New diagnosis for Sophie

[stho1228]

My name is Sandy and my 7 yr old Welsh corgie terrier mix has been diagnosed with adrenal Cushings and the vet wants to start her on Mitotane and I am looking for advice.

2014 She had low dose dex test in 2014: results baseline 2.2 ug/dL, 4 hr <1.0 ug/dL, 8 hr 2.0 ug/dL.

Total protein 7.6 g/dL (High reading) Ref Range 7.0 - 7.4 g/dL
ALT 107 U/L (Normal) Ref Range 12-118 U/L
Alk phosphates 1509 U/L (High reading) Ref Range 5-131U/L
Phosphorus 4.4 mg/dL (Normal) Ref Range 2.5-6 mg/dL
Glucose 105 mg/dL (normal) Ref Range 70-138 mg/dL
calcium 10.3 mg/dL (normal) Ref Range 8.9-11.4 mg/dL
cholesterol 343 mg/dL (high reading) Ref Range 92-324 mg/dL.

At that time she had excessive thirst and would eat rather fast but not excessive. We chose not to start treatment at that time to see how she did.

Now 2 years later, her thirst is excessive, cannot eat fast enough and is now eating paper, ear buds, constantly looking for food.
2016 low dose dex done again and results: baseline 5.4 ug/dL, 4 hr <1 ug/dL, 8 hour 2.5 ug/dL.

Total protein 7.5 g/dL (High reading not much change from 2 years ago) Ref Range 7.0 - 7.4 g/dL
ALT 136 u/L [up from 107- 2 years ago] Ref Range 12-118 U/L
Alk Phosphate 3635 U/L [Double from 1509 U/L -2 years ago] (High reading) Ref Range 5-131U/L
phosphorus 6.4 mg/dL (high reading up from 4.4 2 years ago) Ref Range 2.5-6 mg/dL
glucose 44 mg/dL (lower reading than 2 years ago) Ref Range 70-138 mg/dL
Calcium 8.8 mg/dL (lower reading than 2 years ago) Ref Range 8.9-11.4 mg/dL
cholesterol 488 mg/dL (higher reading than 2 years ago) Ref Range 92-324 mg/dL.

I am overwhelmed with the diagnosis and what is best course of treatment. Mitotane looks dangerous on paper and just looking for some guidance. Thank you for this support group! I am so grateful to see other owners are walking down same road as we are starting on.

[Harley PoMMom]

Hi Sandy,

I have manually approved your membership so now all your posts will be seen right away. Also please just disregard the validation email that was sent to you from k9cushings.


Welcome to you and Sophie! Well to my layperson's eyes those most recent LDDS test results point to the pituitary form of Cushing's and not the adrenal type.

Could you edit your post and add the normal reference ranges for those values you listed?... thanks! What sticks out to me are the abnormal values in the her phosphorus 6.4 mg/dL (which I'm assuming is high) and Calcium 8.8 mg/dL (which may be a bit low), can you clarify that for us?

If Sophie does have Cushing's we do understand how frustrating and confusing this disease can be but we are here to help you and trust me, once you understand more about Cushing's your fear will subside.

The two medications that are usually prescribed for Cushing's are Vetoryl/Trilostane and Lysodren/Mitotane, one is no safer than the other. These are strong drugs and both have some pretty scary side effects, however, adverse effects are minimized when the proper treatment protocols are followed. We have many members that are treating their cushdog with either Vetoryl/Trilostane or Lysodren/Mitotane and are experiencing success.

We realize that you may have some apprehensions in starting treatment but you are not alone and we will walk this journey with you. If you have any questions please do not hesitate to ask them.

Hugs, Lori

[molly muffin]

Hello and welcome to,the forum.

Was an ultrasound done to confirm that there is an adrenal tumor? If not I think it would be worth it to get one to verify. Test don't always tell the full story so if that is feasible I think it will give you good bang for the buck.

It does sound like she needs to get started on treatment as she is eating everything but the kitchen sink :). Pretty normal for Cushing dogs.

We are using vetroyl for our dog but either can work successfully. You do always have to follow protocols for each though to be safe.

