Parathyroid Gland Function & Development

What Are Parathyroid Glands

Unless you have parathyroid disease or know someone who has it, chances are you have never heard of the parathyroid glands. The 4 parathyroid glands are located in the lower neck, behind the thyroid; they are part of the endocrine hormonal system. The thyroid gland and the parathyroid glands are not related in terms of what they do, they are just next to each other. The prefix “para” means next to; since the parathyroid glands were discovered long after the thyroid and their function was not clear at the time, they were simply named parathyroid glands based on their location. They do not have the same function or purpose as the thyroid gland.  

Although they do not have the same function, they do develop in humans at the same time as the thyroid gland and share the same blood vessels.  The major branches of the thyroid arteries and veins go to the the thyroid gland and the very small branches go to the parathyroid glands.

Parathyroid Glands Regulate Calcium

Parathyroid glands are mainly responsible for regulating the calcium levels in the body within a very narrow range so that the body can function properly. Calcium is a vital nutrient that is used by every single cell in the body for normal daily functions; it is responsible for transferring messages inside the cells, building bones, transmitting signals between nerves, flexing muscles and so much more. If calcium levels are not exactly right, a variety of problems can occur, including bone loss, intestinal symptoms, kidney disease, and mental disturbances.

We have 4 parathyroid glands (when 1 would be enough to do the job) because maintaining precise calcium levels is so important to our body’s ability to function properly on a daily basis. To regulate calcium, the parathyroid gland controls the amount of a chemical called Parathyroid Hormone (PTH) it releases into the blood stream. Each individual parathyroid cell has a calcium censor, that acts similar to a thermostat, to detect the level of calcium in the blood. When calcium levels are high, the parathyroid gland “turns off” and the PTH level decreases. Alternatively, when the calcium sensor detects that calcium levels are low, the gland “turns on” and produces PTH, which pours into the blood stream and instructs the body to put more calcium back into the blood.

The parathyroid glands measure the amount of calcium in the blood every minute of every day, and if the calcium levels decrease the glands will recognize it right away and make parathyroid hormone (PTH).  The PTH goes to other parts of the body mainly the bones and kidneys and instructs them to increase the calcium in the blood.  When the calcium level comes up again, the parathyroid gland shuts down and stops making the hormone PTH.  Through this feed back loop the body is able to have precise control over the level of calcium in the blood.

Dr. Strewler published a very interesting article in 2005 that showed the relationship between calcium and PTH.  He clearly showed that there is an inverse relationship between calcium and PTH, with PTH being low when calcium is high, and PTH high when calcium is low.  The first graph below shows his results.  He showed clearly that when the calcium level changes only a minimal amount the parathyroid gland responds immediately to quickly bring the calcium back to the person’s normal (called the Calcium Set Point).  Each individual’s Calcium Set Point is different from others.  Some may be in the lower ranges of the reference values (what laboratories call a normal range), and some in the higher.  As these graphs show clearly, it does not matter what the set point value for each person is, their parathyroid gland is in charge of making sure the calcium level is always either maintained at that level or brought back to that level.

The parathyroid glands are very good at keeping the calcium at the calcium set point or close to it.  If the set point is 9.5 mg/dl as in the graphs above, then the parathyroids will work tirelessly 24 hours a day to keep the calcium close to that, and if there are slight changes the parathyroid glands react immediately to bring the level back to the set point.  The body is able tolerate high or low calciums for short periods of time, but when it occurs for an extended period then all organs begin to become inefficient and malfunction.  So the range of normal that the parathyroid will allow is actually a very a narrow range as seen on Graph 3 above; the set point is 9.5 mg/dl, but the range is the area in the grey box from 9.2-9.8 mg/dl.  Calcium may occasionally go out of that range but as you can see based on the graph the PTH reaction is dramatic to bring the calcium back into range.  The laboratory normal range (also known as the reference range) is shown in the graph as the green shade (8.5-10.2 mg/dl) in between the yellow shaded areas at the two ends of the graph.

The hormone PTH is very interesting in and of itself.  It is a 3 dimensional protein that has parts of it that attach to other proteins called receptors on the surface of other cells in a lock and key fashion.  This is how it gives its instructions to other tissues like bone and kidney.   It is a command, so it has been designed to disintegrate shortly after it has been released in the blood stream.  Half of the PTH proteins disintegrate within 5 minutes of going into the bloodstream.  This is so that if the parathyroids want to give a different command a few minutes later the hormone is not hanging around in the blood to interfere with the new command.   The rapid intra-operative PTH test done during surgery takes advantage of this short lifespan (also called a half-life).

The parathyroid receptor is present on many different areas of the body including kidneys, bone, adrenal glands, cartilage, heart muscle, nerve cells in various parts of the brain.  So when a person has hyperparathyroidism some of the symptoms are due to high calcium in the blood, and others are directly from the PTH.  In fact, some of the symptoms directly correlate with the level PTH in the blood.

Parathyroid Anatomy & Development

The vast majority of people have four parathyroid glands, and they are normally the size of a grain of rice. However, occasionally, they can be as large as a pea and still be normal.  They weigh roughly 50mg and have a yellow tan color. Ther are generally adjacent to the thyroid gland and are flattened against it.  They have the same blood vessels as the thyroid gland not only because they are close to each other but also because they develop at the same stage in the fetus.

During the 6th week of fetal development the parathyroid glands develop as 2 pouches on each side of the throat and then travel down to rest behind the thyroid that is also traveling downwards into the lower neck.  Because of this migration and the fact that all the other organs are also developing at the same time, sometimes the parathyroid glands end up in an unusual area and not behind the thyroid.  They may not travel far and stay up further in the neck or overshoot and travel too far and end up in the chest.

The superior parathyroids have a more consistent location because they have to travel less.  The inferior parathyroids travel a longer distance, so they can end up in an unusual position more often.  The inferior parathyroid glands also develop in the same pouch as the thymus gland which travels along with the parathyroids and ends up finally in the upper middle chest.  So often times when a parathyroid gland cannot be found it maybe inside the thymus.

Adding another twist to the parathyroid travel itinerary is that sometimes the two parathyroid glands traveling on the same side may fuse, and the person may end up having only 3 parathyroid glands.  At other times, as the parathyroid gland travels down, it may leave pieces of itself along the way, so the person may end up have 5 or more parathyroid glands.  Expert parathyroid surgeons keep these possibilities in mind when treating hyperparathyroid patients.  This is also why intra-operative PTH testing is so important, because if your surgeon finds 4 glands and remove one that may seem slightly larger, and doesn’t check the rapid intra-operative PTH then they will not know if a 5th large abnormal gland is there that has not been found yet.

Parathyroid Disease

If there is a disturbance in just a single cell on one of the parathyroid glands and the calcium levels are no longer being monitored properly, you will develop hyperparathyroidism. Watch the video below to learn about hyperparathyroid disease.

Talk To A Parathyroid Disease Expert Today!

If you think you are suffering from parathyroid disease, call the CENTER for Advanced Parathyroid Surgery today! We are here to help you. Dr. Babak Larian is a world-renowned parathyroid surgeon who will give you the customized treatment you deserve so you can get back to living your life!

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