In this article I’d like to address a common misconception — the idea that dogs with SARDS also have Cushing’s disease. This is outdated information. Furthermore, I’ll explain why promoting this idea can be dangerous.
Let’s review some terminology first.
Cushing’s Disease
Cushing’s disease refers to a tumor growing on the pituitary gland (near the brain) or the adrenal glands (in the abdomen). Such tumors cause the adrenal glands to produce excess cortisol. It’s often written as hyperadrenocorticism. Hyper — meaning excessive — activity of the adrenal cortex, the portion of the adrenal gland that secretes cortisol.
Cortisol
Cortisol is the body’s natural anti-inflammatory hormone. You’re probably familiar with man-made versions of cortisol such as cortisone cream or prednisone tablets. Cortisol soothes allergies and inflammation.
Cortisol hormone also provides energy to the body. It signals cells to do their work. Some cortisol is necessary for life.
Cortisol is a steroid hormone. When cortisol is produced in excess by a Cushing’s tumor, it causes signs of steroid excess such as increased appetite, thirst, incontinence, and elevated liver enzymes, cholesterol, and triglycerides.
When SARD dogs are tested for Cushing’s disease, however, they typically do not receive a Cushing’s diagnosis even though they give every appearance of having it. Only 20% of SARD dogs receive a positive Cushing’s diagnosis1. (More on this later.) This is frustrating and confusing to veterinarians who may repeatedly test the dog in an attempt to put a Cushing’s diagnosis on the problems they’re seeing.
Since practitioners are taught only about Cushing’s disease in school, it’s understandable that this is where their thought process takes them. But as more literature becomes available – especially in human health care – it’s clear that other forms of adrenal dysfunction exist.
Adrenal Sex Hormones
There are adrenal steroid hormones that are molecularly very similar to cortisol and when these hormones are elevated they closely mimic Cushing’s disease. Few veterinarians are familiar with this scenario. It’s rare even in humans. But the fact remains that other hormones can mimic Cushing’s disease. These are the adrenal sex hormones.
Like cortisol, adrenal sex hormones are steroids. So, when adrenal sex hormone levels are elevated they produce nearly identical signs/symptoms to those seen in Cushing’s disease. Increased appetite, thirst, incontinence, and elevated liver enzymes, cholesterol, and triglycerides. Read more here.
Because these sex hormones are produced by the adrenal gland, the dog need not be intact to produce them. They are readily produced by spayed females and neutered males.
Over 90% of SARD dogs demonstrate elevated levels of these adrenal sex hormone steroids1. My own statistics suggest it’s about 98%2. In other words, virtually all SARD dogs test positive for elevated adrenal sex hormone steroids.
Elevated sex hormones were first reported in SARD dogs in 2003 by Doctors Carter, Bentley, et al3. My own papers were published in 20074,5. Carter, Bentley, et al were published again in 20096. But since then, this information has generally been ignored. It is not mentioned to the owners of newly diagnosed SARD dogs.
Dog owners deserve to know about the adrenal dysfunction that afflicts these dogs. These owners are up night to let the dogs out. Their job performance suffers during the day. They return home to garbage strewn across the floor. Accidents on the carpet. Aggression. Confusion. Depression. They deserve to know!
Before I proceed, here’s a quick review so far.
- SARD dogs typically do not receive a positive Cushing’s diagnosis
- Virtually all SARD dogs do test positive for elevated adrenal sex hormones
- Adrenal sex hormones are steroids and mimic the signs of Cushing’s disease
- Dog owners deserve to know about adrenal sex hormone excess in SARDS
Positive Cushing’s tests in SARD dogs
“But, wait”, you say, “My dog did test positive for Cushing’s disease! What do you make of this?”
The majority of laboratory tests in the world cannot distinguish between cortisol, its precursor (deoxycortisol), or mirror-image molecules (epi-cortisol). As molecules go, they’re all very similar. Consequently, they’re all identified as “cortisol” on most lab tests. There are only a few facilities in the world (for example the renowned Mayo Clinic) that have sufficiently sensitive tests to distinguish cortisol from deoxycortisol.
That’s probably more than you want to know. The bottom line is that most lab tests lump together cortisol and the “building blocks” of cortisol and identify them both as cortisol. This can produce an inaccurate result known as a false-positive.
Deoxycortisol
Deoxycortisol is one of the building blocks of cortisol. The adrenal gland converts deoxycortisol into cortisol. Deoxycortisol is also a steroid.
Normal cortisol production.
In humans we know that adrenal sex hormones rise when something interrupts cortisol production. In terms of the adrenal activity that SARD dogs seem to demonstrate, that interruption seems to occur where deoxycortisol should be converted to cortisol. When deoxycortisol can no longer be converted into cortisol, levels of deoxycortisol accumulate. Cortisol levels decline, while deoxycortisol levels rise.
Deoxycortisol levels rise, while cortisol levels decline.
Some Examples
Since most lab tests lump together both cortisol and deoxycortisol, a dog can have very low levels of cortisol and very high levels of deoxycortisol, and receive a normal / high “cortisol” reading. Cortisol levels are not really elevated. It’s a false positive reading.
When these dogs — SARD dogs with elevated “cortisol” readings or “positive” Cushing’s tests — are given low-dose, daily cortisol replacement their “cortisol” readings typically drop. This would never occur in a true Cushing’s patient. Read more here and here.
An even more obvious inconsistency is this. Dogs with elevated cortisol (Cushing’s disease) don’t suffer inflammation. Since cortisol soothes inflammation, dogs that truly produce high levels of cortisol (Cushing’s disease) do not suffer allergies or inflammation. SARD dogs, on the other hand, frequently exhibit chronic allergies and irritations.
