New diagnosis - Symptoms returned after 4 wks on meds

[Skylar]

Thank you so much for this amazing site! So much great info. My dog Molly just turned 10 and is a 14 pound poodle mix. In September I noticed her drinking and peeing much more, ravenously hungry and an extended belly. She also had leg muscle weakness, dry skin and occasional panting. I took her to the vet and after several tests (listed below), she was diagnosed with pituitary cushings. After the initial loading and maintenance it was like a miracle. Completely symptom free. But then almost 4 weeks later, all the symptoms returned. First the mg and then the frequency were increased, but the symptoms didn't decrease at all. The vet said it is expected that the dosage would need to be increased, but it's usually after a few months, not weeks. Even though the last ACTH was at the high end of normal at 5.6, the vet said some dogs do better at the lower end. So I'm now back to loading.

I have a few questions that I was hoping someone could answer. I think people on the forum know more than a lot of vets.

• Have you ever heard of a dog doing great on Lysodren initially and then have it stop working in less than 4 weeks?
• Would it be better to switch to Vetoryl? My vet said it's up to me. She has more experience with Lysodren.
• Is pooping more normal? She poops sometimes 5 times a day. The vet said cortisol can speed up the bowels, but 5 times seems excessive.
• She has major gas, mostly after eating. Is that normal? She eats Fromm Chicken a la Veg, which is supposed to be a great brand

Thank you so much for all the support!!! I've been so stressed to see my baby going through this.


10/19/17 - urinalysis (diagnosis of UTI) - put on Clavimox
10/25/17 - CBC, urinalysis, SMAC general, cortisol resting
10/31/17 - Low Dose Dexamethasone
11/8/17 - ACTH, urine creatine ratio (I don't have the numbers yet)
11/11/17 - stated Lysodren loading (1/4 of 500mg twice a day for 7 days). No symptoms on day 7.
11/20/17 - ACTH (pre 1.2, post 1.2)
11/22/17 - started Lysodren maintenance (1/4 of 500mg every 3 days)
12/16/17 - symptoms returned (drinking/peeing/hunger)
12/27/17 - increased mg of Lysodren (not sure as vet compounded it) - given every 3 days
1/5/18 - ACTH (pre 5.2, post 5.6)
1/11/18 - increased dosage to every 2 days - still no change in symptoms
2/3/18 - stated Lysodren loading (1/4 of 500mg twice a day for 7 days) AGAIN

[Squirt's Mom]

Hi and welcome to you and Molly!

It seems the Lyso dose is correct. At 14 lbs her loading dose would be 150mg 2x/day but since the pill only comes in 500mg doses that would usually be rounded down to 125mg 2x/day. So that is a bit lower than the optimal dose but should work. However - there is NO set time limit for the load to be achieved. It may happen in 3 days or it may take 2 months. So simply stopping after 7 days may mean the load was never achieved in the first place. We look at the signs PLUS the ACTH given between the load and starting maintenance. You want to see changes that indicate the cortisol has been lowered - a decrease in water consumption, the pup looking up during a meal when their name is called when before they simply would have continued wolfing the food down. These are the two most common signs we look for during the loading phase that indicate the load has been successful. So watch her carefully for signs and stop even if it has only been a few days instead of 7.

Her ACTH given on Nov. 11 (pre 1.2, post 1.2) is a bit concerning. My mind has gone completely blank at the moment but there is a name for results like this and they can indicate the adrenals have been hit too hard and Addison's is a real possibility. BUT with the next ACTH being almost perfect even with continued use of the Lsyo hopefully this was just a one-off.

What signs are you continuing to see? In some pups the increased urination never resolves but appetite, panting, heat and exercise intolerance usually do improve if not completely resolve.

Did she have an abdominal ultrasound? I ask because conditions, like a tumor, can cause the cortisol to rise NATURALLY and with that rise come the signs of Cushing's. So an US is always a good bet. My Squirt was diagnosed with Cushing's but the US found a tumor on her spleen and once it was removed her cortisol returned to normal. My little Trinket was also diagnosed with Cushing's but she had many known conditions prior to that diagnosis. I always questioned the validity of her diagnosis and the necropsy I asked for following her death proved she did not have Cushing's BUT she did have a couple of new conditions that had never been found. I believe it was the combination of conditions causing her cortisol to be off the charts....not Cushing's. These cases prove that an unrelated source can cause elevated cortisol and Cushing's sign yet not be Cushing's. Something like this could also cause the signs to return even on treatment - my Trinket's signs never improved even with the Lsyodren on board because her conditions continued to progress.

