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
Part 3 summary:
- What to do if your dog is diagnosed with Cushing's disease?
- Does every dog diagnosed with Cushing's disease need drugs?
- What about conventional treatment options for Cushing's disease?
Part 4 summary:
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. 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.
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 (above), 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
Part 3 - Treatment of Cushing's Disease
What to do if your dog is diagnosed with Cushing’s disease
Now that you understand what goes on if a dog has Cushing’s disease and what the diagnostic process is, it is time to look at the treatment. In fact, this condition is a good example of bringing both the knowledge of conventional and alternative medicines that work best for the patient.
There are two areas I will address in the treatment portion of this article:
- Conventional treatment of Cushing’s disease
- Holistic methods of supporting the adrenal glands that can reduce the need for prescription drugs
Does every dog diagnosed with Cushing’s disease need drugs?
If your dog has been diagnosed with Cushing’s disease, the first question you should ask is if your dog needs treatment in the form of a prescription drug.
The key indicator for such a decision is not the diagnosis but your dog’s symptoms and quality of life. If your dog has been diagnosed with Cushing's, it is unlikely that it can be cured. However, not every dog needs to be on prescription drugs.
If your dog drinks excessively but does not seem to have urine soiling accidents and is not ravenous and in constant distress, treatment may not be necessary. However, if your dog has rashes, suffers from recurrent urinary tract and skin infections, and has an insatiable appetite, it may need to be treated with medication.
Some of you may ask why I suggest drug therapy as a holistic vet. Cushing’s is a very unique condition because the over-production of steroids creates a serious obstruction to healing that is very difficult to overcome and creates a vicious medical cycle.
The disease itself shuts down the healing response of the body, and this is why Cushing’s can be managed but rarely cured.
A closer look at conventional Cushing’s disease treatments
A) Lysodren (Mitotane) treatment
This treatment has been used in Cushing’s disease for several decades; however, I do not suggest it unless all the other options have been exhausted.
This medication is, in fact, a chemotherapeutic agent that selectively destroys the steroid-producing tissue of adrenal glands. In the general/soldier analogy I gave you a few paragraphs above, Lysodren selectively kills off the “soldiers” (the adrenal gland cells) so they can’t respond to the exaggerated commands of the “ill” general—the over-reactive pituitary gland.
The big issue with Lysodren is that it may “kill off” too many adrenal cells, which can result in serious crises similar to low adrenal function— Addison’s disease. In such situations, Lysodren must be stopped and corticosteroid administered to supplement the deficiency in natural cortisol. A reversal of such a reaction usually happens in 30 minutes.
What will your vet prescribe? Lysodren is usually started on a twice a day basis until there is a slight decrease in appetite. The ACTH test is usually done then (around day 8 or 9) to see if lower levels of cortisol have been achieved. If the levels are ok, dosing continues at one to two doses per week. If the levels are still high, twice a day dosing continues for 1 more week, and the ACTH test is repeated.
What is the worst case scenario?
Unfortunately, when adrenals are too damaged by Lysodren, a dog can develop Addison’s permanently and must be treated appropriately. This side-effect is life-threatening. It is very important that your veterinarian give you a Lysodren antidote to take home before starting the treatment.
To summarize, Lysodren should be used only if your dog’s quality of life is poor, and it should not be seen as a first resort; rather, it should be considered the last line of defence.
IMPORTANT NOTE: If your dog does not have good or excessive appetite before the treatment is started, it is highly likely that there is another problem present in addition to Cushing’s disease. In such a case, Lysodren treatment should not be started.
B) Trilostane treatment
This drug inhibits the enzyme that participates in steroid (cortisol) production. It can be dosed once or twice daily, and the same attention to testing and monitoring cortisol levels must be paid as with Lysodren. The tests are usually done two weeks after starting the medication regimen and one, three, and then every six months. The blood sample should be taken four to six hours after the medication has been administered.
Opinions are mixed about which of the two drugs, Lysodren or Trilostane, is better, and while the likelihood of side effects with Trilostane is slightly lower, the overall survival on either medication without any further holistic support is around three years.
Starting with one dose a day is more economical and minimizes toxicity and side effects.
How do you recognize when your dog has been overdosed with Lysodren or Trilostane?
