Just diagnosed with Atypical Questions and have plenty of questions

[kewlncguy]

Hello, I have a 10 year old Rottweiler that is 77 lbs. She was the runt of her liter but I love her size. In october of last year she became very sick and would not eat and could barely stand. My vet thought she had liver failure and gave her a week to a month to live. I was too stubborn to allow that so I nursed her back to health.
Here are the anomalies on the first blood test she was given:

10/2016 77 lb Rottweiler
BUN - 5mg/dL, 16-36
CREA - 0.7 mg/dL, 0.8-2.4
CA - 14.1 mg/dL, 7.8-11.3
ALT - 148 U/L, 12-130
ALKP - 489 U/L, 14-111
TBIL - 1.0 mg/dL, 0.0-0.9
CHOL - 307 mg/dL, 65-225

Abby was urinating drinking and urinating frequently so my doctor gave her the all day multi stage Cushings test (Don't know the name) and said it came bad normal so she diagnosed Abby as having Diabetes Insipidous and put her Desmopressin eyedrops. She also put her on Denamarin for her high liver enzymes.
We waited for a while and her her bloodwork redone in January as follows:

01/04/2017 74 lb Rottweiler

Total Protein - 7.7, 5.0-7.4 g/dL
Alk Phospate - 772, 5-131 IU/L
GGTP - 15, 1-12 IU/L
Calcium 13.9, 8.9-11.4 mg/dL
Cholesterol 521, 92-324 mg/dL
PrecisionPSL 178, 24-140 U/L

Link to full 2nd blood work results results (http://www.m1g.net/docs/abby_bloodwork2.pdf)

If you do not see link copy and paste this into your browser:
http://www.m1g.net/docs/abby_bloodwork2.pdf

Here is a link to a PDF containing both LDDS tests and the Ultrasound Notes (http://www.m1g.net/docs/Abby_Shaw_Reports.pdf)

If you do not see link copy and paste this into your browser:
http://www.m1g.net/docs/Abby_Shaw_Reports.pdf

At this point the vet said we needed to do an Ultrasound. We did the ultrasound last week and she noticed one of her Adrenal glands was twice the normal size and her liver was round and looked great. Also she said she had scarring on her Pancreas so she must have had Pancreatitis at one point. She found crystals in Abby's Urinary Tract so Abby was put on Hills prescription Urinary care C/D. Rather than do a liver biopsy she decided to do the Cushings test again and once again it came back negative. The Cortisol levels were normal. She contacted a doctor of internal medicine at the NC State Veterinary school and it was determined that Abby has Atypical Cushings

Abbys symptoms are the excessive thirst (even on desmopressin) and urination, pot belly, panting, and weak rear legs.
The doctor recommended that I put her on 3mg melatonin and 40 mg hmr lignans. I have ordered them and they are coming in today.

My question is ..what else can I give her to make her comfortable. I have heard that milk thistle will help her liver enzyme values and I have seen people talk about somE. Also I saw a lot of good reviews for adrenal harmony. Please advise me the best way to spend my limited funds on other supplements and what would be the best brands and correct dosage for a 77 lb Rottweiler. Any other info would be greatly appreciated

[labblab]

Hello and welcome to you and Abby, although I am very sorry for the problems that have brought you to us. There are a couple of abnormalities that leap out at me, however. The first is her consistently elevated calcium level. This is definitely not normal, and as I understand it, could be associated with many of her symptoms, including excessive thirst/urination/weakness/lethargy. The big question in that vein would be, what is causing the elevated calcium? Unfortunately, cancer in the body is a possibility. Also, I believe that adrenal under-function (Addison's Disease) can be a cause.

http://www.pethealthnetwork.com/dog-health/dog-diseases-conditions-a-z/hypercalcemia-dogs

The single greatly enlarged adrenal gland raises a lot of red flags. Has the vet ruled out the presence of a tumor or a mass? What explanation does she give for the unilateral enlargement?

