Tuesday, February 1, 2011

Diagnosing Cushing's Syndrome in Dogs: When Should I Test? What's the Best Test to Use?

How do we best diagnose hyperadrenocorticism in dogs? Which is the best diagnostic test?  A presumptive diagnosis of should be made from clinical signs, physical examination, routine laboratory tests, and diagnostic imaging findings, but the diagnosis must be confirmed by use of cortisol hormone assays and pituitary-adrenal function tests. For screening tests designed to diagnose Cushing's syndrome, we have three choices:
  • ACTH stimulation test
  • Low-dose dexamethasone suppression test (LDDST)
  • Urinary cortisol:creatinine ratio (UCCR)
Which screening test is best?

Unfortunately, none of the diagnostic tests used in dogs with suspected Cushing's syndrome are totally reliable, and both false-positive and false-negative results are common. Because there are inherent problems with these diagnostic tests, the veterinarian is frequently challenged when attempting to properly interpret the dog’s tests results.

It is important to remember, however, that the predictive value of a positive screening test result for Cushing's increases in direct proportion to the number and severity of clinical signs and biochemical changes that develop in this disease. Therefore, one must always remember the importance of the dog’s signalment, history, and physical examination findings when interpreting the diagnostic test results of all pituitary-adrenal function tests.

Who should be tested for hyperadrenocorticism?

Testing for hyperadrenocorticism in a dog should be done because they have one or more clinical signs of the disease. Typically the disease is insidious and slowly-progressive, so most dogs have had clinical signs, such as abdominal enlargement, panting, muscle weakness, thin skin, lethargy, polyphagia, polyuria and polydipsia (PU/PD) for months to even years before the owners recognize a problem and seek veterinary help.

Who should NOT be tested for hyperadrenocorticism?

Testing for Cushing's syndrome is not recommended if the only abnormality is an increased serum alkaline phosphatase (SAP) activity on a serum chemistry panel, and the dog is otherwise apparently healthy. It is difficult enough to interpret endocrine tests in dogs with clinical signs of the disease; if they have no clinical signs, all of the endocrine tests may be difficult to interpret because of false-positive and false-negative results. The first step in workup in these dogs may include an abdominal ultrasound or bile acid testing.

One should not screen dogs for hyperadrenocorticism when the dog is sick with clinical signs that would not be related to Cushing's syndrome (e.g., vomiting, anorexia, weight loss). Many non-specific illnesses and other systemic diseases will produce false-positive results with the endocrine tests. Remember, hyperadrenocorticism is only slowly progressive, so hyperadrenocorticism is never an emergency diagnosis.

Before diagnostic testing is performed, it is therefore always good to ask oneself: if the test results would indicate hyperadrenocorticism, would I then feel confident to start treating with mitotane (Lysodren®) or trilostane (Vetoryl®) given the clinical picture of the patient? Would treatment help the dog's clinically signs? If either answer is "no," then it is probably best not to screen for hyperadrenocorticism in the first place.

My dog has clinical signs of hyperadrenocorticism and now other nonrelated illness − now can I test?

If the dog has any or all of the clinical signs of hyperadrenocorticism, yes, you should proceed with testing of the pituitary-adrenal axis. However, it is necessary first to ensure that the dog is not being exposed to exogenous glucocorticoids, including topical glucocorticoids on the eyes, ears or skin. First check with the owner to ensure that they are not applying topical glucocorticoids to their own skin − sometimes, dogs may ingest glucocorticoids by licking steroid-containing cream off of the owner's skin. If there is any doubt, ask the owner to bring in all and any medications that dog is receiving (including over the counter preparations) and anything that the owner or owner's family might be using in order to verify that no glucocorticoids are in any of these medications.

Next, obtain a routine database (CBC, serum chemistry analysis, and complete urinalysis) before any endocrine testing is undertaken. Finding the expected clinical pathology changes in a dog with suspected Cushing's syndrome helps confirm what the initial history and physical exam suggested. Typical abnormalities in dogs with hyperadrenocorticism include high values for serum alkaline phosphatase, alanine aminotransferase, low to low-normal serum urea nitrogen, and dilute urine specific gravity.  On the CBC, we may see a  'stress' leukogram (elevated mature neutrophils and monocytes, decreased lymphocytes and eosinophils), and a hematocrit and RBC count at the high end of normal.

What about now? Now should I use one of the screening tests?

If all the analyses point to hyperadrenocorticism at this stage, test away! In an upcoming blog, I'll be discussing the pros and cons of the ACTH stimulation test for Cushing's syndrome.


Lulusmom said...

