Addison’s Disease in Dogs: Disease and Risk

Addison’s disease (hypoadrenocorticism; HA) in dogs is a complex and uncommon medical condition that leads to the deterioration or destruction the adrenal glands. It also has many pathways to manifest and is known as the “Great Pretender Disease” in dogs.

First, we will review the symptoms and other basic details. Our next post on the subject will discuss testing and treatment.

The Basic Dots

#1. The Great Pretender Disease

HA shares many of the same symptoms with other medical conditions such as weakness, weight loss, inappetence, vomiting, diarrhea, increased water consumption, excessive urination, trembling and collapse.

#2. Affected Breeds

Any dog can develop HA. Breeds commonly affected include the Cocker Spaniel, Great Pyrenees, Portuguese Water Dog, Bearded Collie, West Highland White Terrier, Standard Poodle, Nova Scotia Duck Tolling Retriever, Leonberger, Great Dane, Old English Sheepdog, Soft-Coated Wheaten Terrier, Pharaoh Hound, Alaskan Klee Kai, Pomeranian, Labrador Retriever, Labradoodle, Goldendoodle, Eurasier, English Setter, and Weimaraner.

#3. Average Age of Diagnosis

Between four and six years of age. Can be earlier, after puberty, in affected dog families.

#4. Sex

Females are overrepresented.

#5. Basic Adrenal Gland Physiology Need-to-Knows

Potassium is a mineral. Sodium is a mineral. Aldosterone is a mineralocorticoid, a steroid hormone. Aldosterone is produced in the adrenal glands. Aldosterone regulates potassium and sodium in the body.

Cortisol is a glucocorticoid that is also produced in the adrenal glands and is a steroid hormone. It is the “fight or flight” hormone that can help fight inflammation.

The adrenal glands are regulated by interactions with several other organs such as the liver, kidneys, and the hypothalamus and pituitary glands.

The liver releases angiotensinogen. The kidneys release renin. The two mix together and go to the lungs as angiotensin I. The lungs put out angiotensin II that then stimulates the production of aldosterone from the adrenal glands back to the kidneys to excrete potassium, and reabsorb sodium and water.

The hypothalamus gland releases a hormone, which tells the pituitary gland to release another hormone. This other hormone is adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal glands to produce and release cortisol.

#6. What does Addison’s disease entail?

In a nutshell, the adrenal glands are not producing enough cortisol and/or aldosterone for the body’s needs. Other names for the disease are hypoadrenocorticism or adrenal insufficiency.

Without enough aldosterone, sodium levels are too low in the body and potassium is retained. This can lead to heart arrhythmias and dehydration.

Without enough cortisol, dogs are unable to respond to stressors like inflammation. Cortisol also helps to maintain blood pressure and water balance.

#7. Why are the adrenal glands not producing enough cortisol and/or aldosterone?

HA can be placed into categories based on the cause and/or outcome of the insufficiency.

Typical Primary Hypoadrenocorticism – This form of HA is chronic, immune-mediated, and the most common type of HA in dogs. It is the destruction or deterioration of the glands resulting in insufficient output or production of cortisol and aldosterone. Some documented cases of this form of HA have been attributed to trauma to the adrenal glands, cancer, or a fungal infection, but most are heritable in genetically predisposed families of people and pets.

Atypical Primary Hypoadrenocorticism – The only differentiation here from Typical Primary Hypoadrenocorticism is that aldosterone is unaffected by the deterioration of the glands, but there is still an insufficient output or production of cortisol. Patients can progress from Atypical to Typical. Atypical is comparatively rare, and is more difficult to diagnose, probably because the disease is not caught in this stage as often as it is in the Typical stage.

Iatrogenic Primary Hypoadrenocorticism – Iatrogenic simply refers to a medical procedure or treatment that caused another disease. HA is the opposite of Cushing’s Disease. Veterinarians may prescribe mitotane or trilostane for pituitary-dependent Cushing’s Disease. How these medications work to counteract Cushing’s Syndrome are complex, so we will not delve into it. Basically, the adrenal glands are not working at normal levels and begin to atrophy due to these and certain other medications.

Spontaneous Secondary Hypoadrenocorticism – Spontaneous means “naturally occurring”. This condition results from the failure of the pituitary gland to secrete ACTH to stimulate the adrenal glands to produce cortisol. It is secondary because the gland at fault is not the adrenal gland this time, but the pituitary gland.

Iatrogenic Secondary Hypoadrenocorticism – Occurs due to either the abrupt halt or long-term use of glucocorticoid (steroids) administration. In this instance, glucocorticoid usage tells the pituitary gland to stop sending ACTH because there is enough cortisol in the body. This can lead to deterioration of the adrenal glands because they are no longer required to act.

