Bob Church on Adrenal Disease
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The following is the complete and very lengthy series of Ferret Mailing List posts on adrenal disease. Written by Bob Church.  The e-mail address shown is very likely no longer valid.

Date: Sun, 1 Feb 1998 03:50:08 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Stuff

Ok. folks, I'm running a bit behind on finishing the adrenal post, mainly because the data conflicts so much with a couple of papers that I've read. I hesitate to post something that may be obviously biased, so I am setting on the stuff and pondering it. I will post the result no later than next weekend, although, like I said, the results were somewhat different than what I expected.

That's the problem with being a scientist; the ethics of reporting values which are apparently biased without attempting to explain or correct for the problem. I've just been considering reasons for the difference, that's all. I will report the findings, I'll probably just put a lot of disclaimers into the post.

One other problem is the post will be quite long, so I'll probably have to post it directly to Bill (and I know his middle name, naa naa naa) so he can post it as space permits. Its way longer than 125 lines so be prepared for a long read (I can never figure out the 125-lines thing anyway because I use a file size method that doesn't translate in my brain. Sort of like I can use metrics or miles, but I have a hard time translating them. Well, I *know* a pound is .45359237th of a kilogram. Just stuck in my head, like pv=nrt and stuff like that. Just don't ask my phone number...)

As for *why* the adrenal reports were so biased? The FML is *not* composed of typical ferret owners, its that simple. Rather I should say, the people who reported the adrenal stuff are not typical ferret owners. A very large part was reported from ferret shelters or people who adopted ferrets that had a history of illness, neglect or malnutrition. That means the sample was not random. What I'm trying to do is see if I can correct for the skew, but it's not looking favorable. As for any correlations, well, if I can't correct for the skew, then any correlations would be as good as "96% of all Americans who die in accidents are wearing clothing, therefore clothing causes accidents." The skew can hide the cause-effect relationship. Everyone knows its nudity that causes accidents.

Bob C and 20 MO Accidental Biters.


Date: Tue, 10 Feb 1998 05:13:22 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Post, Part Uno.

Ok, folks, here are the official results and commentary, with a few extra tidbits thrown in regarding sampling and observer biases. Up front, I do not trust much of the data gathered from FML members--not because of the dishonesty of FML readership, but because of how *good* we are (I'll explain later). The post quite long, so I've broken it into several parts for bathroom reading over the next few evenings. I'll say some things some of you will *NOT* want to hear (which included me), but please hold off flames or other comments until the entire series is posted. It will save us all a lot of space and time because what offends you today may be answered tomorrow.

What you will be reading is a combination of FML data, compiled with about 20 scientific journal/book sources. Because of the need for brevity, those sources will not be individually cited, but will be added as a bibliography at the end and you can look it up yourselves. Disclaimer: this is *not* a scientific study, and as such, I would never submit it for publication. Do not assume it carries the weight of papers that have undergone rigorous juried review. Also, the FML format limits the length of posts, cannot carry graphics, and is read by people of various educational levels. To write a paper to the level of a scientific journal would require about 8 FMLs dedicated to nothing but the subject, with 5 or 6 graphic attachments to demonstrate the statistics. It is not possible to do such work, and if it were possible to get the space and add the graphics, without being condescending, few readers would have the necessary background to follow the paper properly. Don't be insulted by this; I can fix a car but don't speak "Autoshop," mathematics gives me a headache, and I will never be as smart as the average European because even though I can read in several languages, I can't hardly speak English good. The language of physiology is a difficult one to learn, and no one should be embarrassed because they don't speak or understand it.

With that in mind, let me give the bad news first.

1) Treatment of Adrenal Disease. I'm sorry to say, *no* treatment but one has *any* long term effect on the disease, and that one is only really effective if when the adrenal disease starts early in the life of the ferret. Surgery is the only effective treatment. No chemical treatment, such as Lupron, Lysodren, or Prednisone, has been shown to significantly extend the ferret's life after the initial onset of the disease, nor have they been proven to do anything more than mask or slow the progress of the disease. No environmental treatment has withstood vigorous scientific examination and still result in positive results. Homeopathic remedies have not shown *any* ability to extend the ferret's life, nor do they show any more than a moderate lessening of symptoms. In the significant majority of cases, any type of treatment, other than surgery, only offers superficial and limited results.

HOLD OFF COMMENTS UNTIL THE SERIES IS DONE, PLEASE! I know these statements are going to cause some disagreement, but I will offer explanations in the next posts that will answer many of your questions. Please wait, and we can hash this out at the end. Ok?

The average reported lifespan of ferrets that did not have ANY treatment or surgical intervention was 1 year +/- 6 months. The same times were reported for *ALL* chemical treatments, including Lupron, Lysodren, or Prednisone. If the adrenal disease had an onset when the ferret was under or about 3 years of age, surgery gave the ferret 3 years +/- 6 months. However, if the adrenal disease had an onset after 4-5 years of age, that survivorship dropped down to 1.5 +/- 6 months. In all cases, the average length of life was longer if surgery was performed, however, the risk of sudden death was significantly higher in ferrets older than 4-5 years.

Chemical treatments were reported to partially or completely return the ferret to working order, with partial or complete return of hair as well as an improvement in other symptoms. This was reported about the same in all age classes of ferrets. The interesting thing about the chemical treatments, or even of homeopathic treatments, was the degree of observed improvement was always higher than the degree of actual improvement. In other words, if a ferret had an improvement in hair growth, it was seen as "the ferret getting better," even though the course of the disease was the same as if nothing was being done and the ferret died within a year or so. This is best illustrated by a comment mailed to me, "The vet said the situation was hopeless, that the ferret could not survive surgery, and it could die as early as in six months....But placed on [homeopathic] medicine, the ferret lived another 14 months!!" 14 months is within the "mortality window" of untreated adrenal disease, so there is no evidence the treatment worked at all. What was seen as the improvement was a return of most of the hair and decrease in aggression, which may have occurred anyway, but such those type of improvements in no way should be taken as evidence that microscopic changes took place within the adrenal gland that altered the disease. Maybe it did, but there is *no* factual evidence.

I want to emphasize this. In an extensive search through all ferret-related papers since 1985, not a single published study could demonstrate marked improvement of the ferret by any means other than surgery. That is not so say such studies don't exist, nor am I saying such results are not possible. What I am saying is nothing has been published, other than a few articles with poor sample sizes (or other methodological problems).

Surgery resulted in remission of symptoms in most cases, but in those cases where surgery was not going to work, it was immediately seen as a "non-improvement." If the ferret was left untreated, the disease would kill the ferret between 6 months to 1.5 years, with the average death being about a year into the disease, so on average (worst-case), the ferret got an extra 6 months or more because of surgery, and in the best case, years of extra life.

Personal comments: I am a great believer in "less is better" when it comes to medical care. Personally, I would be dead six times over if not for the surgeries I have placed myself through. Before I took on this self-assignment, I was essentially anti-surgery for the older ferrets, supporting surgery only for those cases with an early onset. For ferrets under 4 years of age, I believe surgery is the only option; do it as soon as possible after blood tests have confirmed the disease. There are a number of risks involved in such surgical procedures, but they only result in a small number of serious complications; the sudden death rate seems to be under 5% from what I can dig up, which is fantastic considering the difficulties of operating on such a small species. From the descriptions of ferrets dying during surgery, they seem to be of two types; either they were extremely ill ferrets with massive tumor involvement, (which suggests a late diagnosis or multiple-organ involvement), or the deaths seem to be anesthetic-related, such as from anesthesia-induced shock (happens even in people). In the former, sudden death should be expected because of the ferret's condition. In the later, such events are unpredictable. In either case, unless some other proof exists of malpractice, these deaths should be considered part of the risks of surgery, and accepted as such without blame being assigned to doctor or owner.

For ferrets older than 5 years, there does not seem to be any significant difference between chemical treatment nor non-treatment. Surgery can add about 6 months on average to the lifespan. I question the poor results from late surgery but cannot find any outside stats to contradict them. I suspect the surgical results would be better if the adrenal disease was of a primary onset rather than a secondary manifestation (like when the ferret has already had an adrenal removed). I just don't have enough data to be able to say that ferrets over 5 years of age who get adrenal disease for the first time have better surgical results than those who have already had adrenal surgery. I strongly suspect it is so, but cannot say for sure. Because of that, I recommend that if your ferret is otherwise healthy and this is their first onset of adrenal disease, do the surgery. As for the second onset, discuss all options with your veterinarian and make your decision to best suit the needs of your ferret. You have to weigh the additional 6 months or so with the surgical risks, knowing the end results will not be much different.