It is not uncommon for a pup to need to reload but we usually see that when the dose is too low OR when the loading dose was stopped before the load was actually achieved. So being in the spot you are in now is not that uncommon....tho in my experience we do see that more often with Vetoryl (Trilostane) than with Lysodren.

As for switching - I would say no right now. First Lysodren is the drug your vet is more experienced with and I have to assume more comfortable with using....and that is crucial. Second, you would have to give Molly a minimum of 30 days drug free before starting the Vetoryl. She would HAVE to have a 30-day wash out between the two drugs to protect her from an overdose. Lyso has a long life in the body and it is never safe to rush into a switch as a result. If I were you, I would give this second load a chance then WHEN her signs improve and the ACTH says her level is between 1-5ug/dl go to maintenance giving the Lyso 3-4 times a week. Then if she loses the load again AND there are no contributing causes like a tumor, etc. you could consider a switch. It is true that some pups simply don't do well or cannot handle one or the other of the drugs used for treatment and need to switch. Just remember - a 30-day washout out is mandatory to protect Molly.

Lyso is hard on the digestive system so seeing more poop at first or a bit of tummy upset is not uncommon, including gas. However, if she starts having loose stools or diarrhea that is cause for concern as is vomiting, loss of appetite, or lethargy. As for food, you do not want to switch right now. Changing foods often causes the same things we look for that indicate the cortisol has dropped too low - like loose stools/diarrhea, nausea/vomiting and loss of appetite. So stick with what she is currently eating as long as it is not causing another problem like allergies.

Was the UTI cleared up before the testing for Cushing's started? If not that could have skewed the cush tests. Would you please post the actual results of the testing done to diagnose the Cushing's - the CBC, urinalysis, SMAC general, cortisol resting, LDDS (Low Dose Dexamethasone Suppression test), ACTH, and UC:CR (urine creatine ratio)? Those results will help us a great deal in offering more meaningful feedback.

Also would you look on the bottle of compounded Lyso - it should tell you the dose even tho it was compounded. If it is a liquid, it will say X mg/ml. I personally would not be comfortable with a vet compounding either Lysodren or Vetoryl. So that is a question in my mind - was the compounded Lyso effective or not? For future reference, a very trustworthy compounding pharmacy is Diamondback Drugs out of AZ. Just FYI should you ever need another compounded drug.

Here is a link from our Helpful Resource section about Lysodren. Many members print this out and have it handy just in case. And we are always here to chat with. I'm sure others will be along soon to offer their ideas.

http://www.k9cushings.com/forum/show...d-related-tips

I'm glad you found us and look forward to learning more as time passes.
Hugs,
Leslie

[molly muffin]

Hello and welcome to the forum.

Leslie definitely has more knowledge about lysodren than I do, but I do wonder if it is the compounded lysodren that might have caused her to lose the load.

Actually the flat line of the 1.2 pre and post wouldn't make me happy either. A nice. pre 2.5 and post 3.5 is where I am happiest at safety wise. (not too low, not too high, perfect with lysodren) so I think that is the goal I'd be aiming for.

An ultrasound might be worth it, especially if she were to lose the load again, but I'm still thinking it might have been the compound. Just so hard to say for sure, but you have done everything right. The low levels on the ACTH does signal that the load was achieved on the first go round even though as Leslie mentioned, there is no set time for how long it takes to load.

Also as leslie mentioned the pooping and gas, can be from the lysodren. It should settle down eventually.
I wouldn't change to vetroyl until you know that the lysodren isn't going to work, then it could be worth it to look into. I'd only change after, having an ultrasound done, and of course the wash out phase between switching drugs.

