There are several pages on Parathyroid.com that describe how parathyroid disease (hyperparathyroidism) occurs. If this is the first parathyroid page you are reading, you should not start here... go back to the Home Page and start from the beginning. This page is an advanced page about the development of parathyroid tumors and will confuse you if you have not read much of the rest of this web site first. You should already know about parathyroid disease and hyperparathyroidism BEFORE you read this page. Make this one of the last pages you read.
We will summarize hyperparathyroidism very briefly in a few bullet points and then spend the rest of our time on this page discussing WHY and HOW the parathyroid gland grew into a tumor in the first place. As a review from other pages on this web site... hyperparathyroidism...
- Occurs when one (occasionally more than one) parathyroid gland grows into a tumor.
- Once the parathyroid gland has become a tumor, it very happily loses control of its hormone regulatory system and starts making parathyroid hormone all the time--way more PTH than your body needs.
- The excess parathyroid hormone circulates in the blood and removes calcium out of the bones and puts the excess calcium into your blood.
- The excess calcium is what makes you sick (causes symptoms). It affects your brain, your nervous system, your bones, your muscles (including your heart), your kidneys, and even your intestinal function.
What Causes the Parathyroid Gland to Develop Into a Tumor?
This is one of the most common questions we get. The answer is usually very simple--in most cases nobody knows. Almost everybody with hyperparathyroidism has the disease because one of their parathyroid glands develops into a tumor...and we don't know what causes tumors! The rest of this page will look at this question more closely. We have divided the page into multiple paragraphs looking at the most common causes of hyperparathyroidism. The most common reason, however, is "we just don't know". Note that the percentages below add up to more than 100% because the causes overlap.
Hyperparathyroidism Cause #1:One of the parathyroid glands grew into a tumor. This is 70% of all parathyroid patients. No Known Cause.
As you already know from our other pages that parathyroid disease is almost always caused by a single bad parathyroid gland. One of the glands develops into a benign tumor called a parathyroid "adenoma". Lets examine this fact closer and examine how this tumor forms (of course we don't know).
We all know that people can get tumors in different parts of their bodies. In fact, we humans develop tumors more often as we get older--its a fact of life that most tumors occur more commonly in our older citizens. Almost every type of tumor that effects us is more common in older patients. Breast tumors and prostate tumors are good examples. Although breast tumors do occur in young females, the vast majority occur in women over the age of 50. It is important to note, however, that parathyroid tumors are essentially never cancerous. We will say that again... parathyroid tumors are nearly always benign. Only about 1 in 2000 are cancerous, so lets not ever talk about parathyroid cancer--you don't have parathyroid cancer. And if you become one of our patients and you bring up the "cancer" word, you will have to do 10 pushups. You do NOT have parathyroid cancer. This is a benign tumor, and a very typical parathyroid tumor (adenoma) is shown here... this is the exact size and this is an average size... some are smaller, and some are bigger. This is a very typical parathyroid adenoma. If we perform your operation, you will be given a picture of your tumor (suitable for framing!) and the amount of hormone it is making will be provided. Your doctors will get a copy of this photo as well.
Parathyroid glands can develop into a tumor just like a breast can develop a tumor; just like you can get a polyp (a form of a tumor) in your colon; just like you can get a tumor in your prostate. (CLICK HERE to look at lots more pictures of parathyroid tumors on a different page). Nobody knows what causes these tumors to form. We don't know why some women get breast tumors while other women do not. Furthermore, we don't know why a woman will get a tumor in one breast and not the other. Similarly, about 90% with parathyroid disease (hyperparathyroidism) will have this disease because ONE of their parathyroid glands developed a tumor while the other 3 parathyroid glands remain perfectly normal. About 8% of people will have two of these parathyroid tumors and two normal glands. We don't know what causes it, but something happens within some of the cells of the parathyroid gland and the cells duplicate themselves over and over again until the gland grows into a tumor. Yep, a "tumor" is simply a mass of cells. A typical parathyroid tumor is about the size of a grape (sometimes as small as an olive, and sometimes as large as a golf ball). Remember, the normal parathyroid gland started out the size of a grain of rice. In summary, we don't know why the normal parathyroid gland grows into this dark red, grape-sized tumor that secretes high amounts of parathyroid hormone (PTH), but we do know that it is not a cancerous tumor and we know that the other glands are normal and if you take out the tumor the patient will be cured. (God gave us 3 spare glands!).
