What do your dog’s adrenals and a toilet have in common?
Whenever I am asked about Cushing’s disease in dogs, my answer is that it is one of the most complicated diseases in medicine. It is hard to recognize and diagnose and it is also very difficult to treat. The main purpose of this Cushing’s disease series is to clarify some misconceptions about this adrenal gland disease, uncover some lesser known connections in the disease developments and openly communicate the benefits and limitations of both, conventional and holistic approaches to treatment and prevention.
The purpose of this article is to help you understand and recognize the possibility of an adrenal gland disorder in your dog and learn about the methods of diagnosis.
Part 1 Summary:
Part 2 summary:
- Symptoms - revisited
- A test to rule out Cushing's disease
- Adrenal gland tests and interpretation
- Distinguishing between Cushing's disease and an adrenal tumour
Adrenal gland function
The adrenal glands could be seen as the soldiers of the body that guard and regulate two distinct life-essential functions:
- Regulation of minerals
- Stress response
Mineral regulation takes place thanks to hormones called mineralocorticoids in the adrenal cortex, the outer layer of the adrenal glands.
Mineralocorticoids regulate mineral levels in cells and the bloodstream through directing the kidneys to conserve or release electrolytes. For example, the adrenal glands ensure that there is just about the right ratio of sodium and potassium in the bloodstream which deeply impacts heart muscle contractions. Without mineralocorticoids, the potassium levels would grow dangerously high and the heart would stop. This is one of the reasons why low adrenal function, hypoadrenocorticism or so-called Addison’s disease can develop into a serious life-threatening disease if left untreated.
The stress response is managed by glucocorticoid production that takes place in the adrenal medulla - the inner layer of the adrenal glands. Unlike Addison’s disease where the main problem is the underproduction of adrenal hormones, Cushing’s disease represents the opposite, adrenal hormone, namely glucocorticoid excess.
A few words about glucocorticoids and their function
There are two forms of glucocorticoid hormones
- Naturally produced by the body
- Administered in a form of prescription medication
Naturally produced glucocorticoids have an important function in glucose regulation and protein metabolism, and they are the key hormone used in a healthy stress response. Glucocorticoids prevent the damaging effect of an injury or excessive inflammation. These hormones also “tone down” the immune system in cases where an excessive immune response would lead to tissue and organ damage.
Drug forms of glucocorticoids are commonly prescribed in veterinary medicine as prednisone, prednisolone, dexamethasone and other similar glucocorticoids. Unfortunately, these prescriptions are, in my opinion, deeply misunderstood and can have severe long-lasting negative effects on a patient’s health. Steroids are often used when the true cause of a disease is not found, putting the immune system and natural healing defences to sleep. For more info on why I do not recommend prescribing glucocorticoids click here.
Cushing’s disease - the primary cause and key points
As you may have guessed, Cushing’s disease is a state of natural overproduction of glucocorticoids. A few paragraphs before, I described the adrenal glands as the soldiers of the body, and every good soldier should have a general.
In case of the adrenal glands, “the general” is the pituitary gland, a tiny gland inside of the brain that produces a hormone that commands the adrenal glands to produce the adrenal hormones. These commands are “sent” based on hormone blood levels.
A healthy dog would have pituitary and adrenal glands working together to ensure that the levels of stress hormones are just right. Another helpful analogy may be to liken this pituitary-adrenal connection to a flushing toilet.
When we flush, the water level in the tank goes down, which triggers the float dropping and opening the water flow. When the tank fills up, the water flow stops until the next flush.
In the case of your dog, the pituitary gland released ACTH (adrenocorticotrophin hormone) which triggers the adrenals to produce more corticosteroids and mineralocorticoids the same way the decreased water level triggers water flow to fill up the empty tank.
When the adrenal hormones reach their optimal level, the pituitary gland stops releasing ACTH and adrenal hormone production halts until the levels drop again.
In Cushing’s disease, this mechanism “breaks down” which causes excess adrenal hormone production which could be compared to a toilet that leaks.
