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View Full Version : Yoyo symptoms and relapsing Please Help (8 y/o Pit Bull mix)



sttrg03
12-29-2012, 05:03 AM
Hi all! I'm hoping you might be able to shed light on a frustrating reoccurring and mind boggling yoyo relapsing my pit bull mix, Penny has been having. I should mention that I adopted her back in September of this year knowing she had been diagnosed with Cushings. I'll list her general info here for easy viewing and what information I have with me, so far.

Breed: Pit bull mix
DOB: 8 years old
Weight:79.6 lbs
Diagnosed with Cushings: April 2012 via Dexamethasone Suppression Test (This was the only recorded record on her medical report I received from the shelter). The shelter had been treating her with:
Melatonin 6 mg 1x a day
Lignans/SDG 1 mg/lb a day
also via abdominal ultrasound the findings read: Both adrenals were symmetrically enlarged. The left was 0.87/0.786 cm and the right was 0.961 cm. The liver had rounded edges but was otherwise within normal limits in echogenicity and structure. The kidneys have small hyperechoic changes in the cortices but were normal in size; left: 4.28 x 6.28/Right: 7.31 x 3.85 cm, shape, corticomedullary region and ratios. The spleen, gall bladder, urinary bladder, stomach, small bowel, large bowel and lymph nodes were within normal limits in the planes viewed. The findings of adrenal enlargement, hepatic enlargement and inflammatory changes to kidneys may well be related to Cushing's syndrome.

Appearance: pot bellied, small tumors around legs, hair loss around neck, shoulders, tail, poor coat quality with blackheads and extremely thin skin. She has also recently developed calcium cutis on her shoulder and a bit on her back.

Symptoms: Extremely lethargic, unwilling to go for walks, not a voracious eater but more of a general grazer (she was being fed 2 cups of dry food 2x a day but would only eat about half then walk away), polydipsia (~2 gallons/day) , polyuria (no warning she would pee in her bed, on the floor, etc. multiple times a day for eg. peeing spontaneously 3 times or more within 1 hour). Hind leg weakness and stiffness.

Induction dose started 10/11: Lysodren 500 mg 2x a day once daily. No change after 10 days except for higher energy, willingness to go for walks, but still peeing just as much and still having accidents, still picky eater.

10/22: Veterinarian decided to only run a basal cortisol (??? - this was what made me start to question my vet) results >10 ug/dL. Instructed to continue with induction dosing.

11/4: Lysodren stopped (by me). No changes in polyuria/polydipsia, during this time energy level seemed to have plateaued and now decreasing to a more lethargic state not as extreme as it once was but not as energetic as she had been. No signs of Addisonian crisis during this stretch of time. Decided to seek another opinion.

11/8: Saw new vet who did general work up including blood tests, fecal flotation, urine analysis, cytology with fine needle aspiration on her little tumor by her leg, and a skin tape with a gram stain. I unfortunately don't have the written report from the general blood test but the veterinarian had told me that everything was normal except her thyroid was low, SG on her urine analysis was extremely low, no bacteria was found but as a precaution she gave me antibiotics just in case Penny had a UTI. Vet suspected possible hypothyrodism although she also suggested cutting food back to 1 cup 2x/day and more detailed thyroid panel was performed.

11/9: ACTH stem test performed *Penny was last given Lysodren on 11/4 supposedly still on induction dose*
Pre 5.4 ug/dL (HIGH) with reference range between 1.0-5.0 ug/dL. Post 7.7 (LOW) with reference range between 8-17 ug/dL
The report states pre and post cortisol levels after Lysodren loading or while on maintenance Lysodren should be between 1-5 ug/dL.

11/23: Thyroid panel performed. Unfortunately I also need to get the written report for this but the vet told me this came back normal.

12/12: My vet had put Penny back on Lysodren 500 mg 2x/day once a week. Penny still had accidents although the spontaneous accidents were less frequent. She now seemed to have more control over her bladder and could tell us she had to go potty. Still drinking the same amount. She slowly reverted back to her lethargic, sleepy state. However, on 12/12 a day after she had gotten off antibiotics (Cephalexin 500 mg 2 tabs/2x day to treat her potential UTI that the vet prescribed back on 11/8 long story short she was only on these antibiotics for her prescribed 10 days we had a delay in receiving the antibiotics) she started having spontaneously accidents and frequently! It got back to 3+ accidents/hour. She couldn't control it.