[stho1228]

We decided against the ultrasound as we would not want to proceed with surgery and put Sophie through that ordeal, which from what I have read is awful.

[stho1228]

I updated the test results with the reference ranges. Thank you for your help with this.

[molly muffin]

I understand not wanting to pursue surgery. We've had several who have had it done successfully though.
Your girl certain does have the hunger that goes with cushings, but there are a couple things on the labs that cause me concern and that I would certainly want to be discussing with a specialist. The low blood glucose and the high phosphorus (which might come down) and specifically the high ALKP, at over 3500. The combination especially of the high liver enzymes with low glucose can be worrying.
Did the vet mention anything about the low blood glucose, which can be indicative of Hypoglycemia.

[Harley PoMMom]

That low glucose level is worrisome to me as well, sometimes vets do miss things so I would definitely bring that to the attention of Sophie's vet.

[stho1228]

Thank you for pointing out the glucose. I will speak to the vet in the morning about that. Should I be seeking out an endocrinologist or specialist?

[lulusmom]

Hi and welcome to you and Sophie.

The results of the LDDS test you posted are consistent with pituitary dependent disease so while I think an abdominal ultrasound is always a good idea, given Sophie's overt symptoms and usual lab abnormalities, I think skipping the abdominal ultrasound is understandable. Unless With respect to the mildly elevated phosphorus, it is not usual to see this in a blood specimen that is hemolized or has sat around too long. Can you check the results to see if the lab noted anything about hemolysis or lipolysis? Unless Sophie was overtly sick when the blood chemistry was done, I suspect the low blood glucose is probably due to improper handling of the blood specimen too. I've shared my life with tiny toy breeds, my own and a steady stream of rescues, so I am intimately familiar with hypoglycemia. If you were to recheck glucose today, it would probably be normal. Regardless, discussing all abnormalities on blood labs with your vet is how you learn and learning as much as you can about the disease will make you a terrific advocate for Sophie.

I am sorry for the circumstances that brought you here but I'm very happy that you found us. We're here to help you in any way we can. I great start would be providing you with some great reading material on Lysodren (mitotane)loading. I suggest you read it and print it out and keep it handy while you are going through loading. I had two cushdogs on compounded mitotane, the active ingredient in Lysodren, and my copy of the Helpful Loading Tips was beyond dog eared. LOL Your role in treatment is to watch Sophie like a hawk during the loading phase. It is within your power to limit and/or eliminate the possibility of any bad side effects. Sophie is the perfect candidate for mitotane because she has a huge appetite and it is the changes, even the most subtle change, in her eating habits that will be the sign to you to quit dosing her. If Sophie is like my dogs, she is a complete glutton who won't lift her head out of her bowl before it's completely devoured and the bowl looks like it just came out of the dishwasher. Right? If she pauses for just a second to look up at you; she finishes her food in 30 seconds instead of 10 seconds and most certainly if she does not finish her food, are all signs she could be loaded and no more mitotane should be given until an acth stimulation test is done. Your vet should not give you any more than 8 days of doses. If Sophie has not shown you any signs of loading in those eight day, you will need to have an acth stimulation test done, preferably on day 10 to see if loading has been achieved. If not, you continue loading. Mitotane is a very serious drug and if you know that going in, you will give it the respect it deserves and you will be a much more effective advocate for Sophie. We're here to help you do that.

Lysodren (mitotane) Loading Instructions and Related Tips
http://www.k9cushings.com/forum/showthread.php?t=181

[stho1228]

We had the ACTH test for Sophie before starting Lysodren.
Pre value 3.3
Post value 16.8

Started Lysodren on 2/27 and had ACTH test done 3/7.
Pre value 1.9
Post value 7.3

I am very encouraged by the significant drop in numbers. We are monitoring water intake to see if that drops.

Are we on the right track?

Thank you!!!

Sandy and Sophie

[molly muffin]

It certainly does seem that you are on the right track. Are you on the maintenance dose of lysodren now?

[stho1228]

Not yet, we are monitoring her water intake which is still at 5 cups per day and per the vet for her 27 lb she should drop to 3 cups a day. When the intake drops we need to do the ACTH test again.

