Gemma's story (12 y/o poodle) - ideas please (currently "Addisonian")

[Gem's Mum]

Gemma a 12 yr old black poodle, was diagnosed with Cushings in Sept 2009 and put on Lysodren 175mg. After induction she had this once a week.

About 5 weeks ago she started licking/chewing at parts of her body. She had ACTH blood test which indicated she was on too high Lysodren. Dose was reduced to 100mg. 10 days later it was obvious she was "depressed" You know - a mum can tell! Back to the vets, more blood tests and the next day we were told Gemma had moved to Addisons end of spectrum. (Electrolytes were out of kilter, but I am unsure of figures). She was put on Prednisone 5mg and Florinef for 5 days. After the second day she bounced back to normal (Cushings)poodle and after 3 we were up again at nights going potty!!
Last Tuesday 11th she had her last doses of these 2 tabs. Friday, she ate her dinner ravenously, vomited shortly after, all her undigested meal. Saturday she wasn't interested in eating and seemed 'flat' again. Back to the vets - Sunday!!. They kept her in, as she was going to be given IV fluids but wasn't and a blood test was done this am.

She is now home, no treatment has been started. She has just vomited 2 times, is not interested in her Dad (whom she adores, and controls). Currently sleeping, and snoring - new for her!

Sorry for my missive. Blood results won't be in till tomorrow.

Question if a dog develops treatment induced Addison's Disease, do they routinely return to Cushings? Should she have had the mineralocorticoid and glucocorticoid steroids for longer? She hasn't eaten and has a history of pancreatitis (common in Cushings??)

I am worried and scared! She is not her normal self.

Thanks for listening
Lesley
NZ

[AlisonandMia]

Hi Lesley,

From what I understand once a dog has got to the point of requiring Florinef to regulate its electrolytes this is likely to be a permanent thing - the dog is now an Addison's dog and needs to be treated as such for the rest of its life.

I'd suspect that the reason you saw the Cushing's symptoms return was that the dose of steroids (Florinef and Prednisone) was too high. But I suspect very strongly she still needs to be on Florinef at least to regulate her electrolytes and that she is probably very sick at the moment because her cortisol is low and her electolytes are out of whack.

I think you need to get her in to the vet ASAP for another electrolyte check.

I can explain more later but it sounds like she is in need of urgent care right now to address the electrolyte problem.

Alison

[zoesmom]

Hi and welcome Leslie -

So sorry for the situation that brought you here. I agree with Alison. If Gemma went addisonian and her electrolytes were messed up, 5 days of pred and the florinef probably not gonna do it.

What does she weigh? That, of course, determines the lysodren dosing and, more importantly now, the pred and florinef dose. So Gemma's last pills were on Tues? And then she became sick again on Friday, right? My guess is she needs to be back on the IV fluids for the electrolytes and probably back on pred for awhile longer, too. I think that the recurrence of thirst can also be an addisonian symptom as well. If she is permanently addisonian, she will probably have to remain on florinef from here on out (I think as an alternative, percorten can be given as an injection every 3 or 4 weeks but I could be wrong.) I guess I wouldn't rule out a bout of pancreatitis either but most likely it's the electrolytes. For sure, I'd take her back in asap. Sue

PS- Do you know or did you get the ACTH results that indicated she was addisonian. If so, please post when you get the chance (later is ok) as it would help to know exactly how low she went. Addison's is very treatable. Some say easier than cushings. BUT she needs to get past the add. crisis and then have regular monitoring for awhile to make sure she's getting the right amount of medication. We've had several here whose dogs have become permanently addisonian from lysodren and hopefully, they'll be along to share their wisdom. I know they will have more to offer than I can.

[Gem's Mum]

Thank you for your help and support! Gemma is in at the vets, on IV fluids and medication again. Results from bloods will be back tomorrow. I will get a copy so I can let you know where we are at.

Thanks again, good night

[Gem's Mum]

Hi! Well Gemma is home! She has had IV dexamethasone last night, IV 5% glucose and IV Normal Saline. She has been recommenced on prednisone 5mg and florinef 1mg. Her electrolytes came back today with elevated potassium and sodium has come back to normal range. Vet got the results on the phone so I don't have numbers!

