More information on Lupron as a "treatment" for adrenal disease in ferrets:
 
>Dr. Williams; your scientific information about Lupron appears
>contradictory to Cathy's (quoted below); but is very technical and probably
>difficult for the average FML'er, at least for me, to follow.  The
>conclusions are clear, though; you say there is no indication Lupron should
>work in treating adrenal disease; and Cathy says there is, and it does.
 
Dear Lynn - Let me say up front that I applaud Dr. Delany for working with
new drugs in combating adrenal disease, and I hope that she, and all other
ferret vets will continue.  However, since your first post, I have reviewed
the available literature on Lupron, the product literature from the
companies that market it, and a number of other articles and recently
written textbooks as well, as well as consulting with several reproductive
endocrinologists.  There is no evidence from any of these sources, that
Lupron has any effect on adrenal tissue.  In fact, in a textook on
endocrinology, The Pituitary, ed. by Shlomo Melmed, one of the leading
endocrinologists in the country, he says (pg.  264) when discussing
therapeutic applications of GnRH agonists (such as Lupron), "It follows that
gonadotropin-independent secretion of sex steroid secretion (for example,
from an adrenal or an ovarian neoplasm) would NOT be affected by GnRH
agonist treatment.) In everyday terms, Lupron and similar drugs have no
impact on estrogen secretion by adrenals.
 
>I also respect you very much and appreciate all you've done for fuzzies,
>but, with all due respect, note that, though you have a vet degree and are
>a ferret parent, on a daily basis you are a pathologist examining tissues,
>not a vet treating diseases.
 
Lynn, I think you are oversimplifying my qualification to speak here.  I
have well BEYOND a vet degree - I am board-certified in veterinary
pathology, which is the study of disease, not the "examination of tissues".
I also have been a private practitioner "treating diseases", as you say for
five years prior to that .  To clarify, I am constantly "treating diseases",
but my armamentarium is a bit different - I use a microscope, an expanded
knowledge base on the processes of diseases in the body, and one of the most
sophisticated medical libraries in the world, as well as a host of
sophisticated technology at hand.  I work in an academic setting equivalent
to a university, with some of the finest minds of human and veterinary
medicine at the Armed Forces Institute of Pathology.  I also "treat disease"
through the advice I give to a minimum of five vets I consult with on
difficult cases each day, and the twenty or so emails I answer each day from
ferret owners.  I don't want to list the numbers of papers on ferret diseases
that I have written, or the numbers of veterinarians and pathologists that I
lecture to on diseases of ferrets each year, or the funded research that I
have been able to do to investigate diseases in ferrets.
 
>From all the relapses from surgery I have read about, and reactions to
>Lysodren or lack of response, there doesn't seem to be a cure for adrenal
>disease at this point.  And Cathy has certainly never called Lupron a cure,
>nor have I.
 
The use of the title - "Lupron, new treatment for Ferret Disease!" is an
attention getter, especially on the Internet.  However, without hard
evidence that this drug is efficacious, I am afraid that many owners will
opt out of surgery, for an easier (and less effective) medical "option".
While I also maintain that Lupron will not physically harm a ferret, the
fact that it does not treat the root cause of the problem, an adrenal tumor,
allowing it to continue to grow, is harmful in itself.
 
>What is there for ferrets who can't have adrenal surgery -whether because
>of age, financial limitations, or the tumor's size and placement - and who
>fail on Lysodren alone?
 
Most ferrets can have surgery these days - surgical technique has improved
greatly in the last five years, thanks to the efforts of people like Dr. Joe
Bock, who pioneered techniques in bilateral adrenalectomy, and Dr. Scott
Citinas, who proved that you can ligate the vena cava in ferrets with
previously deemed "unremovable" tumors.  These have become standard
treatment modalities these days, and we can treat many more ferrets
surgically now that just a few years ago.  Tumor size and placement is
relatively irrelevant in the hands of a ferret-experienced surgeon these
days.  As far as monetary considerations, a cheaper, less effective
treatment is actually a much poorer investment than a more expensive surgery
with a higher potential for cure.
 
>Or for ferrets with prostate problems who need relief, faster relief than
>Lysodren may provide?
 
Surgery still remains the fastest method, and it is well known that Lupron
produces a initial spike in estrogen, which may persist for weeks, and
worsen the prostate problem.
 
>>(BHW) Perhaps the most important point of all - Lupron does not do
>>anything to shrink or kill tumor cells.
>NOTE: The key here is "anything".  Cathy indicates that it can, alone,
>help,but she recommends it most often as adjunct to Lysodren.
 
