what the nervous system of our body uses to conduct electricity. This is why the most common symptoms of parathyroid disease and high calcium levels are related to the nervous system (depression, weakness, tiredness, etc, etc). Much more about symptoms of the parathyroid disease on another page.
  • To provide the electrical energy for our muscular system.  Just like the nerves in our bodies, our muscles use changes in calcium levels inside the cells to provide the energy to contract. When the calcium levels are not correct, people can feel weak and have muscle cramps.
  • To provide strength to our skeletal system.  Everyone knows that calcium is used to make our bones strong, but this is really only half the story. The bones themselves serve as the storage system that we use to make sure we will always have a good supply of calcium. Just like a bank vault where we constantly make deposits and withdrawals, we are constantly putting calcium into our bones, and constantly taking calcium out of our bones… all in small amounts… with the sole purpose of keeping our calcium levels in the blood at the correct level. Remember, the most important role of calcium is to provide for the proper functioning of our nervous system–not to provide strength to our bones–that is secondary.
  • Thus, calcium is the most closely regulated element in our bodies.  In fact, calcium is the ONLY element/mineral that has its own regulatory system (the parathyroid glands).  There are no other glands in our bodies that regulate any other element. Why?  Because its the nervous system that separates us from all other plant and animal life–and calcium provides the electrical system for our nervous system. When our calcium levels get elevated (almost always due to a bad parathyroid gland), then we can have changes in our personality (typically noticed by our loved ones) and many other nervous-system symptoms (depression, etc). So, the parathyroid disease is not just about osteoporosis and kidney stones, it is primarily about us feeling “normal” and enjoying life.
  • The ONLY purpose of the parathyroid glands is to regulate the calcium level in our bodies within a very narrow range –  so that the nervous and muscular systems can function properly. They measure the amount of calcium in the blood every minute of every day… and if the calcium levels go down a little bit, the parathyroid glands recognize it and make parathyroid hormone (PTH) which goes to the bones and takes some calcium out (makes a withdrawal from the calcium vault) and puts it into the blood. When the calcium in the blood is high enough, then the parathyroids shut down and stop making PTH.
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The single major disease of parathyroid glands is over-activity of one or more of the parathyroids which make too much parathyroid hormone causing a potentially serious calcium imbalance (too high calcium in the blood). This is called hyperparathyroidism and this is the disease that this entire website is about.

Organ Systems Involved

Parathyroid hormone is directly involved in the bones, kidneys, and small intestine.

  • Effects of PTH on the Bones – In the bones, PTH stimulates the release of calcium in an indirect process through osteoclasts which ultimately leads to resorption of the bones. However, before osteoclast activity, PTH directly stimulates osteoblasts which increases their expression of RANKL, a receptor activator for nuclear factor kappa-B ligand, allowing for the differentiation of osteoblasts into osteoclasts. PTH also inhibits the secretion of osteoprotegerin, allowing for preferential differentiation into osteoclasts. Osteoprotegerin normally competitively binds with RANKL diminishing the ability to form osteoclasts. Osteoclasts possess the ability to remodel the bones (resorption) by dissolution and degradation of hydroxyapatite and other organic material, releasing calcium into the blood.
  • Effects of PTH on the Kidneys – At the kidneys, the parathyroid hormone has 3 functions in increasing serum calcium levels. Most of the physiologic calcium reabsorption in the nephron takes place in the proximal convoluted tubule and additionally at the ascending loop of Henle. Circulating parathyroid hormone targets the distal convoluted tubule and collecting duct, directly increasing calcium reabsorption. The parathyroid hormone decreases phosphate reabsorption at the proximal convoluted tubule. Phosphate ions in the serum form salts with calcium that are insoluble, resulting in a decreased plasma calcium. The reduction of phosphate ions, therefore, results in more ionized calcium in the blood.
  • PTH Indirect Effects on the Small Intestines and Reabsorption of Calcium – Starting at the kidneys, PTH stimulates the production of 1alpha-hydroxylase in the proximal convoluted tubule. This enzyme, 1alpha-hydroxylase, is required to catalyze the synthesis of active vitamin D – 1,25-dihydroxycholecalciferol from the inactive form 25-hydroxycholecalciferol. Active vitamin D plays a role in calcium reabsorption in the distal convoluted tubule via calbindin-D, a cytosolic vitamin D-dependent calcium-binding protein. In the small intestine, vitamin D allows the absorption of calcium through an active transcellular pathway and a passive paracellular pathway. The transcellular pathway requires energy, while the paracellular pathway allows for the passage of calcium through tight junctions.