Now, this is all very clinical and non-emotive, which is what is needed for this type of discussion. If I wanted to push my belief system, I would be arguing *against* surgical procedures. I have been (mostly) convinced by looking at all available data; I have refused to comment on this (or share this) with anyone associated with the problem so no one could question the ethics of the study. In other words; I can into this thinking I could find better options than surgery. I found I was wrong.

This is *not* to say existing chemical or homeopathic remedies (or future ones) will not eventually replace surgical treatment in many cases. What I have found is a lot of research is needed in those areas. It is also not to say that, for some, such treatments actually result in improvement of symptoms, or even reversal of the disease, but statistically, they are less than 10%. That means, 90 ferrets will take the treatment and will *not* be any better for it, while 10 ferrets will show a reversal or improvement of symptoms. The problem is, are these reversals due to the medicines or because of the animal having a spontaneous remission of the disease? Like I said, rigorous examination of the facts needs to be done, which means, boys and girls, ferrets will die in scientific research. There will be a price to pay for medical advances against this disease. But there *is* something we can all do to help.

The problem with any research is getting the samples. I am studying the differences between wild and domesticated forms of the ferret, which could not be done if caring individuals have not donated (and still donate) their ferrets to the cause. I'm not going to kill an animal for its skeleton, so this allows some people to have the satisfaction of helping determine ferret origins, and I get what I need as well. The same is true here. If you choose to treat your ferret with chemical or homeopathic remedies, at the ferret's death donate whatever is needed to a researcher who is willing to compile the medical and histological data. Perhaps Dr. Williams can make some suggestions here. Special handing of specimens *must* be done, but your vet can do it for you. As far as *I* am concerned, if you want to promote any procedure other than surgery, you have an ethical responsibility to provide proof of your claims, which is tied up in the carcass of your dead and beloved pet. Until these types of studies are done, THERE WILL NEVER BE PROOF that chemical or homeopathic remedies (including light treatment) have any substance in the treatment of ferrets suffering adrenal disease. Like it or not the proof is in the pudding, so put up or close the trap.

I have myself in enough hot water until the next post, which will cover why some forms of treatment seem to help (when they don't really). Following posts will discuss the treatment of symptoms, the USA-World adrenal difference, some genetic-environmental questions, the question of early neutering, and finally, a summary about everything. They will come every-other day, mostly because they are difficult to write and I have school to think about. As I said, please hold off all questions and flames until the series is finished; write your questions down, but hold off on sending them until I finish this thing, ok?

Bob C (C as in Custer) and 20 MO Wild Frettchens


Date: Thu, 12 Feb 1998 17:16:38 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Post Nummer Zwei

I mentioned there seemed to be at least two different things going on in ferrets, resulting in adrenal disease. Mind you, there may actually be more, but from the data collected and the stuff in print, I think right now all you can safely say is more than one factor lurks behind this disease. So what is the implication of "more than one?"

Before we answer, let's address the question of what can *cause* adrenal disease. One of the first steps to any scientific investigation is to try and limit the study to the possibilities, rather than the "but what ifs..." So, making the assumption that adrenal disease is initiated by some sort of abnormal growth within or adjacent to the adrenal gland, what basic things could cause it?

The list could include genetics, environmental pollutants, diet, body condition, stress, chance, or even that the disease is a species "weakness" (like how specific diseases tend to be more common in certain animals than others). While some people may be convinced that only one of these is the "real" reason, remember I said the disease appeared to have at least two different manifestations. Now do you see the implication? It suggests at least two factors may be responsible. These two factors could be linked, or they could be independent, but only scientific testing will ever prove the relationship--or the reasons--one way or another.

I believe there is a genetic component involved; those that kept track of their kits noticed adrenal disease sometimes ran in family lines. The statistics are very poor for this because few breeders care to follow the babies they pump out. This is a shame, because it is quite conceivable that vigorous and healthy hobs and jills may be spreading a recessive trait within the population. This is what all the hoopla about blood lines is all about, as well as the "Marshall Farms Hypothesis," (being that MF ferrets are predisposed to adrenal disease). If you accept the idea that non-American ferrets have a very low incidence of adrenal disease, its quite easy to point the finger at the DNA and blame it, when in fact there may not be any relationship at all and the reason could be because of some other factor within the US and Canadian populations.

For a moment, lets assume it is genetics. Do MF ferrets have a higher proportion of adrenal disease than other ferrets? Not if the people who sent data are to be trusted. About half of the ill ferrets did not come from MF at all. Assuming MF supplies about half of the ferrets for the pet market, if they were more prone to adrenal disease, there would have more cases reported in proportion. The reported statistics suggests parity; in other words, it seems as if all "brands" of ferrets are equally susceptible in contracting the disease. (I don't know what the actual percentages regarding how many MF ferrets are produced compared to other breeders, nor do I suspect anyone does because few breeders report their kit placement. If you disagree with my assumption that 50% of ferrets are MF, then by all means provide a substantiated source). One thing that has struck me is the apparent inability of people to look past what the numbers *are*, and see what they *mean*. For example, suppose 100 ferrets are MF and 100 from other sources. 20 ferrets get adrenal disease and about half are MF. That is parity because all populations contract the disease equally. But what if 150 ferrets are MF and only 50 from other sources and out of 20 cases, 15 are MF and 5 are other? Well, that's STILL parity, but it appears MF ferrets get the disease more than others; after all, its 15 to 5 right? The result is many people point out the majority of adrenal cases occur in MF ferrets, but they never correct for the proportionality of breeder demographics. And even if Path Valley, MF, and all the other major breeders opened their books to our inspection, it would still be useless until you figured out how many ferrets were coming from unnamed hobby breeders.

The underlying assumption behind the idea that New World ferrets get adrenal disease in higher proportions than other ferrets is that some sort of founder's effect or breeding bottleneck has taken place. In other words, if true, then some breeders have inbred their ferrets so much that a genetic mistake has become visible. This looks good on paper, but I don't buy it for many reasons, especially two major ones. First, look around you; you see albinos, sables, silvers, dark eyed whites, and so forth. Body sizes are small to large, whippet, standard and bulldog. The amount of variation within the USA ferret-line suggests inbreeding is not a problem. Remember the old biological axiom; the older the species, the more variation, the older the genera, the more species, and so forth? Of course the exceptions are lines that are dying out, but that is not a problem in our furry mustelids. We have *LOTS* of variation. If inbreeding is a problem anywhere, it would be minor and essentially isolated. Support for this contention comes from there being absolutely *NO* significant difference in the numbers of one type of coloration or of body type being predisposed towards adrenal problems. Albinos had adrenal problems about as frequently as sables. I only had 87 reports of coloration, so obviously the sample is small and better investigation may find such a link....maybe.

I also think the idea is flawed simply because the ferrets in the USA came from Great Britain and Europe, precisely where the ferrets in New Zealand and Australia came from. Those populations tend to follow the basic European lead in lack of adrenal disease. Remember, we are assuming accounts of rare adrenal disease are factual, and without contrary evidence such assumptions are valid. I also have to say that in reading dozens of European ferreting books published during the last 80 years, every medical ailment from blackheads to distemper to swollen prostates to torn nails is discussed, but significantly, no mention of a class of symptoms that could be interpreted as adrenal disease is mentioned. These "ferrets and ferreting" books include three from Germany, one from France and 17 from Britain. I've noticed the same pattern in American ferret books; the mention of adrenal disease only dates back slightly more than a score of years ago. Like I said, interesting. Considering the slow acting nature of the disease, if it was a common problem, it would have been mentioned in one of these books.

The same is true in the veterinary literature. I scoured every possible source, from data bases to biological abstracts to the journal indices to books. Nothing in the laboratory papers, nothing in the literature *UNTIL* about a score of years ago, and those reports were almost exclusively American in origin. This lends great support to foreign claims that the disease is largely an phenomenon of the Americas. This is not a claim that should be ignored nor dismissed. Remember this for later.

