Atypical Cushings

[kspach]

Hello, my name is Kathy and a few weeks ago my 9 year old Norwegian Elkhound Atticus was finally diagnosed with Atypical Cushing's disease. His only symptoms are excessive drinking (now at 2 gallons of water a day), excessive urination and increased appetite. After a myriad of blood tests, urinalysis, cortisol - creatinine ratio test, LDDS test, my vet referred me to an internal medicine specialist who did an ultra- sound and the ACTH test which was sent to University of Tennessee . He has a 4 cm tumor on his left adrenal gland, all other organs look good for his age and his test results are as follows: Neutered male
TEST BASELINE POST ACTH
Cortisol <1.0 1.68 *
Androstendione .68* 3.58*
Estrodiol 74.3* 52.1
Progesterone .55* 1.63*
17 OH Prog. <0.08* .74
Testosterone <15 <15

* above or below normal range

DR. NOTES: Androstenedione and progesterone are elevated in both columns and deviations range from mild to moderate. Unexpectedly, post ACTH cortisol is extremely low and there appears to be a blunted response or no response to ACTH which may be due to some interfering medication.


(He was on no meds --had been on an antibiotic a week or so before the test)

I was told to begin giving him 6 mg of melatonin twice a day. I was not advised to give him legnans?? I notice that most people on this forum give both. While, at this point, he has only had a few accidents in the house--mostly dribbling or a light pee I expect that to get worse. I am diligent about having him go out regularly and luckily have a couple of people who will come and let him out if I will be gone for over 4 hours. Most nights he will go 6 to 6 1/2 hours without needing to go out but then he will pee for so long, I have no idea how he has held it.
I have ordered a couple of washable male diapers (wrap type) and wonder if anyone has suggestions for what works best as disposable liners to use with them. Hopefully, he will wear them! I hate to confine him to the kitchen if his water consumption continues to increase. (Has gone from 112 oz. in June when I first suspected something to over 2 gals a day presently.)
Would love to hear how others are helping their dogs deal with this disease. Kathy

[labblab]

Hello Kathy, and welcome to you and Atticus. Here is a link to a thread on our Resources forum that contains a lot of helpful information about the diagnosis and treatment of elevated adrenal hormones other than cortisol ("Atypical Cushings"). As far as the lignans, it may be the case that UTK did not recommend lignans in addition to the melatonin because Atticus does not have abnormal elevation in his post-ACTH estradiol level. I believe the combo of melatonin/lignans is primarily helpful in that situation. (Quote from UTK summary of treatment considerations: "Melatonin and flax hull product with lignans are used together when estradiol is increased"). The UTK summary and additional info can be found in this thread:

http://www.k9cushings.com/forum/showthread.php?t=198

What I am especially wondering, though, is what your IMS has said about Atticus' extremely low cortisol level? As the lab interpretation stated, that is a very unusual result. As I understand things, that would be a result that would be expected to occur with Addison's Disease but not with Cushing's unless Atticus had been taking steroids ("Iatrogenc Cushing's"). Since Atticus was not taking any medication at the time that might have caused that reading, I would think your IMS would be very anxious to try to sort out the cause for the abnormally low cortisol.

Additionally, what has the IMS said about the adrenal tumor? That would also be a concern to me, especially in combination with the low cortisol. What has your IMS said about both those issues?

Marianne

[labblab]

It's me back again, still puzzling over that extremely low cortisol. :confused:

What antibiotic was Atticus taking during the week preceding the ACTH? Also, is it possible that he was receiving steroids in any form, such as eyedrops, eardrops, skin creams or ointments? How about the humans in your house -- were they using any ointments that could be licked off?

Also, how about his general lab profiles -- any abnormal highs or lows in other blood or urine values?

I apologize for so many questions :o, but Atticus' low cortisol really does seem to me to be an issue that needs to be addressed.

Marianne

[kspach]

Thank you for your response. Atticus had a complete blood work up and chem profile and urinalysis done this summer and nothing showed up other than dilute urine. His creatinine/cortisol ratio test was normal, the low dex test just very slightly out of normal range I believe. (I do not have a copy of those results.) My vet consulted with two specialists who said not to treat at this time, retest in 3 months and suggested going on 10 days of an antibiotics (ampicillin) in case he had a urinary infection that wasn't showing up in tests. They also suggested he have an ultra-sound.
The IMS when he called with the results of the ACTH test did not mention his low cortisol reading in the post test results. I did not see that until he emailed me the test results. He did discuss with me on the day of the ultra-sound and the ACTH test the risks of Cushing meds causing Addison's if dosage is not correct and risks of surgery.
The IMS said that he had a 4 cm tumor on the left adrenal gland
just medial and cranial to the left kidney in the immediate vicinity of where the left adrenal would normally be located. A normal appearing left adrenal gland was not found in this area. The mass was markedly heterogeneous and non-cavity in appearance. The right adrenal gland was difficult to completely visualize due to gas in the GI tract, but no mass effects were located in or around the right adrenal gland. The remainder of the abdominal ultrasound was normal' The liver, gallbladder. kidneys. bladder and prostate were grossly normal in appearance. Abdominal lymph nodes were normal. No free fluid was found.
He suspects the tumor is the most likely source on his increased thirst and urination--most likely a functional adrenal gland tumor and based on previous tests is unlikely that the tumor is making cortisol.

He indicated, which I had previously read that there is a fifty fifty chance that the tumor could be malignant. However, I read somewhere recently that noncortisol adrenal tumors are almost always cancerous????

[kspach]

No one is on any meds but he has in the past year taken to eating wood.
On our walks, he will try to eat sticks, bark--especially from cottonwoods. I have some cedar mulch in the backyard that he also gnaws on occasionally. He was put on a diet a year ago and he lost 20 lbs. in 6 mos. After the first few weeks on the diet he was fine but now he is ravenous--begging for food all the time starting this summer. He has put a couple pounds back on but is still at a good weight for his size but don't want him to gain anymore.