*Please note I know Penny is potty trained. When she was doing her best she would have maybe 1 accident the whole day. I am home most of the day except for running errands and I take her out frequently as soon as she wakes up from her naps. She sleeps most of the day. Since the day I got her she has had very low energy and very laid back so it is hard for me to judge what is her personality and what is the Cushings. I talked to one woman who fostered her and she seemed to have this same "yoyo" effect with Penny: for a couple months she would be energetic and want to go for walks, more alert, then she slowly wanted to not go on walks more and more until she flat out refused unless it was just to go out to pee and then come back inside. Penny was not on any Lysodren treatment when the foster parent had Penny.

12/18: Vet suspects central diabetes insipidus. SG: 1.001. Vet told me to monitor water intake and then administer desmopressin 2 drops/eye 2x day for 3-5 days.

This is the point I am at now. Penny's regular water intake was 5 quarts and with desmopressin it decreased slowly each day from 4.5 quarts to 3 quarts over a span of 3 days but since being on the eye drops she has become even more sleepy. She sleeps all day except to get up every 3-4 hours to go potty. She snores. She just seems depressed. She won't go for walks, just flat out refuses. Her hind leg weakness is back to how it was when I first adopted her. She is very stiff and has a hard time even getting up from sleeping. She has a hard time keeping her legs underneath herself. I decided to stop the drops just because I'm concerned they are making her like this. She was lethargic before but this is probably the worst I've seen her and I'm extremely concerned about her.

Has anyone else experienced this "yoyo" effect? Does anyone have any advice on the induction dose issue? It would appear that she was in some way responding to Lysodren yet at the same time, not. I just have a nagging feeling there is more to this story and it is very frustrating not knowing what or why she is having these types of ups and downs. The vet plans to do another ACTH stem test in the coming weeks to see what is going on and I still need to talk to her about the DI trial test. If anyone has any comments on what I observed for her DI trial I would be happy to hear your opinions.

Any guidance would be MUCH appreciated. I'm just in a bit of a fog right now.

mytil
12-29-2012, 08:01 AM
Hi and welcome to our site. I am very sorry your Penny is having so much trouble here. You are truly a saint for giving her a forever home and taking care of her.

A question I do have is why were Melatonin and Lignans given - was she diagnosed specifically with Atypical Cushing's? (http://www.k9cushings.com/forum/showthread.php?t=198) Was the initial testing results borderline for Cushing's?

This yoyo effect would have me worried as well as this is not typical.

Has Penny been tested for diabetes mellitus? much different than DI. It could be that this yoyo effect could be that she has both conditions and the diabetes is making it hard to regulate the cortisol levels. With her being extremely lethargic, low appetite and both Cushing's and Diabetic symptoms (they are very similar) I would suspect this combination.

I know others with direct experience with both will chime in shortly.
Terry

sttrg03
12-29-2012, 12:55 PM
I'm not sure what the results of the Dexamethasone Suppression Test were since this information was through the shelter back in April. I am trying to get the reports from either the shelter or the vet directly. I sort of assumed they put her on Melatonin and Lignans back in May as a sort of cost-effective first step, first try approach. She had been on these when I got her but I stopped under the scoffing of the old vet I went to who basically said "oh sure I guess you could try that if it makes you feel better"... I know the U of TN did a study showing this treatment could be effective but at the time I didn't so I caved and stopped. The new vet told me to continue with them, that it wouldn't hurt but to be honest I saw no difference with her either on vs. off them.

To my knowledge Penny has not been tested for diabetes mellitus at our current vet unless that was part of the general blood work (still need to get those reports too) but she was tested at the shelter back in January and February. Blood glucose was 96 and 86, respectively and at that time she was reported as having polydipsia, polyuria, and overweight.

mytil
12-29-2012, 04:59 PM
Hi again,

If the UN of TN was sent samples and recommended this treatment of Melatonin and Lignans then it likely points toward Atypical Cushing's and you stopped this treatment because you saw no difference in her with or without it and the old vet should not be making these types of comments without giving you a valid explanation or treatment alternative to help Penny - not very knowledgeable about Cushing's I would bet.

There are some cases where Lysodren is given in conjunction with Melatonin and Lignans for diagnosed Atypical - I do not have any direct experience in this but I am sure several will pop in shortly.

How much experience does the new vet have on treating Cushpups?

Post those results when you can.
Terry

Squirt's Mom
12-29-2012, 05:35 PM
Hi and welcome to you and Penny,

At nearly 80 lbs, the Lyso dose is a bit low. Typical loading (induction) dosage is 50mg/kg/2x a day. Penny weighs 36.18 kg; 38.18 x 50 = 1809 mg/day. So at 1000mg a day (500mg twice a day) that is a tad too low to be quickly effective. So there is one problem. And that is to be taken twice a day EVERY day until the pup shows signs of being loaded...not twice a day once a week. If this is the pattern your vet had you giving the Lyso, they wasted a great deal of your money and time.
12/12: My vet had put Penny back on Lysodren 500 mg 2x/day once a week.