Hyperparathyroidism Cause #2:TWO of the parathyroid glands grew into a tumor. This is 26% of all parathyroid patients. No Known Cause.
This is just like the section above, except that there are two parathyroid tumors and two normal glands. One of the parathyroid tumors (adenomas) will be bigger than the other, and usually the bigger (older) one is the one that shows up on a scan. If your surgeon removes only one of the tumors leaving two normal glands and the other tumor behind you will be a bit better, but not cured. You will need a second operation (see our page on re-operations following failed parathyroid surgery). Now you are seeing that parathyroid surgery can be a bit complicated and why experience is the name of the game. This is why we look at all four parathyroid glands when we perform this operation. If your surgeon only removes the ONE parathyroid tumor that they see on a scan, then you will have a 15-20% chance of needing another operation to remove the second tumor some months or years later. The video of Dr Norman performing a 13 minute min parathyroid operation illustrates this point... the scan showed one parathyroid gland but when all of the others were checked, the patient was found to have a second parathyroid tumor. Watch the video. If your surgeon is not going to examine all four parathyroid glands during your parathyroid operation, then you have a 15% chance of not being cured that day, and a 30% chance of needing another parathyroid operation within the next 15 years. Don't let your surgeon cheat--make sure you ask him/her to look at all four parathyroid glands (watch the movie and you will understand this).
Hyperparathyroidism Cause #3:Radioactive Iodine Therapy in the Past for Thyroid Problems. This is about 1.5% of all parathyroid patients.
As you know by now, the thyroid and the parathyroids are un-related. But, they are next-door neighbors in the neck, and they share the same arteries and veins. Thyroid disease is occasionally treated with radioactive iodine. The thyroid is unique in that it is the ONLY tissue in the body that can absorb iodine. So, doctors can give a poisonous form of radioactive iodine to kill the thyroid. This is used occasionally in patients who's thyroid gland is making too much thyroid hormone (hyperthyroidism) (read more about hyperthyroidism on our sister web site EndocrineWeb.com). This will kill the thyroid cells and thus cure the hyperthyroidism. Radioactive iodine is also given to patients if they have thyroid cancer (read more). Once the thyroid is all removed by a surgeon, an endocrinologist will often give radioactive iodine to kill any more cells that may be left behind. This therapy makes thyroid cancer one of the most curable cancers of all! Please don't get confused with the radioactive iodine that is used for x-ray tests like the thyroid scan. This is a different isotope of radioactive iodine and it does not kill any thyroid cells. We are only concerned about Iodine 131 therapy.
Well, some people who have had radioactive iodine therapy for the treatment of a severe thyroid problem can (rarely) develop parathyroid problems. Just like seen in Lithium therapy, the parathyroid disease that occurs after Iodine 131 therapy occurs 20 or more years later (about 25 years is average but can be seen in as little as 15 years). Unlike the parathyroid disease seen following long-term Lithium therapy, however, the parathyroid disease seen many years after Iodine 131 therapy almost always involves just one parathyroid gland. Yep, one of the parathyroid glands develops an adenoma... just like number one above. It is extremely rare for patients who have been exposed to radiation (as in radioactive iodine, or via radiation treatments discussed below) to involve more than one parathyroid gland. We've seen this only a few times in treating hundreds of these patients. Thus, if you have had radioactive iodine ablation (killing) of your thyroid gland in the past, it is important to tell your parathyroid surgeon (again, hopefully your surgeon will understand the relationship and understand its implications).