Back to the idea of founder populations in the USA/Canada, Australia and New Zealand. Modern day populations in all three countries had origins in initial founding colonies that date to the turn of the century. In Australia and New Zealand, except for a handful of exceptions, the present populations are essentially direct descendants from those founding ferrets, and adrenal disease is rare. In the USA, because of the ratting industry from the 1880s to the 1920s, the initial populations were supplanted several times from fresh European stock. Now, understand, founder effects take place because a breeding restriction took place which shifted *EXISTING* gene frequencies, or introduced a new mutation into the breeding pool; if it isn't in other populations, then it must have been "invented." Now, this begs the following two questions. If the problem preexisted, why hasn't it shown up as much in non-New World ferrets, especially those with similar founding populations? And if it is a New World specific mutation, why is only now showing up and not 40 years ago?

This is the trouble. Ever try to introduce a new trait into a population? It takes time; considering the existing range of variation in body types, coloration, color patterns, and sizes, there is virtually no possibility that such a trait could have become established in such a large population is such a short time; if everyone looked about the same or the variation was limited, weeelll maybe. Of course, this is assuming the trait is recessive, which it has to be because more than 70% of you stated the trait does not effect all siblings in a birthing, and if it were dominant, it would. (Of course, the jill could have been bred to more than one male, but that is not common in USA breeding practices, and induced ovulation makes it basically a moot point). So, if adrenal problems are genetic, it must be something brought in with the original founding ferrets that only affected USA populations, or something that started within a few generations of the founding of USA populations.

But Bob, didn't you say you thought adrenal disease had a genetic component? Yes I did. The truth is, I'm beginning to wonder if the disease doesn't parallel a similar situation in some forms of human diabetes. In Native Americans, diabetes is quite common, but in earlier populations it was never manifested. So a group of people lived in the Americas for 12,000+ years, and diabetes was rare. Europeans come over, teach the locals how to eat better food, and the locals respond with obesity and diabetes. In this case, there is an demonstrated underlying predisposition for the disease, but without the proper environmental factors, the disease never comes out.

Its the old "nature-nurture/genotype-phenotype" debate. And it makes perfect sense. Why is human cancer so difficult to control? Because, in many cancers you don't get cancer unless you have the predisposition AND are exposed to an environmental stimuli. That is why some smokers get lung cancer and others merely die from emphazema or heart disease. Smoking is the environmental component, but some studies have shown that a genetic component is present as well. Remember the last post (and the top of this one) where I said the adrenal problems seem to have more than a single causality? This would go a long way in explaining why more than 60% of you said your adrenal ferret was currently in or came from a shelter. This suggests some sort of commonality that is causing this predisposition to manifest itself. What if the environmental component (if indeed this is the case) was something that was common in the USA/Canada, but rare in Europe, Australia and New Zealand?

Could this help explain 1) why adrenal disease is so common in the New World; 2) why, with the introduction of USA practices, adrenal disease seems to have been lately increasing in Britain; 3) why the disease appears to be common in animals exposed--in mass--to similar environments, such as in shelters or mass groups in pet stores; and 4) why the disease responds poorly to non-surgical treatment (because even with the treatment, the ferret is *still* exposed to the triggering factor)? Stay tuned for further details when Bob pulls down his shorts and dares all to light their flamethrowers.

Bob C and 20 MO Socksharks


Date: Mon, 16 Feb 1998 00:38:27 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Post Numero Trois

The last post left off with my telling you about a bit of the history of adrenal disease. I want to be clear on this; just because something is not mentioned in a reference or it is not diagnosed by veterinarians, it doesn't mean it isn't there. For example, sometime ago I was interested in canine distemper and was looking through the old literature and found very little. However, when I started looking for the sweats, I found a tremendous amount. Just because I couldn't find old references to adrenal disease doesn't mean some are not there. On the other hand, using old documents for an information search is a tried and true part of archaeology; these old records are called ethnologies, and an archaeological report without some reference to one is hard to come by. I have done a similar thing with ferrets to build an ethographic reference. I've read about every ferret book published (the first dates to 1790), put the data concerning disease, life span, weights, reproductive age, etc., into tables and gandered at the results.

What I found is, the ferrets about a hundred years ago are about the same as those today in terms of life spans (6-8 years), body weight, diseases, reproductive cycles, and litter size. Knowing that the quality of diet is very important to the reproductive status, I specifically looked to see if the ferrets were breeding at a year old or older. A good, high-quality diet assures the first, but any mustelid that is nutritionally stressed will delay reproduction until the second year, either by not coming into heat/rut, or by absorption of the embryos. Almost all accounts had ferrets breeding at one year of age, with litters averaging 4-8 kits. You can't expect better today, with all our vast knowledge and vet care. In every field I looked, I found the descriptions from the past to fit exactly in with today's data. (I do feel the average age at death was lower, indicating more ferrets died earlier, but the ranges were the same) To me, this means people treated the ferrets quite well and were concerned with diet and health. Therefore, I feel the assumption that adrenal disease was uncommon a hundred years ago is safe to make. If they didn't know that was causing it, they would have at least mentioned the symptoms.

I am convinced that the proportional differences in adrenal disease rates between the Old and New Worlds have more to do with environmental factors than genetics. I'm not implying genetics is not important, for I actually feel ferrets as a "group" are prone to them. I just feel various environmental factors are also important, and an understanding of what is different between the two groups is in order.

Food: The USA/Canada primarily feed dry kibbled foods; while such foods are being accepted in other countries, pullets, carcass parts and raw meat products are still commonly given. Think about this; as far as I can reconstruct, ferrets in the USA had a low incidence of *reported* adrenal disease until the late 1970s. Now, this might be coincident with better veterinarian diagnoses, more treatment of ill ferrets, or the widespread introduction of dry kibbled foods, which took place at about the same time. A possible problems are a shift from foods having lots of fiber (fur) and roughage to eating something that comes out like paste.

I *have* to get off track just a moment here. I just read Fox et al 1997 paper on Helicobacter. A superb paper and one that left me wondering out loud if some of the problems we are recently having with recurrent bowel inflammatory disease, ECE and the like might be tied to expecting our little fursharks to push their intestinal toxins out the back using paste rather than fur and fiber. It is only a recent discovery that human bowel cancers are tied to fiber content. Kibbled foods are essentially a paste made of finely ground foodstuffs; a vole has fur, bone bits, teeth, and non-digested parts pushing the nasties through. Some recent research has shown dogs and cats are generally healthier with fewer down days when fed a more natural diet. Aside over.

Feeding: Here we generally feed ad libatium; that is, we leave food in a dish and the dish with the ferrets at all times. This is in part because someone once erroneously equated a high metabolic rate and food requirements to mean they have to eat all the time. This is not only untrue in healthy ferrets, but it would be impossible to do in the wild. What do you think fat is for? Ferrets do just fine if fed twice a day, and will adjust their eating habits accordingly. There are some very nasty little papers that suggest animals eating ad lib have fatter bodies and shorter lives that animals on a bidaily diet, which has been a traditional practice in most other places ferrets are kept.

Living Environment: In the USA/Canada, ferrets are house pets and are rarely taken into the out-of-doors. Most other places house ferrets outside and they are rarely taken indoors.

Photoperiodism: In the USA/Canada, indoor ferrets are constantly exposed to unnatural light periods. I remain unconvinced that full-spectrum light is any different than the ol' tungsten lamps, since the latter has been used for decades to control photoperiodic cycles in both birds and mammals, but I am concerned about the photoperiod cycle in general in modern environments. This isn't a problem for ferrets housed outside.

Trace Nutrients: No one can tell you exactly what trace nutrients human beings need, and we have been spending billions to find out. Very little time or effort has been spend on discovering the essential trace nutrients for ferrets. Remember, ferrets were domesticated from polecats, who evolved as primary carnivores eating fresh meat on a frequent basis. In a cosmic blink of an eye, they have shifted from eating carcasses to eaten dried up bits of preground paste.

Exercise: Ever try to work out in closet? Need I say more?

Inactivity: Inactivity is mostly due to boredom rather than small cages. I've included boredom because all systems of the ferret are affected, including the endocrine system. Bored animals and people have been shown to have higher disease and death rates. It might take awhile, but you can be bored to death. Continued in the next post.

