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October 14, 2020 – Hypoadrenocorticism is an uncommon but serious and sometimes life-threatening disease of 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.

Hypoadrenocorticism is a disease of low hormone output from the adrenal glands and can take different forms based on the hormones involved.

Who’s at risk?

Unlike many diseases that tend to strike as dogs age, hypoadrenocorticism is a disease of young to middle-aged dogs although, occasionally, it isn’t diagnosed until a dog is older. Any sex or breed of dog can be affected but some breeds have a higher risk of the disease. These include:

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

Genetic analysis of some of these at-risk breeds has revealed the heritability of the disease. It’s important for prospective pet parents of at-risk breeds to ask their breeder if there is a history of hypoadrenocorticism  in their dog’s family.

Signs of hypoadrenocorticism

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

The most common signs noted include:

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

Unfortunately, physical examination rarely points to hypoadrenocorticism and testing is necessary to establish a diagnosis.

Anatomy and physiology of hypoadrenocorticism

A review of 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 key 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 important substances that influence almost all body functions.

Adrenal glands are shaped like triangles and are divided into two main regions: the outer cortex and the inner medulla. The cortex is further divided 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) – important for metabolism, suppressing inflammation and increasing blood sugar
    • Mineralocorticoids (e.g. aldosterone) – important in sodium, potassium and blood pressure regulation
    • DHEA and androgenic steroids – precursors to testosterone and estrogen
  • Medulla
    • Epinephrine (adrenaline) and norepinephrine (noradrenaline) – important in fight or flight, they increase heart rate, increase blood flow to muscles and brain, relax muscle in airways and help increase blood sugar

Hypoadrenocorticism occurs when there is an underproduction of glucocorticoids and mineralocorticoids. To fully understand hypoadrenocorticism, it’s also important to understand how adrenal hormone secretion is regulated. We’ll 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 important role in cortisol control: the hypothalamus and the pituitary gland. The hypothalamus releases a substance called corticotropin-releasing hormone (CRH) which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream, which in turn travels to the adrenal gland, stimulating cortisol release. It’s a tag-team effort.

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

When everything is working correctly, cortisol levels in the blood 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 an important 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 the retention of sodium which in turn leads to absorption of water. 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.

  • Primary hypoadrenocorticism - 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.

  • Primary hypoadrenocorticism – 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 fairly normal 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 cases of the disease in dogs.

  • Secondary hypoadrenocorticism - spontaneous

This rare form of hypoadrenocorticism occurs when there is a loss of ACTH secretion from the pituitary. These patients are deficient in glucocorticoids so they clinically are similar to primary atypical patients. However, they will not progress and lose their mineralocorticoid production.

  • Secondary hypoadrenocorticism – iatrogenic (illness related to treatment)

This type occurs when dogs that have been on steroid therapy for a long time are suddenly taken off their medication. 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 avoiding this scenario is the reason that dogs receiving steroid therapy (and people) are gradually weaned off medication.

How is hypoadrenocorticism diagnosed?

Although the clinical signs of hypoadrenocorticism are shared by many other diseases, there are often changes on routine bloodwork that can point toward hypoadrenocorticism, and a few other diagnostic tests can confirm the diagnosis.

  • Routine bloodwork – hypoadrenocorticism causes lots of changes that can be picked up on routine bloodwork. These include:
    • Low blood sodium levels coupled with high potassium levels – classic!
    • 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 – this test often is used 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. A tiny amount of ACTH is given and 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, it is used to differentiate between primary atypical hypoadrenocorticism and secondary spontaneous hypoadrenocorticism. Chronically low blood cortisol levels would stimulate the pituitary gland to release ACTH so blood levels would be high in cases of primary atypical hypoadrenocorticism. In secondary spontaneous hypoadrenocorticism, levels would be low.

Your veterinarian will work with you to decide which tests (and in which order) are best for your dog.

How to treat hypoadrenocorticism

The treatment of hypoadrenocorticism is focused on carefully controlled replacement of glucocorticoids and mineralocorticoids with medication.

Several different drugs can be used to treat hypoadrenocorticism and it can take time to determine which drug or drug combinations are best. During times of stress, some patients will need alterations in their medication.

Regardless of which medication is used, it’s important for owners to know that therapy is life-long. 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 with proper veterinary care and medication, long-term prognosis is excellent with the majority of dogs living a normal lifespan.