The Meowing Vet discusses canine Hypoadrenocorticism, or Addison’s Disease, an endocrine system disorder in which the body fails to produce adequate levels of vital hormones.
Learn more about the potentially fatal consequences of untreated Addison’s Disease in our article below…
*Note: the terms “hypoadrenocorticism” and “Addison’s Disease” shall be used interchangeably.*
What Is Hypoadrenocorticism? (Pathophysiology)
Hypoadrenocorticism, more commonly called Addison’s Disease, is an endocrine disorder in which the body’s adrenal glands fail to produce adequate levels of specific steroid hormones, predominately cortisol (the major hormone that helps the body handle stressful situations) and aldosterone. This condition occurs in dogs and humans (albeit uncommon overall) yet is especially rare in cats.
If you’ve read The Meowing Vet’s article on Cushing’s Disease, a condition opposite to Addison’s Disease in which the body produces too much adrenal hormones, you have an understanding of how the hypothalamus and pituitary gland in the brain communicate with the adrenal glands. Here’s what we had to say about this type of hormone signaling in our previous article (with some additional info):
The body’s two adrenal glands lie beside each kidney. The inside of each adrenal gland consists of an innermost region called the medulla which is surrounded by another region termed the cortex. The medulla produces the catecholamine hormones epinephrine (or adrenaline) and norepinephrine. The cortex, on the other hand, produces various steroid hormone groups: glucocorticoids (such as cortisol), mineralocorticoids (such as aldosterone), and to a lesser extent, weak sex steroids (estrogen, etc.). The cortex functions as a member of the hypothalamic-pituitary-adrenal axis, a feedback network in which the brain and adrenal glands communicate during times of stress.
It is the adrenal cortex that is affected by hypoadrenocorticism (Addison’s Disease). With the onset of a situation that the body perceives as either a physical or emotional threat (fear, disease, etc.), the hypothalamus (a region of the brain) normally produces corticotropin-releasing hormone (CRH). CRH then travels to the pituitary gland (known as the “master gland” of the body and residing at the base of the brain). The pituitary gland, in turn, should release adrenocorticotropin hormone (ACTH), which enters the bloodstream to travel to the adrenal glands. The adrenal cortex then produces the glucocorticoid hormone cortisol, the major stress hormone released during the “fight or flight” response. It tells the body the hop into action to deal with the stressful insult. For instance, it triggers the liver to release glucose (blood sugar) into the bloodstream, thereby offering the brain and muscles more energy to plan an escape, fight, or run away from danger. Cortisol also has minor mineralocorticoid activity (see effects below under “aldosterone”).
Other hormones, such as aldosterone (a mineralocorticoid), are also released by the adrenal cortex (though this process is not reliant upon ACTH release, unlike cortisol production). Aldosterone, a component of the RAAS system (renin-angiotensin-aldosterone system) helps control fluid and electrolyte balance in the body as well as blood pressure and acid-base status. Aldosterone is especially important in regulating potassium (K+) and sodium (Na+) levels. The adrenal glands are normally triggered to release aldosterone when high levels of potassium are detected in the bloodstream, thus prompting excess potassium to be excreted by the kidneys into urine. High potassium levels are toxic to the heart, so maintaining a normal potassium concentration is imperative. Low blood pressure (hypotension) also stimulates the release of aldosterone from the adrenals, which then cause the kidneys to retain sodium in the bloodstream rather than excreting it in urine; the intestines also increase absorption of sodium from food. In turn, intravascular sodium then attracts water molecules to follow it into the bloodstream, causing a rise in blood pressure.
With Addison’s Disease, these complex endocrine processes fail to occur properly because the adrenal glands are not releasing sufficient amounts of the vital hormones cortisol and aldosterone. Therefore, the body cannot deal appropriately with stress. During stressful events when these hormones and their effects are needed, sufferers of Addison’s Disease can enter into a dangerous Addisonian crisis (learn more below). Therefore, prompt diagnosis and treatment of hypoadrenocorticism is absolutely necessary!
Click here to learn about Hyperadrenocorticism, or Cushing’s Disease, in which the body produces an excess of cortisol.