Bob C and 20 MO Furrbutts


Date: Wed, 18 Feb 1998 13:20:20 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Post Numerus Quattuor

Before I get into this next part, I just wanted to thank all those who have helped the flow of this discussion by refraining from posting comments until the series is finished because it allows me to concentrate on getting the stuff out rather than defending statements. Trying to take an in-depth look at a complex disease with little published data regarding causes is not only time consuming and difficult, but to then to spread them out in an attempt to lessen reading (and FML space) burdens makes it all the harder. Thanks for (private) letters of encouragement, and more thanks to those possessing the maturity and insightfulness to withhold comments until the series is finished. Especially after today.

So far I have compared basic environmental differences between ferret ownership in the USA/Canada vs. everyplace else. But environmental differences are not just food, housing and lighting. By using the word environment, I am referring to anything not of a genetic nature. In other words, your genes allow the potential of growing to six feet, but outside factors can make you shorter (or taller). American ferrets can be exposed to unique environmental factors that are not typically found in other parts of the world; at least not in the same degree.

Paramount among these factors are two which I will discuss; shelter conditions and neutering. I expect to raise some eyebrows in both areas. When I discuss shelter conditions in the USA, I am not discussing filth nor inadequate conditions, so *NO* comments on that. During my travels, I have visited maybe 35 shelters, and not one, even on a bad day, was unsafe for the ferret. In some shelters, the amount of resources spent was outstanding, with ferrets being given wonderful care.

I'm thinking of something else; specifically, stress. Ferrets are domesticated polecats, and as such follow a predictable mustelid pattern of behavior (albeit somewhat modified by the constraints of domestication). That means ferrets are territorial and solitary animals, and indeed they are, as feral conditions and lab experiments have shown repeatedly. But most mustelids, including ferrets, will establish a sort of dominance structure when forced to live together. Eventually, they accept each other more as siblings than anything else as the community establishes. With a few exceptions, this never happens in shelters. Ferrets come and go, cages are stacked next to and on top of each other, and the entire room is filled from floor to ceiling with the odors of strangers. If the shelter is full, human contact can be short. Its no wonder that shelter ferrets can be nippy, many show signs of immune suppression, or even blow their coats. I commonly heard shelter operators say, "this little ferret is suffering from stress right now..."

Of all the replies, almost 70 percent said their ferret was either adopted from a shelter or lived in shelter conditions for part of their lives (In this category, place getting thrown in a box and stored behind plexiglass in a pet store until sold). Only three out of ten ferrets reported to have adrenal problems came from private breeders. On the surface, this might be seen as evidence that commercial ferret farms are breeding ferrets with compromised genetics, but it could just as easily mean that there may be a common environmental trigger. One other thing; when a privately bred ferret was adopted from a shelter, they also had the same 70% chance of contracting adrenal disease down the line.

Hard to believe, isn't it? I have three fairly good papers describing stress-related problems in ranched mink, who show such symptoms as hyper-aggression, hair loss, diarrhea, extreme apathy, neurotic behaviors and self-mutilation. Another paper talks about how mink will form a ranked social grouping when forced to live together, just like ferrets, and once the dominance relationships are set up, rarely fight, just like in ferrets. But when placed into conditions where they are constantly exposed to unknown mink, even the sight of another mink causes quantifiable stress. Now, the papers are really concerned in reducing fur injury, and the mink become coats long before adrenal disease would have a chance to become apparent. The reason I am mentioning the studies is because 1) no such study exists for ferrets, 2) mink and polecats are acceptable analogs for ferrets, and 3) the confinement and close proximity of mink closely parallel that found in ferret shelters.

BTW, the fur farmers found placing wood barriers between cages to block visual views was effective in reducing stress, even if the mink could easily smell each other. The only other effective stress-reducing procedure was increasing the space between cages. Could this be a factor in adrenal disease in our little furbutts? I suspect it is at least a part of the problem, but I admit there has been no specific study looking into the issue. More comments later.

The other issue is early neutering. This is a monster can-o-worms. Let me define early neutering. Growth patterns vary from species to species; in most, the onset of sexual maturity is prior to the mammal reaching full growth. But not in most mustelids. The ferret reaches 90-95% of its growth in the first six months. By the end of the first year, its bones have stopped growing and are fusing together. This is before or at the onset of the first possible reproductive cycle. I define early neutering as neutering before the growth cycle is complete. Late neutering is after the growth cycle is complete. I assume a growth cycle is complete when the ferret has reached 90% of a typical adult weight, because even though the skeleton has stopped growing, the ferret can still put on weight, especially the males. In an unneutered male ferret, this is muscle mass due to testosterone; in unneutered females, its body fat.

Now here is an instance where statistics can fool you. The survey reported early neuters had almost a 80% higher rate of adrenal disease compared to late neuters. Sounds terrible, right? The problem is, what's the percentage of early neuters compared to late neuters? At least 80%? When I normalized the values, I found early neuters and late neuters to have about the same rate of adrenal disease. The stats have other problems as well; the FML is not a typical slice of ferretdom--not even in the USA--and FMLers are far more likely to adopt sickly ferrets than other people, which has a serious impact on the numbers. For both reasons (and more, including a possible bacterial or viral link) I cannot determine if early neutering has a definite negative impact on the ferret in regards to adrenal disease. Size? Absolutely! Adrenal disease? Just can't tell.

What is interesting about the survey is it showed females were twice as likely to get adrenal disease as males. This could suggest adrenal disease was sex- or hormone-linked. Breeder females had the lowest incidence of adrenal disease, followed by breeder males. I don't trust the numbers because the reported sample was much too small, but it does suggest a hormone-link. Or does it? Are breeder animals housed or handled differently than neutered ferrets? Do they handle stress differently? See how the question becomes convoluted and difficult to define?

We are almost at the end, just a post to tie things together and a post to suggest courses of action. Then feel free to pepper me with any questions you wish; but I'll say right now, I'll only answer those questions asked politely and will ignore any rude question or questioner. This isn't about who is right or wrong, nor is it about me or you. Its about a serious disease attacking our ferrets and a simple exercise attempting to define the questions, because currently, there are no answers.

Bob C and 20 MO Sockoholics


Date: Wed, 25 Feb 1998 17:06:21 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Post Numero Cinque

The statistics gathered from the FML are biased at best and unusable at worst because there is no way I can demonstrate the demographics of the FML is similar to ferret owners as a whole, and between you and me, just the fact that every FML person has or uses a computer daily is evidence of that. Even taking into account several previous surveys, the demographics of the FML cannot be fairly compared to any other group. This has important implications regarding the ferret list in general, and one I need to discuss prior to the adrenal summary, because it sheds light on what we see posted here.

I'm sure you have all heard the joke, "Those who are against me are liars, and those who use statistics against me are damn liars." You can use statistics to prove almost anything. All you need to find are two things that statistically correlate to each other and you can make a point. The problem is, a statistical correlation does not mean there is a cause and effect correlation. My favorite illustration of this is "Nearly 100% of people with severe hemorrhoids use toilet tissue." Statistically this is probably correct. The trouble is, no cause/effect relationship has been demonstrated. Statistics show mathematical correlations, but only people can take those correlations and look for cause/effect relationships. Scientifically, this requires rigorous controlled testing, which for those of you who are squeamish about such things, usually involves the use of ferrets for medical research and their subsequent sacrifice.

The toilet tissue argument is what is happening on the FML regarding adrenal disease. Read carefully; I am *NOT* saying *ANYONE* is wrong or right--all I am saying is not a single person has shown a cause-effect correlation. In addition, each and every one of the supposed solutions are done without scientific rigor nor with controls. By itself, this makes the data essentially useless. Not totally, but pretty much so.

For example, and I am talking not just about homeopathic treatments but any treatment, how do you know the change in the ferret is due to a specific treatment and not because of additional handling? Touch therapy is as old as the beginning of human culture and it works; lots of studies have shown touch to increase immune responses and there are a couple of documented cases where touch therapy has been attributed to the remission of cancers in terminally ill people. So what part of treating the ferret is the additional touching, and what part the medicine? You don't have any controls, so you can never be sure. You can believe what you want, even suggest it as a course of action, but you have no proof.

Another problem with FML data is we are subject to a constant bombardment of symptoms, treatments, theories, etc. We are not the typical ferret owner. I know; I've met some and you would be extremely surprised to discover how little the average ferret owner actually knows about their carpet monkey. The longer you read the FML, the more you learn about ferrets until you reach the point that there are few medical surprises. This does two things; it makes each of us think we know as much as people who have spent a decade learning the physiology of animals, and it makes us feel hopeless in the face of certain severe illnesses.