[labblab]

Hmmmm...I am feeling very concerned that your vet is only taking water consumption into account here. Per expert recommendation, a change in appetite, even slight, may be the first and more predictive indicator that loading has been accomplished and the dosing should shift to the maintenance phase. Please see this:


It is wise for the owner to feed the dog two small meals each day, as previously described. The dog's appetite should be observed prior to each administration of Lysodren. If food is rapidly consumed (with or without polydipsia), medication is warranted.

If food is consumed either slowly or not at all, medication should be discontinued until consultation with the veterinarian.

Usually the initial loading dose phase is complete when a reduction of appetite is noted OR after water intake approaches or falls below 60 ml/kg/day.

Have you noticed any changes at all in Sophie's appetite? I am just really worried that you will continue to load her for too long a time period if water intake is the only criteria your vet is using...:(

Marianne

[stho1228]

No changes in appetite yet. She has always been a fast eater though. She is still active and no other side effects. What is the longest loading phase? As of tomorrow (3/12) it will be 14 days and I wonder if we should test her again? Thank you for all the good advice. still trying to figure this all out.

[Harley PoMMom]

It is highly recommended that a dog not loaded in 8 days needs to have an ACTH stimulation test performed, so if this were me I would have one done.

[stho1228]

These are the results for the ACTH test for Sophie before starting Lysodren.
Pre value 3.3
Post value 16.8

Started Lysodren on 2/27/16 and had ACTH test done 3/7/16.
Pre value 1.9
Post value 7.3

We are also loading her with 375 mg per day which is lower than the dose for her size (27 lb) to prevent adverse side effects. She would be loading with 613 mg/day.

[judymaggie]

Hi! If I could jump in here ... you are right -- Sophie's loading dose should be 613 mg. a day according to all the accepted protocols. I don't know if she will ever be loaded with giving her only 375 mg. a day. The "adverse side effects" that you (and your vet) are trying to avoid may well be the very signals that Sophie is loaded, i.e., drop in water intake and/or reduced appetite. I have no idea how a maintenance dose could be calculated without a successful loading dose. Loading can be a scary time but, with an owner's attention to subtle changes, it can be successfully completed with a move on to maintenance.

[stho1228]

Good point. Will speak to the vet on Saturday. Thank you!1

[molly muffin]

Did you speak to the vet this past Saturday? If so what did he say?

[stho1228]

We ended up having to do blood work as Sophie became very lethargic. Vet did ACTH test and pre test value was 1 and post value was 1 so she has completed induction. We were advised to stop med until tomorrow (3/18) and are giving her low dose of prednisone which is perking her up. Her eating has slowed and water intake is lower. We will be giving her 125 mg 3 days per week and have ACTH redone in 4 months. This is a crazy stressful roller coaster ride and hopefully will be smoother sailing. Thank you so much for checking in!

[labblab]

Whoa, whoa, whoa! With ACTH results as low and flat as 1.0 both pre and post, I do not think it's safe to launch into maintenance dosing until Sophie has demonstrated that she is acting normally while off the prednisone. It is likely that her adrenal function will indeed end up rebounding, but there is always a chance that the Lysodren overdosing that left her lethargic may have permanently suppressed her adrenal function. If that were to be the case, giving her even more Lysodren could have very, very serious consequences.

Has your vet also checked to make sure that Sophie's basic blood chemistries are within normal parameters? When dogs are overdosed with Lysodren, their potassium and sodium levels can also become unbalanced, again with serious consequences if these abnormalities are not addressed.

Either way, waiting four months for another ACTH does not follow accepted protocol. If Sophie's adrenal function remains oversuppressed, it is very dangerous to resume Lysodren without evidence that her ACTH results are rebounding. But even if her cortisol does start rebounding, it is hard to know for certain what a truly appropriate longterm maintenance dose will be given your vet's initial departure from standard dosing protocol. If you wait for four months before monitoring her ACTH level, her cortisol could easily elevate again to a point where you'd have to repeat the loading phase all over again.

First and foremost, though, I truly don't think it's safe to resume any Lysodren at least until Sophie exhibits normal behavior while off the prednisone for a few days.