#8. Addisonian Crisis

An Addisonian Crisis is an acute, severe, and sudden condition entailing diarrhea, vomiting, fluid loss and sudden collapse. It is an heightened and exacerbated spike of the disease. It requires immediate emergency veterinary care because the potential for death is high.

Breed, Age and Immune-Mediated

We need an educational refresher for this next section of our discussion.

Immune-Mediated, Increased Risk vs. Genetic Predisposition, and an Example

Immune-mediated (autoimmune) means the ‘failure of self-tolerance’, whereby the body goes into immunological overdrive and starts attacking itself.

Epigenetics is the study of an environmental trigger or triggers that cause the expression of genes that unleash an immune-mediated disease.

There is a distinction between “increased risk” and “genetic predisposition.”

Risk for a particular disease is based on probability. It takes into account familial disorders, lifestyle, and environmental factors that determine if a particular person or animal has an increased risk to develop a disease based on a population’s probability. For instance, a risk to develop breast cancer in human females is higher if her biological maternal aunt had it more so than her biological paternal aunt. Risk is still an excellent and necessary diagnostic tool to use until a potential genetic basis can be identified.

A genetic predisposition indicates an individual has a set of genes (usually 3-5) that could be the underlying cause of a particular disease, but will not necessarily develop that disease. Development of the disease will be compounded or ‘triggered’ by environmental factors, chemical and toxic exposures, certain types or overdosing of vaccines, food sensitivities, and lifestyle.

Let’s demonstrate with an example of an immune-mediated disease in humans: rheumatoid arthritis. An individual has an increased risk of rheumatoid arthritis if a close biological relative was diagnosed with the disease. Researchers have identified four main genetic markers and there are more than 100 regions across the genome discovered to be associated with the potential of developing the disease across multiple ethnicities. Onset can begin at any age, but is typically between 30 and 60 years of age. Environment, patient sex, nutrition and lifestyle are also factors that could trigger the immune system.

Note: While companion animals also are predisposed to many of the human immune-mediated diseases, the counterpart of human rheumatoid arthritis is rarely seen. Other types of immune-mediated arthritides do occur in animals.

Addison’s Disease in Dogs

Let’s start off with an easy example. The Nova Scotia Duck Tolling Retriever (Toller) breed is one among several breeds that have been extensively studied due to its high incidence of developing HA. Studies of this breed has given researchers insight into the complexity of the disease.

The Toller breed is unique because of a mutation that genetically predisposes it to Juvenile Addison’s Disease (JAD). Bear in mind, this specific mutation is not present in any other breeds based on testing of over 250 individual dogs in 80 different breeds. Approximately 75% of Toller puppies that inherit a copy of the defective gene from both parents will develop JAD. (As an aside, while they should not be used for breeding, they can be excellent companions.)

Why would the other 25% of Toller puppies with both defective genes not develop the disease? That is still unknown and will need to be explored. Again, that unknown is more than likely related to lifestyle, environmental factors, and nutrition.

By the way, University of California – Davis (UCD) has developed the genetic JAD test for Tollers. This is presently the only genetic test available for any form of canine Addison’s disease.

Indeed, as we learn more, research suggests that Tollers also have the genetic potential of an adult-onset form that corresponds to the HA seen in other dog breeds.

Comparative genetic research is now focusing on individual breeds identified at increased risk and then comparing them to other susceptible breeds. They are finding both genetic commonalities and breed-specific genes.

As new information evolves, examples of commonalities include: three breeds that may have the same genes, mutations or sequences that predispose them to HA, but three other breeds lack those. However, the latter set of breeds may have a different set of genes prone to contributing to the development of HA. On top of that, one particular breed of the three may have an additional breed-specific gene.

Compounding the issue is the age of onset of symptoms. This leads researchers to determine that a possible inherited immune-mediated adrenal destructional response has occurred to environmental triggers like certain fungi. Is a fungal infection more likely to trigger HA in a predisposed or increased risk breed compared to other breeds? We could not find any epidemiological data on that particular subject.

In essence, researchers know disease-specific genes can be precipitating factors, but are still figuring out the precise genetic cause in several affected breeds. The next step involves determining the environmental pressures that impact upon the genetic makeup, which can lead to increased susceptibility to HA in some dogs or breeds.


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Gershony, Liza C et al. “DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds.” Canine genetics and epidemiology vol. 6 2. 15 Feb. 2019, doi:10.1186/s40575-019-0070-7,

Gershony, Liza C et al. “Genetic characterization of Addison’s disease in Bearded Collies.” BMC genomics vol. 21,1 833. 26 Nov. 2020, doi:10.1186/s12864-020-07243-0,

“Juvenile Addison’s Disease (JADD) in Nova Scotia Duck Tolling Retrievers.” Veterinary Genetics Laboratory, University of California Davis, Accessed 11 June 2023.

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