[labblab]

Thanks so much for all this additional info. I honestly do not know the statistics about malignancy among functional tumors that are not producing cortisol. But malignancy issue aside, perhaps the tumor is affecting the portion of the adrenal gland that relates to cortisol production and this is actually leading to cortisol suppression?

I remain puzzled that your IMS has not discussed the cortisol with you, though. I do believe that a dog who returned such a suppressed cortisol response on a conventional ACTH stimulation test (testing cortisol alone) would be deemed Addisonian in the absence of a history of steroid use. Since Atticus does have other adrenal hormones that are elevated, presumably he does not have primary Addison's (in which all the adrenal layers are damaged). But is the tumor somehow destroying the layers of the adrenal gland that produce cortisol? With a cortisol level that low, I would think that some of his abnormal behavior might be explained by that issue in and of itself.

Please understand that I am not a vet and I am only musing here. But if Atticus were mine, I would want to recontact the IMS and ask about the cortisol. What does he think is causing the abnormality, and does he perceive it to be a problem? For instance, might Atticus actually need some supplemental glucocorticoid (like prednisone) to make up for the natural cortisol that apparently he is lacking?

Marianne

[kspach]

Thanks, Marianne and I will contact the IMS about that issue and let you know what he says. It appears that his cortisol level was in the normal range before the test if that means anything although < 1 isn't very specific. Kathy

[labblab]

Kathy, I had just written out a reply that I ended up mistakenly deleting :o. In it, I had written that I did not think a baseline cortisol of <1 could be normal. I've just looked back to another member's labwork and see that according to the UTK normal range on her dog's results, <1 does fit within their range for a pre-ACTH result.

However, according to her printout, UTK's normal range for the post-ACTH result is approx. 7-15 ug/dL. Even if Atticus' baseline was normal, the extremely low and blunted post-ACTH result is diagnostically worrisome. For instance, here's a flowchart for IDEXX labs that gives you the diagnostic breakdown for their ACTH results. Their norms different a bit from UTK's, but the chart still conveys the flavor of the issue if a dog's post-ACTH result is significantly low.

http://www.idexx.com.au/pdf/en_au/smallanimal/snap/cortisol/cortisol-acth-stimulation-protocol.pdf

Marianne

[kspach]

Marianne,
I emailed the IMS asking about his low cortisol level and Addison's and hopefully, I will hear back tomorrow or Tuesday. The symptoms of all of these conditions are so similar, except it looks like in Addison's the dog loses weight and has a lack of appetite. For some reason, I am thinking my vet ruled out Addison's based on early lab work but perhaps I am not remembering correctly. He did say that these endocrine issues are really hard to diagnose. Atticus has none of the panting, coat or skin issues so far.
We took a three-mile hike in the woods this morning and he did just fine with a couple breaks for water.
Kathy

[kspach]

Marianne,
I did hear back from the IMS:
" While his cortisol levels are low, he isn't showing any prominent signs of Addison's disease nor would I expect them to be present due to an adrenal tumor. It is possible that there is some natural suppression of the cortisol from the other hormones that are elevated in his case, and unless he starts showing signs (weakness, lethargy, vomiting/diarrhea), I'm not terribly concerned, but of course, we always remain vigilant. It's a good idea to have him periodically evaluated with a routine physical examination and baseline bloodwork (including blood electrolytes - as these can change with true Addison's disease). Given his recent work-up, it would be appropriate (in the absence of any new clinical signs) to wait another month or two and then have him evaluated." Kathy

[molly muffin]

Hi, and welcome to the forum.

That is good that the IMS is at least keeping an eye on the cortisol level and wants to retest to make sure that it isn't going lower than it is already.

Keep in mind that it does take awhile for the melatonin to work. Months usually, 4 - 6 sometimes. So, it is a matter of patience on this treatment.

[labblab]

Kathy, thanks so much for posting the info from your IMS. Just when I think I am kind of a Smarty-Pants after my years here, a new situation will arise that offers me a new learning opportunity :o! Truly, I cannot remember seeing an adrenal profile quite like Atticus', where cortisol is so low in the midst of elevated intermediates. To try to gain a better understanding for myself, I emailed the specifics of Atticus' situation to Dr. David Bruyette, an endocrinological expert in Los Angeles who has been a pioneer in Cushing's treatment and also a great help to several of our members through the years. This is Dr. Bruyette's opinion based on the info I sent him. As you'll see, I do believe it corresponds with what your IMS has told you, and the entire situation is an eye-opener to me because I did not know that elevated progesterone has the potential to suppress cortisol production.


The adrenal suppression seen on the ACTH stim test is consistent with a functional adrenal tumor causing contralateral adrenal suppression. If the dog is really not receiving any topical medications and the owner is not using a topical hormone replacement cream I would agree that the adrenal mass may be secreting progesterone which can cause the clinical signs and suppress the stim test.


So if I'm understanding things correctly, Dr. Bruyette is also thinking that the adrenal tumor is the culprit due to the excessive progesterone production, which in turn is suppressing the cortisol. He told me that, in his opinion, surgical removal of the tumor would be the best-case solution in this situation because the excessive progesterone production would be halted, and hopefully the cortisol production would subsequently normalize as a result. But if surgery is not an option for you, then my impression is that he would do his best to reduce the progesterone through medication, which I'm assuming is indeed your IMS' goal by introducing the melatonin. Of interest to me, though, is Dr. Bruyette's suggestion to use trilostane to accomplish this goal. I would have thought it would be a no-no because of its further suppressive action on the cortisol and because I thought trilostane has the potential to increase progesterone further. But he says that in this case, he thinks trilostane could be helpful. I believe it would require an in-depth conversation with him to understand the specifics, but I at least wanted to convey to you the basics of what he told me.