Marianne

[stho1228]

I will call the vet to run chemistry panel tomorrow. I am very concerned and am wondering if I should seek out a second opinion from a different vet. Any thoughts?

[labblab]

Before making decisions, can you give us more details re: this past week? These are questions that will be helpful for us to know...

When did Sophie have her last Lysodren dose?
Exactly what behavior prompted the ACTH testing?
What day was the test run?
When did she start the prednisone, and at what dose?
Is her energy level normal again now while taking the prednisone?
Are you supposed to stop the prednisone tomorrow, and also start the Lysodren?
Is there any follow-up scheduled with the vet prior to four months from now?

Thanks in advance for your answers!

[labblab]

Hi again! Just checking back this morning to see how things are going for you guys. Also, I want to clarify that my aim is not to worry you unnecessarily. Since the desired therapeutic ACTH range for a dog being treated with Lysodren is between 1-5 ug/dL, Sophie is technically within that range, albeit right at the basement. If she had been behaving normally at the time of the testing, I wouldn't be feeling as uneasy about starting a maintenance phase. But since she was not behaving normally, that signals to me that cortisol levels that low are probably not ideal for her. So that's why I'm concerned that she demonstrate that she is doing OK without the support of prednisone before being given more Lysodren.

If she has been doing fine while taking the pred, then her potassium and sodium levels are probably OK and unaffected by the Lysodren. I was just curious as to whether or not they had been checked at the time that she was initially feeling poorly, because at that stage, they would have been a question mark.

So everything may end up resolving fine. But we worry about the details here, and that's why we are anxious to get the specifics as to exactly what has transpired this past week.

Marianne

[stho1228]

Sophie had her last Lysodren on 3/14/16 in the morning.
We had the ACTH done because she was getting lethargic and could not jump on the couch or climb the stairs to bed like she normally does.
We had the ACTH test done on 3/15/16 and she got 5 mg of prednisone that day.
We have been giving her 2.5 mg of prednisone once a day since 3/15.
She is doing better being on the prednisone. She is still eating and drinking fine and no diarreah.
Vet wanted us to start Lysodren today 3/18 with 125 mg three times a week for a total of 375 mg.
Vet also wants us to give her 2.5 mg orednisone daily with the Lysodren.
Vet wants to see her next Saturday 3/26 to see how she is doing.

[labblab]

So she received her last dose of Lysodren on Monday, and was ACTH tested on Tuesday at which time her "pre" and "post" were both 1.0. This will be only her fourth morning since taking any Lysodren, and your vet already wants her to resume today, along with the prednisone.

Bear in mind that I am not a vet, but it makes no sense to me that your vet would want you to continue with the prednisone simultaneously with beginning the Lysodren maintenance. If Sophie still needs prednisone to feel well, then you should not risk lowering her cortisol any further at this time. Plus, giving the prednisone will mask the side effects (i.e., loss of appetite, vomiting, diarrhea) that would indicate that her cortisol indeed remains oversuppressed or is being lowered even further. Plus, giving prednisone will skew the results of any additional ACTH testing that might be needed during this time. Prednisone must be stopped for at least 24 hours, and preferably even a bit longer, before administering an ACTH test.

I'm hoping other folks will also chime in here. But I believe that most vets wait until at least a week has passed to start in with maintenance dosing, and that is only when a dog is behaving normally with satisfactory ACTH results. As I said earlier, I would not want to give a dog more Lysodren until it has been demonstrated that the dog no longer needs supplemental prednisone in order to function normally.

By loading at a Lysodren dose lower than standard protocol, and now by planning to simultaneously give prednisone and Lysodren, my guess is that your vet is somehow hoping to blunt unwanted side effects. But you've ended up with an extended loading period, and the current risk that giving supplemental pred along with the Lysodren will mask the very effects of oversuppression that are critical for you to monitor.

I hope that others here with Lysodren experience will offer their thoughts, as well. But if Sophie were mine, I would not feel comfortable giving more Lysodren today. I would discuss the gameplan again with your vet, and my personal preference would be to ask that no Lysodren be given until Sophie demonstrates that she is doing well without the aid of supplemental prednisone.

Marianne

[Renee]

No lysodren experience here, but I do want to back up Marianne's concerns.