My dog's blood chemistry, cbc and urine analysis abnormalities are consistent with cushing's. Low Dose Dexamethasone Suppression test was diagnostic for PDH but he has none of the common symptoms associated with the disease. In that clinical signs are a big component of confirming a diagnosis and the goal of treatment is to remedy symptoms, my vet and I have opted out of treatment for the time being. My vet mentioned that he recently attended a veterinary conference and it was mentioned that based on recent studies, treatment with lower doses of Vetoryl may be acceptable for an asymptomatic dog.

I have been a follower of your since my first dog was diagnosed with cushing's seven years ago. You have been consistent with your opinion that clinical signs are a huge component of a diagnosis and subsequent treatment. My dog appears to be otherwise healthy and while I'm concerned about the high liver enzymes, I'm not that comfortable with starting treatment in the absence of symptoms. Has there been a change of heart about asymptomatic dogs and is it now felt that it may be beneficial to begin low dose treatment of Vetoryl to lower liver enzymes and/or stave off diabetes mellitus or other nonadrenal illnesses for which a dog with cushing's may be predisposed?

Thank you for your time.

Lulusmom said...
This comment has been removed by a blog administrator.
Dr. Mark E. Peterson said...

I am not a proponent of treating dogs with asymtomatic Cushing's disease, unless they have secondary hypertension or proteinuria.

Low dose trilostane may be helpful, but I am not aware of any studies that even suggest that, let alone prove that to be the case. With any drug, we have to weight the concerns of side effects.

In general, most dogs with Cushing's syndrome develop a high alkaline phosphatase, with is "induced" to rise because of the cortisol excess. In other words, the fact that this liver (and bone) enzyme is high only means that it is a marker for Cushing's and does not reflect liver damage. So to me, that is not a reason to treat, especially since this value rarely normalizes after successful treatment with trilostane or mitotane.

dolphin1133 said...

I have an 11 year old mixed breed small dog (30lbs). During a routine dental, he had a blood panel run which showed elevated liver enzymes (ALKP 617 U/L, ALT 172 U/L) He was placed on Denosyl 90mg for 6 weeks and on a repeat test (in a new state) his levels were down - ALKP 426 U/L, ALT 115 U/L). The new vet suggested a change in medication to Denamarin and retest in 4 weeks. That appt was last week and instead of running the liver enzymes, the new vet ran an ACTH test...the results were Pre-ACTH - 2.1 ug/dL and Post-ACTH 14.1 ug/dL. From what I'm reading, both of those levels are within the normal range but now the vet is telling us he thinks our dog has Cushings Disease and wants to do an ultrasound at a cost of $300!

My dog is COMPLETELY asymptomatic - I would have never known he had elevated liver enzymes without the dental blood panel. Now I feel like I'm being taken for a ride. He has not been rechecked for liver enzymes so I have no idea if the medication he's been on has been working, and we're chasing this test result that by the vet's own admission can be greatly skewed by stress. Am I wrong for declining the ultrasound and seeking a second opinion or am I missing something here?

Thanks for your help,

Dr. Mark E. Peterson said...

Sorry for the delay. I used your question to write a blog post for my other "pet owner" blog so more owners would see it. You can find it here: http://animalendocrine.blogspot.com/2013/09/working-up-asymptomatic-dog-for.html

alderbaran said...

My 14 year old Chow has many symptoms/signs of Cushing (hair loss, excessive thirst and urination, thin skin, muscle wasting on the spine and rear legs) BUT he has not got the increased appetite--in fact, he has lost a lot of his appetite and it is hard to feed him now b/c he is very picky! He has lost weight and is down to 37 lbs when his normal was 45 or so. His ALP and ALT is high, and the UCCR test was 72. B/c he has a poor appetite, the opinion seems to be it is not Cushings. But is it possible that it is still Cushings in spite of the decreased appetite? He also has had a thyroid condition for the past 2 years and was taking L-thyroxin (I think the dose was too high b/c it started out as .8mg and now is down to .2mg. It was at .4mg but he started pacing so it was cut in half). I was almost ready to euthanize him but my vet put him on amoxicillin and he perked up. But he is still having all the Cushings symptoms and the hair loss seems very sad and maybe is getting worse, so I am unclear what to do next. It was suggested to to a urine test, which has not yet been done. What about a ACTH test? I have been advised not to do this latter test due to the chance of a false positive. I feel he needs treatment but what???

Dr. Mark E. Peterson said...

Dogs with Cushing's have a good to increased appetite. So if your dog isn't eating, then Cushing's isn't the problem OR another issue is causing the poor appetite.

LizNDale said...

