Diagnosing Addison’s Disease in Dogs: A Comprehensive Guide

Primary hypoadrenocorticism, commonly known as Addison’s disease, is a condition that arises from the dysfunction of both adrenal cortices. These adrenal glands, situated in the abdomen near the kidneys, consist of an outer cortex and an inner medulla. The adrenal cortex itself is composed of three distinct layers, each responsible for producing different hormones vital for bodily functions. These layers, from outermost to innermost, are the zona glomerulosa, zona fasciculata, and zona reticularis, producing aldosterone, cortisol, and adrenal androgens, respectively.

Addison’s disease is predominantly diagnosed in dogs, with rare occurrences in cats. It is recognized as a heritable condition, with certain breeds exhibiting a higher predisposition. These breeds include standard poodles, Portuguese water dogs, Nova Scotia duck tolling retrievers, and bearded collies. Other breeds commonly affected are West Highland white terriers, Great Pyrenees, and wheaten terriers. While the exact cause is often undetermined, immune-mediated adrenalitis is suspected to be the most frequent underlying factor. In cases where a definitive cause isn’t identified, the condition is termed idiopathic hypoadrenocorticism. However, it’s important to note that Addison’s can also develop secondary to other conditions that cause bilateral adrenal gland damage, such as amyloidosis, hemorrhage, or neoplasia. A less common cause reported is intravascular lymphoma, as seen in a young German shepherd.

In most instances of Addison’s disease, there’s a deficiency in both glucocorticoids, primarily cortisol, and mineralocorticoids, mainly aldosterone. However, variations exist, such as atypical Addison’s disease, which involves only a glucocorticoid deficiency. Severely affected dogs might experience an Addisonian crisis, a life-threatening state. Beyond the typical gastrointestinal symptoms, dogs in crisis can present with hypovolemic shock and collapse. This article will delve into the diagnostic process and management strategies for the various presentations of hypoadrenocorticism.

Recognizing the Signs: Clinical Presentation of Addison’s Disease

The clinical signs associated with hypoadrenocorticism can vary significantly in severity and how long they have been present. Glucocorticoids play a crucial role in managing stress and maintaining the gastrointestinal tract’s health. Consequently, dogs with glucocorticoid deficiency often initially show vague, intermittent signs. These can include episodic vomiting, diarrhea, melena (dark, tarry stools indicative of digested blood) (FIGURE 1), lethargy, and dehydration. Because these signs can be nonspecific and may temporarily improve with basic supportive care, the underlying Addison’s disease can be easily missed in the early stages.

BOX 1: Classic and Potential Signs of Hypoadrenocorticism

• Decreased appetite
• Vomiting, hematemesis (vomiting blood)
• Diarrhea, melena
• Lethargy or decreased willingness to exercise

Figure 1. Recognizing melena is crucial in diagnosing Addison’s disease in dogs. Although it may not be immediately apparent due to ileus, melena often becomes evident a few days after hospitalization, particularly when packed cell volume drops unexpectedly.

When mineralocorticoid deficiency accompanies glucocorticoid deficiency, the clinical picture can become more acute and severe. Aldosterone is essential for regulating electrolyte balance in the kidneys, promoting sodium and water retention while facilitating potassium excretion. A lack of aldosterone leads to electrolyte imbalances, specifically hypochloremia (low chloride), hyponatremia (low sodium), hyperkalemia (high potassium), hypovolemia (decreased blood volume), and metabolic acidosis.

In atypical Addison’s disease, where only cortisol is deficient, the clinical signs are solely related to hypocortisolism.

It’s important to note that some dogs presenting in Addisonian crisis may have a history of treatment for nonspecific signs, while others may have shown no prior clinical signs before the crisis. This variability underscores the importance of considering Addison’s disease even in seemingly healthy dogs presenting with acute symptoms.

Diagnostic Procedures for Addison’s Disease in Dogs

When Addison’s disease is suspected, several diagnostic steps are crucial to confirm the diagnosis and differentiate it from other conditions.

Initial Screening: Resting Cortisol Levels

A valuable initial screening test is measuring resting cortisol levels. This test is highly sensitive for ruling out Addison’s disease. If a dog’s resting cortisol level is above 2.0 mcg/dL, Addison’s disease is highly unlikely. However, a low resting cortisol level alone is not definitive for Addison’s, as it can be normal in some dogs. Therefore, further testing is necessary to confirm the diagnosis.