For example, I have been told canine distemper is 100% fatal, and I believe it. Yet, I know of at least three ferrets that has survived it, albeit with some sort of permanent disability. A similar thing occurs with the constant influx of adrenal posts; we hear it so much that they become paramount in our mind, making the actual severity, demographics or survival rate shift from reality to FMLity, which you cannot assume to be true or real. In other words, because we hear of it so often, we start to grant it far more importance than it actually deserves.

I think that false sense of danger taints our perceptions of how we view adrenal disease. While I may know what percentage of FML ferrets display adrenal disease (maybe 10%), MOST of them don't die from it until they are past 6 years of age. That is within the mortality window of the average ferret, even without adrenal disease. Think about this; what do you think *you* will die from when you get near that magical 77 year mark? Humans die of strokes, heart disease and cancers (unless you smoke and its much worse). Our species seems to have a weakness in those areas. The same might be true of ferrets; the "large" number of adrenal problems we see might be an indication that the ferret is actually in its declining years. Don't confuse the early onset type of adrenal disease with the late onset. I personally believe we are looking at two different disease processes here, but more on that in the next--and last--post.

So what I seem to be saying is we can come up with all sorts of reasons for the adrenal disease we seem to be seeing, but without proper statistical procedure, known demographics, and careful analysis of the results, we really don't have anything other than rumor and innuendo. Yes, we *know* something is going on, but the relevance and extent of that knowledge is uncertain. What is needed is solid scientific research, the kind that resorts to experimentation on live animals. We need this basic knowledge base in order to accurately assess the true danger that exists to our ferrets.

Science is very much like law (except a scientific dream team rarely gets millions of dollars) in that you must have unbroken links between the suspect and the event. Since arguments are similar to a series of links in a chain, break a single link and the entire argument fails. For every one of the possible reasons I could come up with that could cause adrenal disease, I could break one or more links, each the intellectual equivalent of "If the glove don't fit, you must acquit."

Does this mean that none of the possibilities I've mentioned are possible? Of course not. I'm convinced more than ever that adrenal disease is an environmentally-triggered genetically-predisposed disease. Which is probably old news to those investigating the issue, but, belief is not evidence, and solid evidence for any cause/effect relationship simply does not exist in the literature.

Now, I have a final post after this one and then I'll make myself available to answer questions on any research I've done, the references will be made available, etc. Bear in mind this sort of discussion is necessarily verbose, and with the size of the FMLs lately, when a post goes over 125 lines I have to ship them to Bill who puts them in ASAP. So there is this sort of surreal waiting period until you see stuff. That isn't me back-pedaling or running off finding evidence, but just that I see the question one night, post the answer the next night and you see it the 3rd night (or later depending on various factors). Patience. And keep emotions out of it, ok? For much of this, I could easily do the equivalent of smashing a basketball in your face if I wanted to, but that would detract from the true purpose which is discussing the adrenal issues. It would only force me to use statistical evidence, making me a damn liar instead of just a liar.

Bob C and 20 MO Four-Legged Fursnakes


Date: Sat, 28 Feb 1998 04:55:47 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Post Number Five

This is the last of the adrenal posts, to which I am sure some of you will applaud. It has been hard for me as well, well maybe not from a boredom aspect, but hard nonetheless; I had to give the inter-library loan people a box of designer chocolates so they wouldn't complain. The greatest difficulty has been the long-term posting; I think it would have had a lot more impact if they had ran in a week rather than two. That was unintentional and caused by MF debates, the Ohio bite case, and other stuff which is also important. But those issues filled the FML and placed these posts into the category of "I'll drop them in when I find space." Perhaps I should have divided them into more posts, or posted several parts in a row to get around the FML guidelines, but the work seemed to divide itself into five parts, and I was too busy to argue with it. This last post will also be long but hopefully will be posted sooner than the others. With the publication of this post, feel free to pepper me with objects no larger than a soda can, or questions, whichever you prefer. I will not answer rude comments. I will provide specific references to those with a bonafide interest.

250 years ago, the Philosopher David Hume said that you couldn't infer an infinite cause from a finite effect. I have a photocopy of the paper in which that statement was originally written, and I look at it whenever I work on any scientific paper. While the original purpose behind the statement has little place on the FML, the statement itself can sum up the problems of ferret adrenal disease. What can cause it? I came up with more than a dozen really good ideas, but am no closer today at deciding what causes it that I was three months ago when I started to look into the issue. In fact, I think I know *less* now than then. Perhaps the answer has been scotch-taped to my computer terminal all along; you cannot infer an infinite cause from a finite effect.

What research I've done suggests adrenal disease in ferrets is a multi-factorial problem resulting from a genetic predisposition and an environmental trigger. Because the genetic heritage of ferrets is little understood--we don't have coat colors worked out yet--that aspect of adrenal problems has no current resolution. In other words, ferrets as a group may be predisposed to adrenal problems, or just USA strains, or just specific breeder strains; no one knows. After working on the genetics of the problem, I'm inclined to believe it is a ferrets-as-a group predisposition. Better statistics and controlled testing could resolve this problem in a few years, provided funding and animals for research be provided. There are a few studies, but they do not answer the question of which type of ferret gets the disease, nor location.

Adrenal disease seems to be a geographically isolated disease. Statistically, ferrets in outside of the USA and Canada (or America as in "North") have significantly lower reported rates. Adrenal disease also seems to be a modern disease; that is, after scouring all available records for the last 200 years, I was only able to find a single incidence of what *could* have been adrenal disease, and in that case, my "diagnosis" was based on hair loss and thirst, and could have been something else. Even as soon as thirty years ago, adrenal disease was uncommon enough to not be mentioned in USA publications, including vet-care papers. Some might argue the sudden onset is due to early ferret deaths--they didn't live long enough for the disease to exhibit itself, or that the ferrets were simply killed and no record was made. I reject both arguments because I actually waded through reams of illness reports and cures. The average lifespan of ferrets reported 100 years ago is essentially the same as today, except the average age of death was a little bit lower. Certainly, they lived 4-5 years, which in today's American population, would mean adrenal disease would have been noted. Most authors made every attempt to mention illnesses that only had the faintest possibility of occurrence. In an 1860's version of a vet how-to book, the symptoms of Cushing's Disease is mentioned in dogs, and while the aliments of ferrets took up a dozen pages, nothing similar was even remotely mentioned. I don't think you can assume the disease was there but ignored. These guys LOVED to get their names attached to a disease, as if they invented it. I don't think they saw it or it was extremely rare.

Since the ferrets in the USA, Canada, Australia, and New Zealand all come from the same basic stock, and those same ferrets show a tremendous amount of variation in body shape, patterns, fur color, and other morphological traits, arguing the American ferrets have some sort of inbred genetic problem is rather pointless. It may be that the supposition is true, and it certainly would explain why so many American ferrets get the disease. But then, it doesn't explain why so many American ferrets do NOT get the disease nor why it is so unpredictable. Like cancer, it seems to run in families, but you cannot predict which ferret will or will not get adrenal disease. Which is exactly why I think an environmental trigger is also necessary for the disease to show itself.

I have chosen to assume the genetics are about the same between American ferrets and all others. That is because the initial ferret population in the Americas was so high that a founder's effect or genetic drift becomes improbable. Not impossible, but not very likely either. While I doubt if the America population a century ago rivaled that in Great Britain, it had to equal or exceed those populations in New Zealand and Australia, and guess what? Those ferrets are weaned on environmental conditions similar to those in Britain, and they have similar adrenal disease rates. Assuming the USA has vets better able to diagnose or identify the disease is both nationalistically arrogant and well as unsupported by facts. Did you ever think the reason American vets know more about the disease is because it occurs at rates unnaturally high here? Or that the reason some of reports starting to surface elsewhere might be because American ferret environments are becoming more common?

The trouble is, if this is true, (and at best it is only a working hypothesis), what are the environmental triggers? Either the genetics of the American ferrets and all others are different, or they are about the same. You must assume they are the same UNTIL you can prove otherwise. If they are the same, then some environmental factor must be behind the outbreaks. Since there are a number of environmental differences, ranging from photoperiods to diet to a virus to stress to early neutering, and not a single study has looked into THESE issues, then at this point in time the issue is too complex to resolve. Its that simple. Infinite causes and a finite effect.