Gemma is a 12 yr old miniature poodle who currently weighs 7.9kg
I took her to the vets in Aug 09 as she had voracious apptite and thirst and was getting us up 3-4 times at night to go potty. Her specific gravity came back dilute, and we took her in for ACTH
0 hour =260 Norm 14-170
1 hour =469 170- 470
That was inconclusive, so a low dose dex was done

0 hour =221
4 hours=47
8 hours=118

I don't have ranges for this but comment is In a dog with consistent clinical signs and history, these findings are consistent with pituitary dependent hyperadrenocortcism

16 April, this year she had another ACTH
0 hour =44
1 hour =51

Comment: The cortisol levels are quite low

Her lysodren dose was dropped to 100mg (had been 175mg)

She had one dose, 2nd dose the next week, she vomited then was off her food. Took her to vet 6 May as not eating and droopy. Vet talked abt putting Gem on something for Canine cognitive dysfunction and on some prednisone. I asked that we only do one thing at a time (so we would know what worked!) They took a blood test and we went home with 2.5mg pred daily. The next day, when the electrolytes (sodium 133, potassium 8.1 normal 3.5-5.6)came back she was put on 5mg pred and florinef for 5 days. This was completed 11 May and by 14 May she was vomiting and off her food.

I asked the vet yesterday when I took her back, if lysodren could push Gemma into permanent Addisons. She said "no." This morning, after Gem had 'perked up' she told me after talking with a specialist that it is possible!

We are to give Gem her pred and florinef for one month. I think the vet said we would stop them and see if Gemma reacted, if she does then she will need to be on pred and florinef for life.

Does this sound right/normal????

Thank you so much for your help. The replies yesterday confirmed how I was felling - that she was one sick pup!!

Thanks again
Lesley
NZ

[AlisonandMia]

Hi Lesley,

I'm so glad to hear that Gemma is feeling much better and is out of danger.:) The electrolyte imbalance she experienced can be very dangerous which is why we were so worried about her.

Here's a quick run down on Addison's and Lysodren overdosing:

The adrenal cortex is made up of two layers which produce different hormones - one is responsible for producing the glucocorticoid cortisol (which is what is being overproduced in Cushing's and which produces symptoms you see) and the other is responsible for producing what is called a mineralcorticoid called aldosterone. Aldosterone is the hormone that balances the two very important electrolytes potassium and sodium in the body. Cortisol is essential for normal functioning of cells - which is why a dog with low cortisol looks and feels so sick.

The aim of Lysodren treatment with pituitary Cushing's is the erode just enough of the layer of the adrenal cortex that produces cortisol to the point where the daily dose of cortisol produced is enough for normal physiological functioning. That is the aim of the induction or loading phase. Then a maintenance dose is given to hold that level of erosion stable - often some adjustment of the maintenance dose is needed however. Testing with ACTH stim tests, along with observation of the dog's health and demeanor, are used to check that the cortisol production is being kept at a healthy level - not too high (Cushing's) or too low (Addison's).

If a bit too much Lysodren is given typically all that is affected is the cortisol-producing part of the adrenal cortex and the dog will suffer from low cortisol with normal electrolytes. This needs to be treated by ceasing the Lysodren, giving prednisone and then retesting (ACTH stim test) once the dog feels ok without prednisone. You can then recommence the Lysodren at a lower dose so that it holds the cortisol at a good level but doesn't continue to erode the adrenal cortex. When a dog's cortisol goes very low like that due to a Lysodren OD the cortisol-producing cells usually (but not always!) regenerate and eventually the dog can cease to take prednisone and will even begin to show Cushing's signs again at some point. Some dogs regenerate very fast (mine did) but some are very slow and some never recover their ability to make cortisol for themselves and need to stay on prednisone for life.

