stands for Familial Hypocalciuric Hypercalcemia. FHH is on this page
of parathyroid.com because many endocrinologists mistake FHH for primary
hyperparathyroidism. If your doctor told you that you have FHH, you can
almost bet that you do not have FHH, and instead you have primary
hyperparathyroidism (parathyroid disease caused by a parathyroid tumor). FHH
is so rare, that few doctors will ever see it. FHH is diagnosed
incorrectly about 95-99% of the time. If you were told you have FHH, then go
to Vegas and play poker, because you are a very rare and special person.
FHH is very rare. The odds are you do not have FHH and your
doctor is making a mistake.
you have high blood calcium and low urine calcium, then you almost
certainly have a parathyroid problem and need a parathyroid operation... and
the doctor who told you that you have FHH is making an important
mistake. This page will help you learn more about FHH, and learn why
your endocrinologists could have made this mistake. As a background, the authors of
this page (the doctors at the Norman Parathyroid Center) consult on over
3500 patients with high blood calcium every year (far more than anybody
else). We have removed parathyroid tumors from over 500 people diagnosed with FHH incorrectly by
a doctor that means well, but is confused because of old teachings from the 1950's
and 60's. If your doctor never
mentioned FHH, then please don't read this page, it can confuse you (it
means you have a good endocrinologist). If your doctor said "Your
urine calcium level is low so I think
you have FHH and you don't have primary hyperparathyroidism", then we
can almost guarantee he/she is wrong and this page is absolutely for you. We see thousands of patients every year with high blood calcium,
and we have seen one (1) case of FHH in our entire careers. Yep, tens of
thousands of cases of high blood calcium and one case of FHH. If your calcium is high, and your PTH is above 40, the overwhelming odds are
that you have a parathyroid
tumor and your doctor is wrong--you do not have FHH. This is important because if you have a parathyroid
tumor you need an operation to remove it--if you have FHH, then avoid
surgeons--an operation will not help you. Before we dive into this topic let us say one more
piece of background so you understand
how common this misdiagnosis of FHH problem is: We give all of our patients a photo of their
parathyroid tumor--but the reason we started taking photos of
parathyroid tumors is so we could send the photos to the endocrinologists who
thought that patient had FHH--proving they had a parathyroid tumor not
some rare genetic disorder that few doctors will ever see in their entire
careers. FHH is friggin rare! Trust us
folks, 95% of the people reading this page who were told "you have
FHH" do not have FHH -- you have a parathyroid tumor and a doctor that is confused.
Download the CalciumPro
Parathyroid Diagnosis App. It will tell you if you have primary
hyperparathyroidism or FHH. Before you waste your time collecting your
urine in a jar, spend $5.99 on the Pro-Version of the app so you can stop
all these silly tests. The app has a complete section on urine calcium. If
it doesn't help you, we will send your $5.99 back. Guaranteed!
FHH: What is FHH?
FHH is the abbreviation for a genetic medical condition called:
or: Familial Hypercalcemic Hypocalciuria
|Familial = occurs in multiple members of the same family (it
is a genetic disease).|
|Hypocalciuric = big word meaning low amount of
calcium in your urine.|
|Hypercalcemia = big word meaning high amount of
calcium in your blood.|
Thus, FHH is a very rare disease that runs in families which is
associated with a higher than normal amount of calcium in the
blood and a lower than normal amount of calcium in the urine. It
causes no problems, so you don't do anything about it. People with
FHH have high calcium levels their entire lives -- it is normal
FHH can also be called: Familial
Benign Hypercalcemia. (I hate this dumb name!)
FHH almost always causes zero symptoms and zero
problems, and therefore,
FHH does not
require treatment. We don't do anything about FHH.
then all the fuss? Who cares? Well the problem is that MOST
people with high calcium in the blood (about 99% of people with high
calcium in the blood) have a disease called primary hyperparathyroidism
which is caused by a tumor of one of the parathyroid glands. This DOES
cause symptoms, and doing nothing about primary hyperparathyroidism will
decrease your life expectancy by 5-6 years, double your chances of stroke
and heart attacks, cause severe osteoporosis, and increase your chances of
several cancers (breast, colon, prostate) by about 2-fold (see our page on
the symptoms of
hyperparathyroidism). So it is very important to separate out those people
who have hyperparathyroidism and need an operation to feel better and to
preserve their health, from those with FHH who need nothing done because
nothing is "wrong".
