With an extensive number of studies out there (some veterinary and some
for human health but with ferrets as the animal model used) the route
to adrenal tumors is not only well demonstrated but the phases are
independently verified (Take human health studies done on ferret and
veterinary studies together and you will find *many* dozens of studies
relevant to adrenal health in ferrets.), though there are those who
would like to do some further study into how much of a lesser role
Follicle Stimulating Hormone (FSH) which can cause bone loss may play,
and others who are looking further into treatments and prevention
including Gonadotropic Releasing Hormone vaccines, and a class of
meds for treatment and prevention including Lupron Depot, deslorelin
implant, and Trelstar. Yet another area of on-going investigation
is how much of a role genetics plays because at this time there are
reasons to think it may play a large one. For example, notice how
very rare either adrenal disease or insulinoma were in U.S. ferrets,
including early neutered ones, 20 years ago. (That is not just my
observation. I have heard it from vets who treated ferrets then, too,
such as Dr. Karen Rosenthal.) Genetics has been studied some already
by teams organized by Doctors Bob Wagner (Pitt) and Michelle Hawkins
(UC Davis, and a much larger study).

The big player is LH, Luteinizing Hormone (LH). Normally, the pituitary
releases more LH and FSH in the Spring. That apparently happens in
response to the Pineal Gland producing LESS melatonin. (Melatonin
production is inhibited by light exposure.) So less melatonin then
more LH and FSH production happens in the Spring in response to there
being less darkness. For a ferret in need of reproducing that is a
good thing, but...

Something to recall with melatonin production: if you have night-
lights or those blue or green equipment lights then you are NOT
providing darkness. Blue is the most disruptive light wavelength for
melatonin production and green is the second worst. (White contains
both and others.) If you are stuck having those lights around then find
a way to safely shield them or if they can be changed to amber then do
that since amber is the light wavelength that least reduces the body's
melatonin production.

When a ferret is whole (and if the ferret is not unlucky enough to
have genetics that increase the risk of endocrinological tumors or
decrease the ability to fight early tumors) what normally happens is
that the gonads get the idea that it is time to get busy in terms of
reproduction and that results in the gonads afterward pretty much
shouting "Shut up!" to the pituitary which then turns off the high
production of LH and FSH.

How do they do that? The gonads can produce their own hormones which
have that effect. Other tissues do NOT have the ability to send that
message to shut up. That is important.

Now, the gonads are not the only tissues that produce estrogens and
androgens such as testosterone (so called "sex hormones"). Every one of
us has BOTH estrogens and androgens. They are in different proportions,
but we all have both groups. Like melatonin, estrogens and androgens
are also very ancient hormones that perform a LOT of functions in the
body. There are dozens of ways androgens help our bodies including
muscle building, and the last I read something over a hundred ways
estrogens help including with some brain functions. Also, the two
groups are rather similar and the body can convert each into the other.
So, it should not be a surprise that some other tissues can generate
those particular hormones and thus respond to LH even though they can't
turn it off. Fat is a potent hormonal generator including of estrogens,
and the adrenals certainly can produce both estrogens and androgens.

When LH production is too high it stimulates the hormone generating
portion of the adrenal cortex and that portion not only begins over-
producing hormones, but the longer it overworks the more irritated and
inflamed it becomes and this is what sets the stage for tumors forming.

That cause and those stages are well demonstrated in careful, peer
reviewed studies, and have been independently verified.

So, when people suggest that something is involved in adrenal tumor
production it is essential to show how it would affect the hormone
producing cortex of the adrenal glands, and probably how it would
affect the production of LH (or maybe to a lesser degree FSH). That
is why pituitary disease has been looked for, too, but not found to
date as a real player though exceptions are possible, of course.

Now, as Michelle Hawkins of UC Davis is wont to say, the increasing
levels of some endocrinological tumors in U.S. ferrets (as opposed to
earlier U.S. ferrets or to ferrets in some other locations) "stink of
genetics". In other words, we, as a nation of consumers, could have
bought and bred for something else such as appearance, but in doing so
missed the negative health effects those choices were having. That is
certainly a common problem in multiple species when appearances were
placed first. There are some ways we already know that we've done that.
Just look at the many health problems associated with neural crest
variant genetics. Pretty ferrets? Yes. Less healthy as a population
than others? Yes. Look at the nasal and skull malformations of at least
some angora lines for another example. Want a third? Look at the short
tailed ferrets with increased rates of certain spinal problems. If you
have been following Bob Church's genetic collection project you know
that the materials are for the genetics portion of Dr. Hawkin's team
with data from them to be shared.

And that brings me to a final note: in these times money is tighter
for many and it probably pays to find out which of the ferret health
research projects that are dearest to your hearts can use some
contributions because grant money also gets tighter in such times and
no one can work without the money to fund essential components of that
work. If the possible genetics aspects of health and of descent matter
to you then the mentioned UC Davis project headed by Dr. Hawkins may be
a good place to give money so that they can fully use all the specimens
they now have. If prevention of adrenal disease matters to you then you
may want to see if the Gonadotropin Releasing Hormone vaccine is a good
place to put contributions (Contact Dr. Bob Wagner at Pitt.), or you
may want to get in touch with Dr. Nico Schoemaker in Universiteit
Utrecht due to his deslorelin research, or Kathy Johnson-Delaney who
is looking further at Lupron, or other projects that matter to you
personally.

P.S. Laryssa says that she thinks that Lupron has less effect after a
certain number of years of use. While that may be growths worsening,
her premise is also possible. Some members of this class of drugs
become less effective over time in humans. That is part of what Dr.
Schoemaker is looking at in his large ferret-lifetime deslorelin study
(as well as using it for temporary chemical neutering, and for adrenal
tumor prevention).

[Posted in FML 6169]