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Testing for hyperadrenocorticism; diagnosing Cushing’s

Sometimes we as veterinarians say, this pet did not read the textbook. Which has been my experience with testing for Cushing‘s (hyperadrenocorticism). My typical approach has been blood tests. I was taught that the LDDST (low dose dexamethasome suppression test) was the go-to test. Even at my previous clinic, that was our go-to diagnostic test. That’s textbook, but when you get the results, sometimes you’re puzzled. I’m often on the phone with the lab, that thankfully provides consulting services over the phone with an internal medicine specialist.

At my current practice, our medical director uses the ACTH stimulation test (adrenocorticotropic hormone). It’s a more expensive test because the drug needed for the test is around $200 a bottle. The pros to this test is that if the test is positive, then it’s more likely a true positive. It is less sensitive than the LDDST. Vet students, remember SNOUT - a sensitive test rules the disease out. But the ACTH stim is less likely to get a false positive than the LDDST. So now, I take a look at my patient. Are they going to be anxious or stressed in the hospital for 8 hours? That LDDST requires 3 blood samples, time zero, at 4 hours post-dexamethasone and then again at 8 hours post-injection. Versus the ACTH stimulation - where our protocol is one hour post.

I recall in my 4th year small animal medicine rotation where the 3rd year resident was very tenacious in her approach with students - so I remember vividly my case of hyperadrenocorticism with her. The dog was a senior mini schnauzer. She was in the exam room circling, but she could be called out of this behaviour. She was a bit thin, and not the typical textbook Cushing’s dog with a pot-belly and hair loss. A circling dog may have a mass in its brain causing this behaviour. However, Cushing’s was not really on my mind because she didn’t look like she had Cushing’s. The resident was very disappointed and borderline yelling at me for not knowing that this dog had Cushing’s. But the dog didn’t read the textbook. This dog did have a brain tumour. Most dogs with hyperadrenocorticism have a pituitary tumour called a microadenoma - micro meaning small. This particular dog had a macroadenoma - meaning large. A large pituitary tumour is rare in a dog. So, that day I got trampled by a zebra - and yelled at by the resident.

Recently, I've been having this patient who is a 14-year-old neuter male mixed breed with a historical increase in alkaline phosphatase which in September was around 1600. No vomiting, diarrhea or lack of appetite. The owner notes that he has some skin issues and is always hungry. He also seems to be panting more. We discuss ruling out Cushing’s as a contributor to his clinical signs of skin issues and pot-belly, panting and increased appetite. We ran a LLDST which was consistent with pituitary-dependent hyperadrenocorticism. We started him on Vetoryl, a medication to treat Cushing’s and then recommended to check his electrolytes and an ACTH stimulation test. There is a little chart for Vetoryl monitoring, and based on this information with the ACTH stimulation test, we adjust the dose. I get on the phone with the internal medicine specialist, again, to talk about these results and what to do next. The owner is frustrated with all these tests and coming in and spending more money. Her dog also had bad teeth so she was looking to do a dental cleaning once he was stable. We recommended to recheck the bloodwork prior to anesthesia and there were a lot of changes. The alkaline phosphatase was now in the 3000’s and the total calcium was up, with higher than normal globulins and high normal albumin. There were some changes in the white blood cells that weren’t there before. Give these changes I recommended to do an abdominal ultrasound prior to any anesthetic procedure, as if there was a cancer, then I wouldn’t want to anesthetize him for cleaning of the teeth. It turned out that this patient had a liver mass. The adrenal glands were borderline at best, and that also meant that he may not have hyperadrenocorticism. In hindsight, I thought, next time I'm going to order the abdominal ultrasound first, then use the blood work to confirm.

Fast forward to this past week. This patient is a 14 year old MN Puli, who is losing weight without a decrease in appetite. The owner reports he is urinating more frequently, and waking up in the middle of the night to go. He is also ravenous. He has multiple sebaceous adenoma-like cutaneous masses, and he has a thinner hair coat. We ran blood work to compare with his previous senior screen. He has a consistently elevated pancreatic lipase, and mild increase in alkaline phosphatase, historical, and increasing over time. This time, his blood work showed an elevation in ALT and GGT - two other liver enzymes. The clinical picture has Cushing's on the list of differential cases of his PUPD (polyuria and polydipsia). This time I order an abdominal ultrasound first. His liver was grossly enlarged and only had small changes that were likely due to older age, but no liver mass. Some changes to the gall bladder wall - but no obstruction. The pancreas was appreciated as normal, but the adrenal glands were bilaterally enlarged - no focal mass. Now, I have a clinical picture of a dog, with bilateral adrenal gland enlargement and want to confirm my suspicion with a blood test - which was declined by the owner. She was just happy that it was not a cancer infiltrating his liver.

One final test that I have only run a few times is the urine cortisol/creatinine ratio. This is a sensitive test - in that a negative test result rules the disease out, but has low specificity, in that if the test is positive, you need to run a blood test to confirm. This is because dogs that get stressed when they come in to the vet can have an elevation in cortisol - that means this sample is best taken at home when the dog is calm and in their comfort zone.

All this being said, I think that even if hyperadrenocorticism is lower on your list of differentials, that an abdominal ultrasound is a very non-invasive screening test. When liver enzymes are elevated, we've found early gall bladder mucoceles, liver masses, enlarged adrenal glands, adrenal masses, and in other - splenic changes, kidney calculi, and thickening of the bladder wall - in patients that I wasn't necessarily expecting to see all of this. The majority of dogs don't need any sedation, or are given a small dose of oral sedative. The occasional dog we will give a little bit of butorphanol to make it less stressful for them. Another thing to note, an unremarkable ultrasound report last year in a 13 year old dog, doesn't mean that it will always be unremarkable. Advocate for the pet if your index of suspicion is high in that you will find something abnormal. It is easier to practice preventative medicine than reactive.

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