With CC (calcinosis cutis) Trilostane is often preferred as it takes high doses to address the CC and Lyso cannot be tolerated at high doses. Here is the catch - if you want to switch to Trilostane (Vetoryl) Penny will need to be off the Lysodren a MINIMUM of 30 days to be sure there is no overlap between the two drugs. Do not let anyone tell you differently. Going from Trilo to Lyso isn't quite as risky as the Trilo leaves the body quickly - Lysodren does NOT leave the system quickly.

While the intermediate hormones may well be elevated (they are in most cush pups regardless of the form they have), I don't really think Penny has the form of Cushing's called Atypical (a form in which cortisol is normal but the intermediate hormones are elevated) because CC just doesn't happen with Atypical - that is a hallmark of true Cushing's (elevated cortisol). The presence of the CC is almost 100% guaranteed to indicate Cushing's.

If Penny has not had an abdominal ultrasound, that is something I would look into asap. I would also want to know the results of the full thyroid panel and where the thyroid levels are now on the current dose. If she has not had a complete blood chemistry panel that also needs to be done asap.

The DI is something that can easily cause the urination problems you are seeing and the drops are the only treatment I know of for that. It may be that the dose is too high - something to talk to your vet about. DI is rare but we have seen several cases here.

Hugs,
Leslie and the gang

sttrg03
12-29-2012, 06:53 PM
Thanks so much for all the replies!

I have not flat out asked the new vet about how much experience she has with Cushings but I'm suspecting maybe not as much as I would have hoped for. Although she does seem knowledgeable, respectful, and calls me when I'm available (7 pm) to discuss lab results. Perhaps this is what all vets should do but I'm just grateful since my old vet was anything but.

Penny has had an abdominal ultrasound back in late April. My vet did want to get another more current ultrasound on her because she suspected a possibility of cancer due to finding traces of blood in urine and other "traveling cells" I apologize I forgot the medical term she used. But she wanted to get the thyroid panel, DI test first.

The old vet for the induction dose did have her on 1000 mg a day every day. She was off it for 4 days (I stopped because I was worried she was on induction too long). The old vet said she felt uncomfortable raising the dose due to possible toxic effects.

The new vet did a ACTH to see where she was. The new vet prescribed the 1000 mg a week as a maintenance dose (maybe she was just trying to be conservative or maybe she just doesn't have the experience). She has mentioned Trilostane to me but I just don't know if I can swing that cost. She said she would look into pricing for me but I've heard it is much more expensive then Lysodren and is needed daily whereas Lysodren at maintenance is weekly (I believe).

Does Melatonin/Lignans do anything for a true Cushpup?

addy
12-29-2012, 08:28 PM
Does Melatonin/Lignans do anything for a true Cushpup?

I tried it in the beginning because my pup did not have strong symptoms, mostly hair/coat skin issues. It brought her intermediate hormones down but did not touch her cortisol. Actually her cortisol went higher. When I asked the late Dr. Oliver of UTK if adding a maintenance dose of lysodren would work, he said it was an option, that sometimes it works, sometimes not, depends on the dog but he felt it was an option for me. At the time, I did not want to risk loading Zoe as she had colitis and it was not well controlled. He saw it work enough times to have it on his treatment list as an option to consider.

lulusmom
12-29-2012, 08:35 PM
Hi and a belated welcome to you and Penny.

First let me say that I think you are awesome for adopting Penny who is a mix of a breed that receives a really bad and unmerited rap. You are doubly awesome for adopting Penny knowing that she had cushing's. Wow, you rock! I am a small dog rescuer but pit bulls are near and dear to my heart. Small breed puppies are a lot of work but I had no idea what I was getting into when I agreed to foster six nine week old pitbulls, who are tearing up the place up right now. They are leaving on transport on Wednesday morning and I'm not sure me or my marriage is going to last that long. :D

Now let's get down to the issue at hand. Because Penny was diagnosed while she was in rescue or at the shelter, there are lots of unanswered questions and I am hoping you can find the answers for us.