We brought our 10-year-old 62 pound German shorthair pointer Mandy into the vet because of increased drinking, urination and occasional incontinence. Her only abnormal urine value was a very low specific gravity of 1.006. Her blood work showed elevated liver enzymes. We treated her with Denosyl for two weeks and then brought her back for follow-up appointment. Her enzymes levels had worsened, (see below) and bile acid was high:
BILE ACIDS High 17.9 umol/L (0.0 - 6.9) (This was first Bile test)

ALT High 187 U/L (10-100) **2 WEEKS LATER: 212
ALKP High 353 U/L (23-212) **2 WEEKS LATER: 681
GGT High 12 U/L (0-7) **2 WEEKS LATER: 28 Result verified by repeat analysis

Also on her report:

Re; 281HEMOLYSIS and 282 LIPEMIA Indexes:
Index of N,+,++ exhibits no significant effect on chemistry values.

Vet has asked her to bring her back in on Monday for an all-day test for Cushings.

After research online and some advice given by k9cushings forum participants, I am concerned that Monday's test may result in a false positive. The forum people are suggesting I go straight to an ultrasound. Their chief reasoning is the high GGT and the bile acid. She does not have pot belly, hair loss, or increased appetite. She is very active, energetic and happy.

What do you think, Dr. Peterson?

Thank you very much,


Dr. Mark E. Peterson said...

There are many ways to workup a problem like this, none of them wrong. Based on the clinical signs and low urine specific gravity, I would a certainly do a urine culture as an early step in diagnosis, if not already done.

Doing an ultrasound before a Cushing's test would not be wrong, but it this was terrible liver disease, I would expect your dog to show signs of illness.

I'd consider doing an ultrasound with the plan of collecting a sterile urine sample at the same time. Make sure that they look carefully at the kidneys too (sometimes that is the only way to diagnosis early kidney disease or diagnose pyelonephritis). I'd also consider a liver biopsy at the same time so you get a histopath diagnosis to help figure out the liver values. Finally, they should look carefully at both adrenal glands for an adrenal tumor, which tend to be more common in larger breed, female dogs.

LizNDale said...

Thank you Dr. Peterson, for your prompt reply!

I don't believe she had a Urine culture, just analysis.

I think, since she is not showing signs of illness, we'll go ahead and start with the LDDST.

Rileydog said...

Vet couldnt find anything wrong on exam or labs to deterine why the urine change. Suggested referral and mentioned cushings, diabetes of a different rype - maybe DI?
Thoughts on tests to

Dr. Mark E. Peterson said...

Sounds like your vet knows what to do. I always start with a urine culture and possibly an abdominal ultrasound. If that's negative, I rule out Cushing's based on a low-dose dex suppression test.

pacos_gal said...

Dr. Peterson, in reply to Lulusmoms comment about her dog, you said you do not recommend treatment in an asymtomatic dog unless hypertension and/or proteinuria are occurring.

My dog has had high cortisol for at least 2 years and first started testing LDDS in 2010. ACTH shows high cortisol, LDDS over the years, One each year at minimum, are negative for cushings, but has now in the last 2 months developed hypertension, proteninuria, with retinal bleeds. They are treating for protein loss kidney disease with benazepril 2.5mg, and her BP is now 150 from 180. We are still not addressing the high cortisol as she is still asymptomatic other than the high ALKP, and now her ALT's are going up too.

I'm thinking of asking my IMS to start trilostane, but not sure if we should be addressing the cortisol or just concentrating on the kidneys.

No one seems to be able to say why she has high cortisol levels and no symptoms of typical cushings.

She has had multiple ultrasounds showing enlarged liver, bilaterally enlarged adrenal glands and earlier this year a new nodule was noted on one adrenal gland which they think is benign as a follow up ultrasound showed no change in size.

What are your thoughts and have you encountered this sort of quandary previously?

Thank you for your time.

Dr. Mark E. Peterson said...

If your vet has done the proper testing for Cushing's (ACTH Stimulation, LDDST, and urine cortisol:creatinine ratios) and it is positive, then I would start treatment. If the tests are normal, then the "complications of Cushing's" you are talking about are likely secondary to another problem.

The ALT and AP are not specific tests for Cushing's, and the finding of large adrenal glands could be due to nonadrenal illness (such as primary kidney disease).

Dr. Mark E. Peterson said...

If your vet has done the proper testing for Cushing's (ACTH Stimulation, LDDST, and urine cortisol:creatinine ratios) and it is positive, then I would start treatment. If the tests are normal, then the "complications of Cushing's" you are talking about are likely secondary to another problem.

The ALT and AP are not specific tests for Cushing's, and the finding of large adrenal glands could be due to nonadrenal illness (such as primary kidney disease).