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.
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...
when one (occasionally more than one) parathyroid gland grows into a
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.
excess parathyroid hormone circulates in the blood and removes calcium
out of the bones and puts the excess calcium into your blood.
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
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
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
Hyperparathyroidism Cause #3:
Therapy in the Past for Thyroid Problems. This is about 1.5% of all
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:
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
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
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:
(Hereditary) Forms of Hyperparathyroidism. This is just under 1% of all
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 (38 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
--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
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 is a
worse disease than hypERparathyroid. Patients with kidney stones will
essentially never have 4-gland hyperplasia. Said again, if you have kidney
stones, you do not have 4-gland hyperplasia, you have a single adenoma
(this is a very little-known fact, and I'll bet your doctor does not know
this!). It is also very
rare for 4-gland hyperplasia patients to have a calcium level above 11.5.
Patients with 4-gland hyperplasia 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 presents with mild changes in the blood calcium
and PTH, never presenting with calcium levels above 11.7. It can cause
very significant symptoms, but is usually not accompanied by
osteoporosis, and is never associated with kidney stones. 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 Cause #8:
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
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
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. Running tests to look for MEN Syndromes on all patients who have
hyperparathyroidism is SILLY! And, 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, you can just
print this page and take it to them and educate them (don't slap them with
it). Adults do not need checked for MEN syndromes. Only children with high
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.
We have another page that looks at the ages of patients with
parathyroid disease. On this page is a graph that shows how parathyroid
tumors occur with greater frequency as people get older. Click
Here to see this page and this very interesting graph.
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
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!
This Parathyroid page was last updated 11/30/2013