Why all the fuss? Because the vast majority of people who are told they
have FHH do not have FHH, they have a parathyroid tumor and it will slowly
destroy their bodies while everybody sits back and does nothing. It is
vitally important to differentiate FHH from hyperparathyroidism if your
blood calcium is high.
Keep reading and we will show you how this is done.
Difference in Symptoms Between FHH and Primary
Note this is a partial listing of
symptoms simply to show that FHH doesn't have symptoms and
We have an entire page on the symptoms
of primary hyperparathyroidism.
Thus, there are two potential causes of high blood calcium: 1) primary
hyperparathyroidism (99.99%), and 2) FHH (0.001%). For those with primary
hyperparathyroidism, removing the parathyroid tumor that is causing the
disease will cure the disease (for ever). You will feel better and live
longer. For those with FHH, the high
calcium is not caused by a parathyroid tumor so removing a parathyroid
gland won't help. If you really do have FHH, then parathyroid surgery is
not only unnecessary but also inappropriate.
As stated at least 10 times already, almost everybody who is told they have FHH does NOT have
FHH. They have a doctor who doesn't know how to tell the difference.
We cannot over stress this, and this is the only reason this page is on
this website--because at least 95% of people who are told they have FHH and
therefore should avoid an operation are being given bad advice (life
threatening advice) based upon outdated tests and assumptions.
Diagnosing FHH: How Do We Diagnose FHH?
Where do the Doctors Go Wrong?
has been taught since the 1960's that the only way to tell the difference
between primary hyperparathyroidism and FHH is to measure the amount of
calcium in the urine. We knew back then that this extremely rare disease
ran in families (almost every person in the family has calcium problems,
they all have high blood calcium levels their entire lives, or most of
but there was no way to check a person's DNA for the bad genetic code
(like we can do today--discussed below).
So, for decades, endocrinologists
were taught that when a patient came into their office with high blood
calcium the first thing they were going to do was to measure the amount of
calcium in the urine. If the calcium in the urine was high, the patient
had a parathyroid tumor (and needed an operation to remove the parathyroid
tumor) and if the calcium in the urine was low the patient had FHH and
needed to avoid an operation.
What is low? Who decides what "low" urine calcium
levels are? Well somebody somewhere 45 years ago said that a urine
calcium below 100 mg/24 hours is abnormal (less than 100 mg of calcium found
in a urine sample collected over 24 hours). So the old-time,
out-dated rules are: A)
if your blood calcium is high and your urine calcium is below 100 you have
FHH, B) if your blood calcium is
high and your urine calcium is over 100, you have hyperparathyroidism.
will see that this is a dumb rule, and THIS is the mistake that the
doctors are making. It's the arbitrary number of 100 that is causing all
the troubles and mistakes!
Let's look at our most recent 10,000 patients that we operated on AND
REMOVED A PARATHYROID TUMOR. Each dot on this graph represents a patient
with high blood calcium. They all had primary hyperparathyroidism which is
not in doubt because they had an operation where a parathyroid tumor was
removed from their neck and after the operation they no longer had high
vertical axis shows the blood calcium level, showing that the majority
(but not all) patients with primary hyperparathyroidism have blood calcium
levels above 10.1 mg/dl. The horizontal axis shows the amount of
calcium in the urine of these 10,000 patients (always measured over a 24
hour period). The first thing that you will notice is that the 10,000 dots
are completely random; they flow consistently from very low urine calcium
levels to very high urine calcium levels. The second thing you see is that
patients with parathyroid tumors can have very low urine calcium levels,
medium (normal) urine calcium levels, or very high urine calcium levels.