If far too much Lysodren is given - often with Lysodren dosing continues in a dog with very low cortisol as happened with Gemma - the layer of the adrenal cortex that produces aldosterone is also eroded away. This is what causes the electrolyte imbalance and necessitates the use of Florinef (or Percorten as Sue (Zoesmom) mentioned. These meds artificially replace aldosterone.

In both cases (just low cortisol and low cortisol plus electrolyte imbalance) the dog is said to be in an "Addisonian state". There are two types or degrees of Addison's - one is what is called Atypical Addison's which is when just cortisol production is affected and the other is more typical Addison's where the production of both cortisol and aldosterone are affected. Atypical Addison's is treated with just prednisone (or some other artifical glucocorticoid like dexamethasone or cortisone). Full Addison's is treated by replacing both the missing cortisol and the missing aldosterone.

Addison's (both types) occur naturally and as a result of overtreatment of Cushing's. In some parts of the world Lysodren is actually used to deliberately cause Addison's such as Gemma has and the dog is then managed as an Addison's dog as it is deemed to be easier than managing Cushing's - so what has happened with Gemma is far from the end of the world.

From what we've seen here once a dog has got to the point of needing aldosterone replacement (Florinef) the Addisonian state will be a permanent thing and the adrenal cortex will not be able to regenerate. We've seen a few cases where vets have tried to wean dogs like this off their medication and invariably the dog crashes again.

Now about the medications:

It is more than likely that Gemma won't need anything other than the Florinef - she probably won't need prednisone. This is because Florinef has both mineralcorticoid (aldosterone) properties and glucocorticoid properties - so it replaces both aldosterone and cortisol. When you add some prednisone on top of that the result is way too much cortisol replacement and you see Cushing's symptoms all over again. It sounds like this is what happened the first time she was on these meds. The dose of prednisone (5mg for a 8kg dog) is pretty high too and could cause Cushing's symptoms even without the Florinef. The normal physiologic dose of prednisone is around 0.25mg/kg and Gemma is getting 0.63mg/kg. It is better to over treat at this stage (the first couple of days after a crash) than to under treat though. You might want to talk to your vet about weaning of the prednisone and seeing how she goes on just the Florinef.

Some dogs will actually get too much glucocorticoid supplementation from Florinef and do best on Percorten injections which are given every 25 days. Percorten really only replaces aldosterone and so it is usual to give a small daily dose of prednisone along with it to replace the cortisol. I have heard of one dog that did great on only Percorten and he didn't even need prednisone most of the time! I don't know if Percorten is available in NZ - but it is likely that it is. That may be an option and may be more convenient.

An Addison's dog will often need a bigger dose of prednisone when it is under stress - either physical stress like cold weather, illness, injury, surgery etc or psychological stress like going to the groomer, trip to the vet etc. A normal dog is able to produce extra cortisol to cope with stress but an Addison's dog (or a normally-treated Cushing's dog for that matter) can't and so it can be necessary to give them a bit extra in times of stress. How much this is necessary depends very much on the individual dog.

Different dogs seem to need different amounts of cortisol replacement - it is a very individual thing and can even change as the dog ages. The aim is to keep them happy, healthy and energetic and not showing any Cushing's-type symptoms. With the aldosterone replacement, I believe the way that that is usually monitored (and it does need monitoring particularly at first) is through electrolyte testing. If they are getting too much, the sodium will be too high and they will tend to retain fluid and if it is too low then the potassium level is too high and the sodium too low. It is far better to monitor it this way and tweak the dose if necessary than to try taking the dog off the medication and seeing how it goes - they don't usually go well at all!

I'm glad your vet has been in touch with a specialist and I think you should encourage her to continue to consult that person. A lot of otherwise wonderful vets are not experienced with treating Cushing's or Addison's (it isn't something they will do every day) and need a specialist's guidance. My vet hadn't treated many (or any) Cushing's dogs on his own and I know he consulted regularly about her treatment especially when we started out.

Good luck and keep us posted!

Alison

[zoesmom]

Yayyy. Glad Gemma is home and, no doubt, feeling much better. Alison has given you a good rundown on the treatment of Addison's. Chances are, Gemma will be permanently in need of tx for that. At this point, it's probably going to be trial and error, to find the right dosing to keep her stable. And just know that in times of stress, she may need a little booster dose of pred.