Still, much can be learned if we set aside our prejudices and take a careful look into what is the same between the Americas and Europe, and what is different, because therein lies the answer to the environmental trigger, should one exist. Like links in a chain, it may be possible break a link and prevent the disease from occurring. Sort of like the identical twin smoking study done some time ago. One twin smoked, the other did not. In those cases where the twins had a genetic predisposition towards cancer, the smoker got lung cancer. Smoking was the environmental trigger, and breaking the link--smoking--reduced the chances of lung cancer significantly. Don't buy the comparison? Do you remember what adrenal disease is? A tumorous growth in the adrenal gland? So what is lung cancer? I'm not implying they are the same disease--and in fact they are quite different--but just like comparing a TR-3 to a VW bug, they might be different, but much of the mechanisms is similar. They are inherently comparable.

Of all the possible environmental triggers, the most plausible are some sort of biological agent, like a virus or bacteria, stress, early neutering, diet or some combination of these. Photoperiodism might be a contributing case, but since other animals that are as subject to photoperiodism as ferrets, or more, do not exhibit problems, I discount its contribution. An unknown biological agent is certainly a viable option, but little is known of their relative effects in tumor growth. I'm afraid the major environmental differences between American and all other ferrets must lie in diet, stress and early neutering, or some combination.

Early neutering does not seem to be a problem with other species, so it loses some of its credibility in the ferret issue. Still, dogs and cats are not typically neutered at the same relative stage of growth as many ferrets, especially those neutered at about a month of age. This is because the growth curves of the various species are different, so one being neutered at 6 weeks might be the physiological equal to another species being neutered at 3 weeks. I know of no research into this issue.

Diet can also be an important factor. Adrenal disease really didn't start making headway in the Americas until after kibble became a popular food. It is quite possible that the lack of a micronutrient could be causing a physiological problem resulting in the disease. Convinced kibble is a perfect food? I have three references, none more than 5 years old, that suggest "any kibbled food is an approximation of a natural diet and as such cannot supply the diet the [predator] consumed during its evolution." I have had so many requests that I address the diet issue that I will drop it for now in favor of a future post. Still, as a trigger in adrenal disease? I have some doubts.

That leaves stress. Some human research suggests there is "good" stress and there is "bad" stress. Good stress are those events that either strengthen or condition your body towards some event, such as a sporting event or asking someone out on a date. Bad stress is of the type that is not quickly resolved, like school or work stress, and is thought to be a factor in human heart disease. While I was able to find lots of info regarding maternal-separation stress in lots of different animals, little has been done with ferrets, and nothing looking into the possible link between stress and adrenal disease. Stress is a natural suspect, because it is so intimately involved with the adrenal gland itself. It may well be that unresolved stress might be the triggering mechanism, and early maternal separation, close (unresolved) shelter contact with unknown or strange ferrets, or lack of physical contact be factors as important or more than genetics or early neutering.

Of course, it could be a combination of those (or others) that is trigging adrenal disease. For example, maybe a MF ferret was early separated, early neutered, then shipped to a pet store having a completely new environment, all full of stress. Feed a kibbled diet which could possible cause some physiological stress, the combinations of all the different stresses trigger the growth of a small tumor in the left adrenal. This is just a story, but it is a testable idea.

Complicating the entire argument is the observation that adrenal disease seems to be exhibited in two different manners; one a late onset, and the other is an early onset with often a later recurrence. I cannot distinguish this from being two different diseases, one disease that exhibits differently, or just random happenstance. I know of no study into this issue.

As for treatment, surgery is the only treatment that has any long term benefit for the ferret. As already discussed in the 1st post, drug or chemical treatments do not offer a significant difference in life span compared to no treatment at all. They do provide the ferret with perhaps a slightly higher quality of life during that time, but no real increase in lifespan. It is better to be aggressive and remove the tumor as soon as possible, because the disease gradually weakens the ferret and increases the chances of complications. The younger the ferret, the better the prognosis, although the younger the ferret, the more likely a second adrenal tumor will crop up.

I don't see an easy resolution to this problem. It requires money, intelligent and dedicated people looking into the issues, and time. Genetic and environmental factors need to be ruled out, ferret *will* die to resolve this, that you can be sure. Can we help? Hell yes!

The best way each of us can help is with GOOD records on each and every one of your carpet sharks. As much of the lineage as possible, estimated birth date, diet (including manufacturer of diet), shot record, weekly temperatures and weights, record of treats, social interactions, etc. We can be like Tyco Brahe, who painstakingly measured the distances (time) between stars, knowing there was no real good purpose for the data. Yet, that same data, in the hands of Kepler and Newton, rewrote our history. We can create the data that some smart whipper-snapper down the road can take and solve the problem. I suggest those people who currently are on the adrenal mailing list, work with some quasi-national club to create a scientifically correct adrenal data base, gather info from vets, breeders and owners, and provide it to bonafide researchers. We already have the answers; we just need it in an unbiased and correct form of data.

So that's it. I recommend you go back and read the preceding four posts (or just skim them) before firing off a question just to remind yourself of what had been said already. I have tried very hard not to offend anyone position or platform. Not really, I've tried hard to offend them all. I have my asbestos lonhjohns on, my trusty data base in one hand, and Carbone, just starting his first rut, in the other. I'm ready.

Bob C and the 20 MO Ferrets just relieved its all over.


Date: Mon, 2 Mar 1998 03:09:31 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Round One: Adrenal Reposts

Q: "I have had great success with [homeopathic] remedies in adrenal disease. Why did you ignore such a large body of evidence?"

A: I didn't. I use homeopathic treatments quite often; when I was on high doses of chemicals, I used several teas and even aroma therapy to get past the nausea. But very little is known about homeopathic treatments and how they work in humans; next to nothing has been done on animals of any sort. That isn't to mean they don't have value; they are useful if nothing more than as a touch therapy, and I think I said that. What I said was there is no proof of their ability to extend life or make any changes in the quality of life in a sick ferret. If such proof exists, and is published in a referred scientific journal, please let me know and I will pass it on with my heartfelt apologies.

Q: "I am very interested in the role of diet in ferrets. Can you tell me more?"

A: I've had so many requests to discuss this in the last weeks that I'm compiling the references for a nice post on the subject, and will defer until then.

Q: "OK, Bob. If you don't think it is genetics, then kindly explain why only [MF] ferrets get adrenal disease. I think they accidentally bred it into them."

A: I'm sorry if my explanation wasn't clear. My little survey, as well as others, seem to indicate more actual numbers of MF ferrets get adrenal disease, but when factored to the proportion of MF ferrets, the normalized number drops. I don't know if my numbers are accurate because I don't know how many MF ferrets are sold compared to other breeder's ferrets, and I doubt if such information is possible to obtain. My best guess is the rates are roughly equal. That would make the assumption that MF ferrets have a special flaw rather difficult to support. Besides, if such a "flaw" existed, and adrenal disease was purely a matter of genetics, then the number of adrenal cases could be predictable in large populations, and thus far they are not. While I do believe genetics is a very important factor in the onset of adrenal disease, it simply cannot be the part of what is going on because of the unpredictable nature of the disease.

Now, assuming adrenal disease is only a genetic problem, then it should follow some pattern of heritability, which it does not except in the most broad sense. You can say something like 5-10% of ferrets will get adrenal disease in their lifetime, but you can't say who will get the disease. This "random" selection is not actually random; those with the disease must have some sort of shared characteristic(s) which promote the onset, like smoking and lung cancer, and since it is beyond the genetic level, it must be at the environmental level. Because there are so many possible causes, until each one is ruled out, you cannot define a cause-effect relationship. That is why it is so complex an issue, and also why so few treatments seem to work. For example, assume diet is the trigger. You have a ferret with diseased adrenal glands and you start what promises to be a good therapy. However, during the "cure," the ferret continues with the same diet that caused the disease. What are the chances the cure will work? See the complexity now? Infinite causes and finite effect.

Q: "Do you really think ferrets in Britain are kept differently than in the USA?"

A: Borrow a copy of James McKay's video "Keeping Ferrets." You will not only see some of the fluffiest, largest, most well-behaved ferrets you have ever seen, but you will discover they are housed, fed and treated quite differently make the typical ferret in the Americas. Of course, his ferrets seem to be complete with anal sacs and gonads, so some of what you are seeing is due to hormones. However, nothing McKay has to say is any different than can be found in W. Carnegie's books from the 1910-20s or Ernest's book from the 1890s. They are virtually the same, with a few differences due to technology changes.

