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Post by miamiferret2 on Mar 19, 2011 14:54:17 GMT -5
some of you know that i have implanted our kit with the deslorelin implant to prevent adrenal disease-- a disease that i have had the misfortune of running into with many ferrets that i have owned over the years. I have read a few posts here where people have expressed their doubts that it will prevent adrenal tumors. so i decided to go to the horse's mouth and ask him what he thinks. I am not sure whether any of you are family with dr. jerry murray. he is a well known ferret veterinarian and a ferret owner himself. he works with black footed ferrets too. the guy knows his stuff. i had already used deslorelin to treat tumors that were already present in one of my ferrets who has since passed away. however, i also had doubts of using deslorelin as a preventive so i asked doc murray what he thought and he recommended that i definitely implant Sonny as soon as possible to prevent adrenal disease. i then talked to my vet about it and he backed doc murray up completely. then we implanted Sonny. he was fine. no reactions. no problems and he took that needle like a champ. not a peep out of him and it was a huge needle. so i recently emailed dr. murray and told him about some of the doubts that people have about adrenal prevention and about some vets saying that you are just "treating something that isn't there" , that it will not prevent adrenal tumors, the ferret will not respond to the medication anymore and then you can't use it in the future if he does develop tumors, etc. etc. to be clear, IF there are ALREADY tumors or adrenal lesions present on the glands, then the ferret's tumors will eventually become unresponsive to any and all medications (whether it is lupron, des or melatonin). this is why you see that the ferret doesn't respond to melatonin or lupron anymore. at that point it usually means that the tumors are beyond control and there is nothing else that will work. lupron and deslorelin are not expected to cure tumors that are already there. they will just mask the symptoms. but the tumors are there and the only way to remove is surgery. general consensus is that with a ferret that does NOT have the adrenal tumors, lesions, etc. it is a different story. moving on to the PREVENTION of adrenal disease (which is my goal in life because i am SO sick and tired of dealing with adrenal disease): according to this vet, deslorelin stops the stimulation to the adrenal gland (no LH) so the adrenal gland should not be stimulated to produce hormones OR become hyperplastic or neoplastic as the ferret ages. so it seems that deslorelin IF given early in the ferret's life and before the first hormone spike, should be effective in preventing adrenal disease. although i have already implanted our little meatball, i am not trying to convince anyone to use des or lupron as a preventive. do what thou wilt EDIT ON 8/14/2021: Hi guys! I have kept this practice of implanting my ferrets each year since this post back in 2011. One of my fuzzies just passed away a few months shy of his 6th birthday. He had Lymphoma. Anyway, we had a necropsy performed and there were no adrenal tumors (yay Deslorelin!) and NO insulinoma tumors (yay for the raw feeding).
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Post by Sherry on Mar 19, 2011 15:36:26 GMT -5
Now that IS interesting! Thank you for not only talking to Dr. Murray, but for sharing that conversation Hopefully, this will pan out for the length of the ferret's life. Did he say how often to have the deslorelin redone when used in this particular circumstance?
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Post by Deleted on Mar 19, 2011 15:48:58 GMT -5
I think there is one piece of the puzzle missing in the equation about adrenal prevention - the genetic aspect. Of course, early spay/neuter doesn't help the situation, and might create more aggressive forms of adrenal/quicker spreading cancers, etc. In order for the implant to prevent adrenal, over production of hormones needs to be the cause for adrenal. But if there is a genetic aspect, I don't think there would be a "preventative" for adrenal disease. Maybe postponing. I think, as more research is done on ferret genetics, the adrenal picture will become more clear.
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Post by miamiferret2 on Mar 19, 2011 17:07:11 GMT -5
Sherry, if using deslorelin, Dr. Murray recommended it once per year in January. Jackie, I see what you mean and I think it is a valid point. But the strongest reason for adrenal disease seems to be neutering/spaying regardless of age. I have owned very few "fancy" ferrets. Most have been dark sables. My dad always had dark sables too. his ferrets (we're talking from early to late 80's in the northeast) were from private breeders bc back then they didn't sell ferrets at the petstores everywhere like they do now. I am positive that many of his ferrets were adrenal. but the vets always said it was hair loss from "old age" because they didn't know. So I don't know what to think anymore. all i know is that I'm just tired of it. My last case of adrenal was so bad I seriously considered never owning ferrets again. I am hopeful about the adrenal vaccine but when (and if) it is approved, I'll have to talk to Dr. Murray some more about those vaccine reactions he mentioned.