We operate on patients who have had radioactive iodine therapy about every other day (we do 12 operations per day). It is an interesting observation that these parathyroid tumors are located right next to where the thyroid used to be located. Of course this is because the parathyroid gland which developed into a tumor had to be right next to the thyroid gland in order to be exposed to the radioactive material within the thyroid. It is this radioactive iodine which caused the damage to the parathyroid's DNA which resulted in the formation of a tumor (just like the Incredible Hulk!). Thus, patients who have parathyroid tumors years after having radioactive iodine treatment (I-131) never have a parathyroid tumor that is located in their chest or any other weird location. It's always in the neck!
Hyperparathyroidism Cause #4:Radiation treatments to the neck and face as a youth or teenager, or as an adult for the treatment of certain cancers. This is 1.5% of all parathyroid patients.
In the 1940's, 1950's and 1960's, doctors believed that radiation treatments were a good way to treat acne in teenagers. They also would use radiation to treat swollen glands in the neck (like an enlarged thymus gland in baby's and tonsils in adolescents). Well, we eventually found out that all this radiation aimed at the neck would affect the thyroid and parathyroid glands. These people are at slightly higher risks for developing thyroid cancer late in life (thyroid, not parathyroid... don't confuse thyroid and parathyroid). These people are also at a much higher risk of developing a parathyroid tumor (always benign, not cancer). So, if you have high calcium and hyperparathyroidism your doctor will ask you if you had radiation to your neck/face as a teenager back in the 50's and 60's. If you did, then this is probably what caused your parathyroid to grow into a tumor 20-30 years later. On a good note, these people typically develop one adenoma (one big, benign gland). They get two parathyroid adenomas about 22% of the time, and thus they do not appear to have an increased incidence of having 2 adenomas. But of course, you want your surgeon to look at all four glands because you never know if you are one of the 22% that has more than one parathyroid tumor. Four-gland hyperplasia is never associated with previous radiation treatments. The parathyroid tumors are not cancerous. Your surgeon should know this information so he can take a good look at your thyroid gland during your parathyroid operation... possibly removing a thyroid nodule for biopsy (if appropriate) during your parathyroid operation.
Another group of patients in this category are those that had radiation for cancer. This includes radiation to the neck or chest for Hodgkins' Disease, Non-Hodgkins' Lymphoma, and even breast cancer. Like the group of young people above getting radiation for benign disease, those getting hyperparathyroidism due to radiation to the neck get the parathyroid tumor about 17 years later on average (range 9 years to 40 years). The incidence of multiple tumors is about 16%, and is usually on the side of the radiation (if the radiation was on one side of the neck).
Hyperparathyroidism Cause #5:Long term use of Lithium. This is about 1.5% of all parathyroid patients.
Lithium is a drug that is occasionally given to patients with certain types of psychiatric problems. It isn't used as often now as it was many years ago. We now have many more sophisticated medications for some of these psychiatric problems. Many patients (as many as 40%) who have taken Lithium on a daily basis for 10 or more years will develop parathyroid problems. Almost all of them will develop a single bad gland (a parathyroid adenoma) just like those patients who develop a parathyroid tumor out of the blue. These patients have a higher rate of developing 2, 3 or even 4 bad parathyroid glands, but most still just have one bad gland. Note, it usually takes 10-15 or more years of taking lithium for the parathyroid glands to develop into a parathyroid tumor, but we have seen it in patients who have been on lithium for only 7 years.
If you have been on Lithium for several years in the past, you must tell your surgeon. Hopefully you would have chosen an expert surgeon who will understand the significance of what you are telling him/her; if they don't know about the relationship between Lithium therapy and the development of hyperparathyroidism, then they obviously are not an expert at parathyroid disease. Go somewhere else! The treatment for hyperparathyroidism in a patient who has a history of long-term Lithium therapy is still surgery where all four parathyroid glands must be assessed to see how many are bad (how many tumors exist). Remember, this does NOT mean you can't have mini-parathyroid surgery. We do mini-parathyroid surgery on 100% of patients... but not all surgeons have the experience to do this. We discuss surgery in more detail in other sections of parathyroid.com.