Two types of Cushing's Disease
In order to explain the two main types of Cushing’s disease, I will continue to use the analogy of a general and a soldier with two possible case scenarios:
- PHD (Pituitary-dependent Cushing’s disease) where “the general”, the pituitary gland, never stops producing ACTH, causing hormone overproduction by the adrenals.
- Adrenal gland dependent Cushing’s disease where the adrenals, the soldiers, do not obey the general’s command to stop hormone production which also leads to hormone excess.
What are the symptoms of Cushing’s disease in dogs?
Generally, Cushing’s disease is relatively hard to diagnose especially in the early stages. However, as time progresses, the symptoms become more pronounced and resemble overdoses of steroid medication which is quite common in veterinary practice.
Cushing’s disease is more common in middle-aged dogs and females. There are breeds in which Cushing’s disease is more prevalent such as Dachshunds, Boxers, Boston Terriers, Beagles and Poodles but large breeds can be also affected.
To make it easier to remember some of the most common symptoms, I encourage you to remember the leaky toilet again. More water comes in and out, in other words, Cushing’s dogs drink and urinate excessively, may have a potbellied appearance, weak, loose muscles, a variety of skin problems and symmetrical hair thinning.
Affected dogs may often be smelly, itchy and appear restless and agitated as if responding to stress.
Part 2 - The rocky road to establishing a Cushing’s disease diagnosis
In Part 2 of this article, I dive into the essentials of diagnosing Cushing’s disease, which may resemble a jigsaw puzzle, as one test or symptom is not enough to get the full picture.
Cushing’s disease is a state where the adrenal glands overproduce cortisol — a glucocorticoid hormone produced by the outer layer of the adrenals — the cortex. This condition is hard to distinguish from the side-effects of steroid drugs such as prednisone, prednisolone, and dexamethasone to name a few.
What do a Bavarian pub and Cushing’s symptoms have in common?
Stories make it easier to remember relatively mundane topics such as disease symptoms and I would like to share one with you.
More than twenty years ago, I flew from Vancouver to Munich to visit my family in the Czech Republic. When I arrived in Germany, I picked up a rental car and got lost in the rolling hills of rural Bavaria.
I remember ending up in a small village square where the only place open was the local pub. When I entered the joint, I barely saw the silhouettes of people in the blue thickness of cigarette smoke. The tables were fully occupied by men and most of them showed clear signs of drinking too much and often.
In fact, their symptoms were not unlike Cushing’s in dogs:
Too much drinking, too much peeing, excessive appetite, pot belly appearance, weak muscles, bad odour, unhealthy red and flaky skin, lack of mental clarity. I trust you will remember this visual.
A simple, inexpensive test to rule out Cushing's Disease
There is one inexpensive test TO RULE OUT, NOT TO CONFIRM Cushing’s disease with 97% accuracy, and that is the urine cortisol test because Cushing's dogs have unusually high cortisol levels in their urine.
Here is how to interpret the results:
- Urine cortisol test shows normal levels: your dog does not have Cushing’s with 97% accuracy
- Urine cortisol level is high:
- Your dog has either true Cushing’s disease, OR
- Your dog has iatrogenic Cushing’s disease (caused by prescription of steroids), OR
- Your dog has a disease other than Cushing’s
No matter what the reason for high cortisol is, more testing needs to be done because the urine cortisol test is only good to rule out Cushing’s disease.
Urine cortisol should be the first test whenever you suspect Cushing’s disease as it is inexpensive, urine can be collected at home, and your dog is not subjected to hospitalization and additional stress.
Dog’s that are highly stressed during hospitalization may have a false positive adrenal test, and a urine cortisol test should be performed on a sample collected at home.
PRACTICAL NOTE: If your veterinarian suggests a more expensive adrenal test prior to a urine cortisol test, propose to run the urine cortisol test first to prevent unnecessary hormone injections and a higher test cost.
Adrenal gland specific testing
There are two tests that are used to diagnose Cushing’s disease, and neither of them is perfect.
In PART 1, I likened the pituitary gland to a general, and ACTH is the command for the adrenals to produce cortisol. We collect the baseline cortisol blood sample first and then inject ACTH (Cortrosyn®) to stimulate the adrenals to produce cortisol. The second sample is taken one hour after the injection is given.