It would very helpful if you could track down a copy of the Dex suppression test and post the results here. Given that the shelter was treating with melatonin and lignans, I am wondering if perhaps the LDDS was negative for typical cushing's and it was either assumed that she may have atypical cushing's or they actually send a blood sample to the University of Tennessee Knoxville for a full adrenal panel. Atypical cushing's is diagnosed when cortisol is normal but one or more of the adrenal hormones are elevated. I would like to mention that both typical and atypical cushing's share the same organ abnormalities and many of the symptoms, including calcinosis cutis. Most reference material on calcinosis cutis says that it is diagnostic for hyperadrenocorticism but there have been cases of dogs with atypical cushing's having calcinosis cutis. See URL below for one of those cases:

http://www.vmsg.com/files/Case_Report_Atypical_Hyperadrenocorticism.pdf

Leslie mentioned that Trilostane is preferred over Lysodren for dogs with calcinosis cutis. Actually, the opposite is true. Renown expert, Dr. David Bruyette, who is a huge Vetoryl (Trilostane) fan, admitted that he has not had good luck with resolution of calcinosis cutis with his patients being treated with Vetoryl. I personally believe that's because Vetoryl is known to actually increase the intermediate (sex) hormones, which can exacerbate the calcinosis cutis. However, everything about this disease is confounding and we've had members who report improvement with Vetoryl.

What was the result of the biopsy on the growth on Penny's legs? I ask because if they are Lipomas (fatty tumors), elevated estradiol levels are a possibility. Estradiol is the only adrenal hormone that can also be found outside the adrenals. It is found in adipose (fatty) tissue in the body so fatty tumors seem to be a likely culprit according to our old internal medicine specialist's experience.

Lysodren is often added to the atypical treatment regimen and I see that the vet prescribed a lower loading dose. I do know that some vets do a lower dose induction for atypical pups but so do vets who are not experience with the drug as it is scarey for them. I'm thinking it may be the latter as the vet ran only a basal cortisol after loading. That's highly irrregular unless perhaps, he knew he was dealing with atypical cushing's in which case, I believe basal cortisol reading would be sufficient to determine if a dog was in danger of an addisonian crisis.

Did either one of the vets who saw Penny do their own cushing's testing? If not, it seems to me that they would have wanted to get a copy of the LDDS test done by the shelter.

Your new vet seems to have done a lot of testing and it would be great if you could please get a copy of these tests and post the abnormal results here and please include the normal reference ranges. I noted that this new vet prescribed an antibiotic in case Penny had a UTI. Dogs with dilute urine need to have a urine culture done to determine which types of bacteria, if any, are present so an appropriate antibiotic can be prescribed. Your vet said no bacteria was found but was this the result of a urine culture?

If Penny truly has typical cushing's, a post stimulated cortisol of 7.7 ug/dl is unacceptably high so your vet's prescription of 500mg BID once a week will not be effective as a maintenance dose much less bring cortisol levels down to within the therapeutic range. This medication is not cheap so your vet needs to do things right and according to protocol. Can you ask your vet what form of cushing's he is treating?

Diabetes insipidus (DI) is very rare; however, I know it happens because I lived with a shelter dog with cushing's who was eventually diagnosed with Nephrogenic DI after his cushing's was well controlled. Dogs with Nephrogenic DI do not respond to desmopressin. If your vet is treating for typical cushing's, it is apparent that cortisol is not under control so before having you spend a lot of money on desmopressin, why did he not address the most obvious cause first?

If Penny has either typical or atypical cushing's that has never been effectively controlled, you shouldn't see what you are calling a yoyo effect. Lethargy and muscle weakness are symptoms of the disease so until whatever adrenal steroids/hormones are brought under control, you can't rule out uncontrolled cushing's as the culprit.

Looking forward to your response.

Glynda

P.S. I forgot to mention that melatonin definitely will make a dog more lethargic so if you were on again, off again with Melatonin that could definitely cause on again, off again lethargy.

Squirt's Mom
12-30-2012, 08:36 AM
Hi again,

:o:o I was speaking from memory concerning the Trilo and CC. After reading Glynda's reply, I went searching for the info last nite and cannot find it. SO just ignore my post....other than the welcome and hugs offered.

Hugs,
Leslie and the gang

sttrg03
01-03-2013, 05:54 PM
I finally was able to obtain Penny's results from the shelter:

LDDS (performed 4/12)

Time 1: Pre
Time 2: Post
Time 3: Post

Cortisol Sample 1 4.6 (ref range 1.0 - 5.0 ug/dL)
Cortisol Sample 2 Dex 1.7 (ref range 0.0 - 1.4 ug/dL)
Cortisol Sample 3 Dex 2.1 (ref range 0.0 - 1.4 ug/dL)

Therefore, I believe Penny does not have Atypical Cushings, would this be a fair assumption to make? Penny never had a Tennessee panel done although she did have an abdominal ultrasound 4/2012.