He has, in fact, brought up a point that I was wondering myself: have you considered surgery for Atticus? I do understand that it would be an expensive and risky undertaking, and I honestly don't know what I would do if Atticus was mine. But I am just wondering if you've had this conversation with either your vet or the IMS.

In the alternative, if you prefer to stick to medication management, I don't know whether your IMS would consider trilostane as a viable option if the melatonin does not end up helping. Again, I do not have the knowledge to explain exactly how trilostane treatment would work with an adrenal tumor such as this. But if Dr. Bruyette says it might help, I do believe it could be an option for you. He is a consultant to Dechra, the manufacturer of brandname Vetoryl, and regularly offers continuing ed programs to clinicians. If your vet is ever interested, I'll bet Dr. B would be willing to discuss Atticus' case in more detail.

Marianne

[molly muffin]

I didn't know that either Marianne. Interesting that progesterone can suppress cortisol.

[kspach]

Marianne and Molly,
I had just written a long response and I lost it?? Undo didn't get it back--UGH. It is getting late and I really need to get to bed--will respond tomorrow. From now on will write it on Word then copy and paste it. Kathy

[labblab]

Drat!! I hate it when that happens to me!! :(

You may have noticed this thread already, but here are some suggestions that may help. Having said that, I still periodically lose replies in the midst of writing them, and I realize that I ought to do the same -- compose long replies elsewhere and then paste them in. :rolleyes:

http://www.k9cushings.com/forum/showthread.php?t=1329

Better luck today!

[kspach]

Thank you so much Marianne for all the time you have spent helping me and to both you and Molly for your dedication to this site.
Yes, my IMS did discuss all three options: melatonin, Cushing's drugs and surgery.
He implied that surgery was risky, although he did say he is not the surgeon. If I decided to go that route, I would need to discuss that in more detail with the actual surgeon. From some of the research that I have done, it looks like this surgery carries significant risks during and immediately after the operation. If they survive that period then chances of living a relatively normal lifespan are good.* Other, more general sites on Cushing's seem to impy if the dog has an adrenal tumor, remove it and the dog is cured, not mentioning any complications other than a complicating malignancy factor. Frankly, at the time of his diagnosis, I was glad that it was an adrenal tumor because it could be removed, not realizing that it is a very complicated operation.
The IMS said that the melatonin carried the least risk and was, of course, the least expensive option. If that doesn't work then there is treatment with Cushing's drugs with careful monitoring so as not to cause an Addison's reaction which could be fatal. (SCARY)
I have no idea how much the surgery would cost -- just diagnosing him has been over $1500. I am not sure how much longer we will be able to manage his excessive water intake though. He is now up to 9 quarts a day--seems to add a quart every week or two recently. Waiting 4-6 months to see improvement may prove quite difficult. The Cushing's drug seem scary so I should probably investigate the surgery option.
Thanks again, for all you help.
Kathy

*http://www.animalcancersurgeon.com/Adrenal_Tumors.html
*http://www.marvistavet.com/html/body_adrenal_treatment.html
*http://www.vetsurgerycentral.com/oncology_adrenal_tumors

[molly muffin]

I won't lie. Surgery is always a risk. If you do decide to talk to a surgeon we have a guide to help you with what questions to ask the surgeon. One of us will post those for you. I'm on a tablet at the moment so harder to do the links, etc.

It taks about 4 months maybe longer to know if the melatonin will work. I'd get started on that right away to see if it makes a difference.

[labblab]

Yes, it is indeed true that adrenal surgery can be a risky proposition. We have witnessed highly successful cures here, but we have also suffered through some heart-breaking losses. So it is not a procedure to be taken lightly, but it may be worthwhile to pursue some further consultation just so you'll better know your genuine options.

As for the Cushing's medications, they do indeed carry risks, as well. However, when prescribed and monitored properly, they can provide very successful symptom relief. The vast majority of our membership are using these meds, so as you can see, you would be in very good company should you decide to go that route. I don't disagree with trying the melatonin, but I admit to pessimism that it is going to satisfactorily control Atticus' worsening symptoms in a reasonable timeframe, if at all. I don't tell you this to discourage you, but instead to let you know that there may be other, more effective medication options available. We've had lots and lots of experience with the Cushing's meds, so we'll be here to walk alongside you should you decide to go that route.

Marianne

[molly muffin]

Hi Kathy, just checking in to see how things are going with Atticus. How is he doing?

[kspach]

It has been awhile since I lasted posted as I decided to give the melatonin a try. Just when I thought it might it be working in early March as his water consumption was decreasing, he tore his ACL and needed TTA surgery on his leg. Within a week of his surgery, his water consumption began increasing back to 3 gallons a day. It has been 10 weeks since his surgery, and while he is walking well, his bone still was not healed by his 8-week checkup and so will have to go in for more x-rays in June. The surgeon thought his age and underlying condition of Atypical Cushings were probably affecting his bone healing.I decided to try the trilostane so my vet in consultation with his IMS (who is leaving to take a job in another state at the end of the month) prescribed 120 mg. daily for 30 days followed a blood test to monitor how he is doing. I thought dogs were monitored after 7-10 days initially and then dosage was reduced to a maintenance dose. He weighs 77 pounds. I am quite nervous about giving these meds. I was given a list of side effects to watch out for. Kathy

[DoxieMama]

Hi Kathy,

I'd like to caution against starting trilostane with a dose of 120mg per day. The current recommendation of Dechra (the manufacturer of Vetoryl) is to start with 1mg per day, per pound. This dosage is more than 1.5mg per pound. Also, there should be an ACTH test scheduled for 10-14 days after starting (or changing) any dose. Based on your comments regarding a "maintenance dose", you may be thinking of Lysodren/Mitotane (which is the other drug commonly used to treat Cushing's).