What Causes Addison’s Disease?
Naturally-occurring Addison’s Disease is categorized as either primary, secondary, or tertiary hypoadrenocorticism. Additionally, a transient condition in which the adrenal glands temporarily fail to produce glucocorticoids is termed iatrogenic hypoadrenocorticism.
Primary hypoadrenocorticism is the most common form of Addison’s Disease. With this disorder, the problem is at the level of the adrenal glands themselves, resulting in a deficiency of both glucocorticoids and mineralocorticoids, as discussed above. Primary hypoadrenocorticism is caused by an immune system destruction of the adrenal gland cortices, yet the exact trigger is often unknown.
Secondary hypoadrenocorticism arises due to a problem with the pituitary gland, resulting in failure of ACTH release. Therefore, the adrenal glands do not receive the appropriate signal to release glucocorticoids, resulting in a glucocorticoid deficiency. However, as we mentioned previously, aldosterone is not reliant upon ACTH to be released. Thus, the adrenal glands continue to release adequate amounts of aldosterone. Secondary hypoadrenocorticism is a rare cause of Addison’s Disease and can make for a more challenging diagnosis. Secondary hypoadrenocorticism is most typically caused by neoplasia (or cancer) of the pituitary gland.
Tertiary hypoadrenocorticism is exceedingly rare and occurs due to failure of the hypothalamus.
Iatrogenic hypoadrenocorticism (“iatrogenic” meaning “caused by medical treatment”) can also occur in dogs and cats who have received chronic medical therapy with corticosteroids (such as prednisone or prednisolone). During long-term treatment with such steroids (especially if they are administered at high doses), the adrenal glands temporarily suppress the amount of cortisol that they are releasing because the body is receiving similar steroid hormones from medication. The adrenal glands subsequently go on vacation for awhile since their glucocorticoid production isn’t needed at that time. If the steroid medication dose is gradually decreased a bit at a time before it is stopped (depending on your vet’s directions), this gives the adrenal glands some time to kick in again and begin producing glucocorticoids (i.e. cortisol). (Just like when you return back to work after a relaxing holiday, you may need a bit of time before you’re functioning productively in the workplace again.) This gradual reduction in steroid therapy is termed a “taper” and will likely be strongly advised by your vet. If, however, you abruptly stop your pet’s steroid medication without slowly tapering the dose (and even if a dose is missed, in some circumstances), iatrogenic Addison’s Disease can temporarily arise, and the missing steroid must be again supplemented until the adrenal glands get to work and start producing their own hormones. Therefore, NEVER SUDDENLY STOP YOUR PET’S STEROID MEDICATION WITHOUT TAPERING THE DOSE unless specifically directed by your veterinarian.
FACT TIME: The late U.S. President John F. Kennedy suffered from Addison’s Disease.
Clinical Signs
The following are the most common signs of Addison’s Disease. Your pet may seem to worsen at some times and appear better at others.
- Weakness and lethargy (especially during events that may be stressful to your dog: a house guest, thunderstorms, firework noise, boarding, a trip to the vet, etc.)
- Decreased appetite, weight loss
- Vomiting and/or diarrhea
- Increased urination and thirst (polyuria and polydipsia, or PU/PD, respectively)
- Hair loss (in rare cases)
Addisonian Crisis
Consequences of untreated or poorly managed Addison’s Disease can be deadly, resulting in severe dehydration, dangerously low blood sugar, and electrolyte abnormalities if glucocorticoid and mineralocorticoid levels dip too low. The signs listed above may escalate acutely, advancing to what is known as an Addisonian crisis. This is a medical EMERGENCY! Should your dog display the following signs, seek the closest veterinary clinic immediately!