Can you please give us the actual numbers for the two blood tests that were done in the attempt to diagnose Cushing's? Depending upon the tests and the results, here are my concerns. If it was used, the ACTH stimulation test would rule out Addison's Disease, but it frequently returns a "false negative" for Cushing's in dogs who suffer from adrenal tumors (as opposed to pituitary) tumors. On the other hand, if the LDDS was used, it is more reliable in terms of accurately diagnosing a Cushing's dog with an adrenal tumor, but it cannot be used to diagnose Addison's. So additional info about Abby's Cushing's tests and the actual numbers will be a big help to us.

The diagnosis of "Atypical Cushing's" is typically reserved for dogs who have normal cortisol levels but other adrenal hormones are elevated. To make this diagnosis, again, specialized testing would have been necessary. Typically, blood from an ACTH stimulation test would have been sent to the vet school in Knoxville, TN for analysis. Unless this was done, I'm guessing the "Atypical" diagnosis may have been kind of a stab in the dark :o.

So, going full circle, these are my greatest concerns. The high calcium level, the single enlarged adrenal gland, and the results of any specialized Cushing's testing. Sorry for so many questions, but your answers will be very helpful.

Marianne

[DoxieMama]

Hello and welcome to you and Abby, though I'm sorry for the health issues she's been going through. Good job nursing her through the winter. I'm no expert by any stretch, but that high PrecisionPSL in January suggests pancreatitis (so the scarring seen in the u/s makes sense). I'm glad your vet contacted a specialist about Abby's results.

I don't know very much about atypical so don't have any ideas, but I'm sure others will reply later.

Hang in there!

[kewlncguy]

On my receipt for the cushings tests it says:
Cortisol 3 Samples (low dose Dex)
Dexamethasone Naphos inj

[kewlncguy]

Abby does not have any of the symptoms of Addisons - lethargy, anorexia, vomiting, and muscle weakness. Also - "Dogs with Addison's disease often have elevated blood urea nitrogen (BUN) and an elevated creatinine, as well as decreased blood glucose. The blood count may show a chronic anemia. If the blood work supports the diagnosis of Addison's diseaes, then an ACTH challenge test is performed."

She doesn't have any of these

[labblab]

OK, then, those are the LDDS test (Low Dose Dexamethasone Suppression test). Each test should have three numbers along with a normal range. The first is a baseline or resting cortisol reading. Then an injection is given, and subsequent readings are taken at the 4 and 8 hour marks. If you weren't given the actual numbers, I'd try to get them from your vet tomorrow.

Marianne

[labblab]

Plus, I'm still wondering about the elevated calcium and the single enlarged adrenal gland. What does your vet make of those issues?

[kewlncguy]

My vet brought in a specialist to do the Ultrasound and gave me the increase in the Adrenal gland in Millimeters. She did not seem concerned. So I did not ask. Before we did the Ultrasound she was concerned about the calcium level but after she did not mention it. I think she was concerned that it was cancer of the liver but when the liver appeared in such good shape she decided not to do the biopsy

Isnt an increase in the size of the Adrenal gland, or a tumor an indication of cushings?

[kewlncguy]

I received the result of the LDDS on Friday afternoon and before I had time to call back and ask more questions about Atypical Cushings (I had to read about it first) the doctor had already left

[labblab]

Hi again, yes indeed, an adrenal tumor can be responsible for the elevated cortisol associated with traditional Cushing's and/or other elevated adrenal hormone levels as well. But that's why I will hope your vet will be discussing those ultrasound results with you in greater detail. A possible adrenal tumor can carry a range of outcomes depending upon position, growth rate, hormonal secretion patterns, invasion into important blood vessels, and whether or not it is cancerous. The question of cancer is one that I'm especially wondering about in conjunction with the consistently elevated calcium level, although I am not knowledgeable enough to know whether or not adrenal malignancies are likely to be associated with hypercalcemia. But it is something I would wonder about.

Surgical removal (and thus complete cure) of adrenal tumors can be possible, but it is major surgery that carries physical and financial risks. Still, if your vet suspects an adrenal tumor, I'd want to know her thoughts and impressions about any additional related diagnostics. Also, before committing longterm to treatment for "Atypical Cushing's," I would want to pursue the specialized ACTH testing that would be necessary to determine whether elevated adrenal hormones are actually present.

