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Updated January 18, 2024 – Hypoadrenocorticism is an uncommon yet severe and sometimes life-threatening disease in dogs. It is a chameleon of a disease, mimicking the signs of other more common canine health problems, which makes it a diagnostic challenge for veterinarians.   

Who’s at Risk?  
Hypoadrenocorticism is a disease of low hormone output from the adrenal glands and can take different forms based on the hormones involved.  

Unlike many diseases manifest in older dogs, hypoadrenocorticism primarily affects young to middle-aged dogs, though older dogs are occasionally diagnosed with the ailment. While it can affect any sex or breed, certain breeds have a higher predisposition. These breeds include:   

  • Nova Scotia duck tolling retrievers 
  • Great Danes  
  • Portuguese water dogs  
  • West Highland white terriers  
  • Bearded collies  
  • Poodles  
  • Rottweilers  
  • Soft-coated wheaten terriers  
  • Leonbergers  

Genetic analysis has revealed the heritability of the disease in some of these at-risk breeds. Prospective pet parents of these breeds should inquire about the history of hypoadrenocorticism in their dog's family.  

Signs of Hypoadrenocorticism  
Signs of the disease can wax and wane for a long time. If left untreated, however, hypoadrenocorticism can be life-threatening.  

Common Signs Include:  

  • Weakness  
  • Anorexia  
  • Vomiting  
  • Diarrhea (sometimes with blood)  
  • Increased water consumption and urination  
  • Trembling  
  • Collapse   

Unfortunately, physical examination findings rarely point to hypoadrenocorticism, making testing necessary for a conclusive diagnosis.  

Anatomy and Physiology of Hypoadrenocorticism  
Understanding the basic anatomy and physiology of the organs involved in the disease helps explain why some dogs show certain clinical signs and others do not, as well as the reasoning behind different ways to diagnose and treat hypoadrenocorticism.    

The critical organ at the center of hypoadrenocorticism is the adrenal gland. There are two adrenal glands, one sitting next to each kidney. Although small, the adrenal glands produce many essential substances influencing almost all body functions. The adrenal glands, divided into two central regions — the outer cortex and the inner medulla — have a triangular shape. 

It further divides the cortex into three zones, each producing specific hormones, many of which people will recognize. 

The specific hormones produced in each region include:  

  • Cortex   
  • Glucocorticoids (e.g., cortisol): essential for metabolism, suppressing inflammation and increasing blood sugar   
  • Mineralocorticoids (e.g., aldosterone): essential in sodium, potassium and blood pressure regulation  
  • DHEA and androgenic steroids: precursors to testosterone and estrogen  
  • Medulla   
  • Epinephrine (adrenaline) and norepinephrine (noradrenaline): critical in fight, flight, or freeze. They increase heart rate, increase blood flow to muscles and the brain, relax muscles in the airways and help increase blood sugar. 

Hypoadrenocorticism occurs when there is an underproduction of glucocorticoids and mineralocorticoids. To fully understand hypoadrenocorticism, it’s essential to understand how adrenal hormone secretion is regulated. Let’s start with the regulation of cortisol, the most important of the glucocorticoids, and then move on to the regulation of aldosterone.  

Regulation of Cortisol Secretion  
Two structures in the brain also play an essential role in cortisol control: the hypothalamus and the pituitary gland. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream. This hormone, in turn, travels to the adrenal gland, promoting cortisol release. It’s a tag-team effort.  

The hypothalamus releases CRH in response to many stimuli, including low blood cortisol levels, stress, illness, physical activity and waking from sleep. The pituitary gland also detects changes in blood cortisol levels and can decrease ACTH release in response to either decreased CRH or increased cortisol in the bloodstream.  

When everything works correctly, cortisol levels go up and down, and the hypothalamus and the pituitary gland respond accordingly to maintain appropriate blood levels.   

Low cortisol levels can lead to low blood sugar, gastrointestinal upsets, weakness and contribute to low blood pressure.    

The second important hormone released by the adrenal gland is aldosterone.   

Regulation of Aldosterone Secretion    
Aldosterone plays a vital role in regulating sodium and potassium balance in the body. The triggers that result in aldosterone secretion are different than those for cortisol. Low blood pressure secondary to decreased blood volume and high blood potassium levels are the primary stimuli of aldosterone release.   