The symptoms are very much the same as those of Addison’s disease: decreased appetite, vomiting, diarrhea, listlessness, and dehydration. If your dog is on medication and displays these symptoms, administer the antidote (a corticosteroid prescription you should have on hand) and see your veterinarian immediately to perform an ACTH response test. The drug should be discontinued immediately and started again in seven days with a 25% lower dose.
Part 4 - Holistic and natural approach to treating Cushing’s disease
Cushing's disease is a serious problem that must be addressed by the primary veterinarian in your area. The following part of this article includes additional steps to support your dog.
Any disease is a result of a combination of a genetic predisposition with environmental factors, poor nutrition, deficiencies, toxicity, and drug and vaccine side-effects, to name a few. Our primary goal in the treatment of any disease should be to strengthen the body so we can eliminate or at least reduce the need for drugs and surgery.
Earlier on in this article, I mentioned that a dog diagnosed with Cushing's disease should only be put on Trilostane or Lysodren if clinical signs cause serious problems such as excessive urination, recurrent infections, skin problems, and insatiable hunger.
If your dog is relatively comfortable, it may be a good opportunity to attempt to restore the body’s balance.
If your dog needs treatment, adding the following steps may help reduce the medication and increase life expectancy. If your dog belongs to genetically predisposed breeds, implementing the following steps may also reduce the likelihood of Cushing’s disease.
The predisposed breeds are Poodle, Dachshund, German Shepherd, Yorkie, Boston Terrier, Labrador Retriever, Australian Shepherd, Maltese, and Cocker Spaniel, but any breed can be affected.
Holistic Approach to Dogs Diagnosed or Predisposed With Cushing’s Disease
1. Reduce stress
One of the reasons for the rise in Cushing’s disease may be increased stress among humans and less of a natural lifestyle in cities and the industrial world.
The canine adrenal glands have evolved in very different settings. Today, when many dogs are exposed to toxins and chronic low-grade stress, their taxed adrenals are more likely to be affected by Cushing’s disease or Addison’s disease.
Healthy, appropriate exercise, spending enough time in nature, and giving your dog “activities,” playtime, and other opportunities to socialize are important parts of adrenal gland health.
It is also important not to over-exert your dog, which could lead to additional stress.
2. Minimize vaccinations
The arguments about whether all of the vaccines that conventional veterinary medicine recommends are necessary have been going on for many decades and may not stop any time soon.
However, in a natural case scenario, a dog would usually be exposed to one pathogen at the time while some vaccination schedules suggest administering seven or more vaccines in a combo.
Logically, such a situation puts the immune system and the adrenal glands under tremendous stress, which can lead to a variety of health problems. Here is more info on a holistic approach to vaccination in dogs.
3. Switch your dog to a healthy raw or natural diet
I do not know a medical doctor who would dispute that healthy non-processed food is better for human health. Ironically, there is still a large group of veterinarians who propose that our dogs do the best on heavily processed kibble that sits on the shelf for months and sometimes longer.
If you are new to the idea of a raw or cooked homemade diet, I urge you to learn more and switch your dog as soon as possible. This is, in fact, a very important cornerstone of preventing or treating Cushing’s disease.
Humans do poorly on junk food, and dogs are no different.
4. Use this Healthy Dog Tool to give your dog a full spectrum of vitamins, minerals, amino acids, omega oils, and probiotics.
I have written many articles on the topic of essential nutrients. We learned about them in biology and biochemistry classes, but strangely, medicine focuses much more on diagnoses and drug treatments than the depletion of essential nutrients.
The problem starts with processed food, but even the most natural diet no longer provides all the nutrients. One reason for this deficiency is the lack of variety in the diet, but the main one is nutrient depletion of the soil.
Most people acknowledge that plants in a garden that has depleted soil are weak and produce less. Yet, strangely, in medicine, the issue of nutrient depletion often remains unaddressed.
Depleted food makes our dogs weak and sick!
It is absolutely crucial that your dog receives these nutrients. If in doubt, you can read what other dog lovers have experienced on the natural essentials for dogs page.
Over the years, I have formulated four essentials that cover the spectrum of your canine's nutritional needs:
Cushing’s dogs need the building blocks to do well. You can use this Healthy Dog Tool to receive a complete supplement plan.
