When is Cushings not Cushings?

RE: When is Cushings not Cushings?

Beats — Fri, 05 May 2017 08:37:43 GMT

[quote user="Bill Nolan"]

That was a great article. It's definitely cleared up some questions I had on diagnosing liver disease. I also didn't realise that

Elevated ALP activity is noted with a concurrent increase in serum GGT activity, specificity for liver disease increases to 94%. Center SA, Slater MR, Manwarren BS, et al. Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980-1990). J Am Vet Med Assoc 1992;201:1258-1264.

[quote user="Anthony Dennison"]ALKP was >2000, ALT, GGT and Cholesterol also high.[/quote]

[/quote]

Good point, Bill.

Just remember that "hepatobiliary disease" is not always the primary problem. Classic example is acute pancreatitis with a big swollen pancreas blocking the bile duct and giving elevated liver enzymes and even elevated serum bilirubin levels if severe obstruction. In a hepatobiliary disease versus cushings disease debate, any changes in liver blood results, including measures of function such as bile acids, could indicate that there is primary hepatobiliary disease, or they could indicate that there is secondary steroid-induced hepatopathy from the cushings... and of course any non-cushing's disease can confound cushings testing... in this dog I think the strongest suggestion that the liver enzyme elevation is from primary hepatobiliary disease (and with that high an ALKP, which is an inducible enzyme related primarily to cholestasis as I understand it, most likely biliary) is that the LDDST, which is highly sensitive (i.e. few false negatives) for cushings, is normal in this patient.

RE: When is Cushings not Cushings?

Bill Nolan — Fri, 05 May 2017 06:35:25 GMT

That was a great article. It's definitely cleared up some questions I had on diagnosing liver disease. I also didn't realise that

[quote user="Anthony Dennison"]ALKP was >2000, ALT, GGT and Cholesterol also high.[/quote]

RE: When is Cushings not Cushings?

Beats — Thu, 04 May 2017 23:26:58 GMT

Miniature SChnauzers often have a very high ALKP from biliary stasis with (mild) cholestatic liver disease secondary to hypertriglyceridemia in my limited expereince. Did the gall bladder look at all sludgy?

Often subclinically.

The high ALKP being irrelevant until the dog is blood smapled for some other reason (like PUPD) and then a cushings chase commences.

Old-fashioned (as shown not to be that useful!) again, but "steroid-induced" ALKP is still available at some labs for under £20 if you want yet more things to do. Was there a stress leukogram?

Bile acids and biliary aspirate (cytology and culture) and fasting Triglycerides and cholesterol, not to mention some acute phase proteins (say CRP and haptoglobin for starters) can all be considered that might lead to feeding a super low fat diet and some ursodeoxycholic acid.

Repeating thorouhg urine testing also of course

Have you considered it might be the hot weather making it drink more

I chased a min schnauzer for persistent hypercalcemia a number of years ago after it developed PUPD and odd keratinising foot pad lesions and I decided to take a comprehensive blood sample... Multiple blood samples later, not to mention some dry ice and being black-listed from a national courier service I stopped for the summer and said I'd recommence the investigation in the winter when the weather was on my side. Of course 6 months later it was no longer PUPD and 6 years on at the ripe old age of 13 he looks just fine.

If I'm getting equivocal cushings results, I always stop and ask myself "would I recommend any treatment for this dog in light of further cushings testing". The answer is usually no, or at least not presently, so the quest can be shelved or at least kicked to the long grass.

A dog flap and a bigger water bowl can solve some PUPD problems for little dogs.

RE: When is Cushings not Cushings?

Anthony Todd — Thu, 04 May 2017 22:19:29 GMT

Just one of a number:

Although elevated serum hepatobiliary enzyme activities are frequently identified, they do not necessarily indicate clinically important hepatic disease.

From: http://veterinarymedicine.dvm360.com/diagnostic-approach-asymptomatic-dogs-with-elevated-liver-enzyme-activities

and we don't even know if the dog is actually polydipsic.....

RE: When is Cushings not Cushings?

Jenny Harris — Thu, 04 May 2017 21:55:08 GMT

Yes as Caroline suggested could be primary liver problem? Tricky to rule out without some sort of biopsy though. Sounds Like a tricky and potentially expensive case! Good luck

RE: When is Cushings not Cushings?

Caroline Allen — Thu, 04 May 2017 20:20:38 GMT

How high are the other liver enzymes? Is there any liver dysfunction (BAS)? Assume USG is low?

It could be a primary liver pathology in which case you'll need a biopsy to confirm what is going on. However I've seen a few cases like this where a SHAP test confirmed high levels of 17-OH-progesterone. If I remember rightly these dogs don't have the final enzyme to convert this to cortisol.

I have treated a Min Schnauzer with both primary inflammatory liver disease, hyperlipaemia, pancreatitis and Cushings. Unmasking the liver disease while treating the Cushings with Vetoryl was 'challenging' but I have to say the advice from the drug company vets was very helpful- we achieved a nice balance of treatment of a much happier dog.

RE: When is Cushings not Cushings?