The only other thing . . . I'm not sure but it seems to me like they'd want to retest her while she is still on the pred and florinef, rather than risk her 'crashing' again. She may eventually be ok w/o the pred and just need the florinef or percoten. Did they recommend a taper off the pred. Because the pred should never be stopped cold turkey if a dog has been on a high dose - for even a few days - or if they've been on it for awhile. For Gemma's size, that is a high dose of pred, but probably ok for the time being, considering. But it's definitely a dose that she'd need to be tapered off of. Keep us in the loop and hugs to Gemma. Sue

[Gem's Mum]

Thank you Alison and Sue for your help and advice.
The info about lysodren and overdosing is invaluable. I am now operating from a better position, one of information.

Gemma still quiet for her, but hugely better than she was :)
Thanks
Lesley
NZ

[AlisonandMia]

Just one more thing: I thought it might help you in your conversations with the vet to know that when Lysodren is used to deliberately induce full Addison's (not producing cortisol or aldosterone) it is called variously the "Utrecht protocol", "ablation protocol", or the "non-selective protocol" and is sometimes referred to as a "medical adrenalectomy". This way of using Lysodren was originally pioneered and promoted by drs at the University of Utrecht in the Netherlands and that is how Lysodren generally is used in the Netherlands when it is used (they usually treat by pituitary surgery, actually). In North America, Australia and NZ it is more usually used to simply inhibit cortisol production with the complete ablation being something only used if the dog cannot be stabilized in the more usual way - and it sometimes happens by accident too, as in Gemma's case.

I'll try to dig out some references to the Utrecht/ablation/non-selective protocol for you so you can show them to your vet if need be.

Alison

PS: In the past humans with pituitary Cushing's were treated with a surgical adrenalectomy and then lived as Addison's patients - it was the only way to treat the disease until relatively recently. (Natural Addison's happens in humans too although it is a rare disease as is human Cushing's. Both diseases (particularly Cushing's) are far more common in dogs.)

[AlisonandMia]

Found one link so far: http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2006&PID=15787&O=Generic

Here's a quote from that article (the bolding is mine):


The selective protocol consists of an induction period of approximately 7 days and is followed by a life-long maintenance therapy with Lysodren®. The protocol aims at a selective destruction of the adrenal cortex sparing the zona glomerulosa and decreasing cortisol secretion.

With the non-selective protocol (Utrecht protocol), a high dosage of Lysodren® is administered during a limited period. This protocol aims at a complete destruction of the adrenal cortex (zona fasciculata, zona reticularis and zona glomerulosa). Hypocortisolism and hypoaldosteronism will ensue. A life-long therapy with glucocorticoids and mineralocorticoids is mandatory.

Alison

[Gem's Mum]

Hi
An update about Gemma! She completed her first month on gluco and mineralocorticoids. She is continiung with her florinef and we are slowly reducing the prednisone while keeping a careful watch!

She is doing so well. VERY healthy appetite!

I would like to thank you all for your support - I thought she was going to die the afternoon I first posted, and the vet wasn't listening. You empowered me, and gave me the info to fight for her.

A great forum - thank you very very much

Lesley
NZ

[meggle]

Hi Lesley

I'm not surprised you thought you were going to lose Gem when her Na/k levels were that bad :( You need to make sure her sodium/potassium ratio is ideally around the 34 mark, when those results came through she was down to 16.4, anything below 29 can easily result in a crisis. Each time she has an electrolytes test divide the sodium (Na) by the potassium (k) and if it's lower than 30 then she will need an increase in Florinef. My girl started off on 3 Florinef daily and eventually ended up on 15 a day! Always split the dose and feed her twice a day too. Once the dose has been increased she should NEVER have a reduction in Florinef again, it can go up or stay the same but it should never come down. She should be able to come off the preds completely unless you feel she is going to experience something quite stressful then you might need to have some on standby for her.
Good luck with Gem, on the correct dose she will be back to normal just like my girl was.

Sandy