Hyperparathyroidism Cause #6:Familial (Hereditary) Forms of Hyperparathyroidism. This is just under 1% of all parathyroid patients.
Occasionally, parathyroid disease occurs in families. This is uncommon, so please don't ask me about it when you come to see us. However, because of the volume of surgery we perform (68 per week), we see patients who have a family member with hyperparathyroidism about once per week. Hyperparathyroidism that occurs in families can occur in women and men, however, it can show up at any age. We once operated on a man and a woman (brother and sister) on the same day... the brother was 74 years old, and the sister was 76. So, although parathyroid tumors can occur in families, it is uncommon. It would be prudent to have your siblings tell their doctors about your parathyroid disease so they have their calcium and PTH tested... realizing that 97-98% of the time the testing will turn out negative. Beware when asking your relatives about parathyroid disease, however, since most people you ask will say "YES", when they are actually talking about THYROID disease and not parathyroid disease. Thyroid problems are common, parathyroid problems are uncommon.
Familial forms of hyperparathyroidism often show up with kidney stones in young adults. HOWEVER, so does form number 1 above (a single adenoma)... so therefore, ALMOST all young adults that get hyperparathyroidism have form number 1 above, and NOT this form.
Almost all patients who have familial hyperparathyroidism will have a single adenoma (number 1 above), but a slightly higher percentage will have 2 bad glands or 4-gland hyperplasia (number 2 above). The treatment is exactly like the treatment for numbers 1 and 2 above. The biggest exception is that patients with familial hyperparathyroidism can get kidney stones, while those with NON-familial hyperparathyroidism due to 4-gland hyperplasia will never get kidney stones. (remember, its the patients with one (or two) bad parathyroid adenoma (tumor) that makes up >97% of all parathyroid patients and they are the ones with kidney stones).
An often asked question is: Should my children be tested for parathyroid disease now that I have it? Nope, no more than your children should be checked for broken bones after you slip and fall and break your ankle. The exception is this... if two people in the family have hyperparathyroidism, then everybody needs to be checked (again, this is so uncommon I can't believe that I'm writing about it... I should be watching TV). Another exception is that the brothers and sisters of a teenager with hyperparathyroidism should have their calcium and PTH checked.
Bottom line, patients with first-degree relatives with hyperparathyroidism have a slightly higher rate of 4-gland disease, but at least 95% will still have a single or a double adenoma. Do NOT let your surgeon tell you that you can't have mini surgery just because you have family members with hyperparathyroidism. If they say that... go somewhere else! The surgeon's skills determine who can have a mini-parathyroid operation--not the patient's disease.
Hyperparathyroidism Cause #7:All Four of the parathyroid glands grow big
These are not true tumors, but just bigger, juicy, happy parathyroid glands. This is about 1.5% of all parathyroid patients. The bigger, fatter parathyroid glands are called "Hyperplastic" parathyroid glands. Also called Parathyroid Hyperplasia. No Known Cause.
Much fewer patients with hyperparathyroidism have the disease because something happened to all four parathyroid glands making them all grow too big. This is a very different disease from those above. Sadly, most people think they have this problem because they had a scan that was negative and it didn't find the one or two tumors that 98% of people have. Well, as discussed on another page (click here), your scan was negative because scans just aren't very good at finding parathyroid tumors. If your scan is negative, it is wrong. If your scan was positive, it is wrong 60% of the time. Don't get a scan. A negative scan does NOT mean hyperplasia is present. Parathyroid hyperplasia is RARE.