Here's the link to Dechra's monitoring chart that outlines their protocol.
http://www.dechra-us.com/Admin/Public/DWSDownload.aspx?File=%2fFiles%2fFiles%2fSupportMa terialDownloads%2fus%2fUS-046-TEC.pdf

Hope this helps!
Shana

[kspach]

Thanks, Shana. I am going to call my vet tomorrow and express my concerns about the dosage and testing protocol. I know he is between pill sizes and would either have to take 60mg. which would be under 1 mg. per pound or 90 mg. which would be over. I do have the package insert that came with the pills which you posted. Kathy

[Harley PoMMom]

Hi Kathy, and welcome back, although I am sorry for the reason you need to be here.

From rereading your thread I see where Atticus' cortisol actually tested low on his initial ACTH stimulation test so I am very worried with starting him on Vetoryl and especially at that very high dose, 120 mg is too high for a dog weighing 77 pounds.

Dechra, the makers of Vetoryl, recommend a starting dose of no more than 1 mg per pound of a dog's weight, which means that Atticus' Vetoryl dose should not exceed 70 mg, here's a link to that info: http://www.vettimes.co.uk/news/new-lower-starting-dose-for-vetoryl/

Is Atticus still drinking/urinating a lot? Is he taking any pain or other medications?

Hugs, Lori

[kspach]

Yes--he is drinking upwards of 3 gallons a day and peeing the same! I see his surgeon the first week in June who is at the same specialty clinic where he was diagnosed with Atypical Cushings Disease by their IMS, who is leaving to work elsewhere. Supposedly he told my vet (who sent me there) to give him this dose ????? So glad you people are here--I read the insert and am very uncomfortable with the dosage and even the choice of meds. Will not treat until I can talk to another IMS who can answer my questions. Thanks so much for your support. Kathy

[kspach]

Lori,
I am also concerned that trilostane also may raise androstenedione which is one of his hormones that is elevated in his Atypical Cushings diagnosis. K

[kspach]

The only other meds he is taking right now is melatonin and Dasuquin.

[labblab]

Hi again, Kathy. I know the notion of giving trilostane to a dog with low cortisol seems odd. But back in January, when I corresponded with Dr. David Bruyette in L.A. about Atticus' unusual presentation, he also recommended trilostane as a possibility if surgical removal of the adrenal mass was not going to be considered. Earlier on in your thread, I gave a brief summary of what Dr. B wrote. But I'm going to go ahead now and give you our entire email conversation.


ME: Happy New Year, Dr. Bruyette! We have a new forum member who has presented an adrenal profile that is very puzzling to me. Here is part of the initial post ...

Even though the cause of the low cortisol is unknown, the member's IMS is not terribly concerned in the absence of Addisonian symptoms such as lethargy, vomiting/diarrhea. Apparently he doesn't think the adrenal tumor is the culprit, and he suggests that the elevated intermediates may be having a suppressive effect. However, I find the situation very puzzling because I have never seen a UTK adrenal profile like this, and I worry about giving melatonin to a dog who already has such abnormally low cortisol. Do you have any thoughts?

[I]Dr. B: The adrenal suppression seen on the ACTH stim test is consistent with a functional adrenal tumor causing contralateral adrenal suppression. If the dog is really not receiving any topical medications and the owner is not using a topical hormone replacement cream I would agree that the adrenal mass may be secreting progesterone which can cause the clinical signs and suppress the stim test.

Do we have the measurement of the right adrenal gland?

Me: P.S. I did already ask the owner about hormone/steroid creams or ointments used by other family members, and she said there are none.

[I]Dr. B: Thanks. I would remove the adrenal mass, get histopath and recheck the ACTH stim in 4-6 weeks. In the immediate post op period I would also use replacement doses of steroids given the adrenal suppression.

Me: If surgery is not an option for this patient, what would you do? Would you continue with the melatonin? What about replacement steroids now?

Dr. B: I would probably treat with trilostane to see if we can get the progesterone down and then see if adrenal function returns. I would probably not treat with steroids as the symptoms would only get worse.

Me: So you're not worried the trilostane would lower the suppressed cortisol even more? That was already my worry with even very mild cortisol reduction from melatonin...

Dr. B: No. Its really being suppressed by the progesterone so the cortisols will probably rise post trilostane in this case. Surgery for sure would be best.

So it appears as though Dr. Bruyette might also favor treatment with trilostane in Atticus' specific and somewaht unusual case. The only reservation I would have now would also be dosage. If it was me, I'd feel more comfortable starting with no more than 90 mg., but that will be more expensive for you since you will have to combine capsules unless you obtain a compounded trilostane product.

I just want to add that, across-the-board, Cushing's specialists do tend to recommend surgery as the preferred option for treatment of adrenal tumors in dogs who are able to withstand the procedure. But as we've already discussed earlier in your thread, surgery is a major consideration and we do understand that it is not an option that all members wish to consider. I honestly don't even know what I would decide to do if a dog of my own had an adrenal tumor.

Marianne

[Harley PoMMom]

According to the late Dr. Jack Oliver,
Enzyme inhibition by trilostane occurs for 3-beta hydroxysteroid dehydrogenase, but also for 11-beta hydroxylase.30 Thus, 11-deoxycortisol levels build-up in dogs treated with trilostane. It is also apparent that other intermediate steroid levels increase (androstenedione, 17-hydroxy progesterone, estradiol and progesterone) in dogs treated with trilostane,29 which could be due to the 11-beta hydroxylase inhibition, and possibly 21-hydroxylase enzyme inhibition. 29

https://vetmed.tennessee.edu/vmc/dls/endocrinology/Documents/Steroids_Profiles_in_the_Diagnosis_.pdf

The study that this quote refers to was performed by Dr. Oliver...hmmm

[labblab]

Yeah, I had wondered about that, too, Lori. But maybe the hormonal situation with a functional adrenal tumor is somwhat different from the more common situation of a dog with pituitary Cushing's? I definitely don't have enough knowledge to know whether the trilo may have a differential effect on progesterone in those two situations :o. That's why, even back in January, I was thinking that perhaps Kathy's IMS might want to consult with Dr. Bruyette directly. But now, since her IMS is also suggesting trilo, it would seem as though there is consensus among the two specialists, regardless. Atticus' situation is definitely different from any that I've seen here before, that's for sure.

