By Dr. Becker
In parts one and two of this three-part series, Dr. Karen Becker explains the mechanism of Cushing’s disease in pets, the various forms it can take, symptoms to watch for, and how to get a definitive diagnosis of this complex, confusing disorder.
Cushing’s disease was originally diagnosed in a human in 1932 by Dr. Harvey Cushing.
I actually prefer the medical term for the disorder: hyperadrenocorticism. It’s a mouthful, but it’s more descriptive of the condition.
‘Hyper’ means too much, ‘adreno’ refers to the adrenal glands, and ‘corticism’ refers to a syndrome involving the hormone cortisol. Hyperadrenocorticism, loosely translated, means too much cortisol released by the adrenal glands.
Cushing’s disease is rarely seen in kitties. The condition is most often seen in dogs.
Cortisol: The Fight-or-Flight Hormone
Cortisol serves a very important function in the body – it is the ‘fight or flight’ hormone. It is designed to be released by the adrenal glands only intermittently and in small amounts, when your dog’s body perceives stress.
When for one reason or another the body up-regulates (turns up) its demand for cortisol, the adrenal glands begin producing the hormone in large amounts, causing toxicity in your pet’s body.
A release of cortisol by the adrenal glands ultimately triggers a glucose release from the liver.
Glucose, which is sugar, provides energy to the cells of the muscles your pet will need to either ‘fight’ or take flight – a dog making a fast escape from a bear, for example -- or a tomcat taking on a new male feline that has invaded his turf.
A release of cortisol doesn’t just trigger a release of glucose and energy to muscles, however.
This powerful hormone impacts a number of important functions in your pet’s body, including:
- Blood pressure
- Electrolyte balance
- Immune function
- Bone and fat metabolism
Too Much of a Good Thing
Your pet needs cortisol in small amounts, but when the adrenal glands over-secrete it, the situation can turn toxic. If your pet experiences symptoms of chronic stress, his adrenal glands will release too much cortisol in response.
It’s important to understand your pet’s body makes no distinction between good and bad stress – it’s all stress. Your dog will have the same physiologic response to an unexpected rabbit in the yard as he will a visit to the groomer. His body interprets the excitement of a trip to the dog park and dealing with a cancerous tumor in the same way.
The Dangers of Excess Cortisol
Chronic stress leads to chronic over-secretion of cortisol, which can result in a multitude of serious health problems, including:
- Elevated blood sugar, which can lead to diabetes
- Elevated blood pressure, which can result in cardiovascular disease
- Extreme hunger from burning all the extra glucose
- Thinning of the skin and coat
- Decreased muscle and bone mass
- Increased risk of infection
Pets that are chronically over-secreting cortisol are considered to be immunosuppressed. They can develop an infection anywhere in their bodies – wherever there is a weak link. Infections of the gums, eyes, ears, skin and the urinary tract are common.
If your dog has recurrent infections or an infection he can’t seem to get rid of, it’s possible too much cortisol is to blame.
Types of Cushing’s Disease
There are actually several forms of hyperadrenocorticism and it can be confusing to keep them all straight. I’ll do my best to spell it out in an easy-to-understand manner here.
If you have a pet diagnosed with Cushing’s, it’s important for your animal’s health to know exactly what’s going on.
If your pet is healthy, I want to help you keep her that way.
The adrenals are small paired glands covered in fat located in the front of each of your pet’s kidneys.
The adrenal glands are composed of three layers:
- Zona glomerulosa, the outer, most superficial layer
- Zona fasciculata, the middle layer
- Zona reticularis, the deepest layer
The type of Cushing’s your pet acquires depends on which layer of the adrenals is over-secreting hormones.
The middle layer of your pet’s adrenal gland, the zona fasciculata, can over produce glucocorticoids and create what is traditionally known as ‘typical’ Cushing’s disease. Glucocorticoids also go by the name steroids, cortisol, cortisone or prednisone, which is the synthetic version prescribed by veterinarians.
It’s not uncommon for a veterinarian to inadvertently induce typical Cushing’s by prescribing a too-high dose of oral prednisone – or a course of prednisone therapy that is too long in duration. If your pet has taken prednisone, he is predisposed to acquire Cushing’s disease.
While typical Cushing’s involves too much cortisol, ‘atypical’ Cushing’s can occur when the outer layer of the adrenals – the zona glomerulosa – overproduces the hormone aldosterone. Aldosterone balances the electrolytes in your pet’s body.