Chem panel (performed 1/12, I'm posting this as a reference since these values are highly elevated currently)

Alk Phosphatase 127 ref range 5-131 U/L
ALT (SGPT) 49 ref range 12-118 U/L

Urine Microalbumin (performed 1/12)
Microalbuminuria 7.0 (ref range <2.5 mg/dL) HIGH

Urinalysis (performed 1/12)
SG 1.007 (ref range 1.015-1.050)
pH 6.0 (ref range 5.5-7.0)
-----------------------------------------------------------------------
Urinalysis (performed 12/12)
SG 1.001
pH 7.5 (ref range 5.5-7.0)

**The vet had put Penny on antibiotics (Cephalexin 500 mg, 2 tabs 2x day). A urine culture was performed and was negative but my vet told me she wanted to put her on antibiotics anyways because she still suspected Penny might have a UTI, but nothing could be growing because SG was so low

Chem Panel (performed 11/9)
ALT 142 ref range: 12-118 U/L
Alk Phosp 2137 ref range: 5-131 U/L
GGTP 32 ref range: 1-12 U/L

CBC (performed 11/9)
Platelet Count 539 ref range: 170-400 10^3/uL

Urinalysis
SG 1.003 ref range: 1.015-1.050
pH 7.5 ref range: 5.5-7.0
Transitional Epithelia 2-3 ref range: 0-1 HPF
Blood Trace

**Urine was obtained by free catch

Thyroid Panel (performed 11/29)
Total Thyroxine (TT4) 13 Ref range: 11-60 nmol/L
Total Triiodothyronine (TT3) 0.7 L Ref range 0.8-2.1 nmol/L
Free T4 by dialysis 12 Ref range 6-42 pmol/L
Free Triiodothyronine (FT3) 3.0 Ref range 1.2-8.2 pmol/L
T4 AutoAb 13 Ref range 0-20 %
T3 AutoAb 6 Ref range 0-10 %
Thyroid Stimulating Hormone 17 Ref range 0-30 mU/L
Thyroglobulin AutoAb 6 Ref range 0-35 %
<20% Neg
>35 % Pos
Endocrinology Interpretation:
Circulating concentrations of thyroid hormones are generally normal and thyroid stimulating hormone is not elevated. The slight decrease of T3 is unlikely to be of clinical significance. The negative autoantibody results further decrease the likelihood of lymphocytic thyroiditis in the thyroid glands of this dog. The results of this profile do not offer support for a differential diagnosis of hypothyroidism.

**Penny was on Lysodren 1000 mg/day every day up until 11/4. There were no further thyroid tests performed since she has now been on 1000 mg once a week (again, I suppose the vet had this in mind as a maintenance dose?)

My vet is still playing around with the idea of Diabetes Insipidus and wants me to lower the drops to 1x/day and try again since last time my dog became extremely lethargic and I was extremely worried.

My vet said after this she will do an ACTH stem test and adjust Penny's Lysodren dose. It seems to me that we might have to put her back on an induction dose because she never really got loaded. I'm confused by DI because I feel it might control some symptoms but then how do you tell whether the dog needs to be induced again or just up'd on the maintenance dose? If DI is controlling accidents and she never really had a crazy voracious appetite?

When a dog is effectively controlled for Cushings, does he/she still have accidents in the house?

Right now Penny has gotten back to her "normal" which still isn't 100% but it's a lot better than where she was at just a couple weeks ago. She still has low energy (she always had since I've adopted her) but she seems more willing to explore and be curious. She still has accidents at least once a day but they are not uncontrollable like before when she would just get up from sleeping and immediately pee right in her bed and then walk two steps and pee again. It's basically like when she gets up from sleeping you have to be right there and take her out. She only has a 1-2 min window where she will let us know without letting it go (so to speak) if you miss it, she'll have an accident.

Thanks again for all your support and replies!
Theresa

lulusmom
01-03-2013, 07:08 PM
Hi Theresa and thank you for posting all those test results.

You are correct....Penny does not have atypical cushing's. According to the LDDS test results, a more correct diagnosis would be pituitary dependent cushing's. That's not surprising as the majority of dogs diagnosed do have pituitary dependent disease.

According to the the information you have provided thus far, Penny's cushing's has never been controlled so I have no idea why your vet doesn't understand the importance of getting the post stimulated cortisol in the therapeutic range of 1 tio 5 ug/dl before pursuing a diabetes insipidus diagnosis. Your vet is doing things bass akwards and unfortunately, that costs you money. The first order of business is to get the cortisol under control. Once you do that, the excessiving drinking and peeing should resolve. All symptoms usually resolve once the disease is well controlled.

If at all possible, I would try to find another vet who is well versed in cushing's and knows Lysodren very well. I suspect that you are basically going to have to start from square one and reload.

Glynda