So, something happens (again, we have no idea what the cause is) and all four glands grow big. These glands are very different from the tumor (parathyroid adenoma) that develops in number 1 above. These hyperactive glands are called parathyroid "hyperplasia", or "hyperplastic" parathyroid glands. These are never cancer. The treatment of this form of parathyroid disease (caused by 4 bad hyperplastic parathyroid glands) is different from the treatment of a single adenoma. The surgeon can't just remove one parathyroid gland... because the excess parathyroid hormone is coming from all four parathyroid glands. Removing just one will not cure the patient. The objective of the surgeon would be to remove just the right amount of the parathyroid glands so that what is left will make the correct amount. This is usually about 3 1/2 (three and one-half) parathyroid glands, leaving about 1/2 of the most normal gland behind. Sometimes the surgeon will remove all four glands and then put part of one of them (about 1/2 of one) into a muscle where it will grow. This was done more commonly in the past, but isn't done that often any more (unless the patient has kidney disease... but this is a different disease and not discussed here). Usually, 3 1/2 of the glands are removed and the patient is cured. Remember, get a good surgeon, because if all four are removed and none is transplanted back into a muscle, the patient will become hypOparathyroid, which can be worse than being hypERparathyroid. It is rare for 4-gland hyperplasia patients to have a calcium level above 11.5. Patients with 4-gland hyperplasia often have MILD or very little elevations in their calcium and PTH levels (almost normal). Beware, however, many patients in category 1 above will also have mild elevations in their labs. Also beware, as stated on the Symptoms Page, the symptoms you get from high calcium are NOT related to how high the calcium is. Very mild elevations in calcium can give people lots of bad symptoms.
In summary, 4-gland hyperplasia accounts for a small percentage (less than 1.5%) of all patients with primary hyperparathyroidism (that don't have MEN). We don't know what causes it (except in some cases outlined below). All four glands are bad and need to be dealt with. It usually presents with mild changes in the blood calcium and PTH, rarely presenting with calcium levels above 11.7. It can cause very significant symptoms. The good news is that these people are usually very happy after a successful operation, as they often feel the worst. Please, if you become one of our patients, don't assume you have 4-gland hyperplasia. It is quite uncommon. Also, know that any doctor that tells you that you "probably have hyperplasia" prior to the operation, then they are not an expert in parathyroid disease. Be instantly suspect of their experience in this disease if they tell you this. The only people that are known PRIOR to the operation to have 4 bad glands (hyperplasia) are those who have been on dialysis for kidney failure and those who have MEN Syndrome (see below). One last item... if your surgeon tells you they they might have to take out all 4 glands and put a piece of one of them into your arm... then get up and walk out. This should NEVER be done for primary hyperparathyroidism. Never.
Hyperparathyroidism Cause #8:Multiple Endocrine Neoplasia Syndromes (MEN Syndromes). This is far less than 1% of all parathyroid patients.
Multiple Endocrine Neoplasia Syndromes (MEN Syndromes) are covered in detail on a different page of this web site (click here) as well as several pages on our sister website EndocrineWeb.com. This is so rare that it does not deserve too much space on this particular page. The average parathyroid patient does not need to know about this at all. MEN Syndromes are the cause of only 1 in 500 cases of hyperparathyroidism. All of these patients have 4-gland hyperplasia just like Number 2 above. Thus, the bad piece of DNA that these patients have is inside all 4 of the parathyroid glands, and therefore, all four parathyroid glands get big and juicy, and happily produce lots of PTH. Like every other type of patient of this page, however, these tumors are NOT cancer.
Patients with MEN syndromes will almost always show up as teenagers. Often as young as 10-12 years old. Most will get kidney stones by age 14 from their parathyroid tumors. If the surgeon removes only one parathyroid tumor, these patients will always get the disease again and they will always need another operation. All patients with MEN syndromes should be taken care of by an expert so the surgeon knows what to do.