Atypical Cushing’s disease can also result if the innermost layer, the zona reticularis, begins overproducing sex hormones such as estrogen, progesterone or testosterone precursors.
A Closer Look at ‘Typical’ Cushing’s Disease
And as if typical versus atypical hyperadrenocorticism wasn’t confusing enough, the traditional or typical form of the disorder, which involves overproduction of cortisol, also has two types:
- Adrenal dependent typical Cushing’s
- Pituitary dependent typical Cushing’s
Hands down, the most common form of Cushing’s disease in pets is the pituitary dependent form.
About 85 percent of dogs with Cushing’s acquire the pituitary dependent form, in which the pituitary gland – the ‘master gland’ in the brain – sends too much stimulating hormone to the adrenals. The adrenal glands respond by over secreting cortisol.
In the remaining 15 percent of adrenal-dependent Cushing’s cases, a tumor develops in an adrenal gland and triggers an up-regulation of cortisol production in the animal’s body.
Which Pets are Most Likely to Acquire Cushing’s Disease?
As I mentioned earlier, it’s very rare for cats to develop Cushing’s.
In the canine population, there are certain breeds genetically predisposed to the disorder including:
- Terriers (silkies, Yorkies, bull terriers and Boston terriers)
- American Eskimo dogs/Spitz
Symptoms of Cushing’s Disease
Cortisol is a diverse hormone, which means in excessive amounts it creates a whole host of diverse symptoms.
Most dogs have a few, but not all of the symptoms of the disorder unless diagnosis comes very late in the course of the disease.
The symptoms most commonly seen in dogs with beginning Cushing’s include:
- Increased thirst and urination (which can lead to the symptom of incontinence)
- Increased panting
- Weight gain in the abdominal area, in spite of a reduction in calories
- Thinning skin and change in the pigment of skin, from pink to grey or even black; bruising
- Hair loss
- Irritability or restlessness
Much less common are symptoms of rear limb weakness and blood clots.
Cushing’s syndrome is so incredibly diverse because every inch of your pet’s body contains cortisol receptors. Because of this, it is often the immunosuppressive aspect of the disease that prompts the first vet visit.
If, for example, your pet has a recurrent urinary tract infection or one that she can’t get rid of, along with one or two other symptoms – perhaps thinning skin or a developing pot bellied appearance, you should ask your veterinarian about Cushing’s disease as a possible cause.
In my practice, most Cushing’s dogs get referred after a misdiagnosed liver disease. The liver of an animal with hyperadrenocorticism gets overtaxed from trying to process the excess cortisol in circulation throughout the body. This causes an elevation in the liver enzyme alanine aminotransferase (ALT) and the inducible liver enzyme, alkaline phosphatase (ALP).
It isn’t uncommon for vets to stop looking once they see the elevated liver enzymes and diagnose liver disease when the problem is actually Cushing’s.
I recommend you ask for a copy of your dog’s blood test results whenever your vet has them done.
So many dog owners referred to Natural Pet, my hospital, are completely surprised to find out from me that their pet’s liver enzymes have been elevated for two or three years in a row. They want to know why their regular vet didn’t mention it.
Unfortunately, many ‘reactive’ veterinarians just do not address the possibility of Cushing’s until several of the symptoms are present, or a client comes in complaining that a pup is suddenly urinating in the house or losing her hair.
The better, proactive approach is to try to prevent the disease from taking hold. This is why you should get copies of your pet’s blood test results and why every single value that is showing out of the normal range should be investigated.
Your veterinarian should partner with you to identify whether your dog is at risk for pre-Cushing’s symptoms, or is already Cushingoid. If your pet’s ALP value is elevated, ask your vet if this could be the start of Cushing’s disease.
The actual diagnosis of the disease can be difficult. It is typically done through blood tests like the ACTH stimulation test and the low-dose dexamethasone suppression test. Both these tests require at least two blood draws to compare cortisol levels in your dog’s body for a definitive diagnosis of Cushing’s.
When Cushing’s is confirmed, your vet will want to determine if it’s pituitary or adrenal dependent. In my opinion, the best way to rule out an adrenal gland tumor is with a non-invasive ultrasound test.
Some veterinarians prefer to do a third blood test called a high-dose dexamethasone suppression test to determine whether the source of the cortisol production is adrenal or pituitary dependent.
Whichever method is used, it’s important not only to establish a definitive diagnosis for Cushing’s, but also to determine whether the form of the disease is adrenal or pituitary dependent.
This information will help you and your vet determine the best treatment options available for your sick pet.
