suprelorin in ferrets

Re: suprelorin in ferrets

Mark Hedberg — Sun, 04 Sep 2011 14:25:35 GMT

Ooh, colleague just had a case of an aggressive beardie...must make a note to tell her.

Re: suprelorin in ferrets

Mark Rowland — Sun, 04 Sep 2011 13:18:31 GMT

Yep I agree, I love the implants. In fact I was the first to report their use to treat aggression in a male Bearded dragonVeterinary Record 2011;169:127 doi:10.1136/vr.d2007.

However here is the difference for me.

We as exotic animal vets use unlicensed products to treat conditions in various species with great regularity.

We rely on our experience and those of our peers for dosages and novel treatments.

In a case like this however, If I am asked to take a healthy animal and implant every year under sedation a product that is not licensed and has no lifelong studies for safety to prevent a condition that there is no evidence it prevents, im sorry but my answer is no and will remain so until safety and efficacy trials have been completed.

Using unlicensed products to treat is a world apart from using them to prevent in the absence of safety and efficacy trials.

Im afraid I will just have to agree to disagree with others who hold different views but would warn against the overzealous use of unlicensed products for regular use as prevention without sufficient data as I do not want them taken from me for treatment.

Sorry

Re: suprelorin in ferrets

Mark Holmes — Sun, 04 Sep 2011 10:21:03 GMT

Not just with regards to ferrets but I use quite a large number of implants and I think that they are one of the (or quite possibly THE) best new product(s) in the last 10 years

Re: suprelorin in ferrets

Ian Mostyn — Sat, 03 Sep 2011 22:11:42 GMT

I'm with Mark on this one. Schoemaker only found an incidence of 0.55% hyperadrenocorticism and an average time of 3.5 years from neutering to development of clinical signs. I can see that there is a higher incidence in females spayed under 12 months old but I would accept a 0.55% risk compared to the risks of hyperoestrogenism. With Delvosteron now an expensive option, surely hyperoestrogenism is more likely than 0.55%. Plus the fact that Suprelorin is the treatment of choice for HAC, why not spay and use Suprelorin 3.5 years later in 1 in 181 ferrets? I would still like to see more safety data for the Suprelorin implant.

Ian

Re: suprelorin in ferrets

Mark Rowland — Sat, 03 Sep 2011 18:13:24 GMT

. Nico Schoemaker in Utrecht authored a paper dealing with chemical castration in male ferrets using deslorelin implants so data is available for this.
2. He also (within his thesis) identified a temporal relationship between the time of neutering and the development of adrenal disease in ferrets (males and females). What this means is that no matter the age at neuter/spay, if AGD was to develop, it developed predictably in a certain timeframe after neuter. So in theory, the later you neuter, the later in age they are when they get AGD,.
3. There is no data to suggest that use of deslorelin to effect "prevention of AGD" makes sense...
4. The problem is we do not know what causes AGD in ferrets.. it has been seen in non-neutered males and females as well but much less commonly.

If the proof was there, why isnt there a general recommendation here... and in the US or do we just like to keep things to ourselves.

Why is the procedure even outlined in the BSAVA manual if it is contraindicated.

I dont want much, Just a paper that concludes that "neuter causes HAC" as has been stated here. If it were that obvious, why didnt NS conclude this in his studies. There is ongoing research into the role of genetics, including evaluation of a gene linked to Multiple Endocrine Neoplasia in humans .In the UK, when ferrets were housed outside, fed scrap meat diets, and kept individually and not in large groups, the incidence of adrenal disease was quite rare. Since their adaptation to house pets and the increase in social grouping and the increased photoperiod related to living indoors, adrenal gland disease incidence has increased.

You simply CANNOT say conclusively that neuter is the sole factor contributing to HAC development. No-one is denying that it is implicated. But the sole cause assumption and subsequent reliance on an unlicensed treatment as a prevention isn't 100% justified. I dont want the treat by assumption route in a case like this. If it is so cut and dried why hasn't anyone said so. To be the first would surely get all the accolades (as well as a big fat contract from Virbac).