For what it's worth, here's a quote from a Dechra write-up re: Vetoryl.


VETORYL Capsules are available in 3 sizes (10, 30 and 60 mg) for oral administration based on body weight. Trilostane (4α, 5α-epoxy-17β-hydroxy-3-oxoandrostane-2α-carbonitrile) is an orally active synthetic steroid analogue that selectively inhibits 3 β-hydroxysteroid dehydrogenase in the adrenal cortex, thereby inhibiting the conversion of pregnenolone to progesterone. This inhibition blocks production of glucocorticoids and to a lesser extent, mineralocorticoids and sex hormones while steroid precursor levels increase.

Perhaps that effect somehow outweighs the effect that Dr. Oliver was talking about???? I dunno.

[kspach]

Again, thanks for everyone's info and support. I talked to my vet about my concerns over the dosage and waiting 30 days to evaluate and he said that was what the IMS reccommended and what his dosaging chart stated. I told him I wasn't going to give it to him and so he said he would get in contact with Michigan State and see what they said. He was able to get in touch with Atticus's IMS at Blue Pearl (his last day on the job) who called me and left an extended message (I was not home) assuring me that 120 mg. was at the low end of treatment dosage and he should be tested after 30 days. So, I guess I will try it. I did read somewhere to start treatment on a Friday because if they were to go into a Addisonion reaction it takes a few days -- does anyone know anything about that?Kathy

[Renee]

I am always doubly disappointed when an IMS gives bad information. :( It's a travesty that so many general vets aren't better versed in cushings ... but, it's downright criminal when an IMS is ill informed.

The new protocols per Dechra are to start at a dose of no more than 1mg per 1lb of weight. This is even more important with bigger dogs, who generally need less over-all of the medication. There, of course, are exceptions to this, however, it is a generalized truth.

An addisonian crisis can happen at any time and at any dose. Given that you will be starting at nearly double the correct dose, I would think any adverse reaction may happen quickly within those first few days to week.

[DoxieMama]

Kathy,

Did you get the dosage all in one capsule - 120mg? I'm kind of hoping you happened to get 2x60 so could start with the 60mg without having to return/exchange the ones you have.

While only one example, my personal experience .... My gp vet wanted to start my 11 pound dog on a dose of either 22mg compounded or 30mg Vetoryl. After reading the information here, I insisted that I wanted to start him on the 1mg per pound recommendations of Dechra. I argued with the vet tech about it, but held my ground in my refusal to give him more than 11mg once per day. Both my vet and his vet tech disagreed with this BUT provided me with that prescription anyway. The way I see it (and explained to them) is that there is little harm in starting too low... it just may take longer to see effects. I was okay with that, because I wanted to reduce or eliminate possible side effects as much as possible, and THAT they could understand.

As it turned out, even a dose of 1mg per pound was a bit too much. After less than 30 days, we decreased from 11mg to 8mg per day.

[labblab]

As folks here know, I am usually always at the forefront of endorsing the 1 mg. per pound formula for initial dosing. However, the wild card for me here is that Atticus' case is so unusual -- due to the function of his adrenal tumor, presumably the trilostane is being given with the aim of reducing progesterone and thereby actually increasing cortisol levels. I have never encountered a case like this before, and therefore I have absolutely no idea as to whether or not that affects the optimal trilostane dose.

In this situation, I have to defer to the experts. However, in honesty, I would probably wait until AFTER the long holiday weekend to start the dosing so that you will be able to easily consult with a vet if Atticus exhibits problems with his initial doses.

Marianne

[kspach]

No-- it is one capsule. The package insert says starting dose of 1-3 mg. per pound which 1.55 would be in the middle which and what he would be getting. I could wait until they get a new IMS at Blue Pearl as they are trying to get a replacement by the end of June. Ths whole thing has me so upset and I am operating on a lack on sleep since I am getting up multiple times in the night to let him out. I did read that functional adrenal tumors that are non-cortisol producing are usually cancerous so I am thinking his time is limited. http://www.dogaware.com/articles/wdjcushings.html#atypical
I decided not to have surgery, at first mainly because of the risk, and glad I didn't as he needed TTA surgery in March. I am retired and while comfortable certainly not wealthy. Having spent amost 7 grand in the past 9 mos. to have his ACD dagnosed and TTA surgery I really wonder sometimes what I am doing --was hoping this med might give us both some relief and some semblence of our old lifestyle back --at least for a little while.

[dsbailey]

In this situation, I have to defer to the experts. However, in honesty, I would probably wait until AFTER the long holiday weekend to start the dosing so that you will be able to easily consult with a vet if Atticus exhibits problems with his initial doses.

Marianne

I agree with Marianne about the long weekend. I started out my 57 lb girl on 60 mg and after 10 days was well on her way to an Addison's Crisis. I'm sure if she were started on say 90 mg or 120 mg that would have happened in a few days. I restarted her on 30 mg and we're still working on finding the proper dosage. Her next ACTH Stim test is Friday and from the clinical signs I'm assuming an upward adjustment. My vet is pretty open to my suggestions and if an adjustment is needed I'll suggest / insist on 40 mg, 30 mg in the morning and 10 mg in the evening (She seems to get all spun up "CushWound" in the evenings). As everyone here says "Low and Slow".

Good Luck,

Darrell - Lolita's Dad

[Harley PoMMom]

No-- it is one capsule. The package insert says starting dose of 1-3 mg. per pound which 1.55 would be in the middle which and what he would be getting.