I am afraid your vet has strayed from protocols a bit too much and Sophie is bearing the brunt of it unnecessarily. The loading phase has specific protocols to follow for a reason. Your vet may have thought to avoid certain side affects by reducing the initial loading doses ... but, even with that plan in mind, it didn't really work, and now Sophie has dropped too low.

Please, take Marianne's advice. Do not start lysodren until Sophie is well enough without prednisone and her ACTH results are in the proper range to start maintenance.

[Harley PoMMom]

I, also, completely agree with Marianne and Renee. The vet had Sophie take her loading dose for 14 days before an ACTH stimulation test was performed, that's a huge deviate from the established Lysodren protocol.

Sophie's adrenal glands need to be producing a sufficient amount of cortisol before any Lysodren is restarted, if this is not done there is a high chance of her becoming an Addison's dog permanently.

Lori

[labblab]

These are the results for the ACTH test for Sophie before starting Lysodren.
Pre value 3.3
Post value 16.8

Started Lysodren on 2/27/16 and had ACTH test done 3/7/16.
Pre value 1.9
Post value 7.3

Hey Lori, I believe Sophie had her first monitoring ACTH on the tenth day after starting the Lysodren with the results given above. Now, after she became lethargic, this second monitoring ACTH was done on the 18th day after starting the Lysodren. I guess we don't know when the vet would have otherwise tested again had Sophie not started having the problems jumping up and climbing. I'm definitely worried about the gameplan not to perform another ACTH until four months from now.

Sophie's parent, I have a couple more questions for you, though. Even at this point, had you still not noticed any reduction at all in Sophie's thirst, urination and appetite? Now that she's taking the prednisone, it would mask any of those changes. But back earlier this week, before the prednisone, had you still not seen any changes?

I am really scratching my head at this point, especially because I am just now really noticing her initial diagnostic ACTH results. I know that Sophie indeed tested positive on the LDDS, but I am wondering whether the diagnostic "post" value of 16.8 was actually elevated enough to register as positive for Cushing's per that lab's norms. I am not saying that Sophie doesn't have Cushing's -- the ACTH misses returning a correct positive more often than does the LDDS. But I'm puzzling a bit as to why you would not be seeing any improvement in her overt symptoms with a cortisol level that is now this low...

Marianne

[stho1228]

Sophie did begin to slow down with water intake and would pause one or two times while eating which she never does. She also began urinating less as she was drinking less. She then started to become lethargic around the 3/12 and call to the vet. We stopped lysodren on 3/12, gave 2.5 mg prednisone 3/12 and 3/13. Stopped prednisone and we had the ACTH test done on the 15th because the vet said the prednisone had to be out of her system for 48 hours for the test to be accurate.

I expressed my concerns again to the vet today that we will not know if she is getting too much lysodren if we are masking the side effects with the prednisone - and the prednisone will increase thirst and eating.

I was told that the lysodren works to suppress the mineralocorticoids the prednisone will keep the glucocorticoids in balance which he said would keep the lethargy at bay.

Vet asked to start maintenance phase on Monday 3/21 (375mg on M/W/F and he wants to see her on 3/24 and redo ACTH test 3-4 weeks later (around 4/11). He also wants her to have 2.5 mg prednisone daily.

My regular vet is out with back surgery so I am working with the covering vet.

Any thoughts/advice are greatly appreciated.

[labblab]

Thanks once again for providing us with such complete info -- it is super helpful. For the most part, I am in agreement with the path moving forward, especially these things:

Sophie is to receive the maintenance Lysodren in three divided weekly doses;
I am glad he wants to eyeball her on the 24th;
I am glad he wants to retest her again 3-4 weeks later.

I'm really not sure how to evaluate the maintenance dosage amount since it took Sophie so very long to load (18 days) while taking the lower amount of 375 mg. daily. Since your vet is sticking with that as her weekly total, her cortisol may end up rebounding faster than you'd like. I just don't know. But that is why you definitely don't want to wait longer than a month to retest her.