The third thing that you can see is that patients with parathyroid tumors
who have very high blood calcium levels are NOT more prone
to have high urine calcium levels (patients with higher blood calcium
levels do not have a higher propensity to have high urine calcium levels).
And finally, notice that we colored the dots red and blue, with red dots
representing patients with primary hyperparathyroidism due to a
parathyroid tumor in their neck who had calcium kidney stones, while the
blue dots represent those patients with a parathyroid tumor but they do
not have kidney stones. You can easily see that patients with parathyroid
tumors can have kidney stones regardless of their blood calcium levels,
and regardless of their urine calcium levels. Said differently, you cannot
predict which patients with primary hyperparathyroidism will get kidney
stones based upon how high their blood calcium levels are or how high
their 24-hour urine calcium levels are.
is the same graph but we removed all the patients who had a 24-hour urine
calcium level of less than 100 mg. If the decades-old teachings were right
and the level of 100 was accurate in determining who had FHH and who had
primary hyperparathyroidism then the graph would look like this. Of course
this is absurd. The number 100 is simply arbitrary because it is a nice
round number, but the real world is not this simple. The data clearly
shows that patients with primary hyperparathyroidism don't naturally fall
with a nice grouping above the number 100. They fall with a nice grouping
from way down around 20 to way up to 1000 (as seen in the first graph).
The problem is the arbitrary number of 100--it is simply dumb. So if your
doctor told you that you have FHH because your 24-hour urine calcium is
below 100, then he/she is wrong.
It is IMPOSSIBLE to tell the difference between FHH and primary
hyperparathyroidism based upon the results of a 24-hour urine test.
NOTE: these graphs are included in the CalciumPro
Parathyroid Diagnosis App. You can learn more about parathyroid
problems and interact with the graphs on this page on your iPad or Android
device. If you are reading this far on this page, then you need to spend
$5.99 on the Pro-Version of the CalciumPro app. We will send your money
back if this app doesn't save you from getting silly, unnecessary tests
and wasting your time.
third graph in this series shows 418 patients (out of 10,000 = 4.2%) that
we have operated on for primary hyperparathyroidism and removed a
parathyroid tumor. Some of them had doctors who knew they had a
parathyroid problem even though their 24-hour urine was less than 100.
Importantly, 306 of these 418 patients (74%) were told that they had FHH
and that they should not have a parathyroid operation because they did not
have a parathyroid tumor--simply because their 24-hour urine calcium was
less than 100. The patients either sought the
advice of a different endocrinologist, or they (and their primary care
doctor) figured it out for themselves and the patient was appropriately
referred for surgery.
Every patient represented by the red and blue dots on this (third)
graph had primary hyperparathyroidism but their 24-hour urine calcium was
less than 100 mg/24 hours. One fourth of these folks had a doctor who
disregarded the dumb cut-off of 100, while the other three-fourths were
WRONGLY given the diagnosis of FHH. A different doctor then sent them
for surgery (or they sent themselves!).
It is IMPOSSIBLE to tell the difference between FHH and primary
hyperparathyroidism based upon the results of a 24-hour urine test.
Another important point that is made clear by the third graph is that
there are lots of patients here that have kidney stones. As you will
recall from the blue symptom table at the top of this page, patients with
FHH do not get kidney stones, but patients with primary
hyperparathyroidism can get stones. You simply cannot differentiate
between FHH and primary hyperparathyroidism based upon the amount of
calcium in the urine.
next graph shows the 24-hour urine calcium results for the same 10,000
patients with primary hyperparathyroidism. This time we present the data
in a bar graph so you can see how often patients with a parathyroid tumor
actually have a 24-hour urine test with a result less than 100. It
happens 4.2%, thus one out of 20 people with primary hyperparathyroidism
will have a low 24-hour urine test, and if their doctor doesn't know
better, he/she will tell the patient that they have FHH and they do not.