I'm reposting this as I believe it is very important. I would print out these revised dosing protocols from Dechra and have the vet/IMS look at them.


Hi Kathy, and welcome back, although I am sorry for the reason you need to be here.

Dechra, the makers of Vetoryl, recommend a starting dose of no more than 1 mg per pound of a dog's weight, which means that Atticus' Vetoryl dose should not exceed 70 mg, here's a link to that info: http://www.vettimes.co.uk/news/new-lower-starting-dose-for-vetoryl/
Hugs, Lori

[kspach]

Thank you so much for that link. I will email it to my vet. Also, both my vet and the IMS said he doesn't need to be tested until 30 days after starting the medication--everything I have read states 10-14 days then again at 30 days. How important is the 10-14 day check if no adverse reactions are apparent?

[dsbailey]

Very Important

From my post earlier "I started out my 57 lb girl on 60 mg and after 10 days was well on her way to an Addison's Crisis". There were no negative clinical signs at 10 days (pre <1.0, post 1.2) Range (1.5 - 9.1). I don't like to even guess where she'd be if left on 60 mg for another 20 days.

Darrell - Lolita's Dad

[Renee]

Some clinicians have started delaying the first stim test until 30 days in the absence of adverse reactions. I don't completely disagree with that in some cases. However, in your case, I most definitely would re-check in 10-14 days.

The standard protocol is to test 10-14 days after starting medication. This is to determine one of two outcomes. You either keep the current dose or you lower it due to over suppression. Dosing changes should never be upwards at that first check. The point of the 10-14 day check is to look for over suppression.

Given that your pup does not have traditional cushings or highly elevated cortisol, I would think it is doubly important to run that 10-14 day check.

[kspach]

I was on the Dechra website and looked at their Hyperadrenocorticism Brochure copyright 2015--still saying 1-3 mg. per pound as starting dose. I could find nothing similar to the UK article in Vet Times???? There is a phone no. on my package and website for Dechra support that I will call tomorrow but will most likely insist on a lower dosage to begin with as I would much rather be safe than sorry. Kathy

[labblab]

Kathy, take a look at this post, and I think it will help clarify the discrepancy between the language of the brochure and that of the UK article. I am guessing that when you call Dechra USA, if pressed, they will still verbally cite the 1-3 mg. dosing range since that is the wording that is retained in the FDA approved brochure. However, at every other opportunity now, you will see the written references to the range qualified by additional language re: starting "at the lowest possible dose" which would be 1 mg. per pound.


The starting dose is 1-3 mg/lb (2.2-6.7 mg/kg) once a day for the treatment of hyperadrenocorticism in dogs. Start with the lowest possible dose based on body weight and available combinations of capsule sizes.

Anyway, please do read this post for additional history and clarification re: Dechra's dosing recommendations:

http://www.k9cushings.com/forum/showthread.php?p=1251#post1251

If you do call Dechra, please explain Atticus' unusual situation of functional adrenal tumor, high progesterone, but abnormally low cortisol.

Marianne

[kspach]

I am in the process of emailing my vet with the Vet News article from the UK and the dosing and testing chart on the Dechra website. I was thinking of having him order 60 mg and 10 mg caps and starting at 70mg or is that too low? He last weighed in at 77 lbs --may be closer to 80 now. Kathy

[DoxieMama]

That sounds like a good idea, Kathy.

[labblab]

Sounds like a good plan to me, too. The 10 mg. capsules give you a lot of flexibility, because you can add more in if you end up wanting to increase the dose incrementally.

Marianne

[kspach]

A couple questions:

1. Does Vetroyl interact negatively with joint meds (Dasaquin), heartworm (Sentinel) or melatonin? I was thinking of still giving a small dose of melatonin to see if it will help in his fear of thunderstorms and fireworks this summer. His surgeon wants me to use a joint med.

2. Does this medication help wth muscle wasting as well as the other symptoms?

[lulusmom]

It should be fine to give Vetoryl with Dasaquin, Sentinel or melatonin. Vetoryl does help muscle wasting but it takes some time for a dog to regain the muscle mass and strength. You therefore probably won't see see an immediate improvement but it will get better in time. However, we have had some members report improvements much sooner than expected so you just never know.

[judymaggie]

Hi! I used to give Abbie melatonin for thunderstorm anxiety. It worked best if I could keep an eye on the weather and give it about 30 minutes before the thunderstorm would head our way. Of course, that is not always possible --- if I gave it to her when the thunderstorm had already started, it didn't seem as effective but still had some calming effect. I also used a thundershirt along with the melatonin and the combination seemed to work.

Strangely, Abbie no longer has any reaction to thunderstorms. Maybe some senility is a good thing ...

[kspach]

Thank you Lulusmom and Judy. I love this site as everyone is so helpful and supportive. A few more questions:

1. I assume it is ok if they chew the tablet. My dog will take a pill--flavored or not--right out of my hand or thrown in his kibble. I know it must be taken with food.

2. I understand that he must be tested at 30 days to check if the dosage needs to be lowered or increased. Since the pills come in packs of 30 I would have to reorder before the test and getting the results back since my vet orders the pills --otherwise, he would be without pills for several days. How do other people handle this? I am starting him out on 70 mg. --if he needs to increase I would probably go to 90. I assume I would still order the 60’s and 10’s-- give him a 60 and 3 tens until the 30’s came in.

3. Has anyone else used Valley Vet online pharmacy? I see that their prices for Vetoryl are a lot lower than what my vet charges. I do have a compounding pharmacy in the area that I could use once his dosage is established-- is the generic an acceptable equivilant?

[kspach]

Lablab-- this is the response I got when I emailed support at Dechra:
Thank you for contacting Dechra Veterinary Products.

