Frustrated and Confused - Possible Cushings?

[rkengineering]

We have been through the ringer on tests with our yellow lab over the last 12 months. Initial bloodwork was taken and shown to have highly elevated ALP and moderately elevated ALT levels. In regards to outward symptoms, she acts very normal and does not show many that we notice. We have always thought she drinks a lot of water but never so much that it was very alarming. Our vet suggested we look for both cushings and copper storage disease.

The first treatment was antibiotics (Clavamox). Bloodwork work was rested after a couple weeks with no change.

Next we did an abdominal ultrasound. Liver was "subjectively large". Only the left adrenal gland was imaged due to gas or feces blocking the right and it appeared normal.

Next was Cortisol Urine test. Cortisol/creatine ration came back High at 28 (with >13 as considered high for her)

We proceeded with a Low-dose dexamethasone suppression test and results came back negative for cushings.

At that point we moved to an ultrasound guided biopsy. Microscopic findings were mild to moderate chronic active portal hepatitis and vacuolar hepatopathy. Comments said the special stain was positive for mild to moderate copper accumulation. Comments also said the heptocellular swelling/vacuolation are non-specific changes but commonly seen in cushings syndrome. The vet diagnosed her with copper storage disease and recommended a treatment process:

Treatment started with a month on cyclosporine and then we spent the next 3 months treating with chelation therapy and no-copper prescription liver diet. Her bloodwork was retested after 3 months and ALP and ALT were higher than before.

I started asking more questions and got the feeling the copper storage disease was not a very certain diagnosis. My gut feeling is still cushings syndrome but we currently do not have a plan forward.

After looking more into possible signs of cushings, we have noticed the dogs skins could be darker on her stomach than it was before.

[Haleth]

Welcome! I'm pretty new here, but I can say that the people on the comm are friendly and helpful.

I've no experience with the copper storage condition, so I can't speak to that. I can tell you that we spent over a year figuring out what was wrong with Haleth, so you are not alone in the frustrating diagnosis process. It sounds like Cushing's can be a bear to diagnose.

I wonder if you shouldn't get a look at that other adrenal gland. You really need to see both, in case it is adrenal-dependent Cushing's and only the one is enlarged. In Haleth's case, she was "lucky" to have liver cancer first, as well as a gall bladder mucocele, which means she gets regular abdominal ultrasounds to check the status of both organs. That's how the IM specialist caught that both adrenal glands were enlarged back in June 2015. We had an LDDS test done then because of that and because of elevated cholesterol and liver enzymes, which can be linked to Cushing's. At that time the results were "inconclusive", and they remained that way in subsequent repeat tests, until signs of excessive thirst, hunger, and urinary accidents caused us to test once again around New Year's. Only then had she crossed over into full-blown Cushing's. So you can see clear signs of the disease sometimes long before the test results show it is definitely Cushing's and you may end up testing multiple times before the condition progresses to where it clearly is present. Frustrating.

I'll let the more experienced hands chime in.

[Harley PoMMom]

Hi and welcome to you and your girl!

I am sorry that you and your girl have been going through so much and it must be frustrating that there isn't a definite answer for those elevated liver enzymes. How old is your sweet girl? I don't think it is uncommon to see these types of elevations in a geriatric dog. And according to this article found on the dvm360 website:
In another study of both healthy and ill dogs, elevations in ALP, ALT, GGT, and AST activities were found in 39%, 17%, 19%, and 11% of cases, respectively. http://veterinarymedicine.dvm360.com/diagnostic-approach-asymptomatic-dogs-with-elevated-liver-enzyme-activities

Increased ALP and ALT are found in dogs with hypothyroidism, also their skin is known to turn a darker color (Hyperpigmentation.) The thyroid is usually checked when a regular chemistry is done and is known as the T4, has a thyroid problem been ruled out?

The Low-dose dexamethasone suppression (LDDS) is considered the gold standard test for Cushing's and it yielding a false negative result is low. In light of your girl being asymptomatic and having a negative response on the LDDS test I'm inclined to believe that a Cushing's diagnosis is unlikely.

If you could get copies of all the tests that were done on your girl and post those results here that would be great. With respect to the blood chemistry and CBC, you need only post the highs and lows and please include the normal reference ranges. Is your girl taking any other herbs/supplements/medications? I'm assuming that the pancreas was found to be WNL on the ultrasound and no bile duct blockage or sludge was found, right? Could you get a copy of that LDDS test and post those results here too?

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

Hugs, Lori

[judymaggie]

Hi and welcome to you and your pup! I was typing as Lori was posting and she has covered all the bases to get you started. Hopefully, we can help you sort out what is going on.

[rkengineering]

Thanks so much for the quick responses. I left our Remi's age. She is 5 years old. I will post up test results shortly.

[rkengineering]

I am attaching 6 pages of the test results in chronological order. The first page is the initial bloodwork and the last page is the most recent bloodwork.

Bloodwork 1 http://s30.postimg.org/sg6im0ev5/Test_Results_Page_1.jpg

Abdominal Ultrasound http://s30.postimg.org/j9o7yq9mp/Test_Results_Page_2.jpg

Creatine Cortisol Ratio http://s30.postimg.org/y86mt5oox/Test_Results_Page_3.jpg

Low Dose Dex http://s30.postimg.org/caa5zd9oh/Test_Results_Page_4.jpg

Liver Biopsy http://s30.postimg.org/toue7n6td/Test_Results_Page_5.jpg

Final Bloodwork http://s30.postimg.org/muk3hye69/Test_Results_Page_6.jpg

[PennysDad]

Welcome to the family! Soon enough you will have everything figured out! This place is amazing and some of the people here know what seems like everything! Keep your head up!

[Harley PoMMom]

I think a diagnosis of Cushing's is unlikely, and I believe the finding of chronic active portal hepatitis from the ultrasound guided biopsy fits better with those elevated liver enzymes. I found this article was helpful to me in understanding that particular hepatitis: http://www.merckvetmanual.com/mvm/digestive_system/hepatic_disease_in_small_animals/canine_chronic_hepatitis.html

How is your sweet girl doing?

Hugs, Lori

[molly muffin]

Lori that s an excellent xplsnation and does arm to fit the biopsy results better than Cushing's.
Especially with the ldds being negative. I would not be surprised though if the cortisol levels are high but this would be the result of the hepatitis as it is the bodies natural response to produce higher cortisol when any chronic disease is involved so you could see symptoms as a result of the high cortisol but it is the root cause that has to be treated. The high cortisol would affect the liver.