Re: suprelorin in ferrets

Marie Kubiak — Sat, 03 Sep 2011 17:29:49 GMT

As I mentioned earlier, it would be worth reviewing Dr. Schoemaker's thesis and subsequent published work for discussion on HAC and neutering. I don't know what more can be done - it has been demonstrated that in the US and Netherlands where neutering is standard that HAC is a much more common problem than in the UK where many ferrets remain entire. Dramatic incidence differences have been demonstrated in neutered and entire populations that have no other consistent variables. HAC develops a predictable time after neutering (not seen with any other factor) showing that neutering has a strong inciting factor. The hormonal changes in the hypothalamic pituitary axis following neutering and the corresponding alteration of receptors on the adrenal glands has been well documented with immunohistochemistry of abnormal glands supporting this.

What would you suggest as proof?

Re: suprelorin in ferrets

Mark Rowland — Sat, 03 Sep 2011 17:03:57 GMT

Of course you are relying on the owners to bring them back when you tell them. A bit different from a vaccine. If they dont show its their fault if their dog gets lepto. If we have started something in the adrenals do we share part of the blame?

?deliterious effects on truncated cells. No studies. What happens to them if the implant dissolves now we have activated them. No studies

Im just playing Devils advocate but the scenario Ive suggested isnt impossible

Just link me to the paper that says" neuter causes HAC" and that will do.

Re: suprelorin in ferrets

Marie Kubiak — Sat, 03 Sep 2011 16:43:43 GMT

GnRH doesn't affect the gonadotrophin receptors on the gonads/adrenals rather it prevents secretion of the normal gonadotrophin ligands. Yes at initial implant placement you get a brief surge in FSH and LH but then FSH and LH levels drop to inconsequential. Unless you actually leave the implant to be completely reabsorbed there should be no restimulation at next implantation- just a constant high level of GnRH suppressing normal LH and FSH release, hence why 18months is recommended rather than leaving it till the implant is believed to be inactive at 2yrs.

Re: suprelorin in ferrets

Mark Rowland — Sat, 03 Sep 2011 16:19:53 GMT

For me there are still too many unanswered questions and again even NS would confirm that there is no conclusive proof to back up the statements in this thread.

I think we should still exercise caution.

Consider this as an example:

By implanting a GnRH analogue you are hyperstimulating receptors in the gonads. However you are also hyperstimulating receptors that would normally be latent in the adrenals. Then it all down regulates, then you hyperstimulate the adrenal cells again for a month. year on year. I dont think it is implausible to envisage a situation where you could actually predispose latent cells to cancerous changes by overstimulation from a normally latent state. So wouldnt it be ironic that one actually predisposes to the condition one is trying to prevent.

Also there is the issue of the less common but still present cases of HAC in entire animals

This is why we need to wait for studies to actually prove you are achieving what you set out to do. You cannot provide me with any solid evidence right now to say that neuter causes HAC nor can NS. if that changes then so will my opinions.

Believe me I use sup implants a lot but I think its always a good idea to ask the questions especially in these non license uses.

Re: suprelorin in ferrets

Marie Kubiak — Sat, 03 Sep 2011 15:59:50 GMT

[quote user="Mark Rowland"]

A bit of a sweeping statement I think.

[/quote]

Which bit?

HAC is incredibly strongly linked to neutering and I don't see that there is really anything more that can be done to confirm the link and Dr. Schoemaker firmly advises against surgical neutering based on his work as prevention of HAC. If you read back through his thesis discussing the evidence that neutering is the major risk factor, it is incredibly convincing.