Remember from above, this is very important because FHH is a
"nothing" problem (you don't do anything about it because it
causes no problems), whereas primary hyperparathyroidism causes lots of
problems, lots of symptoms, and will slowly destroy a patient's body and
shown in this blue bar graph, it is clear that many endocrinologists are
figuring out that the 24-hour urine test has little (or no) value in
evaluating patients with primary hyperparathyroidism. We have over 500
different endocrinologists refer patients to our center every year, with
over 1,750 endocrinologists in our database (who have sent us at least one
patient). Because our patients come from all over the country (and not one
part of one city), we get to observe what the endocrinologists around the
country (and around the world) are doing in their office when a patient
with high blood calcium comes to see them. In the year 2000, 79% of the
patients that were sent to us for surgery had a 24-hour urine test
performed (they made the patient pee in a jug and collect their urine for
24 hours). By 2005 the number of patients referred to us who had a 24 hour
urine test prior to surgical referral had decreased to 56% (p<0.0001).
The trend has continued, with only 37% of the patients referred to us in
2010 having had a 24-hour urine test (p<0.0001). Thus, two-thirds of
endocrinologists no longer obtain a 24-hour urine test on their
patients--they have learned that the arbitrary number of 100 mg of calcium
in the urine has no meaning. (Note, if you want to read
more about this, then our advanced
diagnosis page is for you. This is advanced stuff, for doctors and
patients who are really getting into this).
so now we all understand that almost all people who have high blood
calcium will have a parathyroid tumor in their neck and this high calcium
is not normal for them. They have not had high calcium their entire
life... they had normal calcium levels (typically in the mid 9's) their
entire life until they grew a tumor on one of their parathyroid glands.
The parathyroid tumor makes too much parathyroid hormone which in turn
takes calcium out of the bones and puts it into the blood. The high blood
calcium in these folks came from their bones! These people get symptoms,
they get sick, they get bad osteoporosis, they get kidney stones, they get
high blood pressure, they get all sorts of bad things happening because of
the high calcium and PTH in their blood.
In contrast, a very small minority of people with high calcium in their
blood (extremely rare) will have FHH. This means it is normal for them to
have this slightly higher blood calcium. They don't get sick. They don't
get osteoporosis or stones. They just have a higher "normal"
calcium level in the blood. (I remind you, we've seen one case in over
20,000 cases of high blood calcium).
if FHH is a genetic disease, we should be able to use modern technology to
examine a patient's DNA to find the bad gene that is responsible for this
"higher normal" blood calcium level. And yes we can. There are
several companies now that can do this test for you. Two things to
remember, 1) it is not cheap, and 2) it is not always correct either! Most
of the times the results will say "moderate probability of FHH",
or "high probability of FHH". See, even these genetic tests are
not always correct (because they have "control" DNA in their
database that came from people with primary hyperparathyroidism but were
misdiagnosed as FHH because of a urine calcium level below 100!
How crazy is that?!). Even the companies that do the genetic testing
will tell you that 10% of patients with FHH will not have a genetic
defect. Of course they wont! Because they don't have the friggin
disease! They have primary hyperparathyroidism with low urine calcium and
their doctor has made a mistake in their diagnosis!
Technical Genetic Information
Familial hypocalciuric hypercalcemia (FHH) is an
autosomal dominant condition caused by mutations in the calcium sensing
receptor gene (CASR). FHH is characterized by hypercalcemia,
hypocalciuria, hypermagnesemia, and normal to low levels of parathyroid
FHH is caused by loss-of-function mutations in
the CASR gene. To
date over 100 different alterations in the CASR
gene have been described. Many of these cause diseases of abnormal
serum calcium regulation. Inactivating
mutations result in undersensing of Ca(++) concentrations and
consequent PTH overproduction and secretion. This leads to either
familial hypocalciuric hypercalcemia (FHH) or neonatal severe
primary hyperparathyroidism (NSPHT), depending on the severity of the
functional impairment. Homozygous or compound heterozygous
loss-of-function mutations in CASR result in neonatal
severe hyperparathyroidism (NSHPT) a severe and possibly lethal
condition. Symptoms appear in infancy and include extreme
hypercalcemia, failure to thrive, hypotonia, skeletal
demineralization, and severe parathyroid hyperplasia. Some de
novo mutations may cause a mild or transient version of NSHPT.
