There
are several pages on this web site 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 parathyroid page is an advanced
page 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. DO NOT LET THIS PAGE BE ONE
OF THE FIRST PAGES YOU READ! 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 looses 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--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".
Cause Number One: One of the parathyroid
glands grew into a tumor. This is 94-95% of all parathyroid patients. NO
KNOWN CAUSE
As you already know from other pages on this large web site,
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, us 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 1,500 are
cancerous, so lets not ever talk about parathyroid cancer--you don't have
parathyroid cancer. And if you become one of my 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.
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, almost
everybody 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. 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!).
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.
Cause Number Two: All Four of the
parathyroid glands grow big--not true tumors, but just bigger, juicy,
happy parathyroid glands. This is 3.5% 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 single tumor that 95% of people have. Well, as
discussed on another page (click here),
your scan was negative because you had a very poorly performed scan. The
sestamibi scan is hard to do, and most places do it it incorrectly.
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 11.4.
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 (about
3.5%) of all parathyroid patients. 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 usually 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.
Cause Number Three: Long term use of
Lithium. This is less than 1% 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. Virtually ALL of them will develop 4-gland hyperplasia and NOT a
single adenoma. Note, it usually takes 20 to 30 YEARS for the parathyroid
glands to manifest as overproducing hyperplastic glands. In other words,
you typically have to be on Lithium for 10 or 20 years, and the disease
doesn't show up until about 20 or 30 years after you started the
Lithium.
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! The treatment for hyperparathyroidism in a patient
who has a history of long-term Lithium therapy is exactly the same as it
is in number 2 above, because all of these patients will have 4-gland
hyperplasia of their parathyroid glands.
Cause Number Four: Radioactive Iodine
Therapy in the Past for Thyroid Problems. This is less than 1% 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). 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). Unlike the parathyroid disease seen following long-term
Lithium therapy, however, the parathyroid disease seen many years after
Iodine 131 therapy usually involves just one parathyroid gland. Yep, one
of the parathyroid glands develops an adenoma... just like number one
above. Occasionally it can involve more than one parathyroid gland, and
thus the patient can get more than one adenoma. 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).
Cause Number Five: Radiation treatments
to the neck and face as a youth or teenager. Less than 1% of all
parathyroid patients.
In the 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). 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 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 30 years later. On a good note,
these people almost always develop an adenoma (one big, benign gland).
They do not appear to have an increased incidence of having 2 adenomas or
4-gland hyperplasia. 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.
Cause Number Six: Familial
(Hereditary) Forms of Hyperparathyroidism. This is less than 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 me! 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.
However, don't ask if your disease is hereditary... the answer is NO
unless you have a brother or sister with this disease... On the flip side,
if you have a first-degree relative that had parathyroid disease, it is
very important to tell your doctor. Beware, however, most people you ask
will say "YES", when they are actually talking about THYROID
disease and not parathyroid disease. This is so uncommon, that you
should not be reading this... DO NOT WORRY about being in this group...
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.
Most patients who have familial hyperparathyroidism will have a single
adenoma (number 1 above), but a slightly higher percentage will have
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 bad parathyroid adenoma (tumor) that makes up >96% 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 rare 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 must 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 90% will still have a single adenoma. Do NOT let your surgeon tell
you that you can't have mini surgery just because you have family members
with hyperparathyroidism.
Cause Number Seven: Multiple Endocrine
Neoplasia Syndromes. This is FAR less than 1% of all parathyroid patients.
Multiple Endocrine Neoplasia 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 the space on this web site. The
average parathyroid patient does NOT need to know about this at all. MEN
Syndromes are the cause of only 1 in 1000 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.
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 every few years (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). I have NEVER seen a MEN Syndrome patient show up with
hyperparathyroidism FIRST... the disease is manifest by the tumors in the
pancreas, thyroid, or adrenal glands first. Let me say this again... MEN
Syndromes show up with pancreas, thyroid, or adrenal tumors FIRST. These
patients should have their calcium checked... NOT the other way around.
Cause Number Eight: 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.
If your surgeon can't tell you
with a high degree of certainty which parathyroid gland is bad and with a
high degree of certainty if you have one single adenoma or 4-gland
hyperplasia... you may want to see an endocrine surgeon...he/she may not know for sure, but
they should have a good guess! IMPORTANTLY, if they tell you that you
have 4 bad glands (hyperplasia) because your scan is negative... then you may want to
find an endocrine surgeon... this is not true! ALMOST ALL patients with a
negative scan will still have an adenoma. 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! This is NOT correct! If your surgeon is not
performing parathyroid surgery at least every week or two, you may want to
find a more experienced one. For an expert... it
is VERY EASY OPERATION!!! DO NOT BE AFRAID OF THIS SIMPLE OPERATION IF YOU
HAVE AN EXPERT!
This Parathyroid page was last updated 06/13/2007