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Post by Sherry on Mar 19, 2011 17:18:29 GMT -5
You know something? Even if it delays it by two or three years from when it would have normally started- it's worth it!
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Post by Deleted on Mar 19, 2011 17:21:50 GMT -5
Oh, most definitely! There is no doubting that. Any extra time is worth it!
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Post by Deleted on Mar 19, 2011 17:30:38 GMT -5
My guess is that the genetic factor is in the form of a predisposition to develop adrenal disease IF the ferret is exposed to certain triggers. The most likely trigger being surgical castration. The vast majority of the ferrets that seem to be the most affected, are also typically surgically altered at a young age. It would be interesting to see how many of them would get adrenal if they hadn't been altered. At least in the original European ferret populations, adrenal disease in intact ferrets is very rare. The reproductive system is controlled by the HPG axis (hypothalamic-pituitary-gonadal axis). The hypothalamus releases GnRH in short pulses, and the amount and frequency of those pulses controls the pituitary gland's production of gonadotropines (like LH and FSH). The gonadotropines then work on the gonads (ovaries or testicles) to activate various functions and start production of sex hormones etc. The response from the gonads also works as a negative feedback mechanism so that production of the hormones can be turned on and off and kept within functional levels. In the absence of the gonads, this negative (down regulating) mechanism will no longer be there which can poptentially cause problems (adrenal disease) when there is no down regulation of the production of gonadotropines. This is the current theory, at least. I believe it was Shoemaker et al who first showed that there are indeed LH-receptors in the adrenal glands. So these receptors would then react to the continued production of LH. The glands eventually become hyperplastic and/or neoplastic over time. And, possibly, somewhere in this partially shut down hormonal system lies the predisposition, the vulnerability, which will casue some ferrets to get adrenal. Since all ferrets are very sensitive to photoperiods, it might be that all ferrets are relatively sensitive to "tampering" with the system, but that some due to a probably genetic reason, are extra sensitive. Maybe it's linked to the breeding for fancy colours, maybe it's the breeding for the "overly" hormonal traits that is common among farm ferrets and domesticated animals in general. Nobody knows. Deslorelin and leuprolide (Lupron) are both GnRH-agonists which means they simulate the action of the body's own GnRH. When administered in a continuiously released form (such as from an implant) instead of the the body's own short pulses, it will work by desensitizing the pituitary gland to GnRH, thus reducing the output of the gonadotropines (LH being of specific interest). And this is how the des and the lupron are supposed to work as preventatives. Without, or with or only very little production of LH, there will be no response or activation of the LH-receptors in the adrenal glands. Provided that you start before things have developed into a problem, it might be possible to avoid what is believed to be the trigger of the disease in the first place. At least in theory It'll be interesting to see how it pans out.
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Post by miamiferret2 on Mar 19, 2011 18:06:10 GMT -5
Marie that is an interesting (statement you made about breeders and "overly hormonal" traits in their ferrets.). I think you may on the money with that one. If some ferrets are more hormonal than others, have larger hormone spikes, than others, then it makes sense that when they are altered they will be more prone to developing adrenal tumors.