The one instruction that I still take exception to is giving prednisone simultaneously with the Lysodren maintenance. I have been a member of these forums now for over a decade, and I truly don't recall this being done with any other dogs. On occasion, vets do prescribe prednisone alongside Lysodren during the loading phase in order to offset side effects from rapidly lowering cortisol levels. But that is not a protocol that is widely recommended for all the reasons we've already stated: you can end up masking the symptoms that are critical for signaling the completion of the load. But I truly don't understand the rationale for giving pred alongside a maintenance dose.

For the sake of discussion, here's a link to the Lysodren dosing protocol published by IDEXX Labs. I'm guessing that a majority of vets here in the U.S. use IDEXX for their lab analysis. What you'll see is that according to their recommendations, prednisone and maintenance Lysodren is an either/or situation. Depending upon the dog's condition, you give one or the other, but not both simultaneously. If a dog's post-ACTH result is <1 after loading and the dog is listless or ill, prednisone is to be administered in a tapering dose for two weeks during which time the Lysodren is discontinued. If the dog is clinically well but the post-ACTH result is <1, no pred is given but you wait two weeks before starting a low maintenance dose of Lysodren.

In Sophie's case, her post-ACTH was right at 1.0 instead of being lower. But since she was acting lethargic and was right at the "cusp," I don't disagree at all with giving her some pred to make her feel better while her cortisol level is low. But if you are opting to give pred, then per these guidelines, I don't believe you'd turn around and also restart maintenance Lysodren after one week while continuing to give the pred. If she were mine, my personal preference would have been to taper her off the pred, see how she does, and wait for two weeks before beginning maintenance dosing (assuming she's doing OK off the pred). Anyway, here's the link:

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

In reality, it probably won't harm her to continue with the pred until the vet eyeballs her again next week. And since she's taking a lower dose of Lysodren, as well, maybe it's OK to start up again after her week's break. But when you take her in next week, I'd really pin him down re: the purpose of ongoing prednisone beyond that point. You can even print out this chart to take in and discuss. Because I just don't think there are two ways around it. Giving her ongoing pred alongside Lysodren dosing can mask important signals that her cortisol is not rebounding properly. If he persists in wanting to continue the prednisone indefinitely, I would seek out a second opinion from another vet because from our experience here, it is neither standard procedure nor safe.

Marianne

[stho1228]

Thank you so much for the advice and I am not a vet either but also do not feel she should have both drugs at the same time. The regular vet returns Monday and will call to address my concerns. It is reassuring to have people who have dealt with this complicated disease and medication régime to look to for advice and reassurance. Thank you!!!!

[molly muffin]

Hi! Just want to check in and see how Sophie is doing.

[stho1228]

She is doing well, thank you for checking. We weaned her off prednisone 3/18 as she was perking up and acting her old self. The protocol says to wait two weeks before staring maintenance which would put her at 3 weeks without lysodren. Will we loose the effects of the loading phase?

[labblab]

So glad to get this report and to hear that Sophie is off the prednisone and doing well!! :) :)

We'll all keep our fingers crossed alongside you that this turns out to be the perfect dose for her. Definitely let us know how you guys are doing!

Marianne

[Harley PoMMom]

Will we loose the effects of the loading phase?

This is dependent on how fast her adrenal glands regenerate, so lets cross our fingers that when it's time to start the maintenance dosing regimen that those Cushing's symptoms have not rebounded.

[labblab]

Since Sophie's test results were not below 1.0 and she seems to be fine after only the four days of pred which is now discontinued, my own thought is that you might go ahead with the maintenance dosing after the two-week Lysodren break. I don't know that you would need to wait three weeks to begin. Since her last dose was Monday 3-14, I'd think you could resume next Monday 3-28 as long as she continues to feel well during the interim.

Actually, I thought your vet had planned to start back yesterday which did seem early to me. Has he shifted the game plan now, and is wanting to wait for two more additional weeks?

Marianne

[stho1228]

Vet had us start maintenance on 3/21. He is going to check her out on Friday and we will retest in 3-4 weeks for ACTH. She is doing very well and seems herself so we are pleased that so far so good. We are keeping a close eye on her. Thank you for checking in!

[molly muffin]

That is wonderful to hear she is doing well on maintenance. We'll be watching for updates!