Related Testing

Parathyroid gland dysfunctions will be characterized as under-activity or overactivity of the gland and will be evaluated in the context of serum calcium. Whenever there is a calcium imbalance suspected or found, the following pertinent labs are initially obtained: PTH, calcium, phosphate, albumin, vitamin D, and magnesium.

  • PTH in the Context of Hypercalcemia – If your blood is found to have high levels of calcium, you would expect to find suppressed levels of PTH in circulation, lower than the normal range of 10 to 65 ng/L. If serum PTH is found to be elevated in the context of hypercalcemia, further investigation of the parathyroid gland is warranted and will be initiated with imaging.
  • Parathyroid Pathology and Ultrasound  – For suspected parathyroid gland pathology, ultrasound is the first imaging modality utilized due to its efficiency and cost-effectiveness. Ultrasound will usually be able to identify the presence of an adenoma as a hypoechoic mass-a a darker area representing a structure that isn’t bouncing back sound waves very well. The ultrasound can also be useful for anatomy orientation in a preoperative setting once surgery has been determined.
  • Parathyroid Pathology and Scintigraphy – Scintigraphy is another effective imaging modality that is gaining more favor in identifying parathyroid abnormalities. Scintigraphy utilizes a radioisotope tracer that gets taken up by local structures and allows for visualization of specific anatomy. The specific tracer utilized in this setting is sestamibi combined with 99mTC. In practice, it is found that adenomatous and hyperplastic parathyroid glands will take up a greater amount of tracer and will retain it longer than other adjacent benign structures.
  • Other Imaging Modalities – Other imaging such as enhanced contrast CT and MRI have their place in the clinical investigation of hyperparathyroidism.
  • PTH in the Context of Hypocalcemia – If hypocalcemia and low levels of PTH characterize the clinical scenario, then the concern is that the parathyroid glands are not producing enough PTH. Hypoparathyroidism can be caused by a variety of different conditions and can manifest in various ways. The underproduction of PTH can be chronic or transient, depending on the etiology. More common causes of hypoparathyroidism are the autoimmune destruction of the gland, damage during thyroid resections, or severe illnesses. Each of those conditions would need to be investigated further.
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Parathyroid Quick Facts

  • There are 4 parathyroids glands. We all have 4 parathyroids glands.
  • Except in rare cases, parathyroid glands are in the neck behind the thyroid.
  • Parathyroids are NOT related to the thyroid (except they are neighbors in the neck).
  • The thyroid gland controls much of your body’s metabolism, but the parathyroid glands control body calcium. They have no relationship except they are neighbors.
  • Parathyroid glands make a hormone, called “Parathyroid Hormone”.
  • Doctors and labs abbreviate Parathyroid Hormone as “PTH”.
  • Just like calcium, PTH has a normal range in our blood…we can measure it to see how good or bad a job the parathyroid glands are doing.
  • All four parathyroid glands do the exact same thing.
  • Parathyroid glands control the amount of calcium in your blood.
  • Parathyroid glands control the amount of calcium in your bones.
  • You can easily live with one (or even 1/2) parathyroid gland.
  • Removing all 4 parathyroid glands will cause very bad symptoms of too little calcium (hypoparathyroidism). HypOparathyroidism is the opposite of hypERparathyroidism and it is very rare… only one page of this entire site is about hypoparathyroidism disease.
  • When parathyroid glands go bad, it is just one gland that goes bad about 91% of the time–it just grows big (develops a benign tumor) and makes too much hormone. About 8% of the time people with hyperparathyroidism will have two bad glands. It is quite uncommon for 3 or 4 glands to go bad.
  • When one of your parathyroid glands goes bad and makes too much hormone, the excess hormone goes to the bones and takes calcium out of the bones, and puts it in your blood. It’s the high calcium in the blood that makes you feel bad.
  • Everybody with a bad parathyroid gland will eventually develop bad osteoporosis–unless the bad gland is removed.
  • Parathyroids almost never develop cancer–so stop worrying about that!
  • However, not removing the parathyroid tumor and leaving the calcium high for a number of years will increase the chance of developing other cancers in your body (breast, colon, kidney, and prostate).
  • There is only ONE way to treat parathyroid problems–Surgery.
  • Mini-Surgery is now available that almost everyone can/should have. You should educate yourself about the new surgical treatments available. Do not have an “exploratory” operation to find the bad parathyroid tumor–this old-fashioned operation is too big and dangerous.

References

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