In further summation:
- Elevated adrenal sex hormone steroids result from low cortisol levels
- Low cortisol occurs when the adrenals can’t convert deoxycortisol to cortisol
- Rising levels of deoxycortisol can be falsely identified as cortisol/Cushing’s
The Dangers of Cushing’s Treatments in SARD Dogs
Many articles online and veterinary handouts continue to erroneously link SARDS to Cushing’s disease. It’s amazing to see this idea still promoted when the statistics fail to bear it out. Now I’m going to explain why it’s dangerous.
Since true Cushing’s disease is an elevation in cortisol, treatments for Cushing’s disease lower cortisol levels. Remember that. Cushing’s treatments lower cortisol.
Elevated sex hormone steroids are caused by insufficient cortisol levels. If this article is your introduction to my work, I realize how counter-intuitive this sounds. You can learn more here.
So in dogs with elevated sex hormones (and low cortisol) Cushing’s medications such as Trilostane and Lysodren can be very dangerous. These treatments destroy what little cortisol SARD dogs do produce. This is why SARD dogs on traditional Cushing’s treatment often experience a life-threatening “crash”. As I’ve mentioned earlier, cortisol is necessary for life and insufficient cortisol can lead to death. Read more here.
Newer treatments such as melatonin and lignans do not address the underlying cortisol insufficiency. In fact, they further disrupt adrenal activity. According to the University of Tennessee Veterinary College, these treatments may reduce adrenal estrogen levels but also reduce cortisol levels. The underlying problem remains uncorrected.
Practitioners continue to assume that this is a problem of excess cortisol. It is not. The term “atypical Cushing’s disease” is counterproductive because “Cushing’s” implies that cortisol must be reduced. It does not. It’s just the opposite.
A more accurate term would be: “Elevated sex-hormones due to insufficient cortisol production.” Read more here. Perhaps, if veterinary medicine becomes sufficiently advanced, a lab assay will be developed to measure 11-Beta-hydroxylase type 1 levels — the enzyme that converts deoxycortisol to cortisol — or deoxycorticosterone levels as are measured in humans. And at that time, if my thesis is correct, this condition may earn the more accurate name of 11-Beta-hydroxylase Type 1 deficiency in dogs.
A Better Approach
Since virtually all SARD dogs test positive for elevated adrenal sex hormones, and since elevated adrenal sex hormones are caused by low cortisol production, the natural conclusion is to supplement the low cortisol levels. Read more here. This is very different from the high, anti-inflammatory doses of prednisone that dogs typically receive. Read more here.
Prescribing low dose cortisol replacement for elevated adrenal sex hormones has been the standard of care for 65 years in human medicine. It’s surprising to me that this treatment remains ignored by the veterinary community.
When the low cortisol production is supplemented, 95% of the SARDS cases I’ve followed demonstrate a correction in sex hormone levels. Read more here.
You can find more about the SARDS protocol here. You will have the most luck securing treatment by approaching your general practice veterinarian.
If on the other hand, you pursue Cushing’s treatments for your SARD dog, please ask the veterinarian to also prescribe some emergency prednisone in case your dog experiences a “crash”.
If you own a dog who has not been diagnosed with SARDS, but instead has only been diagnosed with atypical Cushing’s disease, the above information may be even more valuable to you and your dog. You see, all SARD dogs demonstrate elevated adrenal sex hormones. By correcting the underlying cortisol deficiency now, you may prevent your dog from going blind!
I hope this information has been useful to you. I hope it helps your dog.
Best,
Caroline
In final review:
- SARD dogs typically do not receive a positive Cushing’s diagnosis
- Virtually all SARD dogs do test positive for elevated adrenal sex hormones
- Adrenal sex hormones are steroids and mimic the signs of Cushing’s disease
- Elevated adrenal sex hormone steroids result from low cortisol levels
- Cushing’s treatments that destroy cortisol production can be dangerous to SARD dogs
- Therapies such as melatonin and lignans do not address the insufficient cortisol production
- Low. LOW. LOW– level, daily cortisol replacement normalize sex hormone production
1. Komáromy AM, Abrams KL, Heckenlively JR, Lundy SK, Maggs DJ, Leeth CM, MohanKumar PS, Petersen‐Jones SM, Serreze DV, Van der Woerdt A. Sudden acquired retinal degeneration syndrome (SARDS) – a review and proposed strategies toward a better understanding of pathogenesis, early diagnosis, and therapy. Veterinary Ophthalmology 2016; 19: 319-331.
2. Levin C. Adrenal Exhaustion and Immunoglobulin Suppression: Common Findings in 54 Dogs with Sudden Acquired Retinal Degeneration (SARD). Copyright © 2008 Lantern Publications.
3. Carter RT, Bentley E, Oliver JW, Miller PE, Herring IP. Elevations in Adrenal Sex Hormones in Canine Sudden Acquired Retinal Degeneration Syndrome (SARDS). Proceedings of the 34th Annual Meeting of the American College of Veterinary Ophthalmologists 2003;34: 40.
4. Levin C. Sudden Acquired Retinal Degeneration, Associated Pattern of Adrenal Activity, and Hormone Replacement in Three Dogs – a Retrospective Study. Proceedings of the 38th Annual Meeting of the American College of Veterinary Ophthalmologists 2007; 38: 32.
5. Levin C. Sudden Acquired Retinal Degeneration, Associated Pattern of Adrenal Activity, and Hormone Replacement in a Brittany Spaniel – Case Report. Proceedings of the 38th Annual Meeting of the American College of Veterinary Ophthalmologists 2007; 38: 33.
6. Carter RT, Oliver JW, Stepien RL et al. Elevations in sex hormones in dogs with sudden acquired retinal degeneration syndrome (SARDS). Journal of the American Animal Hospital Association 2009; 45: 207–214.