The following links will take you to our pages on the two main types of MEN Syndrome that are located on our sister website EndocrineWeb.com
More about MEN-1: Parathyroid tumors with pancreas and pituitary tumors (the three "P"s). More about MEN-2: Parathyroid tumors associated with medullary cancer of the thyroid and tumors of the adrenal medulla (pheochromocytoma)
One final note about MEN Syndromes. Often an endocrinologist (or less frequently a family doctor or internist) will see a very routine patient with hyperparathyroidism and then run all sorts of tests on this patient to see if the patient has one of the two MEN Syndromes. This is great medicine in theory, but shows that the doctor has READ more about hyperparathyroidism patients than he/she has actually SEEN. In other words, this doctor is over thinking the problem and doing unnecessary tests! Patients who have hyperparathyroidism do NOT need tests to determine if they have tumors in their pancreas, or adrenal, or thyroid gland. This type of "shotgun" medicine is one of the causes of the high cost of medicine. I deal with parathyroid patients every day of my life, and I see a MEN syndrome patient once or twice a month (and I deal with thousands of parathyroid patients per year). So when your doctor (who sees extremely few parathyroid patients) wants to check you for MEN Syndromes, question him or her on it. Adults do not need to be checked for MEN syndromes. Only children with high calcium.
Hyperparathyroidism Cause #9:Kidney Disease. This is actually a different disease -- Secondary Hyperparathyroidism.
Nowhere else on this site do we talk about secondary hyperparathyroidism. This entire web site is about PRIMARY hyperparathyroidism, with the exception of this paragraph.
Secondary hyperparathyroidism is a VERY DIFFERENT DISEASE. It ONLY occurs in patients who have renal failure, and almost always in patients who have been on kidney dialysis for several years. If you don't have kidney failure, you do NOT have this disease. The term "Secondary" simply is a descriptive term, implying that the parathyroid glands grew big and juicy and are overproducing PTH in response to the kidney disease. Said differently, the parathyroid disease is secondary to the kidney disease.
As you can guess, ALL patients with secondary hyperparathyroidism will have 4-gland hyperplasia. The bad kidney causes its bad influence to be felt by all the parathyroid glands and not just one. Thus, these people do NOT have a single adenoma, they all have 4 bad glands.
Yep, there is such a thing as Tertiary Hyperparathyroidism. Tertiary hyperparathyroidism occurs in patients who have mild secondary hyperparathyroidism and then get a functioning kidney transplant. Usually the normal functioning kidney transplant will cause the parathyroid glands to return to normal also... but not always. If these patients continue to have overactive parathyroid glands, they must have an operation or risk killing their new good kidney with the high calcium in the blood.
You can see from this list, many people have more than 1 bad parathyroid gland. There is absolutely no way for any surgeon to know before the operation which patient has only 1 parathyroid tumor and which patients have more than one. Therefore, if you want to be cured and want to feel better, your surgeon needs to examine all four parathyroid glands during your operation. Taking out a huge tumor and leaving a small second tumor will provide you with zero benefits.
If your surgeon isn't going to look at all four parathyroid glands then he/she is cheating. This is not expertise so don't fall for this gimmic. If he/she says they think you have hyperplasia because your scan is negative, then get up and RUN! Don't walk out of their office, run! This is not true. Almost all patients with a negative scan will still have one or two adenomas (situations 1 and 2 above). Saying you probably have hyperplasia because your scan is negative clearly means that surgeon doesn't do many parathyroid operations! Your surgeon should know all the information on this page. If your surgeon says that he/she wants to remove all four parathyroid glands and put a piece of one into your arm... THEN RUN even faster! This is not correct unless you have been on kidney dialysis and have a different disease (even that hasn't been done in 10 years). If your surgeon is not performing parathyroid surgery at least every week, you may want to find a more experienced one. For an expert this should be a very safe operation. Can you tell we see some of the craziest stuff every day? You wouldn't believe the things doctors tell patients when they don't know what to do. Be careful out there folks... education is power!