An Alternative to More Expensive Diagnostic Testing to Rule Out Cushing’s
If your pet has symptoms of Cushing’s disease but you can’t afford the expensive tests required for a definitive diagnosis, you can ask your veterinarian to do a urine test called the urine cortisol to creatinine ratio test, or the UCC.
The UCC must be run using the first urine of the morning. Results will help your vet determine if your dog is excreting an abnormally high amount of cortisol in his urine.
Circulating levels of cortisol in healthy dogs are quite low, so if there’s a high measurable amount of cortisol in your pup’s urine, it’s a solid clue that Cushing’s may be present and further testing is warranted.
The UCC is a less expensive way to rule out Cushing’s disease. If your dog’s urine cortisol is within the normal range he most likely does not have typical Cushing’s disease.
Another clue can come from a blood test called the Cortisol Induced Alkaline Phosphate (CiALP) test. Many dogs with adrenal disease have elevated ALP values when bloodwork is done. ALP can be induced (elevated) from a variety of bodily dysfunctions including bone, gallbladder, liver and adrenal disease. This test can determine what percentage of the ALP enzyme level is being caused specifically by the adrenal glands.
The CiALP is a simple and effective screening test to determine whether your pet is starting down the path toward Cushing’s disease. When I have patients with an elevated ALP on routine bloodwork that are also exhibiting any symptoms of Cushing’s disease, I use this simple test to determine if further testing is warranted.
Unfortunately, in the majority of cases, the disease is diagnosed only after full-blown Cushing’s has developed and there’s no holding it back.
Once a dog has full-blown Cushing’s, he will live with the disease for the rest of his life. It’s a horrible illness that can be managed in many cases, but never cured.
Most of the drugs currently available to treat Cushing’s disease have many undesirable side effects.
It’s extremely important that you discuss your concerns about the possible side effects of any drugs your veterinarian recommends for your pet. Do your own research as well and gauge your own comfort level with giving the medications to your animal.
In my practice, we don’t use most of the Cushing’s drugs because in my opinion, the side effects are usually worse than the symptoms of the disease itself.
In addition to side effects, Cushing’s medications are very expensive and require a great deal of monitoring of bloodwork to ensure the drugs are managed correctly.
Detecting Symptoms Early -- Taking Advantage of the “Gray Zone”
Identifying pre-Cushing’s syndrome as early as possible and reducing your pet’s risk for acquiring the full-blown disease is the approach I recommend.
Dogs don’t suddenly wake up and have Cushing’s disease. The disease happens over time.
Many allopathic vets refuse to acknowledge the beginning of adrenal dysfunction because they don’t know what to do about it until a dog fails the ACTH stimulation (stim) test.
The problem with this approach is it takes months and sometimes years for an animal to be officially labeled with Cushing’s. Waiting this long to take action often means the vet has waited too long.
Most degenerative diseases are not black and white -- non-Cushingoid or Cushingoid. The health of most pets with adrenal symptoms and mild abnormalities on diagnostic tests is somewhere between black and white -- the ‘gray zone.’
Dogs headed toward Cushing’s disease, but not yet completely Cushingoid are in the gray zone.
I consider your dog as having pre-Cushing’s syndrome when he exhibits symptoms of Cushing’s disease, but is still able to pass an ACTH stim test. Often there are minor changes in bloodwork; the UCC is borderline or elevated above normal range, and the elevation in ALP has been proven to be cortisol induced.
The majority of allopathic vets will simply wait until a dog becomes Cushingoid, then treat the animal with toxic drugs.
This is never my approach. I am able to reverse many pre-Cushing’s patients with nutraceuticals, Chinese herbs, homeopathics, diet therapy and lifestyle management (reducing biologic stress).
Finding an integrative vet if your pet has Cushing’s symptoms is critical, as this can mean the difference between resolving the problem before it starts, or managing the disease in your pet for the remainder of his life.
Be proactive by having your pet’s ALP level checked annually. Ask your vet to establish a baseline level and address any elevation from the baseline through a screening test like the UCC or CiALP to determine if your dog’s body is over secreting cortisol.
Having this information will help you better manage a pre-Cushing’s situation before it develops to full-blown disease.
Don’t ignore symptoms. If your pup has consistent Cushing’s-type symptoms, no matter how minor, they are absolutely worth investigating for a possible endocrine or adrenal disorder.
Stay tuned for the third and final portion of this three-part series in which I’ll discuss the atypical form of Cushing’s disease, as well as natural treatment and prevention options.