[Harley PoMMom]

After the initial loading and maintenance it was like a miracle. Completely symptom free. But then almost 4 weeks later, all the symptoms returned. First the mg and then the frequency were increased, but the symptoms didn't decrease at all. The vet said it is expected that the dosage would need to be increased, but it's usually after a few months, not weeks. Even though the last ACTH was at the high end of normal at 5.6, the vet said some dogs do better at the lower end. So I'm now back to loading.

Her most ACTH stimulation test is a bit higher than what is recommended (pre and post 1 ug/dl - 5 ug/dl), which may be why her increased drinking and urination have returned. However, was an urine culture and sensitivity test done to make absolutely sure that the UTI is completely gone? And were her electrolytes checked to see if an imbalance occurred?

10/19/17 - urinalysis (diagnosis of UTI) - put on Clavimox
10/25/17 - CBC, urinalysis, SMAC general, cortisol resting
10/31/17 - Low Dose Dexamethasone
11/8/17 - ACTH, urine creatine ratio (I don't have the numbers yet)
11/11/17 - stated Lysodren loading (1/4 of 500mg twice a day for 7 days). No symptoms on day 7.
11/20/17 - ACTH (pre 1.2, post 1.2)
11/22/17 - started Lysodren maintenance (1/4 of 500mg every 3 days)
12/16/17 - symptoms returned (drinking/peeing/hunger)
12/27/17 - increased mg of Lysodren (not sure as vet compounded it) - given every 3 days
1/5/18 - ACTH (pre 5.2, post 5.6)
1/11/18 - increased dosage to every 2 days - still no change in symptoms
2/3/18 - stated Lysodren loading (1/4 of 500mg twice a day for 7 days) AGAIN

Could you get the results of the CBC/chemistry blood panel and the LDDS test and post them here for us? With respect to the blood panel we need to see only those values that are abnormal along with their reference ranges; for the LDDS, there will be 3 number included for that test....thanks!

With Lysodren, the maintenance dose is usually just about the same dose as you used to give in just one day of the loading but sometimes it does have to be tweaked. Since Lysodren is a fat soluble drug is Molly getting her Lysodren with some fat?

Gastric upset is common with Lysodren so giving Pepcid AC 20-30 minutes before the meal with which the Lysodren is given may help, now if it is flatulence Gas-X may be more beneficial.

I'm sorry for the reasons that brought you here but so glad you found us and we will help in any way we can.

Lori

[Skylar]

I can't thank you all enough for your wonderful information! Having this site has really reduced my stress. I know I will get accurate information. It's hard for me to believe that so many vets aren't more skilled on this disease. It seems like a pretty common illness in older dogs. I will post all the blood/urine results tomorrow after I get them.

Her UTI was cleared before the first load on 11/11. She loaded on the 7th day. The increased thirst, peeing and hunger completely went away. And that lasted for 3 weeks. Then those 3 symptoms returned. The symptoms continued even with starting an increased dosage for a week and then increased frequency (every 2 versus 3 days). I'm now wondering as well if it was from the compounding. I kind of like my vet, but her staff, including the vet tech, aren't knowledgable at all. If one of them did the compounding, I can't be sure it was done correctly. The reason I had them compound the 500 mg into four 125 capsules was that I thought if I cut the pill into fourths, I wouldn't be able to get them perfectly even.

My vet was not quick to diagnose Cushing's. She said that a UTI might be causing the increased drinking/peeing. But then when I asked if that would cause increased hunger, pot belly, dry skin, and muscle weakness, she said no. That made me question her competency. How could she say it might be only a UTI without considering all the other symptoms. When she did say it was Cushing's and told me there were 2 meds available, she said it was my decision. I would choose whichever worked the best. I wanted her to recommend one, not leave the decision up to me. She is more familiar with Lysodren, but if the other works better, I would have gone with that. When Molly's symptoms returned after 3 weeks, she said we can load again on Lysodren or switch to Veteroyl. She said the waiting time was one week. I told her I read it was 30 days and she said she would have to look it up. That concerns me. She should have known. Except I think all her patients are on Lysodren. But still.

She also said the increased pooping was from excess cortisol, not from the Lysodren. Is that your experience? She poopled 5 times the last few days. Some were soft, but not watery.

So now we're on the 5th day of Lysodren loading. No decrease in water/peeing. It's actually increased believe it or not. Her hunger seems a tiny bit decreased. Last time it took her the full 7 days to decrease the water consumption. Friday, 11/9, will be the 7th day. I'm going to bring a urine sample tomorrow to get tested for infection and electrolytes.