"You are correct, our label directions are to start the dog on 1-3mg/lb/day and ideally begin the dog at the lowest dose that will control the clinical signs of hyperadrenocorticism. Although 120mg may seem like a high dose, it is still well within the range of our suggested starting dose of 1-3 mg/lb/day (1.55mg/lb/day), and even at the lower end of the range. If you are concerned this dose is still too high, you may want to try a 60mg and a 30mg capsule once daily (90mg total) which would put his dose at 1.16 mg/lb/day. I would definitely suggest consulting with your veterinarian.

As far as our recommendations on the ACTH stimulation test, we do recommend testing at 10-14 days, after starting your dog on the medication, then again at one month. Just to be sure his body is responding to the medication and his cortisol levels are within optimal range. Once your dog has adjusted to the correct amount of Vetoryl, then you can re-test him in 3-6 months, as long as he is doing well on the drug."

[labblab]

Hello again! As far as allowing your dog to chew up the Vetoryl capsule before swallowing it, no, actually I doubt that is a good idea. Most medications that are packaged in capsule form are intended to be swallowed intact so that the powder does not get released until it has reached the stomach where the desired absorption occurs. I do not know if the drug will be metabolized properly if absorption begins in the mouth. This could be another question for Dechra. However, for a couple of reasons, probably the best route for administration is to give the capsule by hand, wrapped in something appealing (cheese, cold cut, etc.). That way, you can visually confirm that the capsule has been swallowed and not spit out unnoticed during the course of a meal.

Since it is best to avoid a lapse in treatment, you really have no choice but to either perform the ACTH a few days short of the 30 days, or else to proceed just the way you are suggesting -- reorder the 60s and 10s in advance, and then decide on the future dosing once the test results are in. Yes, we definitely have folks who use Valley Vet and also other reputable internet providers in order to reduce costs. As far as pros and cons of using Vetoryl vs. compounded trilostane, I'll come back and add another reply later.

Re: Dechra's response about the 120 mg. dosing, I am not surprised because other folks have gotten similar answers from the U.S. office. However, the response continues to annoy me enormously, since in my own mind, the phrase "lowest possible dose" is quite straightforward and certainly not identical to "kind of at the lower part of an extended range." You don't have to be a mathematical genius to calculate 1 mg. per pound. But my personal suspicion is that since the range is what was originally OK'd in the FDA approval submission, they don't feel as though they can flat-out say the range is wrong. Anyway, whether it's a cover-their-butt reflex or not, I would still start my own dog at the lowest end of the range and then work upward if need be.

Marianne

[molly muffin]

I am a big proponent of starting low and slow and the 1mg/1lb has worked out better than for most than starting higher. You may end up needing to go higher (or lower) but there is less risk of running into trouble.

[kspach]

What kind of results should I be looking for in his first ACTH test after starting Vetoryl? His post cortisol reading was very low in the test sent to Univ. of Tenn.in Dec.--supposedly as a result of other hormones being elevated. Should we be looking for his cortisol to increase or stay the same and be alarmed if it it is lower? Is a complete blood chemistry also done at this time?

[labblab]

Dechra recommends that a blood chemistry be performed alongside every ACTH test, primarily to assess potassium, sodium, kidney and liver values. I do believe it is good to check these at least routinely, if not at every ACTH testing. And if a dog is acting unwell, they definitely should be checked.

As far as what to expect re: cortisol level, I can only guess based on what Dr. Bruyette wrote. And yes, it sounds as though the hope is that you'll start seeing symptom improvement as well as at least a slight increase in cortisol. It will be very interesting to see what happens!

Marianne

[molly muffin]

Just checking in to see how he is doing.

[kspach]

I gave him his first dose today--70 mg. We go tomorrow to his surgeon to see if his knee is healing. It will be 3 months since his TTA surgery --2-month x-rays showed slow healing ( surgeon thought probably due to age and underlying condition) so am hoping things have improved. One question-- I know lethargy is a symptom of Addison reaction but my dog has wanted to go home or lie down on our walks, stares off into space--rather unusual for the last few weeks. I don't know if his leg or the Atypical Cushings is a problem. What is the best place to buy Vetroyl online? My vet's prices are way above what I have seen online. K

[kspach]

Dechra called, after I left a message this weekend, and said that there is no problem if the dog happens to chew the capsule just as long as he consumes the entire contents and it is given with food. I find sticking them on a spoon with a little peanut butter, then turning the spoon over he will lick it off and immediately swallow as he continues to lick the spoon.

[lozadaNY76]

I have read threw this thread and I was wondering how Atticus is doing?

[kspach]

So far he is doing ok, He just started Vetroyl --took his fourth dose today. Still no improvement in symptoms but hope I will in the next few weeks.
You have come to the right place! You need to start your own thread so you can share your dog's test results and take full advantage of this site. This is a wonderful forum and there are so many helpful and knowledgeable people here and a lot of resources. Welcome to the forum --I know you will find a lot of support here and so sorry your pup is having so many problems.

[Harley PoMMom]

You have come to the right place! You need to start your own thread so you can share your dog's test results and take full advantage of this site. This is a wonderful forum and there are so many helpful and knowledgeable people here and a lot of resources. Welcome to the forum --I know you will find a lot of support here and so sorry your pup is having so many problems.

Shannon (lozadaNY76) and Jordan's have a thread and it is located at this link: http://www.k9cushings.com/forum/showthread.php?t=7750 ;)

[kspach]

After six days on Vetroyl (70mg) I am quite concerned. Atticus is VERY listless today, picked at his breakfast--ate much of it lying down eventually. He has always gulped his meals with great enthusiam. Did not give his morning meds and the vet is going to see him later this morning.

[labblab]

I'm so sorry Atticus isn't feeling well! You are definitely doing the right thing by holding his meds and taking him in. Please let us know how things unfold through the day.

Sending big hugs to your sweet boy,
Marianne

[DoxieMama]

I'm glad your vet is available to see him today. Hope he's feeling better soon!

[judymaggie]

Thinking good thoughts for Atticus -- please do let us know what the vet says.