I know I keep harping on the issue of the high calcium, but if it were me I'd want to press my vet on this issue, especially since excessive thirst and urination can be symptoms of that problem. As that article says:


Then, since hypercalcemia is a symptom of an underlying disorder, identifying the primary problem is of paramount importance for long term management and control. Sometimes a thorough history and a complete physical examination will narrow the list of possibilities and thus dictate the next diagnostic steps (blood work, XRays, aspirates, or biopsies of enlarged lymph nodes or palpable masses). Other times those tests will only serve to rule out the most common causes. In those cases more advanced tests (parathyroid hormone levels and ultrasound imaging) may be necessary to uncover the cause.

Marianne

[Squirt's Mom]

In addition, there is one type of adrenal tumor that has nothing to do with Cushing's - a pheochromocytoma. Rare but we have seen several here over the years. This is not the only type of adrenal tumor that does not secret cortisol either. One thing to keep in mind always - canine Cushing's is one of, if not THE, most difficult of canine conditions to correctly diagnose. ;)

[kewlncguy]

I will ask her when she returns on Tuesday. she may be taking into consideration my very limited funds as I am on disability right now and it took me a month and a gofundme campaign just to raise the money for the ultrasound and LDDS. But, she has never had a problem telling me that Abby needed this or that test. We have already spent a small fortune last year with Abbys illness and other tests.

[kewlncguy]

Ok, Now I have this question. How do they determine why the Adrenal gland is enlarged? and also how do they determine why the calcium level is high?

[Harley PoMMom]

Ok, Now I have this question. How do they determine why the Adrenal gland is enlarged? and also how do they determine why the calcium level is high?

Both are really good questions and unfortunately the only way to really tell are with more tests. :(

Regarding the calcium, If you have results from previous chemistry blood panel tests you'll want to look and see if the calcium has been trending upward, if so than usually an ionized calcium test is performed.

As for the enlarged adrenal, sometimes they can get information just from looking at the ultrasound because of the shape, thickness, etc. of the adrenal gland.

[kewlncguy]

I am getting the LDDS test info plus the Ultrasound Notes sent over to me today and will post on the original post. I will give a heads up when that info is there. Also, I am going to get a second opinion from NC State Veterinary School so I am waiting on my referral to get that appointment

[labblab]

I will ask her when she returns on Tuesday. she may be taking into consideration my very limited funds as I am on disability right now and it took me a month and a gofundme campaign just to raise the money for the ultrasound and LDDS. But, she has never had a problem telling me that Abby needed this or that test. We have already spent a small fortune last year with Abbys illness and other tests.
I give you enormous kudos for going to such lengths to care for Abby!! She is a very, very lucky girl to have you as her parent.

Once you have the chance to talk again with your regular vet, it may well be the case that she will already have some of the answers that we are looking for. But I think it's great that the NC State vet school may be an option for you should you need or desire more specialized input.

You already know my main questions at this point -- about the unilateral adrenal enlargement and the elevated calcium. Your vet may already have thoughts or suspicions in mind about the presence (or absence) of an adrenal tumor, and talking to her on Tuesday should help clarify that. I don't know enough about adrenal imaging to know whether a CT or MRI would give you more definitive info than the ultrasound (and also their relative expense), but she should be able to tell you that.

However, before entering into additional expense, you may wish to also consider how/if the additional info will change things. As I mentioned earlier, adrenal surgery is very expensive and quite risky. I had to decide against some different but expensive imaging and treatment procedures for my own Cushpup for multiple reasons, of which cost was one :o. And we may be missing the boat entirely, in that I am assuming your vet believes the adrenal enlargement is due to a growth -- but that may not be true, after all.

My main goal here is to help you get more definitive answers so that you'll be as well-informed as possible re: Abby's likely options and prognosis. Going full circle, melatonin and lignans are largely benign supplements that ought not to harm Abby, regardless of her condition. But I'm hoping you can learn more about the vets' reasoning behind their use, and thereby also be armed with realistic expectations re: Abby's health in the future.