If the load works and her ACTH on Monday is within range, my question is:

- Should she get 1/4 pill every other day or every 3 days. She is loading at 1/4 pill twice a day. I don't want it to wear off after 3 weeks, like before. But this time I won't have them compound it. Or should it be 1/3 of a pill every 3 days. (that would have to be compounded, but I would go to a pharmacist this time).

Again, thanks for all the help! I was trying to find a certified endocrinologist, not just an internal medicine specialist. But there are none in Cincinnati where I live.

[Harley PoMMom]

I've got a couple questions about those monitoring ACTH stimulation tests. Molly started the loading phase on Nov 11th and her symptoms stopped on the 17th of Novemeber, right? If this is correct that monitoring ACTH stim test should of been performed on the 18th day of November not the 20th. Did the vet say why they perform the ACTH stimulation test in this way? The monitoring ACTH tests should be done right away so as to gauge how the Lysodren is working and to get an accurate reading of the cortisol levels.

An imbalance in the electrolytes can cause increased drinking and urinating so I think it is a really good idea to have her electrolytes checked but she would need to go to the vets to have this done as they need to draw blood for this.

Also, is Molly getting her Lysodren with some fat? Lysodren is a fat soluble drug and needs that fat to be properly absorbed. I have used cream cheese or peanut butter to hid those Lysodren pills.


Regarding the 30 day washout period; This excerpt comes from Dr. Feldman, who is a renown veterinarian that specializes in endocrinology:

DVM: So has trilostane become your first choice in the treatment of hyperadrenocorticism, or do you continue to use mitotane (o,p'-DDD)? Is there a particular protocol you use if you switch between the two medications to avoid possible complications, in light of a couple of reported cases of acute adrenocortical necrosis following a switch?

Feldman: Trilostane is my first choice in dogs with an adrenal tumor. My first choice for dogs with pituitary-dependent hyperadrenocorticism is mitotane. However, trilostane at an initial dose of 0.5 mg/kg given twice daily is an excellent second choice. No veterinarian should consider the use of trilostane before thoroughly reading the insert provided with the drug — not the insert for pet owners, the insert for veterinarians. Any dog switched from one to the other should receive no medication for at least six weeks.

You can find this info here: Cushing's disease and other adrenal gland disorders

Dechra, the makers of Vetoryl, also recommend a washout period:

PRECAUTIONS:
Mitotane (o,p’-DDD) treatment will reduce adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an interval of at least one month should elapse before the introduction of VETORYL Capsules. It is important to wait for both the recurrence of clinical signs consistent with hyperadrenocorticism, and a post-ACTH cortisol level of > 9.1 g/dL (> 250 nmol/L) before treatment with VETORYL Capsules is initiated. Close monitoring of adrenal function is advised, as dogs previously treated with mitotane may be more responsive to the effects of VETORYL Capsules.

This information can be found here: Dechra's U.S. Product Insert***

Lori

[Skylar]

I have all the test results listed below. I also originally had the maintenance dosage incorrect. I changed it all to the correct numbers. The original loading was for 7 days at 125 mg twice a day, which would be around 50 mg/kg/day. The vet said after the last dose on the 7th day she should be off the Lysodren for 2 days and then an ACTH on the 3rd day. Is this right? Should it be done sooner? Plus she has to send out for test results and it could take a couple of days. So she could be not taking anything after the load for around 5 days.

The initial maintenance was 50 mg every 3 days. My vet said she determined this by 25 mg/kg/week (low end of range). Symptoms returned and was increased to 100 mg every 3 days. After 2 weeks no decrease in symptoms so increase to 100 mg every 2 days.

The vet said Molly probably needs to be on a higher maintenance dose. After the loading, if the maintenance doesn't hold she will do an ultrasound.

