>From:    Sheila Crompton <[log in to unmask]>
>... If the gonads are removed at this very early stage of development,
>these gonadotrophins from the pituitary act somewhere else.  And that place
>is on certain embryonic cells in the adrenal cortex.  In the course of
>time, these cells become an adenoma and this in turn produces oestrogens...
 
>From:    "Deborah W. Kemmerer, DVM" <[log in to unmask]>
>... I know of no data to support your statement.  In fact, if it were
>correct, then we should be seeing the same endocrine problems in dogs and
>cats.
 
Hi.  Dr. Kemmerer.  But are dogs and cats breeding cycles triggered by
photoperiods?  (I don't know).
 
Sheila.  I'd be interested in your source of this information.  It is
similar to the theory that Dr. Johnson-Delaney and Dr. Judith Bell seem to
be following in exploring the theorized relationship between
pituitary/photoperiods/adrenals/early spay & neutering.
 
Dr. Johnson-Delaney has written:
"I think there is something to the pituitary-adrenal feedback loop and why
it gets turned on, then the adrenal gets "super stimulated" and
hyperplastic, and eventually neoplastic.  Dr. Judith Bell is now theorizing
that this pituitary "turn-on" or over stimulation (the pineal gland is also
involved) may have something to do with light cycle: ferrets evolved fairly
nocturnal, and from northern latitudes: we give them 16 hour plus light
cycles all year.  She is proposing testing light amounts and measurements of
melatonin, and looking into keeping your ferrets on 8 hour light cycles etc.
She may be on to something.  We have this problem in birds: they go into
constant laying.  We have to regulate light exposure.  Maybe ferrets need to
too, but it's going to be very difficult given human hours and the companion
aspect.  If the pituitary is busy churning out the hormones that in turn
cause the adrenal to think it's breeding season and the gonads aren't
working right (which they're not, cuz they're gone!), then the adrenal picks
up the slack to tell the brain, pituitary that the reproductive tract is
gearing up....you can kind of see the progression: ferrets are seasonal
reproductive animals, and are shut off by 1.  breeding and copulation-
ovulation, pregnancy, end of season; 2.  males, end of season (light cycle)
and females are pregnant so that stimulation is turned off.  Any tissue
which is constantly stimulated over a long period goes hyperplastic, and the
more cell cycles and stimualtion, the greater the chance for neoplasia.
Particularly with secreting tissue, i.e. endocrine tissue.  This is why I
think Lupron is important in this: it interrupts that stimulation cycle...
The Lupron hits before the signals reach the sex steroid secreting tissue:
it sends the message to back down on the reproductive steroidogenesis.
Metabolically, this is probably the key.  ..."
"...Theorectically, if you can shut the pituitary down with the light cycle,
you may be able to decrease stimulation of the adrenal.  Problem is, that if
the adrenal has been stimulated so long and the cells progressed from
hyperplasia to adenoma or adenocarcinoma, you may have a harder time
shutting it down - and somewhere along the neoplastic progression, the cells
are going on their own and not responsive to external signals.  We usually
think of this at the adenocarcinoma level.  That is why I think it is still
important to go with mitotane to kill off the adrenal cells.... Lupron
worked in Robbie's case but we still weren't able to get tissue from the
brain at necropsy.  Mitotane worked as well.  I don't feel that one or the
other is totally the answer.  Those showing adrenal disease, I'm about ready
to try melatonin.  I would have it compounded so that the 1 mg is a
reasonable amount.  I need to find out from Betsy Bailey at UT if we can do
some sort of a blood assay for melatonin.  We don't know toxicity levels of
it, nor other side effects.
 
"Adrenal disease treatment therefore must be hit on several levels: Shut off
the stimulus to the adrenal tissue to produce the sex steroids.  Decrease
the amount of adrenal tissue that can do so.  There are various ways to do
these steps.  Each ferret's case must be handled individually.  Genetics may
play a role, as does time of neutering.  We don't know all the answers.  All
therapy must be aimed at providing the best quality of life for the time
remaining."
 
>Subject: Lupron for adrenal disease
        Lynn McIntosh wrote:
>>(With Lupron therapy only) Estradial went down, blood (I think it was
>>hematocrit) went up, hair regrew, and, best of all, frequent urinating
>>returned to normal.  Coincidence?  Perhaps, but this is a lot of change
>>soon after starting Lupron.  Unfortunately after a few months, adrenal
>>sympto ms returned.
 
Ilena Ayala wrote:
>Hmmn.  Don't ferrets with no treatment at all frequently regrow their hair
>and then have it all fall out agan?... This makes me think th at one
>possible explanation is that it doesn't work at all, but that in some
>ferrets the treatment coincides with the cycle, which I suspect is tied to
>photoperiod??
 
The interesting thing about the above case was that it was in mid-winter
when the symptoms returned, whereas they might be more expected to return
with spring.  This ferret may have a tumor independently operating, which
outstripped the Lupron's effect.  Theories only.  For the record though, I'm
the last one that would like to see surgery, where it is a solid option,
delayed for any treatment that will only alleviate symptoms.  Theoretically,
though, Lupron, used with Lysodren, would be acting on the disease, not the
symptoms.  If it does nothing, it at least wouldn't dangerously mask
symptoms.  I have to agree with Bob Church and Dr. Bruce Williams, that
surgery is the one thing that can stop the disease, though, unfortunately,
it sometimes doesn't, or only buys time (if it buys a year, that's a good
bit of time, though).  Lysodren is a very serious drug, scary to use but
still, I think, is better than having nothing to try.  Perhaps Lupron will
help on another front.  Hopefully, time will tell.
 
Dr. Johnson-Delaney, DVM, has said that she and other vets have seen some
good preliminary results using Lupron with Lysodren as therapy for adrenal
symptoms, when surgery isn't an option.  This seems to lend credence to the
theory that adrenal disease is related to pituitary stimulation.
Unfortunately Lupron has only begun to be used and there isn't enough data
collected, nearly enough, to be conclusive.  Nor are there funds for
research studies.  Since it is said to be harmless, I would be inclined to
try it where other options, sugical and chemical, weren't available and/or
working.
 
Lynn McIntosh and the Gang of Seven (always remembering Squeek,
Schroeder Boat, and Percy)
[Posted in FML issue 2226]