Using the implant to prevent HAC is well recognised but the data to prove efficacy is still being collected (obviously you need to study the implanted population over their lifespan to be able to compare incidence so it takes time). If you look at the hormonal pathways involved (oversecretion of gonadotrophin releasing hormone and secondary LH and FSH overstimulation of the adrenals) then using GnRH makes perfect theoretical sense but as mentioned the conclusive studies are still being carried out at present. It is interesting to note that surgical removal of one affected gland is usually followed by hyperplasia of the other within 18months, but if suprelorin is implanted at the time of surgery then this is avoided (Forbes, 2010) suggesting an inhibitory effect. Anecdotally there is much support in the US and Europe to support the lack of clinical HAC in implanted ferrets and no adverse effects reported so I will continue to recommend implanting neutered ferrets as a presumed preventative measure but am honest with clients that we cannot 100% guarantee success. Do you refuse to neuter all ferrets or do you neuter and wait for adrenal disease?

Marie

Re: suprelorin in ferrets

Chris Geddes — Fri, 02 Sep 2011 21:35:59 GMT

[quote user="Andrew Kent"]Chris, Any info on duration of action of the new 12 month implant in ferrets?

[/quote]

Hi Andrew. I should know the answer to this, but again, maybe us marketers should stick to drawing pretty pictures and leave the technical stuff to the technical department!

Interesting because it was my understanding that S6 lasted 2 years in a ferret, but someone said earlier 12-18 months. I guess it partly depends on when in the year it is given in relation to breeding season.

Anyway, I'm not sure about S12, sorry, but I'll definitely seek clarification when back in the office on Monday and let you know.

Chris

Re: suprelorin in ferrets

Chris Geddes — Fri, 02 Sep 2011 21:32:24 GMT

[quote user="Mark Rowland"]
2. He also (within his thesis) identified a temporal relationship between the time of neutering and the development of adrenal disease in ferrets (males and females). What this means is that no matter the age at neuter/spay, if AGD was to develop, it developed predictably in a certain timeframe after neuter. So in theory, the later you neuter, the later in age they are when they get AGD,.

[/quote]

Very interesting....as one of the other conditions thought to be caused by high LH/FSH due to lack of negative feedback from sex hormones from neutering...i.e. urinary incontinence in bitches, as I referred to earlier.....has also been shown to have a temporal relationship to time of neutering!

Re: suprelorin in ferrets

Chris Geddes — Fri, 02 Sep 2011 21:29:30 GMT

[quote user="Mark Rowland"]

Chris

If you study the post, the piece you have quoted talks about increased secretion in the case of an adrenal cortical neoplasm and its treatment. Not the normal "pulsatile action"

[/quote]

Thank you for the clarification Mark. Sorry, it's Friday evening, and I'm in marketing rather than technical for a reason ;-)

So, I understand, the inc LH you referred to is in the diseases state, not the initial rise in LH you get after implanting deslorelin.

But still, the mechanism of action of deslorelin is by decreasing LH, not downregulation of LH receptors, right? Or is it both? Sorry, I should perhaps be referring to my own technical department here, but I'm intrigued! I thought I understood this but maybe not....

Re: suprelorin in ferrets

Chris Geddes — Fri, 02 Sep 2011 21:26:34 GMT

[quote user="Mark Rowland"]

Chris

If you study the post, the piece you have quoted talks about increased secretion in the case of an adrenal cortical neoplasm and its treatment. Not the normal "pulsatile action"

[/quote]

Thank you for the clarification. Sorry, it's Friday evening, and, clearly I'm in marketing rather than technical for a reason ;-)

So yes, you were talking about increased LH in the diseased state, not the increased LH you get immediately after the deslorelin is implanted.

But.....still....surely the deslorelin is working due to abolition of LH, not through downregulation of receptors for LH in the adrenal?

Re: suprelorin in ferrets

Mark Rowland — Fri, 02 Sep 2011 21:06:53 GMT

Chris

If you study the post, the piece you have quoted talks about increased secretion in the case of an adrenal cortical neoplasm and its treatment. Not the normal "pulsatile action"

Re: suprelorin in ferrets

Andrew Kent — Fri, 02 Sep 2011 21:02:24 GMT

Chris, Any info on duration of action of the new 12 month implant in ferrets?