10/9/17 - urinalysis (diagnosis of UTI) - put on Clavimox

10/25/17
• Urinalysis - UTI gone
• Cortisol resting – 8.0 High (1-5)
• SMAC general/CBC
o ALT High 263 (12-118), ALK Phosphate High 913 (5-131); GGT High 36 (1-12), Creatinine Low 0.3 (0.5-1.6), Amylase Low 198 (290-1125), Platelet Count High 414 (170-400), Neutrophils High 83 (60-77), Lymphocytes Low 8 (12-30), Absolute Lymphocytes Low 648 (690-4500)

10/31/17 - Low Dose Dexamethasone – sample 1 High 6.4 (1-5), sample 2 Normal 0.7 (0-1.4), sample 3 High 1.5 (0-1.4)

11/8/17
• ACTH – pre 7.9 High (1-5), post 19.4 High (8-17)
• Urine cortisol creatinine ratio – 272
• Urine protein creatinine ratio – 0.9 Normal (<0.5)

11/11/17 - stated Lysodren loading (1/4 of 500mg twice a day for 7 days). No symptoms on day 7.

11/20/17 - ACTH (pre 1.2, post 1.2)

11/22/17 - started Lysodren maintenance (50mg once a day every 3 days)

12/16/17 - symptoms returned (drinking/peeing/hunger)

12/27/17 - increased Lysodren (100mg once a day every 3 days)

1/5/18 - ACTH (pre 5.2, post 5.6)

1/11/18 - increased dosage to every 2 days - still no change in symptoms after almost 3 weeks

2/3/18 - stated Lysodren loading (1/4 of 500mg twice a day for 7 days)

2/8/18 – urinalysis (no UTI), stool (normal)

[Squirt's Mom]

ah HA! The maintenance dose is more than likely why she lost the load. The maintenance dose should be the same mg used for the load, just spread out over a week VS daily. ie if a pup loads on 500mg a day (250mg 2x/day) then that dog's maintenance dose would be 500mg a WEEK. So since Molly is being loaded on 250mg a day (125mg 2x/day or 1/4 tablet twice a day) she would need 250mg a week for maintenance. The accepted protocol is to use a week but I have always gone by days. Like every other day or every 3rd day to keep the dosing even. So I would use 125mg every 3rd day to start. If it seems she is losing the load again, I would up that to 125mg every other day. OR to keep to the standard protocol you would give her 125mg on Mon, Wed, and Fri or Sat. Be sure to give with a meal since the Lyso is fat soluble and the food will assure it is absorbed and used.

[Skylar]

Thanks Squirt's Mom! If I give her 125mg every 3 days that would be 375mg per week. That is more than the 250mg.

I do give her the Lyso with her dog food.

Also, what are your thoughts on: The vet said after the last dose on the 7th day she should be off the Lysodren for 2 days and then an ACTH on the 3rd day. Is this right? Should it be done sooner? Plus she has to send out for test results and it could take a couple of days. So she could be not taking anything after the load for around 5 days.

Thanks!!

[Squirt's Mom]

You're right! Math is not my forte! So 1/4 tablet twice a week OR every 3 days is what I would try.

As for the timing - I can't stress enough that "7 days" is not how this is done. You stop the load when you see signs it has been achieved - decrease in water consumption or the change in how they eat a meal. That may happen in 3 days OR it could take months. If you stop giving the loading dose at 7 days and the load has not been achieved (no change in signs) then she will end up right back where she was before the second load - all the signs will come roaring back. So keep a VERY close eye on her and stop when you see those signs regardless of how long it has been.

For as long as I've been involved with Canine Cushing's the standard for starting maintenance is just as your vet has recommended. Wait for 48 hours after the last dose, do the ACTH, and if the ACTH + signs indicate the cortisol within range then the maintenance phase starts. However a few years ago someone here questioned that "protocol" and search as we may, we have found no source that says that is how it must be done...or that it is wrong to do it that way. Lysodren has a very long life in the body so this protocol more than likely came about as a result of that fact. That length of time gives the Lyso time to reach peak level and produce the optimal cortisol level. So unless you see signs that the load has gone too far and lowered the cortisol TOO low, it will be fine as your vet has set up. The signs the load has gone too far are loss of appetite, nausea/vomiting, loose stool/diarrhea, and/or lethargy. If you see ANY of these signs STOP the med immediately and get an ACTH immediately - do NOT wait under those circumstances to get the ACTH.

You're doing a good job, Mom!
Hugs,
Leslie