- Cortisol levels are above 22 µg/dl (or 607 nmol/l) - Cushing’s disease is highly likely
- Cortisol levels below 22 µg/dl (or 607 nmol/l) mean either that:
- Your dog does not have Cushing’s, OR
- There is a 40-60% chance that your dog has a FALSE NEGATIVE result.
This is why the ACTH test is NOT A RELIABLE TEST to diagnose Cushing’s disease.
What is ACTH good for?
- To see if a dog has iatrogenic Cushing’s (caused by a doctor’s prescription)
- To diagnose under-functioning adrenal glands – Addison’s disease
- To see if drug treatment of Cushing’s disease (Trilostane or Lysodren) works (This will be discussed in PART3)
2. Low Dose Dexamethasone Suppression Test (LDDS)
The cortisol levels are taken before the injection then four and eight hours post injection.
When the pituitary gland stops issuing any more ACTH commands to the adrenals, they will produce more cortisol. If the adrenals are healthy, they will “listen” and stop producing cortisol.
However, if the pituitary or the adrenal glands are affected by a tumour, ACTH and/or cortisol production will continue, resulting in an excess of cortisol (injected dexamethasone) in the bloodstream.
Here is how to interpret the test results:
CAUTION! LDDS can be falsely positive if a dog has another symptom or acute disease or has been on a prescription of steroids.
- Cortisol levels above >1.4 µg/dl (or 39 nmol/l) after 8 hrs: Pituitary-dependent Cushing’s disease is 90% likely.
- Borderline cortisol levels between 0.9 and 1.3 µg/dl (or between 25 and 36 nmol/) after 8 hrs: Pituitary-dependent Cushing’s disease can’t be completely ruled out.
- Cortisol levels are lower than 0.9 µg/dl (or 25 nmol/l) after 8 hours: Cushing’s disease is unlikely.
How to distinguish between pituitary-dependent disease and an adrenal tumour?
CASE SCENARIO A: Pituitary-dependent Cushing’s is highly likely if all three conditions below are met:
- Cortisol level is greater than 1.4 µg/dl (or 39 nmol/l) 8 hrs post injection but lower than 50% of pre-injection cortisol (the resting level).
Example of a positive pituitary-dependent Cushing’s: pre-value: 4 µg/dl (or 110 nmol/l) (50% = 2 µg/dl or 55 nmol/l) and 1.6 µg/dl (or 44 nmol/l) after 8hrs.
- Cortisol level is lower than 1 µg/dl (or 28 nmol/l), 4 hrs post injection cortisol.
- Four-hour cortisol level is lower than 50% of the pre-injection cortisol level
CASE SCENARIO B: If any one of the above three conditions ARE NOT met, one of the following tests should be done:
- High dose dexamethasone suppression test HDDS (exposes dogs to high steroid doses and may end up not being conclusive)
- Endogenous ACTH concentration test (measure blood levels of ACTH - expensive and sensitive to errors in sample collection and storage)
- Abdominal ultrasound to assess the size of the adrenal glands (check for an adrenal gland tumour)
What test out of the three would I choose if LDDS is not enough to distinguish pituitary- and adrenal-dependent Cushing’s?
ULTRASOUND IS MY CHOICE as I always prefer diagnostic methods that do not involve an injection of steroids. Such an examination will rule out an adrenal gland tumour and if there is no tumour present, then pituitary-dependent Cushing’s disease is highly likely.
In such situations, treatment is indicated if at least several clinical signs mentioned above are present:
Too much drinking – too much peeing – excessive appetite – pot belly appearance – weak muscles – bad odour – unhealthy red and flaky skin – lack of mental clarity
The treatment of Cushing’s disease will be discussed in PART 3 of the adrenal gland series. If you don’t want to miss PART 3 of the adrenal gland series, SUBSCRIBE below.
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PS: If you are eager to learn more about the essentials of keeping your dogs healthy naturally, our Health and Longevity Course for Dogs is available online for instant access.
© Dr. Peter Dobias, DVM