- Depressed mental status (your dog may not appear aware of his or her surroundings)
- Collapse
- Seizure activity (due to severely low blood sugar, or hypoglycemia)
- Bloody stool
- Slow and/or irregular heart rate, weak pulse
- Cool to the touch (due to hypothermia, or low body temperature)
An Addisonian crisis can develop due to the following scenarios:
A patient receiving chronic steroids that does not actually have naturally-occurring Addison’s Disease but develops iatrogenic hypoadrenocorticism if the steroids are abruptly stopped without tapering the dose- A patient with Addison’s Disease that has not yet been diagnosed yet has entered into a crisis state
- A patient that has previously diagnosed Addison’s Disease that…
- has missed a dose of his or her medication used to manage Addison’s Disease (read more below under “Treatment”). It is vitally important that your dog receives his or her medication prescribed by your vet EXACTLY as instructed. Skipping a dose can yield dire consequences.
- is not well-managed on his or her current medical therapy and shall require a prescription adjustment. Your pet will require periodic rechecks throughout his or her lifetime to ensure that the Addison’s Disease is being adequately controlled.
- was previously well-controlled with medication but is experiencing an especially stressful event and cannot cope sufficiently with that stressor even on medication (i.e. a change in your dog’s household routine, a simultaneous illness, etc.). In such scenarios, your vet may recommend that you administer a temporarily increased dose of medication used to manage Addison’s Disease.
What PATIENTS Are Most Commonly Affected?
In veterinary medicine, dogs are the species most affected by Addison’s Disease while the disorder is very rare in cats. (Cats receiving chronic steroid drugs can sometimes develop iatrogenic hypoadrenocorticism, however, if such medications are abruptly stopped without an appropriate taper.)
The age of onset in dogs typically occurs in young adulthood, predominately between 4 to 4-1/2 years of age. However, dogs between 3 months to 14 years have been affected. Females (especially un-spayed, or intact, females) are more likely to be affected than males. Though Addison’s Disease can occur in any breed of dog, the following breeds are at increased risk of being affected:
- Standard Poodle
- Great Dane
- Rottweiler
- Springer Spaniel
- German Shorthaired Pointer
- Portuguese Water Dog
- Wheaten Terrier
- Basset Hound
- West Highland White Terrier (“westie”)
Labrador Retrievers and German Shepherds may also be at moderately increased risk. Some dog breeds, however, are actually at a decreased risk of developing Addison’s Disease. (Hooray!) These breeds include the Golden Retrievers, Pit Bull, Lhasa Apso, Cocker Spaniel, Schnauzer, Yorkshire Terrier, and Chihuahua.
Diagnosis
In addition to taking your report of your dog’s clinical signs into account, your veterinarian will also recommend the following diagnostic tests in order to make a definitive diagnosis of Addison’s Disease.
Specialized Adrenal Function Blood Tests
|
Test |
Description | Strengths |
Weaknesses |
| Basal plasma cortisol level | A blood sample is collected to measure the level of cortisol in the bloodstream. Cortisol should theoretically be decreased in this sample if the patient has Addison’s Disease (read exceptions under ‘Disadvantages’). | Easy to perform. Inexpensive. | Not very accurate: cortisol levels fluctuate throughout the day, so a single measurement may not reflect the overall cortisol trend in the bloodstream (i.e. a patient with Addison’s Disease may not always have a low cortisol level at every moment of the day, while a patient withOUT Addison’s disease may have a temporary decrease in cortisol). |
| ACTH stimulation test (“ACTH stim”) | A basal cortisol level is taken via a blood sample, then synthetic ACTH is administered to the patient, and a second blood sample to measure a potential change in cortisol in the bloodstream is taken. This mimics how the body would respond to a natural release of ACTH by the pituitary gland. In patients with Addison’s Disease, there should be no change in cortisol levels following ACTH administration, and both readings should be low. | GOLD STANDARD TEST FOR DIAGNOSING ADDISON’S DISEASE. Fewer false positives. | Can be expensive. |
Other Diagnostic Tools
Though these tests do not specifically rule in or rule out Addison’s Disease, certain abnormalities detected via these diagnostic tools help support a diagnosis of Addison’s Disease. Once hypoadrenocorticism has been diagnosed and medication has been started, some of these same tests will also be used during periodic rechecks to ensure that your dog’s medication dosage is at the proper level to help manage the Addison’s Disease.