[kspach]

Vet did a CBC w/DIFFERENTIAL and Health profile with electrolytes. He called and said potassium was a little low and chloride a pinch high and everything else ok. He thought when he examined him that he was nauseous although he hasn't vomited. He thought maybe the meds might be upsetting his stomach. Gave him a shot for that and told me to stop meds for the weekend and call if he wasn't eating. Said he was not dehydrated. He has perked up--ate his afternoon meal fine. Has not drunk a lot of water today and has not defecated. Very hot here but have him inside with the air conditioning except to potty. Since the purpose of the meds is to reduce his appetite and water consumption how do you tell if it is working or if he is having a bad reaction? But in his 91/2 years I have never seen him react to his food like he did this morning, and while he is more lethargic this past year--not as bad as he was this morning.

[labblab]

Hmmmm...I would have thought your vet would have checked his cortisol level since that is the primary worry in a situation like this, especially since we know that Atticus' cortisol level was abnormally low to begin with. It's good that his electrolytes were not significantly unbalanced, but low cortisol can be a problem even when the electrolytes are unaffected, and the symptoms that Atticus has exhibited could certainly be consistent with low cortisol.

I think it's a good call to hold the trilostane for the rest of the weekend. But did the vet mention cortisol as a worry at all? Under normal treatment conditions, you are indeed seeking reduction in ravenous appetite and excessive thirst. But your goal is to see a dog that is acting normally -- not extreme lethargy and total loss of appetite.

Marianne

[kspach]

My vet called today to see how Atticus was doing and we decided to start him back up again tomorrow on 60 mg. I asked about getting some prednisone for an emergency . What exactly does that do? I believe that is a steroid and am wondering about Dr. Bruyette’s comment from Marianne ‘s (Labblab’s) correspondence with him. "I would probably treat with trilostane to see if we can get the progesterone down and then see if adrenal function returns. I would probably not treat with steroids as the symptoms would only get worse."

[Harley PoMMom]

Cortisol is a natural glucocorticoid (steroid) that a body makes and when a dog's cortisol drops too low a supplemental steroid is needed such as predisone. Prednisone mimics cortisol in a dog's system.

Hugs, Lori

[kspach]

Thanks, Lori. Do you just give it to them until they return to normal--like a day or two? I know my last dog was on prednisone once for an allergy and had to taper dosage before stopping --but I think he as on a ten-day regimen.

[Harley PoMMom]

The dog would need the prednsione until the adrenals start producing the cortisol their body needs, the length of time for the prednsione is dependent on how fast those adrenals regenerate which is monitored with an ACTH stim test.

[kspach]

has been a week since Atticus has taken Vetroyl. I stopped it after he only had 6 doses. His morning appetite is good, although one day mid week he acted as he did the Saturday I took him to the vet thinking he was having a bad reaction to the medication. He is still more lethargic than before he started Vetroyl however, his water consumption has been cut in half since he stopped it. The last 3 nights I have not had to get up with him to let him out to urinate. He has gone from slightly over 3 gallons a day a week ago to about a gallon and a half a day. Does this make sense to anyone? At no time has he vomited or had diarrhea.

[lulusmom]

How is Atticus doing now? I just refreshed my memory of your boy's history and see that a full six months passed between the results of the UTK adrenal panel results and starting Vetoryl treatment. Since the specialist felt that the abnormally low pre and post cortisol on that panel could have been been caused by a medication, was any adrenal function tests, specifically an acth stimulation test, done in the last six months to see if cortisol levels were still very low before starting Vetoryl treatment? Were any follow up abdominal ultrasounds done in the last six months to check the progression of the tumor and to see if the right adrenal gland could be visualized?

Glynda

[kspach]

No tests were done recently before starting Vetoryl. After 6 days on the medication he became so lethargic and he eat slowly lying down. (From the day I got him he has gobbled him food in lightening speed, so that was alarming.) I really thought I was going to lose him within a few weeks at that point. My vet did blood tests (this was a Sat.) and nothing seemed to be wrong--no cortisol testing though. I don't think my vet has the drug for the ACTH test on hand. For about 10 days after stopping Vetoryl his water consumption dropped considerably (still above what would be considered normal) but this it started to go up to pre meds. Not sure what all that means-- was the adrenal function impaired by the drug and has now recovered and so is back to where he was before starting Vetoryl? Anyway. he is wagging his tail again, eating normally and acting like he did pre-Vetoyl. Funny--he is certainly not the dog he used to be but I was so elated this week that he at least was alert and functioning more normally.
My vet suggested another ultra sound but I am at the point where my liquid savings is much lower than I am comfortable with due to the amount of money I am spending on vet bills and am going to take a breather and assess the situation. My vet, while he is good at contacting specialists, seems to know less about this disease than I do which makes me uncomfortable. As an example, the instructions on the Vetoryl says take one tablet daily --nothing about having to be given with food in the morning. I knew that from being on this website.
Today I had to take him in as he has developed an interdigital cyst on his right rear toe, so he had a laser treatment and has put on antibiotics. I know I will not start up Vetoryl treatment again until I have a personal consultation with the permanent replacement IMS (as soon as they get one) at my specialty clinic as I have a lot of questions such as how they plan to monitor dosage considering his low cortisol readings on the ACTH test.
I have put him back on melatonin--may not be helping with the Cushings but does seem to have a mild effect on his fear of fireworks and thunder. Also, he water consumption has never gone above 3 gallons a day -- seems to have stabilized there since April.

[lulusmom]

Thank you so much for responding. I am very happy to hear that Atticus is doing so well right now and for what it's worth, I am equally happy with your plan of action for him. If he's doing much better off of Vetoryl and not symptomatic, there really isn't a reason to continue treatment at this point. Hopefully symptoms will stay at bay permanently which does happen on rare occasions. I will be very interested to know what the new IMS has to say so please keep up posted.

Glynda