There are more questions which I will answer in the next day's post.

Bob C and 20 MO Rasslin' Weasels


Date: Tue, 3 Mar 1998 05:37:56 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Responses, Part Two.

I have a basket of them, so if I don't mention yours. I'll get to it soon.

Q: "You really didn't get into deep detail on early neutering. Can you expand it a bit?"

A: Its simply a matter of trying to keep the post as short as possible, so lots of stuff I want to say is never mentioned. Sometimes, the effort of minimizing leaves the wrong impression. Sorry.

What early neutering is proven to do:

1) Reduces the odor in males. 2) Make males more effeminate. 3) Reduces muscle mass, especially in males. 4) Reduces over-all growth by preventing the hormone-mediated growth spurt near the end of the growth cycle. 5) Prevent unwanted baby ferrets. 6) Prevent female estrogen-related anemia. 7) Reduces aggression. 8) Reduces (to a degree) the territorial desire.

What early neutering has never been proven to do:

1) Cause adrenal disease.

I have a fairly good understanding of the endocrine system, I know exactly were the to find the hypophysis (and have physically dissected it out in a dozen or more vertebrates, including humans [I've taught human anatomy labs]), and I have read my share of research papers on hormone balance/counterbalance. I even have a copy of a 1966 MSc thesis that touches on the interaction of pituitary hormones, anal sac secretions and, yes, the adrenal glands. The problem is twofold. A) No one has published an in-depth study of these interactions in ferrets, and B) No one has published a link (that is, an independently verifiable, reproducible cause/effect correlation) between early neutering and *any* serious disease. I stress "published" because such scientific papers normally undergo a review process which weeds out those experiments that are faulty or containing serious flaws.

That doesn't mean such links do or do not exist. It only means nothing has been shown to link the one with the other. If my goal was to remain impartial, or to allow all points to be equally expressed in a fair and open manner, then I had no choice but to draw the line between the proven and the unproven, and only mention the possibilities as such. Since I have heard from both sides of the issue, I suspect I might have met that goal.

Personally, I am a strong supporter of late neutering. I won't neuter a male until he ruts, which is usually the first spring after he is born, providing he has had good nutrition. Foster and Chrys are late neuters, Moose and Bear were neutered between 6-8 months, and Apollo, Simon, and Sam are early neuters. Carbone is almost a year old and not yet neutered. I can see a gradient in muscle mass and body size between these males, with the early-neutered guys far more girlish than the middle or late neuters. The difference between the early and middle neuters is not nearly so noticeable as between them and the late neutered guys, who are truly impressive in their size. Chrys is 4.3 lbs. (3 years old), Foster is 3.3 lbs (13 years old) and Carbone is 5.7 lbs (1 year old). My next largest male is Bear, who is 2.8 lbs (4 years old) and was neutered at 8 months. To get larger than this, you would have to have unaltered hobbs.

But even though I support late neutering, I also feel it is more important to neuter ferrets BEFORE they are sold, especially those sold through pet stores. The reason is simple; we already have enough ferrets in shelters, and I hate to consider the day when animal shelters are killing as many ferrets as they kill dogs or cats. That will continue to be my position until some link between adrenal disease and early neutering is proven, no matter what I personally may suspect.

Q: "Is there a link between adrenal disease and coat color?"

A: Not that I could find. If such a link existed, it could be evidence the trait was carried near on of the genes coding for pattern or color. But I could find no link, not even a possibility, between color, pattern or adrenal disease.

From a personal perspective, Buddy died of adrenal disease at 10 years old; he was a dark silver mitt. Sandy has suffered from adrenal disease for most of a year; she is thought to be 5 years old and is an albino. Razz died of a stroke, but her necropsy showed she had a massive abdominal cancer that had spread into some of her bones, and which included the adrenal glands. She was a chocolate sable, and died at 8 years of age. I don't see a pattern in my own ferrets, I didn't see one in the published accounts of adrenal disease, and I didn't from the FML survey.

More to come....

Bob C and 20 MO Furrbutts


Date: Wed, 4 Mar 1998 18:16:22 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Adrenal Responses part 3

Q: "Do you think adrenal disease may be more closely related to the type of process than results in breast cancer than the possible reasons you listed?"

A: If you mean just another type of tumor or cancer? Maybe so, but keep in mind that many (if not most) human cancers have multiple causes, such as genetics and environmental triggers. Some even have viral triggers. So I can accept the statement in the broad sense, but reserve judgment in the narrow sense.

Q: "Do you know....of a type of experiment that could prove one way or another if [MF] ferrets had more adrenal disease than other ferrets?

A: Sure. Get 300 unneutered kits from MF and 300 from randomly selected private breeders. House each kit identically, feed the same food, allow to socialize with people identically. Early neuter 100 from both groups (4 weeks), middle neuter 100 from both groups (6 months) and late neuter 100 from both groups (1 year). Raise them in identical conditions until they all die; about 8-10 years. Count up the number that had adrenal disease. You would then know just about for sure, but first you need the 600 baby ferrets, the space to care for them, the money to feed them, vets to care for them, and the people to help you do the experiment. I'll run the experiment if someone will get me the grant.

Q: "I wasn't lost because of your writing, but the long time between posts hurt my understanding of what you were talking about...."

A: Yeah, I've heard this from several people now. In the case of the adrenal posts, they were long, but there was quite a bit of stuff to cover. This type of post is rare, even for my particular style of long-windedness. Also, you have to remember the MF debate and the ferret biting incident took place at the same time--both important issues-- which made Bill's job all the harder. I have no complaints, and suggest you print out those particular posts for ease of bathroom reading.

Q: "Have you read anything relating Post-traumatic stress syndrome to adrenal disease?"

A: There is a lot of information on this in humans, but I'm not sure of any study done in ferrets. I've read that, in humans, those subjected to long term stress will have elevated stress indicators for a long period of time, even after the stress is removed, including elevated adrenal hormones. However, each species has an unique evolutionary history resulting in a unique physiology, so just because it occurs in one species is not necessarily proof it occurs in other species. Some drugs which have no side effects in animals are dangerous in humans.

However, there are more more similarities in physiology than differences, and I would suspect there might be some sort of relatedness between the two. Ferrets are energetic, have metabolisms on afterburner, and have a strong sense territory toward strangers. In essence, they are fairly easy to stress. While suspecting a correlation isn't proof, if I were actively looking into the causes of the disease, this would be one of the first places I would check.

Q: "How many references did you consult for this adrenal posts and can you download them for me?"

A: I managed to beg, borrow, photocopy, or buy a total of 18 MA/MSc/PhD Theses/Dissertations, 36 books, 6 edited books, and 97 journal articles. In addition, I was able to consult an additional 21 paper abstracts, where the original was in a foreign language or unavailable. The cost to me was in excess of $330 for the mailing costs, photocopies, and purchased books. Quite honestly, if I were to do an experiment or two, I could easily turn this in for a master's degree. Of course, it would even be *longer* and more involved.

This represents a tremendous effort on my part to collect, collate, and just type in the references, which I haven't had time to do as of yet. So I will make specific references available, but as for the sum total, they are in a pile beside my desk, which makes them hard to download.

Also, in most cases, having the entire list of references is unnecessary unless you want to do academic research in this area. If that is the case, I have two objections. First, researching a subject is part of the learning process which shapes your personal work, and second, I plan on using the references for some work of my own which means you'll just have to wait and cite me.

Still a few more,

Bob C and 20 MO Poopmeisters


Date: Thu, 5 Mar 1998 08:35:50 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Last Adrenal Questions (for now)

This is the last I've received so far. Most of the private questions were also mentioned in FML posts, a couple, like the post-stress question, were asked by three or more people. Many questions were adrenal-off topic, or just FML off-topic. But this is basically it (for now).

Q: "Can I use your [adrenal] posts in [my local ferret club newsletter]?"

A: Its against the law to mail dangerous things, and people have fallen asleep on the seat and almost drowned after reading them! I'm not sure I want to be called the Unabob.

Sure. Send me a copy if you have an extra.

Q: "If the adrenal issue is so complex...and the ferret is the third most popular pet, why isn't someone researching a cure?"