Re: suprelorin in ferrets

Chris Geddes — Fri, 02 Sep 2011 19:35:08 GMT

[quote user="Mark Rowland"]

6. We know that some of the most effective meds for AGD treatment are GnRH receptor agonists like leuprolide and deslorelin. Both act to down regulate the LH receptor and decrease the effect of increased LH secretion. Deslorelin also acts to truncate the LH receptor ( I do not think the same work has been done with leuprolide)

[/quote]

I'm a little confused. You talk of increased LH secretion. Whilst I am a marketer not a technical bod, my understanding is that deslorelin causes increased LH/FSH secretion for a very short period, after which it abolishes LH/FSH production as there is sustained presence of the GnRH analogue, compared with the normal pulsatile release. Decreased LH/FSH leading to decreased sex hormone production is the whole point of the product...and presumably the reason why use is not thought to cause AGD whereas neutering is thought to cause it (with the high LH/FSH in neutered animals seen due to lack of negative feedback - also thought by some to be responsible for urinary incontinence in bitches, for example.

Re: suprelorin in ferrets

Mark Rowland — Fri, 02 Sep 2011 18:56:37 GMT

A bit of a sweeping statement I think.

Regarding ACD

1. Nico Schoemaker in Utrecht authored a paper dealing with chemical castration in male ferrets using deslorelin implants so data is available for this.
2. He also (within his thesis) identified a temporal relationship between the time of neutering and the development of adrenal disease in ferrets (males and females). What this means is that no matter the age at neuter/spay, if AGD was to develop, it developed predictably in a certain timeframe after neuter. So in theory, the later you neuter, the later in age they are when they get AGD,.
3. There is no data to suggest that use of deslorelin to effect "prevention of AGD" makes sense...
4. The problem is we do not know what causes AGD in ferrets.. it has been seen in non-neutered males and females as well but much less commonly. Is it more common in US? Was it underreported in the UK and Netherlands before 'cos working ferrets were not presented to the vet? The understanding is that once pet ferrets became popular in these areas, the rate of AGD rose.
So is this a US problem or a neutered pet ferret problem?
5. We do know that (according again to Dr, S's work) that in the normal male and female ferret, the gonads have a receptor for LH that is intact and functional and a truncated, non-functional LH receptor in some adrenal cells. We also know that in AGD, the adrenal receptors for LH are no longer truncated and are functional.
6. We know that some of the most effective meds for AGD treatment are GnRH receptor agonists like leuprolide and deslorelin. Both act to down regulate the LH receptor and decrease the effect of increased LH secretion. Deslorelin also acts to truncate the LH receptor ( I do not think the same work has been done with leuprolide)

I think even Nico would echo this

I think the idea of using implants to control HAC and chemically neuter has founding but there is no data that suggests conclusively that HAC is caused by neutering at the moment

Re: suprelorin in ferrets

Kate Everett — Fri, 02 Sep 2011 16:16:32 GMT

HI Alexa!

The work of Nico Schormaker has pretty much established that surgical neutering causes hyperadrenocorticism in ferrets so suprelorin is used as an alternative to this an also as a treatment for hyperadrenocorticism. Try googling his PhD work if you're interested or I can try and find the link,

Bye, Kate

www.exoticsmadeeasy.co.uk

Re: suprelorin in ferrets

Chris Geddes — Tue, 09 Aug 2011 11:08:38 GMT

Hi Alexa

I'm sorry you had trouble getting hold of someone. Hopefully someone got back to you - if not please private message me with your details and a convenient time to call you back.

Best wishes

Chris

Re: suprelorin in ferrets

Rachael Winder — Mon, 08 Aug 2011 20:44:30 GMT

We've been using them as an alternative to speying with great success. Virbac will be really helpful when you get hold of them- they've got loads of info. I'd recommend a very quick iso gas down though to insert- it's a big needle!

Re: suprelorin in ferrets

Mark Rowland — Mon, 08 Aug 2011 17:33:11 GMT

Yes we use them lots for treatment of hyperadrenocorticism in ferrets. There is a suggestion that they may prevent the disease so some are using them as an alternative to neutering and also to bring jills out of oestrus. Duration 12-18 months.

Hope this helps