Marianne

[labblab]

Also, to better arm you with info about an "Atypical Cushing's" diagnosis, I am going to give you two links. The first is to a thread on our Resources forum that contains a lot of reference material. The second is to a 2015 article that discusses a number of questions that still remain re: the "Atypical" diagnosis. As you may already know, that diagnosis is made by some clinicians and researchers when a dog suffers from classic Cushing's symptoms, tests "negative" for elevated cortisol on the LDDS and ACTH stimulation tests, but exhibits other elevated adrenal hormones on the ACTH stimulation test. But a lot of question marks are still swirling around this condition. Here are the two links (unfortunately, a lot of the language is pretty technical).

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

http://sewvma.org/files/march_2015_meeting/atypical_cushings.pdf

Univ. of Tenn. vet school in Knoxville has been a primary research center for this condition, and historically, they have been the only lab in the U.S. that analyzes the complete profile of post-ACTH stimulated adrenal hormones that forms the basis of the diagnosis. So unless Abby has had an ACTH stimulation test performed and sent to UTK for analysis, you would not know whether she has elevations in those hormones or not.

Since melatonin and lignans are not thought to do harm, the vets may be suggesting you give them a try while saving you the expense of the testing. But even for dogs diagnosed via testing, those supplements don't always result in improvement, and even when they do, it may take months to see any changes. So I just want you to be armed with the big picture about the "Atypical" diagnosis, and also the uncertainty that surrounds it.

Marianne

[kewlncguy]

I put up a link to a PDF that contains both LDDS tests and the Ultrasound findings

[Squirt's Mom]

Links don't always work for everyone...for example I don't see any link. We typically type out the results in the thread. ;)

[kewlncguy]

Way too much info to type out. I gave you the bare link in red. You should not miss that

[Squirt's Mom]

Sorry but it's not visible for me. Did you put it here in the thread or somewhere else?

[kewlncguy]

I put it in the original post I made.

[kewlncguy]

Here I will put it again below. Just copy and paste it into a new browser/window:

http://www.m1g.net/docs/Abby_Shaw_Reports.pdf

or
Just click the link below

http://www.m1g.net/docs/Abby_Shaw_Reports.pdf

[Squirt's Mom]

ahhh there it is! Thanks! Hopefully everyone else can see it, too, now. ;)

[Squirt's Mom]

I will leave the interpretation of the LDDS to others but I would be asking about the bladder stones, myself.

Just to share our story with you - my first cush pup, Squirt, was diagnosed based on the LDDS, HDDS, ACTH, UTK panel, and 2 ultrasounds. However, after the second US I was told about a tumor on her spleen (it was present on the first one given 4 months prior but that's another story. :mad:). Once that tumor and half her spleen were removed, her cortisol returned to normal. The stress caused by that tumor resulted in false-positives on all the testing for Cushing's. She WAS Atypical tho, proven by the UTK panel, or full adrenal panel from the University of TN in Knoxville. This form seems to be a precursor for true Cushing's in which the cortisol is elevated. In Atypical, the cortisol is normal but two or more of the intermediate, or sex, hormones are elevated. After a few years of treatment for Atypical, she was diagnosed with PDH. She passed at the age of 16+ in 2014 from old age.

I now have a second pup who has been diagnosed with Cushing's. Initially they said it was probably adrenal based because of a growth on her left adrenal gland. But a low-dose treatment with Lysodren has resulted in that growth shrinking. BOTH her adrenals are enlarged, not one smaller as typically seen with ADH. Since that growth has shrunk, her IMS feels it is more likely a cyst, not a cortisol secreting tumor, and they are now leaning toward PDH. Myself, I am not convinced she has Cushing's at all. She is blind, has colitis, COPD, anal gland disease, and other health issues. All that on top of the growth on her adrenal gland could easily cause her cortisol to be elevated. However, her ACTH results give me pause - her post # is over 50....50 is as high as the scale goes. She does have some of the signs of Cushing's but they can all be laid at the feet of her medications. For example, when she does not need the Lasix her drinking and peeing is normal and her urine has a nice yellow color. So I am not convinced she has Cushing's. I believe it is possible she is exhibiting signs of Cushing's and suffering some of the results of elevated cortisol but that elevation is caused by other things, not the disease Cushing's. Her IMS and GP vet who are treating her agree this is feasible but they are not ready to settle on a consensus just yet.