A: That's 3rd most popular carnivore. The problem in the USA is ferrets have a minor economic potential when compared to livestock, horses, dogs, cats and even fish. There are three ways to easily confirm this. First, look at the book section of your local book store. At my favorite store, there were 7 shelves on dogs, 4 shelves on cats, 3 on horses, 3 on fish, and 4 on everything else. There were exactly 4 books on ferrets from 3 authors, two were first printed more than 10 years ago (The other two were Modern Mary Shefferman's book "The Ferret," and the rebundled 1996 "Ferrets Today" disguised as a new 1997 book, which it ain't).

The second way to tell is to look at the back of pet magazines and see who pays for the slick ads and what they are advertising. Large incomes = large ad budgets = slick ads. Advertisers put their money where they think the profits are. I suspect most of the big players are still waiting to see if ferrets pan out to be more than just a passing fancy.

The third way is to see how many graduate students are doing their research on ferret issues. Quite literally, scores of theses (rhymes with feces) are approved each year for livestock, dozens for companion pets, and very few on ferrets themselves; that is, not including those using ferrets as research models for other species.

The reason for the disappointing lack of interest in all three categories is nothing but economics. The bottom line is there are not enough bucks being spent by the ferret community to attract the players who typically pay for the research grants that cure this type of stuff. This isn't new; pets weren't really exploited for the big bucks until the last couple of decades. Now, if the disease affected cattle or sheep, it would have been called the "Mad Adrenal" disease and livestock would have been recalled from pet shops and people would have stopped eating hamburger. If it affected dogs or cats, then a serious yet sensitive professor would have been asked to the Today Show to profess his or hers serious yet sensitive views. But stinky attack-ferrets are owned by tattooed weirdo nuts who only spend millions instead of billions on our one-tracked begonia diggers, so there is absolutely no incentive to exploit the market "at the present time." Need I say more? Of course!

There are some ways to cure this problem. 1) Start a program to make ferrets MORE popular than dogs or cats, possibly by exploiting the Bud commercials. 2) Convince ferret owners to buy cartons of tacky products with anything even resembling a ferret rubber-stamped on it. 3) Get a couple hundred internet people to boycott, badger, or belittle the players to make more monies available. 4) Get all the little clubs to get over their regional squabbles and ego flailing, band together and form a truly (Inter) National Ferret Club with enough members and money to carry a politically big stick. 5) Form your own little club so you have your own opportunity for regional squabbles and ego flailing. 6) Wait and hope for the best, while bitching about how unfair things are. 7) Write incredibly long posts that incite people to riot, while wearing a t-shirt reading "David Hume and Patrick Henry for President!"

This is America, where the currency says "In God We Trust" on one side and "but all others pay cash" on the other. If you want the players to take notice, you have to be noticeable. That means money or political power and usually both. Are we, as ferret owners, capable of such feats? Well, we beat rabies hysteria, have had most anti-ferret laws changed, and just recently saved the life of a "child-attacking ferret." Those times we banded together and chose to ignore our differences, we beat or changed the system. Then we just drift away to resume regional squabbles and ego flailing. Ever wonder why you never see a dozen different Audubon Societies, or a half dozen different Sierra Clubs? Its simply because ten clubs are never as large as one single, giant, powerful "hit bad guys out of the park" club. One voice, pooled resources, political strength. I have been asked why *I* haven't formed a club, and the reason is simple; ferrets DO NOT NEED yet another personality-based club that only divides and fragments our meager resources and unity. What they need is all the existing clubs to become a single strong organization! Its just too bad the clubs won't see the light (or take the hint) and merge themselves into a single national club with enough membership and strength to show the big players we will be still be around in the twenty years it will take their research money to turn the big profits so when they die they can have all kinds of stuff for their children to fight over.

Whatever happens, you can etch this in brass and take bets on it. 1) No serious money for ferret research will be made available until big business catches a whiff of profit, 2) No serious advances in ferret diseases such as adrenal disease will be made until serious research funds are made available, and 3) No serious political power will be welded by the ferret community until it speaks with one voice instead of 20. Or 21.

Bob C and 20 MO Silly Snapping FurSnakes


Date: Fri, 6 Mar 1998 04:16:19 -0600
From: Bob Church <c620213@SHOWME.MISSOURI.EDU>
Subject: Bob C: Ok, some more Adrenal Questions

Q: "Do you really think [kibbled foods] can cause adrenal problems...and is there any type of evidence?"

A: Most of my comments will be held off for a future post series on diet. But as for the adrenal-specific part, it is difficult to say. I think without research, ANY discussion is error-prone, so I am reluctant to say anything is certain. But here are some things to consider; bear in mind not a single point has been proven to cause any problem in ferrets.

Using pet ads, ferret books and articles as a window to the past, there was virtually *no* mention of adrenal problems until the mid-to-late 1980s. Those articles initially treated adrenal problems as a rarity, but that started to change in the late 1990s-to-early 1990s. Now it may be one of the most common reason for surgery in ferrets, rivaling abdominal blockages (and excluding neutering). NOW, either all the ferrets in the Americas since the mid-1980s are cousins and the traits is a genetic defect, or there must be an environmental cause or trigger.

Using that same window of history, kibbled foods for ferrets have also become quite popular. Create a graph in your mind. One line the is increase in adrenal disease in the last 20 years. The other line is the increase in the use of kibbled foods (for ferrets) during the same period of time. I have made such a rough chart, and I have to tell you, the lines parallel each other. They are correlated. Add a third line for the popularity of ferrets in the Americas. That line also rises, but it rises at a lower curve than the other two lines. They are not correlated. Adrenal disease is rising at a faster rate than ferrets are becoming pets.

Ok, the lines are correlated, but are they cause and effect? That I don't know, and it is definitely an area where research is needed. Maybe ALL kibbled diets are missing something and those ferrets suffering adrenal disease are lacking a specific trace nutrient. Maybe the meat used to make the kibble contains nutrients that *IN EXCESS* causes adrenal disease, and the ferrets are suffering from overnutrition of a specific nutrient. This has happened in people, where hamburger containing excess thyroid hormones seriously--and negatively--impacted growing children. Maybe the kidneys added to the kibble still have some adrenal tissue added, and the hormones are not being destroyed during manufacturing. I can't tell you what is happening, but I do know what a fish smells like when it rots, and this mess has a very strange odor.

Q: "Can't inbreeding at [MF] have caused adrenal problems?"

A: So why do non-MF ferrets get adrenal disease? I'll let you in on a secret. Ferrets in Britain are often quite inbred, and father X daughter, mother X son crosses are far more common than you might think. The practice is normally done to "set" a characteristic, such as size, temperament or build. They have an adrenal disease rate far lower than our own. Also, IF adrenal disease was the result of a random mutation in American stock, and increased in the population because of inbreeding, why is it so prevailant in both MF and non-MF ferrets? If the trait was dominant, all the offspring of an host parent would have adrenal disease, but they don't. And you would expect at least 25% to have the disease if it were a recessive trait and both parents carried only a single copy of the defective gene, but even that is way too high of a figure. At the very worse, adrenal disease effects 10% of the population (FMLality), and the figure is probably less than 3% (Reality). And it would *never* show at all if it were recessive and only a single parent had the gene. This is not strictly a genetic problem, so inbreeding is probably not much of a factor. The key to the problem has to be something in the environment, and will probably be found in the lifeway differences between American and other ferrets. Genetics might be behind the locked door, but the key is hidden somewhere in the environment.

Q: "How has [the adrenal posts] changed your opinions?"

A: Before I really looked into the question, I suspected MF breeding practices, photoperiods and diet or some combination. Now I realize the problem is a bit more complicated than that. Perhaps I was secretly hoping I could brilliantly discover some sort of commonality that would let me pontificate a cure.

I literally have almost everything written on adrenal disease in ferrets, and lots of stuff on comparable diseases in other animals, yet I cannot definitely say one aspect is more important than another. Its a black box where everything goes in and adrenal disease comes out, and I'm just as much in the dark as the rest of you.

But here is where I stick my butt out for all to flame. IF I am right and the key in something in the American ferret lifeway, adrenal disease will begin to increase all over the world as our ferret lifeway practices are exported. IF I am right, then adrenal disease will continue to increase out of proportion to the number of ferrets being produced and yearly totals of adrenal treatments will increase. IF I am wrong, then the status quo will be maintained, those breeders importing foreign blood into their ferret lines will reduce the incidence of adrenal disease in their lineage, and adrenal disease outside of the Americas will remain rare.