How Serotonin and Other Hormones Affect Carcinoid Heart Disease with Jerome S. Zacks, MD

How Serotonin and Other Hormones Affect Carcinoid Heart Disease with Jerome S. Zacks, MD


Yeah. So this has been looked at and the
nutritionists have recommended diets which are low in these vasoactive amines.
However, there does not appear to be an effective
nutritional approach to getting a high serotonin down to a normal level. Maybe a little bit of change, but
probably not that significant… Yeah, a mild amount of change,
but probably not significant. So the tumor markers that we
have found most appropriate, at this point in time, are
serotonin, as represented by blood tests of serotonin or its
breakdown product in the blood of 5HIAA. We no longer recommend the 24 hour urine
5HIAA collection because it’s difficult and we have the blood tests for 5HIAA. So the blood test for 5HIAA or serotonin will give you the handle
on how high your serotonin is. And then concerning Chromogranin A, that was the gold standard until we
realized that many different things affect the Chromogranin A level. So it’s not sensitive or specific. However its breakdown product is not
affected by these things such as diet and Proton pump inhibitors, which many people with
gastritis have to take. And that is called pancreastatin. So we now measure pancreastatin and
Serotonin or 5HIAA in the blood as the primary markers for neuroendocrine tumors. And I must tell you that despite all
of our colleagues who are knowledgeable knowing about this,
these developments in terms of testing, many of them still will do
a 24 hour urine collection, which we do not feel is very accurate
and many of them will still do Chromogranin A and not pancreastatin. So it takes a while to get
people to look at the data on what’s most sensitive and specific
for neuroendocrine tumors. So the two tests that I would recommend
is the blood serotonin level and, or the plasma 5HIAA.
And Dr. Ed Wolin and I have an ongoing
dialogue on which one we should do because I’ve… Dr. Warner and I have been doing the blood
serotonin levels for many years and Ed Wolin pointed out that the plasma 5HIAA is a more stable marker. It doesn’t fluctuate as much as Serotonin. And it’s the breakdown
product of serotonin. So he would recommend
doing the plasma 5HIAA. So I’ve now started to do both. So they’re both good. Absolutely.
Everybody’s right? Absolutely. So this is a great question. It’s a very appropriate question because
unfortunately we’ve not been able to get labs to standardize it.
So each lab has their own range. For example,
in our lab, the upper limit of normal
of serotonin is about 250. But I have seen labs in which the upper
level of the upper level of normal is 450. So what I say is find out your lab’s
normal range and then track it knowing which lab you’re using and try to use
the same lab so that you can compare over time what your level is doing. Raising the issue of Chromogranin A… can be a confusing because many patients
are on Proton pump inhibitor therapy, PPIs, such as Omeprazole, Nexium, drugs like that.
They all raise Chromogranin A very high. So the first thing I would do if I had
a patient that an unexplained elevation of Chromogranin A,
is I would do the breakdown product, check the pancreastatin level and to search for some other cause
of an elevated Chromogranin A. So the first thing is to do the
appropriate markers to see if Serotonin is elevated and do something about that. Recognizing that even if you’re
echocardiogram is normal, if you’re walking around with an
elevated serotonin, you’re at risk. And so make sure that somebody is focusing
on that and trying to get serotonin down to normal. And if you succeed
in getting it down to normal, you have essentially prevented
carcinoid heart disease. So once somebody knows that they have
some evidence of scarring of the valves, that’s what the lesions are
that are caused by Serotonin, they should immediately
focus on addressing the
issue of the high serotonin. Now that involves number one
doing something about the
amount of tumor that they have secreting
serotonin. So sometimes just reducing tumor with
surgery and other anti-tumor approaches and medications will be
enough to reduce serotonin. The other thing is that there
are somatostatin analogs that are given to almost every
neuroendocrine tumor patient. If they have somatostatin
receptors on the tumor, and a large percentage of them do, they should be on a somatostatin analog
and that reduces serotonin also. It helps block the release of this
overproduction of serotonin from the tumor cells. It doesn’t stop the production
of serotonin inside the cell, but it helps block its release
and now as I mentioned, we have a new drug which is called Xermelo That’s a tryptophan hydroxylase inhibitor, very targeted. And the enzyme involved in the first
step in the production of Serotonin, which can in a large percentage of
patients reduce serotonin down to a normal level. And if you achieve
a normal level serotonin, you can halt the progression
of carcinoid heart disease. So that’s a pretty good development
lately. It’s incredible. And when I learned that they were
developing this drug I spoke with Lexicon, the company that has
produced the drug and said, my one hope is that
you’re producing the drug, which will put me out of business. So this is an area that our group at Mount Sinai in New York
and the group in Jerusalem, Israel has focused on
and the doctor is astute to raise the issue of fixing a valve
and then having a recurrence because he realizes serotonin is still high. This is a very valid issue.
It’s an important issue. And up until Xermelo was FDA approved, we actually focused on this issue and
recommended serious discussion before someone got a valve replaced as to
whether you should use a tissue valve, which most neuroendocrine tumor
specialists prefer because it doesn’t necessarily require a
longterm anticoagulation, putting them at risk for
bleeds if they need surgery. And our recommendation in that situation, after looking at the statistics was that you seriously consider
the use of mechanical valves, which would require anticoagulation
but would prevent the recurrence of the effects of serotonin. Our study showed that there is a 46%
recurrence rate shortly after you put in new tissue valves if you don’t
get serotonin down to normal. Now, initially when we started
doing this type of surgery, the neuroendocrine tumor specialist said,
well, we’re going to get serotonin down to
normal, so go ahead and put tissue valves. So we presented 29 patients
who underwent surgery. Almost all of them got tissue valves
and we showed that there was this 46% recurrence rate and only
one of the patients actually
was successful in getting serotonin down to normal. So that’s
when we published our results and said, you should seriously consider
mechanical valves. However, now we have Xermelo, and there is nothing as effective as
Xermelo for reducing serotonin down to a normal level. And so now we feel we can still
go ahead use tissue valves, but make sure that anyone with an
elevated serotonin gets on to Xermelo, along with other tumor
reductive procedures, to get serotonin down to normal.
If you get serotonin down to normal, you will halt the risk that you’re
going to have recurrent carcinoid heart disease.