Nicola Lawlor — Thu, 04 May 2017 20:10:15 GMT

I have treated a cushings patient that had a similarly frustrating presentation and set of results. We ended up with an external referral who did a similarly thorough workup and concluded the dog probably had cushings. The then did an ACTH stim test but measuring hydroxyprogesterone instead of cortisol which finally proved the point. Vetoryl controlled her symptoms for the most part however she did eventually develop diabetes mellitus as well which may be because we could never be totally sure if her levels were acceptable on ACTH stim monitoring - we did this more by clinical signs and knowing she wasn't being over medicated at least via her bloods.
https://www.ncbi.nlm.nih.gov/pubmed/12141305

RE: When is Cushings not Cushings?

Bill Nolan — Thu, 04 May 2017 19:12:54 GMT

[quote user="Anthony Todd"]Crikey, look at all the expensive possibles above and we don't even know for sure if the dog actually is polydipsic![/quote]

We do know that the patient does have a significantly elevated ALP, however.

RE: When is Cushings not Cushings?

Anthony Todd — Thu, 04 May 2017 19:00:26 GMT

This, for the probable few openminded, seems a good starting point:

http://www.vetbook.org/wiki/dog/index.php?title=Psychogenic_polydipsia

RE: When is Cushings not Cushings?

Anthony Todd — Thu, 04 May 2017 18:45:24 GMT

[quote user="Anthony Todd"]May avoid, what, £200+ of unnecessary diagnostics, and owner concern......[/quote]

Nah, as I expected, the obvious isn't considered, the basics are ignored.

Let's go for the weird expensive and complicated even before we know if the "symptom" is actually true and, amazingly, often it isn't.

RE: When is Cushings not Cushings?

Anthony Todd — Thu, 04 May 2017 18:30:07 GMT

[quote user="Clive Ansell"]Start with the basics: early morning urine SG +/- water deprivation test[/quote]

Here we go again!

Start with the basic, cheap, definitive, as above, but boil the water and make sure the owner measures the water consumption accurately, which sounds obvious but isn't to many owners.

Expecting the usual one star or derision, but some will be surprised by the numbers of psychogenic drinkers.....

May avoid, what, £200+ of unnecessary diagnostics, and owner concern......

Crikey, look at all the expensive possibles above and we don't even know for sure if the dog actually is polydipsic!

RE: When is Cushings not Cushings?

Thomas Johnson — Thu, 04 May 2017 18:10:00 GMT

[quote user="Martin Atkinson"]

Atypical Cushings - i.e producing other steroid hormones, or HAC just over-producing gluco-corticoids? How good is you scanning technique looking at the adrenal glands?

[/quote]

I would also think atypical Cushing's and would do an ACTH stim but testing 17-hydroxyprogesterone rather than cortisol.

RE: When is Cushings not Cushings?

Anthony Dennison — Thu, 04 May 2017 13:48:34 GMT

[quote user="Martin Atkinson"]Atypical Cushings - i.e producing other steroid hormones, or HAC just over-producing gluco-corticoids? How good is you scanning technique looking at the adrenal glands?[/quote]

My scanning technique is pretty good, but for something as borderline as this I may look at getting a more experienced scanner in.

[quote user="Clive Ansell"]

Start with the basics: early morning urine SG +/- water deprivation test, which could rule out DI.

maybe imaging of adrenals and pituitary if finances allow?

[/quote]

I was considering DI, that was going to be my next step. Dog is insured with Pet Plan and the owner is happy to go with anything.

[quote user="Robin Grimmer"]In this breed idiopathic hypertryglyceridaemia (+- pancreatitis) could account for the biochemical changes.[/quote]

But the dog isn't showing any signs of pancreatitis. He's just PU/PD.

Thanks for the responses. Will do a USG on the first pee of the day and then if that's normal check adrenals.

RE: When is Cushings not Cushings?

Martin Atkinson — Thu, 04 May 2017 10:51:50 GMT

[quote user="Bill Nolan"]

If the tests you've run are throwing out false negatives you could always try a urine cortisol creatinine ratio (sensitivity 100%). That way it rule it out for sure?

[/quote]UC/C ratio is a screening test, if the blood tests are normal it hasn't got HAC, they are still gold standard. My money is still on my previous 2 suggestions.

RE: When is Cushings not Cushings?

Robin Grimmer — Thu, 04 May 2017 10:27:09 GMT

In this breed idiopathic hypertryglyceridaemia (+- pancreatitis) could account for the biochemical changes.

RE: When is Cushings not Cushings?

Clive Ansell — Thu, 04 May 2017 09:35:31 GMT

[quote user="Bill Nolan"]If the tests you've run are throwing out false negatives you could always try a urine cortisol creatinine ratio (sensitivity 100%). That way it rule it out for sure?[/quote]

Certainly worth doing; a negative result will pretty much rule out Cushing's, but a high level will not help much diagnostically.

RE: When is Cushings not Cushings?

Clive Ansell — Thu, 04 May 2017 09:33:33 GMT

Start with the basics: early morning urine SG +/- water deprivation test, which could rule out DI.

maybe imaging of adrenals and pituitary if finances allow?

RE: When is Cushings not Cushings?

Martin Atkinson — Thu, 04 May 2017 09:29:33 GMT

Atypical Cushings - i.e producing other steroid hormones, or HAC just over-producing gluco-corticoids? How good is you scanning technique looking at the adrenal glands?

RE: When is Cushings not Cushings?

Bill Nolan — Thu, 04 May 2017 09:25:02 GMT

If the tests you've run are throwing out false negatives you could always try a urine cortisol creatinine ratio (sensitivity 100%). That way it rule it out for sure?