- Physical examination: Your vet will note many of the clinical signs of Addison’s Disease as discussed previously: weakness, dull mental state, possible seizure activity, hypothermia, signs of dehydration, slow heart rate (bradycardia), irregular heart rhythm (cardiac arrhythmia), and weak pulses.
Bloodwork: The most common bloodwork abnormalities associated with Addison’s Disease that your vet may discover include:
- An absence of a stress leukogram: Normally, the CBC of stressed or ill dogs features a special white blood cell (WBC) appearance known as a stress leukogram. This is described by a high segmented neutrophil count, decreased lymphocytes, and decreased eosinophils. Dogs with Addison’s Disease, however, do not respond to stress normally. Therefore, there will be a lack of a stress leukogram, resulting in a normal neutrophil count with normal to increased lymphocytes and eosinophils.
- Mild anemia (i.e. low red blood cells, RBCs): due to the lack of normal glucocorticoid effects upon bone marrow; this may not become apparent on bloodwork until after your pet is rehydrated during treatment
- Low blood glucose (low blood sugar, or hypoglycemia): Cortisol normally triggers a rise in blood sugar as part of the “fight-or-flight response” when an animal is faced with a stressful situation. However, due to failure of the adrenal glands to produce glucocorticoids (cortisol) with Addison’s Disease, blood sugar may be normal or low. Severely low blood sugar can result in weakness and possible seizures.
- Azotemia: Increased BUN (blood urea nitrogen) and increased creatinine. This is a consequence of dehydration. The kidneys cannot work effectively to filter out these toxins from the bloodstream because cardiac output is low secondarily to dehydration (i.e. low blood volume pumping through the heart to the rest of the body, including the kidneys). Similarly, high phosphorus (hyperphosphatemia) also occurs due to decreased GFR (glomerular filtration rate), i.e. filtration of blood through the kidneys.
- High potassium (hyperkalemia) with low sodium (hyponatremia). Therefore, the sodium to potassium ratio will be decreased (below 27:1). As explained at the beginning of this article, aldosterone typically lowers the amount of potassium in the body while increasing sodium in the bloodstream. Without aldosterone’s action, these electrolytes become imbalanced, resulting in dangerous consequences: low blood pressure, slow heart rate, and cardiac arrhythmia.
- High calcium (hypercalcemia).
Urinalysis: Urine concentration (USG) is often dilute (a counter-intuitive finding due to the concurrent dehydration). This is due to medullary washout, in which the renal medulla (the inner region of each kidney) loses its normal salt balance and cannot prevent water from escaping the body as urine fluid. With Addison’s Disease, medullary washout occurs due to a prolonged state of low sodium levels secondary to the absence of aldosterone.- Electrocardiogram (ECG): As stated, high potassium levels (hyperkalemia) are toxic to the heart muscle, causing worsening dysfunction as potassium levels rise in the bloodstream. In addition to slowing your dog’s heart rate (bradycardia), cardiac arrhythmias (abnormalities in heart rhythm) can also develop. These arrhythmias can be analyzed via an ECG (or EKG). The typical ECG configuration associated with hyperkalemia is a wide QRS complex with tall T waves. Higher potassium concentrations can also cause A-V block, ventricular fibrillation (v-fib), or ventricular asystole. Death can occur in some cases.
- Blood pressure measurement: As mentioned prior, hypotension (low blood pressure) due to dehydration (i.e. low fluid volume in the circulatory system) can arise with Addison’s Disease.
Thoracic radiographs (chest X-rays): Your vet may recommend chest films to rule out congestive heart failure (CHF), which may mimic some of the cardiovascular abnormalities also seen with Addison’s Disease and hyperkalemia. With hypoadrenocorticism, the heart may appear small due to dehydration (i.e. low blood volume coursing through the heart). Temporary megaesophagus (dilation and nerve dysfunction of the esophagus) can also rarely occur with Addison’s Disease, yet this condition tends to resolve by treating the Addison’s.- Abdominal ultrasound (sonogram): Your vet may suggest an abdominal ultrasound to view your dog’s adrenal glands as well as rule out other look-alikes of Addison’s Disease, including GI disease and kidney failure. With Addison’s Disease, the left adrenal gland tends to be smaller than normal.