5. Add LiverTune at the start of the program to cleanse and support the liver
One of the symptoms of Cushing’s disease is liver inflammation and elevated liver enzymes. This is why it is important that you support your dog’s liver by adding LiverTune which contains milk thistle and other liver-supporting and -cleansing herbs.
You can use LiverTune as a preventive and detox preparation in healthy dogs for six weeks initially and then for four weeks every six months, or on an ongoing basis in dogs with Liver or Cushing's disease. All you need to do is to follow the protocol on the product page.
6. Ensure good spinal lumbar alignment
The third lumbar intervertebral space plays a crucial role in supplying energy, blood, and nerve flow to the kidneys and also the adrenal glands, which are adjacent to the kidneys. Any injuries, inflammation, and tightness of the lumbar spine, especially in this region, will compromise the adrenals and may contribute to their dysfunction.
There are several techniques that you can use to address spinal injuries and misalignments. The most common ones are chiropractic, physiotherapy, osteopathy, acupuncture, and massage.
Once again, I will use the analogy of the adrenals being the soldiers of the body. If they do not receive “supplies,” they will not thrive.
7. Can tight or wrong collars play a role?
While I can’t answer this question with absolute confidence, wrong collars such as choke chains, prong, or martingale collars usually obstruct blood flow from the brain and head. A dog that pulls on the leash will have a similar feeling as if you constrict your neck. Blood will pool in his head, and this congestion can negatively affect the pituitary gland.
This is why any dog, especially Cushing’s dogs, should always wear a harness.
Here is some more information about tried and tested collar alternatives.
8. How to look after your dog’s skin and urinary tract infections.
The ideal goal should be to reduce the amount of medication that your dog receives. No matter if the diagnosis has been established or if your healthy dog is of a predisposed breed, using any foreign chemical substances should always be a last resort.
If your dog has a propensity to skin issues, a raw diet and the addition of essentials may help; however, sometimes, further steps are necessary.
If your dog suffers from moderate to severe Cushing’s, conventional medication may be needed to control the skin problem. However, in milder conditions, the application of Skin Spray may help address skin irritation, inflammation, and eruptions.
As for urinary tract infections, you can try adding organic cranberry extract (not powder) to your dog’s food at a dose of 10–15 mg/lb two to three times daily.
9. Are melatonin and lignans (from flax hull) beneficial for dogs with Cushing’s disease?
In recent years, dog lovers have been wondering if the use of melatonin and lignans are good for dogs with Cushing’s disease.
To date, there has only been one published study on the effects of melatonin and lignans on human adrenal gland tumours, and no studies have examined the effects of melatonin and lignans on dogs with Cushing’s disease.
The human in vitro study on adrenal carcinoma cells confirmed there was a reduction in cortisol production when melatonin and lignans were applied to the cell culture*.
To summarize, the use of melatonin and lignans in the treatment of Cushing’s disease is still in the early stages -and therefore any health benefits are yet to be determined.
However, the use of melatonin for dogs with Cushing's disease appears to be safe, and if you and your veterinarian are considering this therapy you may give melatonin at 0.1 mg/kg PO 1-2 times daily, rounded to the nearest 1 mg for ease of dosing.
As for lignans, the best way to supplement them is in fresh form by adding 1 tsp of ground flaxseed per 20 lbs of body weight up to 3 tsp, the maximum dose. You can use a clean coffee grinder to grind the flax hull.
Note: Flaxseed does not replace a good source EPA and DHA, and it can cause diarrhea in sensitive dogs. If your dog suffers from these side-effects, either reduce the dose or stop the administration.
Based on the information above and perhaps even practical experience with living with a dog affected by Cushing’s disease, you now have a good understanding that this is one of the most difficult problems to treat.
While it is less likely that a Cushing’s dog will be completely cured, it is reasonable to expect that when the right steps are taken, we can reduce the chances that a predisposed dog will contract Cushing’s.
My hope that the information published on this page will help you manage the condition better and that you will use this knowledge when you are deciding on the treatment plan for your dog and get the gift of extra time.
Thank you for caring!
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.
*Fecteau KA, et al. Am J Vet Res. 2011;72(5):675.
© Dr. Peter Dobias, DVM
Items referenced in this article.