Is it essential to determine type of Cushing's?

[Zircon]

I am so glad to find this very helpful forum. This is my first post and I hope someone can help me. My dachshund, Freckle's will be 14 in three months. Until recently she has never had any health problems and was energetic and playful. I started to notice changes earlier this year. She was drinking more water, urinating a lot, and developed a voracious appetite. She does not have other signs of Cushing's such as hair loss, panting, infections. Just recently I noticed her hind legs are weak, her belly is bigger, she has less energy and her water consumption is even higher; 28 oz/day an increase from 17 oz in April. She had her annual physical on April 16 and I told the vet I suspected she might have Cushing's. A blood chemistry and hematology profile, fecal test and urinalysis followed. The chemistry part was all within the normal range. The hematology had some highs and lows and my vet said some of these (I don't remember which) were due to clotting in the blood caused by the blood that was drawn for the heartworm/lyme test first; it was difficult getting enough blood for the hematology profile and apparently caused blood to clot which affected the test results. Does that make sense? The out of range results were:
HCT 60.30% range 37-55, HGB 19.2 g/dl range 12-18, PLT 28 range 165-500, RBC 8.89 range 5.50-8.50, LYMPHS 0.66 range 1.00-4.80.
On April 29 a urine/creatinine ratio test and urinalysis was done from a sample I collected. The results:
Urine Cortisol 41.2 ug/dL
Urine Creatinine 71.5 mg/dL
Urine Cortisol Creatinine Ratio 180
> 34 Cushing's possible
Urinalysis Results:
Specific Gravity: 1.020, PH: 6, Protein: Trace
A low-dose Dexamethasone Suppression test followed on May 28 :
Cortisol - Pre Dex 2.7 Ref Value 1-6 ug/dL
Cortisol - 4 hr Post Dex 5.1
Cortisol - 8hr Post Dex 5.7
Lab's Interpretation:
> 1.5 and > 50% of baseline consistant with hyperadrenocorticism. Further testing required to differentiate adrenal tumor from pituitary-dependent
After the LDDS test results came back my vet sent in an email that it does appear that Freckle's has Cushing's and she is trying to determine if an ACTH Stimulation or a High Dose Dexamethasone Suppression test would be the best choice to determine if pituitary or adrenal based. I am still waiting to hear! I would like to know if it really is important to know which one Freckle's has? I have read that the FDA has approved Trilostane for BOTH pituitary and adrenal based Cushing's in dog's. If she has an adrenal tumor I would not consider surgery anyway because she is elderly and I think it would be too risky. So why are further tests needed before medication can begin? Also I was under the impression that the ACTH test can not determine the type of Cushing's.
Thank you in advance for any information.

Laurel

[labblab]

After the LDDS test results came back my vet sent in an email that it does appear that Freckle's has Cushing's and she is trying to determine if an ACTH Stimulation or a High Dose Dexamethasone Suppression test would be the best choice to determine if pituitary or adrenal based. I am still waiting to hear! I would like to know if it really is important to know which one Freckle's has? I have read that the FDA has approved Trilostane for BOTH pituitary and adrenal based Cushing's in dog's. If she has an adrenal tumor I would not consider surgery anyway because she is elderly and I think it would be too risky. So why are further tests needed before medication can begin? Also I was under the impression that the ACTH test can not determine the type of Cushing's.
Thank you in advance for any information.

Hello Laurel, and welcome to you and Freckles! Thanks so much for all the helpful introductory info that you've given us, and I'm giving you an A+ on your research thus far! You've obviously been researching Cushing's, and already come armed with some excellent knowledge. All of your observations in the above quote seem to be accurate to me.

You are correct that the ACTH stimulation test cannot determine the type of Cushing's, and my impression is that the HDDS has fallen out of favor in recent years in terms of best methods for determining the type of Cushing's. However, your vet may be referring to an alternative blood test: the Endogenous ACTH. This test differs from the ACTH stimulation test, and is indeed used as a distinguishing test. However, my understanding is that this test is tricky to analyze properly (the blood has to be handled and shipped very carefully). So we seldom see it being used. Most commonly, we now see vets performing abdominal ultrasounds in the face of nondiagnostic LDDS results. The plus to an abdominal ultrasound is that all the other internal organs can be seen and assessed in addition to the adrenal glands. This can be especially helpful in circumstances where the overall Cushing's diagnosis is suspect. Which, in honesty, seems to be somewhat the case to me with Freckles. Here's why...

Dogs with Cushing's typically exhibit a common pattern of abnormality on their blood chemistry profile. The vast majority have elevated ALKP (often highly elevated), which is a liver-related marker. Other liver enzymes may also be mildly elevated. In addition, elevated cholesterol is quite common, as are elevated platelet counts and certain other white blood cell count abnormalities. Cushing's dogs also typically exhibit highly dilute urine.

From the info you've given us, Freckles basically misses the mark on all those abnormalities. She does have a low level of lympocytes, which would be consistent. But basically, that's it. So even though she presents with some classic outward Cushing's symptoms, her labwork is not at all typical of the disorder. And that makes me scratch my head. It's true that her UC:CR urine test and the LDDS are consistent with elevated adrenal activity. But both of those tests can return "false positives" in the face of other illnesses that are placing stress on the body. Unfortunately, they cannot definitively diagnosis Cushing's, itself.

So, in my own mind, here's the dilemma. Does Freckles actually have Cushing's at all? In this situation and given her age, I'm thinking you may want to take a bit more time before launching into treatment. I know it may sound basic, but has a urinary tract infection been definitively ruled out? That could certainly account for increased thirst and urination. Another diagnostic option might be to proceed with that previously mentioned abdominal ultrasound. Going full circle to your initial question, no, it probably doesn't matter if you distinguish between adrenal or pituitary Cushing's if surgery is not an option, regardless. But in this case, you might want to check to see whether there are any other internal abnormalities that might account for the abnormally high cortisol levels reflected in the UC:CR and LDDS. It's just a thought.

I'm especially relating to your dilemma because I spent two hours at the vet yesterday with my nearly 11-year-old Lab, with some of your same concerns. My dog had been active and perky until about six months ago, and now seems to have aged two years within that time period. Having had a Cushing's dog before, I was especially noticing a bunch of suspicious issues: increased thirst/urination, panting, poor coat, hot all the time, exercise intolerance, high end weakness. I thought to myself "UH OH, here we go again...!" But lo and behold, absolutely all her lab values are within normal range. Her ALKP is even low normal as opposed to being elevated. So neither her vet nor I believe that Cushing's can be the culprit. Her basic thyroid result (T4) is within the the low normal range, so we're sending off a more complete thyroid panel since hypothyroidism could account for some of her symptoms. But the bottom line is that she's old, and getting older by the day :-(. So that may truly be all that's involved here.

I surely don't mean to hijack your thread with a report on my own dog! But I just want to emphasize the challenges in sorting through symptoms of Cushing's vs. general signs of aging. Sometimes it can be really tough. And having said all this, it may be the case that Freckles truly has the disease. But given so many of these inconsistencies, I don't know that I can encourage you to leap into treatment unless the excessive thirst/urination/hunger is genuinely creating problems for you, or are making Freckles visibly uncomfortable. If so, then the judgement call may be harder. So these are my initial thoughts, and I'll be happy to talk all of this over with you in more detail. Hopefully, some other folks will chime in, as well!

In the meantime, once again, welcome to you both.
Marianne