- Fecal exam: A heavy whipworm infestation can mimic some of the electrolyte abnormalities similar to Addison’s Disease, so ruling out a whipworm problem may be necessary to differentiate from Addison’s Disease.
Learn how to interpret your pet’s bloodwork or urinalysis results with The Meowing Vet’s other articles:
Treatment
Though Addison’s Disease cannot be cured, this endocrine disorder tends to be well managed with simple lifelong medications to supplement the body with glucocorticoids and mineralocorticoids. This can be achieved with either oral prednisone or prednisolone to replenish glucocorticoids (i.e. what cortisol would normally do in the body) as well as either oral fludrocortisone or injectable DOCP (desoxycorticosterone pivalate) for mineralocorticoid replacement (mimicking the effects of aldosterone). After a period of adjustment, half of dogs taking both pred and fludrocortisone can stop the fludrocortisone and continue taking pred only. (Why? Because in addition to being a potent corticosteroid, prednisone/prednisolone has some weak mineralocorticoid action as well.) However, most dogs receiving monthly DOCP injections by their vet typically require continued administration of both DOCP and pred. While treatment for Addison’s Disease is typically cost-effective, medications can become somewhat expensive for some large breed dogs since they require larger doses compared to small dogs.
Dogs experiencing an Addisonian crisis (remember: a medical EMERGENCY!) require hospitalization for several days with intensive treatment to correct hydration status, electrolyte balance, hypoglycemia, and cardiovascular stability. In an effort to save these dogs’ lives, they must be stabilized even before concrete diagnostic tests can be performed. Such dogs will receive shock doses of 0.9% NaCl (sodium chloride) IV fluids to correct dehydration and sodium/potassium imbalance. Glucocorticoids will also be supplemented via either injectable dexamethasone-sodium chloride (Dex-SP), hydrocortisone sodium succinate (which also has mineralocorticoid action), or prednisolone sodium succinate. Fludricortisone, DOCP, or hydrocortisone sodium succinate will be used to replenish mineralocorticoids. Hyperkalemia will also be corrected; the IV fluid therapy tends to do the trick, but if potassium levels remain high, other medications may be administered to lower it to a safe concentration. Fluid therapy and potassium regulation should also correct most cardiac abnormalities. If the patient is also suffering from severely low blood sugar (hypoglycemia), IV dextrose (a type of sugar) may be administered in some cases. To avoid the onset of vomiting, your dog’s food and water bowls will be withheld for a day or so until bloodwork abnormalities resolve. Strict monitoring will be performed by your veterinary team until your dog improves, and diagnostic tests shall be performed to ensure that hypoadrenocorticism is indeed the culprit. Once stable, the patient will be sent home with oral prednisone or prednisolone and either oral fludricortisone or orders to receive monthly DOCP injections.
Prognosis
Primary hypoadrenocorticism carries an overall excellent prognosis with appropriate medical therapy, and most patients go on to live out a normal lifespan. Keep in mind, however, that some dogs may enter a crisis if a medication dose is skipped or if an additional stressor arises (illness, fright, change in routine, etc.). With prompt detection and treatment, patients undergoing an Addisonian crisis emergency tend to do well. However, failure to seek veterinary care in such scenarios can be fatal.
Conversely, the prognosis for secondary and tertiary hypoadrenocorticism are much worse, yet fortunately, these conditions are very rare. Iatrogenic hypoadrenocorticism resolves with time so long as side effects are managed; a gradual taper off chronic steroid medications can help prevent this problem from arising in the first place.
– Maranda Elswick, DVM
Looking for the condensed “CliffsNotes™” version of highlights for Addison’s Disease?
Check out The Meowing Vet’s Instagram post from June 14, 2017. Follow The Meowing Vet on Instagram @themeowingvet for behind-the-scenes photos and regular veterinary and pet-themed content.
If your dog is displaying signs consistent with hypoadrenocorticism, or if you suspect that your pet is experiencing an Addisonian Crisis, The Meowing Vet recommends that you seek immediate veterinary assistance!