Aldosterone increases sodium retention, which in turn leads to water absorption. It also promotes potassium excretion. Low aldosterone levels can lead to low blood pressure, decreased blood pH, heart arrhythmias and dehydration.  

Different Forms of Hypoadrenocorticism  
Hypoadrenocorticism comes in several forms that relate to which adrenal hormones are deficient.  

  • People sometimes refer to primary hypoadrenocorticism as "typical." This is the most common form of hypoadrenocorticism and occurs due to bilateral adrenal gland destruction, resulting in the loss of both glucocorticoids and mineralocorticoids.   
  • People sometimes refer to primary hypoadrenocorticism as “atypical.” Atypical hypoadrenocorticism occurs when only glucocorticoids are deficient, but there is no deficiency of mineralocorticoids. These patients exhibit signs consistent with just glucocorticoid deficiency and often have relatively regular bloodwork, making this disease a real challenge to diagnose. Some of these patients will go on to develop mineralocorticoid deficiency, too. Primary hypoadrenocorticism accounts for more than 95% of disease cases in dogs.  
  • Secondary hypoadrenocorticism is spontaneous. Loss of ACTH secretion from the pituitary causes this rare form of hypoadrenocorticism. These patients are deficient in glucocorticoids, so their signs are similar to primary atypical patients. However, they will not progress and lose their mineralocorticoid production.  
  • Secondary hypoadrenocorticism is iatrogenic (illness related to treatment). When abruptly discontinuing medication, this type arises in dogs that have been on long-term steroid therapy. 
  • Long-term glucocorticoid therapy causes the adrenal glands to shrink, so these patients need time for adrenal function to return to normal. Dogs suddenly taken off their medication can develop signs of hypoadrenocorticism and can become very ill. Many people might recognize that the reason for gradually weaning off medication in dogs receiving steroid therapy (and people) is to avoid this scenario. 

 
Diagnosing Hypoadrenocorticism   
Diagnosing hypoadrenocorticism involves routine bloodwork and specific diagnostic tests, including:  

  • Routine bloodwork: Routine bloodwork can pick up many changes caused by hypoadrenocorticism. 
  • These include:   
  • Low blood sodium levels coupled with high potassium levels.  
  • Mild anemia  
  • Lack of an increased white blood cell count (a stress leukogram) in a very ill dog  
  • Increased kidney values due to dehydration  
  • Increased blood calcium  
  • Low blood glucose  
  • Dilute urine in a dehydrated dog  
  • Low blood albumin  
  • Baseline cortisol measurement: Doctors often use this as a screening test for the disease. If low, additional testing is required to confirm the diagnosis.  
  • ACTH stimulation test. This test is the definitive diagnostic test for hypoadrenocorticism. Doctors administer a small amount of ACTH; if the adrenal gland is normal, it will release cortisol into the blood. Dogs with hypoadrenocorticism will show no increase in blood cortisol levels after stimulation.   
  • Endogenous ACTH (eACTH) measurement: This test is rarely used but can help differentiate between primary and secondary hypoadrenocorticism in rare cases where sodium and potassium levels are normal. In other words, this test determines between primary atypical hypoadrenocorticism and secondary spontaneous hypoadrenocorticism. Chronically low blood cortisol levels would stimulate the pituitary gland to release ACTH so that blood levels would be high in cases of primary atypical hypoadrenocorticism. In secondary spontaneous hypoadrenocorticism, levels would be low.  

Your veterinarian will recommend tests based on your dog's symptoms and health status.  

Treatment of Hypoadrenocorticism  
The treatment focuses on carefully controlled replacement of glucocorticoids and mineralocorticoids with medication. During stress, veterinarians may use various drugs and may need to make adjustments. Owners should know that therapy is lifelong, and proper care ensures an excellent long-term prognosis. It’s often tempting for owners to decrease or stop medications once their dogs have recovered (and seem back to normal), but this can lead to a life-threatening crisis. The good news is that the long-term prognosis is excellent with proper veterinary care and medication, with most dogs living an average lifespan.  
 
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