Treatment may require parathyroidectomy in these very young
Except for a very small percentage of cases with
no apparent CASR
mutations (maybe because they don't have the disease?), FHH is due
to heterozygous inactivating CASR
mutations. Serum calcium levels are mildly-to-moderately elevated
(never above 11.0). Parathyroid hormone (PTH) levels are within
the normal range, phosphate is normal, and urinary calcium
excretion is low for the degree of hypercalcemia. In contrast to
patients with primary hyperparathyroidism, the majority of FHH
patients do not seem to suffer any adverse long-term problems from
their high blood calcium (hypercalcemia).
Calcium Clearance to Creatinine
Patients with apparent mild-to-moderate
hyperparathyroidism, who have a ratio of calcium clearance to
creatinine clearance that is <0.01, could possibly have
familial hypocalciuric hypercalcemia (FHH). Identification of a
heterozygous inactivating CASR
mutation confirms this diagnosis, while identification of novel
alteration(s) increases the likelihood of a FHH diagnosis, but
does not confirm it until family studies or functional studies
support the diagnosis. Absence of any mutations or the presence of
polymorphism(s) that are known to be functionally neutral makes
the diagnosis very unlikely.
Approximately 20% of FHH patients are reported
to have calcium to creatinine clearance ratios of >0.01
(editorial comment: Many of these patents do NOT have FHH, they
have primary hyperparathyroidism). These patients can be difficult
or impossible to distinguish from individuals with primary
Companies Providing Genetic Testing for FHH
Athena Diagnostics. Athena Diagnostics is a leader in the field of genetic testing for
Diagnostics Website for FHH.
Ambry Genetics. Ambry Genetics is also a very reputable company
for genetic testing for FHH.
Genetics Website for FHH.
FHH vs Primary Hyperparathyroidism: The Bottom
Bottom line is this: If your blood calcium is high, you almost
certainly have a parathyroid tumor that is causing primary
hyperparathyroidism. If your blood calcium is high and your PTH is high,
then there is no question, you have primary hyperparathyroidism (it
doesn't matter what your 24-hour urine is, so don't get one). There is no
chance you have FHH. If your blood calcium is high and your PTH is above
40, then you have primary hyperparathyroidism. Period. If your blood
calcium is high and your PTH is between 20 and 40 (on repeated measures),
then you almost certainly have primary hyperparathyroidism. The only time
you need to check your 24-hour urine calcium is if your calcium is mildly
elevated (in the low to mid 10's, and less than 10.7 on every test) and
your PTH is less than 60 (in the normal range if you have a different
normal range on your labs). See our Advanced
Diagnosis Page to see how we make the diagnosis of primary
hyperparathyroidism in a step by step fashion.
Remember, MOST people diagnosed with FHH do not have FHH. The
diagnosis is incorrect. If your doctor says you have FHH based upon your
urine calcium level, then you laugh at them and demand a genetic test. The
diagnosis of FHH should NEVER be made without a genetic test. And
then, know that most genetic tests for FHH will be equivocal and they will
not come out and say yes/no. Remember, we've seen FHH diagnosed correctly
ONE time, and have seen it misdiagnosed 306 times in our most recent
10,000 patients (most recent patients ending January, 2011). FHH is rare
as hen's teeth. Very few endocrinologists will ever see a single case of
Editorial Note from Dr. Norman: Folks,
there are few things in our practice that makes us scream and pull our
hair out like doctors getting 24-hour urine calcium levels. The ignorance
on this issue is phenomenal, and the difficulties that many
endocrinologists have in making the diagnosis of primary
hyperparathyroidism is astounding. Every day we are disappointed in our
peers who practice endocrinology (and nephrology) like it was 1965. There
are lots of incredibly talented endocrinologists, but there are some that
are not so smart, and lazy to boot -- a terrible combination. Be smart and keep reading. We
are just one source, keep reading!
This page was last updated: October 11, 2013