I would have to ask for some data here before saying it is a treatment for
adrenal disease.  Does she also mention that the product literature and
studies on Lupron have shown that there is a significant INCREASE in the
occurrence of INSULINOMA in patients taking Lupron?  This is also cause for
concern for using this drug in ferrets.
 
>"...Leuprolide acetate4 may be an extremely useful adjunct therapy along
>with the lysodren.  Administered at 100mcg/kg IM every 3 weeks, it
>suppresses sex steroidogenesis.
 
Yes, but it only suppresses sex steroidogenesis by the testis or ovary in
humans, NOT the adrenal gland.  There are no claims by the manufacturer or
any reports in the medical literature that says it effects the adrenals.
And as most of our ferrets are neutered, they have no gonads for Lupron to
work on.  We could get very technical here about FSH and LH, but let's not
to keep the discussion relevant to most FML'ers.
 
>It inhibits the growth of hormone-dependent tumors and tissues.  Effects
>include reduction in size of the prostate or vulva, and hair growth through
>follicle reactivation.
 
But how?  It only works in intact males and females.  Also, there is no
evidence that Lupron affects hair follicles at all.
 
>Although theoretically it primarily acts to interrupt the feedback system
>from the pituitary to the adrenal/auxillary endocrine tissue, it essentially
>acts to block estradiol receptors.
 
This is simply not supported by any report or medical literature.  IT DOES
NOT BLOCK ESTRADIOL RECEPTORS.  Nor does it have any effect on the
pituitary-adrenal axis (or every human using the product for endometriosis
or prostate cancer would be dead.) I only affects the pituitary-gonad axis.
I have gone to great lengths to find out if it does, but all sources say it
does not.  This is a totally incorrect explanation of Lupron's effects in
the body.  If I am wrong, or my research has missed something in the
literature, please let me know.  I want to be wrong on this one, I really do.
 
>"...If you have elevated estradiol, somewhere, something is going wrong.
>If the biopsy comes back normal adrenal, and you do have elevated sex
>steroids, I think I'd opt for the Lupron to begin with and hold on the
>mitotane.
 
If the biopsy comes back normal , in my experience of literally thousands of
adrenal cases, you are dealing with either a) a pathologist who does not
know what adrenal hyperplasia looks like (which is very common - many cases
are very subtle) or b) the wrong adrenal was taken out, and you still have
an adrenal left with a lesion in it.  In both cases, I recommend a second
surgery.  In my experience, extra-adrenal tissue is not a significant cause
of hyperestrogenism.
 
>"...I do think, as I've said all along, that surgery is only one part of
>dealing with adrenal tumors.  Debulking is fine, but it doesn't stop the
>pituitary-adrenal feedback loop which is busy stimulating the remaining
>tissue to churn out sex steroids, and although you get some drop in steroid
>production because of the tissue removal, there is still production going on
>with the detrimental side effects (bone marrow depression, electrolyte
>changes if cortisol is involved, which it is a little, prostatic changes
>which puts pressure on the urinary system, etc etc ).
 
No, this is simply not true.  Adrenal tumors are autonomous, they do not
respond to the pituitary in any way.  Plus, as all available reviews on this
product point out, Lupron's effects are on the pituitary-ovary or
pituitary-testis axis, not the pituitary-adrenal axis.
 
>The neoplastic tissue will churn out the steroids on its own, but it seems
>conclusive that the pituitary stimuli encourages it and probably does have
>some effects.  That is why the Lupron works - cuts into the feedback, as
>well as acts to block estradiol receptors.
 
There is no medical evidence that adrenal tumors or even hyperplastic
lesions, respond to pituitary signals to secrete estrogen.And once again,
Lupron neither cuts into the feedback, or blocks estradiol receptors.
 
>So there you have it... Thank you for listening!
 
Lynn, I am listening.  I am not being argumentative here, but this is too
serious a subject to for me to ignore.  I too, would love to find a surgical
alternative for ferrets with adrenal disease; I have lost four in the last
six years to it or to it's complications.  However, there is no evidence,
even theoretical, that Lupron would be effective in this disease.  The
explanations which are being put forth on this drug are not in agreement
with what is accepted medical fact about how it works.  Until even a
legitimate theory is put forth as to its efficacy, I cannot endorse it as a
treatment for adrenal disease, especially as it will likely prolong the
amount of time before surgical intervention occurs.
 
Bruce Williams, DVM, DACVP
[Posted in FML issue 2211]