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Post by Deleted on Mar 20, 2011 4:30:12 GMT -5
Here's Schoemaker's article on the role of LH in causing adrenal disease in neutered ferrets (full PDF attached): Schoemaker NJ, Teerds KJ, Mol JA, et al. The role of luteinizing hormone in the pathogenesis of hyperadrenocorticism in neutered ferrets. Mol Cell Endocrinol. 2002;197:117–125. Abstract: tinyurl.com/dckagt"Four studies were performed to test the hypothesis that gonadotrophic hormones, and particularly luteinizing hormone (LH), play a role in the pathogenesis of hyperadrenocorticism in ferrets: (I) adrenal glands of ferrets with hyperadrenocorticism were studied immunohistochemically to detect LH-receptors (LH-R); (II) gonadotrophin-releasing hormone (GnRH) stimulation tests were performed in 10 neutered ferrets, with measurement of androstenedione, 17á-hydroxyprogesterone and cortisol as endpoints; (III) GnRH stimulation tests were performed in 15 ferrets of which 8 had hyperadrenocorticism, via puncture of the vena cava under anesthesia; and (IV) urinary corticoid/creatinine (C/C) ratios were measured at 2-week intervals for 1 year in the same ferrets as used in study II. Clear cells in hyperplastic or neoplastic adrenal glands of hyperadrenocorticoid ferrets stained positive with the LH-R antibody. Plasma androstenedione and 17á-hydroxyprogesterone concentrations increased after stimulation with GnRH in 7 out of 8 hyperadrenocorticoid ferrets but in only 1 out of 7 healthy ferrets. Hyperadrenocorticoid ferrets had elevated urinary C/C ratios during the breeding season. The observations support the hypothesis that gonadotrophic hormones play a role in the pathogenesis of hyperadrenocorticism in ferrets. This condition may be defined as a disease resulting from the expression of LH-R on sex steroid-producing adrenocortical cells." Attachments:
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Post by Deleted on Mar 20, 2011 4:52:20 GMT -5
This is Schoemaker's dissertation on adrenal disease. It's from 2003 and there have been some more progress since then, but it's still an interesting and easy to read article. igitur-archive.library.uu.nl/dissertations/2003-1128-094343/inhoud.htmOne interesting thing in the absract in regard to my previous post: " The next step was to study the presence and function of gonadotropin receptors in the adrenal glands of healthy ferrets and of ferrets with hyperadrenocorticism. Positive immunohistochemical staining with a luteinizing hormone receptor (LH-R) antibody was found in adrenal glands from young, healthy, intact ferrets. In addition, adrenal hyperplasias and neoplasias from ferrets with hyperadrenocorticism stained positive for the LH-R. To investigate the functionality of the LH-Rs, in vivo GnRH stimulation tests were performed with healthy neutered ferrets and neutered ferrets with hyperadrenocorticism. These studies showed that although LH-Rs are present in the adrenals of young healthy ferrets, they are not functional. Based on in vitro stimulation test, performed with adrenal cells suspended in culture medium, it became clear that neither GnRH nor FSH had a significant influence on the production of adrenocortical steroids, whereas hCG induced the production of these hormones.
" So all ferrets, healthy and adrenal diseased, have the LH receptors, but in healthy ferrets they are not functional, not "activated". (The hCG that is mentioned in the abstract results in an LH surge when administered, so this is to test the respons to LH).
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Post by Deleted on Mar 20, 2011 4:59:34 GMT -5
Some other interesting articles.. There are certain mouse strains (and since it's specific strains it would be obvious that it's genetic in those cases) that has a similar adrenal problem as ferrets, in that they will develop adrenal disease if surgically castrated. endo.endojournals.org/cgi/content/abstract/144/9/4123Mouse Strain Susceptibility to Gonadectomy-Induced Adrenocortical Tumor Formation Correlates with the Expression of GATA-4 and Luteinizing Hormone Receptor Certain inbred strains of mice, including DBA/2J, develop adrenocortical tumors in response to gonadectomy. Spindle-shaped cells with limited steroidogenic capacity, termed A cells, appear in the subcapsular region of the adrenal gland, followed by sex steroid-producing cells known as B cells. These changes result from unopposed gonadotropin production by the pituitary, but the adrenocortical factors involved in tumorigenesis have not been characterized. GATA-4, a transcription factor normally expressed in fetal, but not adult, adrenocortical cells, was found in neoplastic cells that proliferate in the adrenal cortex of gonadectomized DBA/2J mice. <SNIP>
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Post by Deleted on Mar 20, 2011 5:02:58 GMT -5
The possible correlation between adrenal ferrets and adrenal mice is discussed: Gonadectomy-induced adrenocortical neoplasia in the domestic ferret (Mustela putorius furo) and laboratory mouse.www.ncbi.nlm.nih.gov/pubmed/16537928
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Post by Deleted on Mar 20, 2011 5:03:41 GMT -5
Okay, I'll stop my article spamming for now.. ;D
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Post by Sherry on Mar 20, 2011 10:21:37 GMT -5
Hey, the more we can understand about this horrible disease, the better prepared we'll be when we have to ask the vet questions about it because our own are showing symptoms.
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Post by miamiferret2 on Mar 20, 2011 10:34:04 GMT -5
I think that is what the adrenal vaccine is supposed to do (prevent LH-R's from becoming "functional"). I'll ask Dr. Murray to be sure since he said he is involved in that study. I'm sure if the vaccine works and is approved it won't be out for another 5 years or so. Maybe more since they'd have to wait for the ferrets to get up there in age to see whether they develop adrenal disease.
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