Again, this goes to show you how difficult it can be to diagnose Cushing's. ;) I would ask about the stones.

[Harley PoMMom]

On the LDDS test the last blood draw, which is generally taken at the 8 hour mark, is looked at first to see if there was suppression, if that value is over the cut-off mark (shown as 1.4 ug/dl) Cushing's is likely. Looking at Abby's LDDS number at that 8 hour timeline shows that she did suppress at <1 ug/dl which is a negative result for Cushing's.

As Marianne mentioned, the increased calcium is concerning, and when this is elevated an ionized calcium test is usually performed.

Lori

[kewlncguy]

My Vet told me the stones were very small and small enough for to be passed without any trouble. She switched Abby to Hills Prescription Urinary Care C/D and said that would inhibit the growth of any further stones. Basically she said as long as we get her on the right diet there is nothing to worry about

[labblab]

Thanks so much for posting the results for the LDDS and the ultrasound interpretation. I'm not exactly sure what to make of the adrenal imaging. Clearly, there's an abnormality with the left adrenal gland. But whether or not it warrants launching into more advanced imaging right at the moment, I do not know. So that abnormality is definitely something I'd want to talk over in more detail with your vet tomorrow, in addition to the elevated calcium.

Marianne

[kewlncguy]

Does anyone know how much it costs to have the ACTH blood sample sent to The University of Tennessee College of Veterinary Medicine for analysis?

[Squirt's Mom]

UTK charges something like $140 - 150 but your vet does the blood draw and then the sample has to be packed and sent in a very specific way to preserve it. So your vet will tack their costs for the ACTH draw and shipping on top of UTK's cost.

[labblab]

It looks to me as though UTK is currently charging $150 for analysis of the full adrenal panel (which ought to be both baseline and post-ACTH values for each of several adrenal hormones including cortisol). I'm guessing the full panel is the first-listed charge on this price list:

https://vetmed.tennessee.edu/vmc/dls/Endocrinology/Documents/Price%20List.pdf

In addition to UTK's charge for analysis, your local vet will also charge you for performimg the two blood draws and also the cost of the ACTH stimulating agent. This agent can be pricey, so if you're interested in the test, you can ask her on Tuesday as to what she'd charge for her part of things.

[kewlncguy]

They (My Vet) gave me an estimate for the ACTH and it looks like their charge for the drug plus injections and blood draw is around $123

[kewlncguy]

I spoke with my Vet this morning and she told me that she is still consulting with the NC State Veterinary School about Abby's case. She said that the enlarged adrenal gland could be due to the amount of hormones and she had put her on the Melatonin, and Lignans for the time being to see if it brought the size down. She said the increased calcium levels could be due to diet and wanted to see if the new prescription food had an effect on it. Also she was speaking with NC State about the University of Tennessee ACTH test and also a special low dose test that NC State could do. One of her options was to do a Cat Scan but at $2000 a pop there was no way I could afford that.

[labblab]

Thanks so much for this update, and I'm glad your vet is still discussing Abby with the vet school since it seems as there are remaining questions. If elevated adrenal hormone levels are caused by a pituitary tumor rather than an adrenal tumor, we expect to see enlargement of both adrenal glands, not one alone. The fact that Abby's left adrenal is nearly twice the size of the right doesn't fit that profile and, to me, still points to an abnormality related to that gland alone. I totally understand why the cost of the CT is out of the question, though, and especially if surgery would not be an option anyway. So let's see what NC State thinks about any other good diagnostic considerations.

Thanks again for keeping us in the loop.
Marianne

[molly muffin]

Well you know the one adrenal is enlarged already, so not sure what they would be looking for with a CT scan at this point. So I'd probably skip that too. Maybe the UofT adrenal panel, but yea I agree with Marianne, that enlarged single gland rather points to it being the culprit.