Bloodwork Analysis: Serum Chemistry and Complete Blood Count (CBC)

Classic bloodwork abnormalities are strong indicators of Addison’s disease, particularly hyperkalemia, hyponatremia, and the absence of a stress leukogram on a complete blood count.

Serum Chemistry:

In dogs with a suggestive history and clinical signs, a sodium to potassium ratio (Na:K ratio) of less than 27 is a significant indicator and should prompt further definitive testing. It’s important to remember that a low Na:K ratio isn’t exclusive to Addison’s disease and can be seen in other conditions (BOX 2).

BOX 2: Differential Diagnoses for Low Sodium:Potassium Ratio in Dogs

Digestive System Disorders:

• Acute kidney injury (especially with anuria or oliguria)
• Whipworm infection (Trichuriasis)
• Cavitary effusions (e.g., chylothorax, pleural effusion, ascites)
• Pregnancy and periparturient illnesses
• Side effect of Angiotensin-converting enzyme (ACE) inhibitor medications

Additional abnormalities that may be seen on serum biochemistry include azotemia (increased waste products in blood), hypoalbuminemia (low albumin), hypocholesterolemia (low cholesterol), hypoglycemia (low blood sugar), hypercalcemia (high calcium), and elevated liver enzymes (BOX 3). Not all dogs will exhibit all these abnormalities, and some may present with only a few, but severely deranged, values like hypoglycemia or azotemia. The vague symptoms often associated with Addison’s disease can mimic gastrointestinal or kidney disorders, making it essential to consider Addison’s as a differential diagnosis in dogs presenting with similar laboratory findings to acute kidney injury (e.g., azotemia, electrolyte imbalances, and isosthenuria – urine with a specific gravity similar to plasma).

In atypical Addison’s disease, electrolyte imbalances are typically absent. Diagnosis in these cases relies more heavily on recognizing signs of hypocortisolism such as vomiting, diarrhea, lethargy, and melena, which should raise suspicion and prompt further endocrine testing. Some studies suggest that aldosterone levels might still be low in atypical Addison’s, although the reason for the lack of electrolyte abnormalities remains unclear.

BOX 3: Common Clinicopathologic Abnormalities in Dogs with Hypoadrenocorticism

• Hyperkalemia (High Potassium)
• Hyponatremia (Low Sodium)
• Hypochloremia (Low Chloride)
• Metabolic Acidosis
• Azotemia (Increased waste products in blood)
• Hypoglycemia (Low Blood Sugar)
• Elevated Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels (Liver enzymes)
• Hypercalcemia (High Calcium)
• Hypoalbuminemia (Low Albumin)
• Hypocholesterolemia (Low Cholesterol)
• Anemia
• Eosinophilia (Increased eosinophils – a type of white blood cell)
• Lack of Stress Leukogram

Complete Blood Count (CBC):

Alongside serum chemistry, the CBC can provide additional clues. A normal lymphocyte count in a sick dog should increase suspicion for Addison’s disease. Typically, a dog ill from another cause would exhibit lymphopenia (decreased lymphocytes) due to cortisol release (a stress leukogram). Studies have shown that dogs with Addison’s disease tend to have lymphocyte counts greater than 750/mcL. Therefore, in dogs with lymphocyte counts below 750/mcL (and no prior glucocorticoid administration), Addison’s disease is less likely.

Anemia, ranging from mild to severe, can also be present in dogs with Addison’s disease. Severe anemia may be associated with melena and/or hematochezia (fresh blood in stool), resulting from gastrointestinal bleeding due to increased vascular permeability in the absence of cortisol. In Addisonian crisis, the packed cell volume (PCV) might initially be normal or mildly decreased but can drop significantly 1-2 days post-rehydration and ongoing blood loss. Ileus, common in Addisonian dogs, can delay the appearance of melena for 2-3 days.

Imaging Techniques

While not typically required for diagnosing Addison’s disease, diagnostic imaging, including thoracic and abdominal radiographs and ultrasonography, is often part of the workup due to the nonspecific nature of Addison’s signs.

Ultrasonography: Studies have shown that the adrenal glands in dogs with Addison’s disease may appear smaller and thinner compared to healthy dogs.

Radiography: Radiographs may reveal signs of hypovolemia, such as a small heart and liver, and reduced diameter of the cranial lobar pulmonary artery and caudal vena cava.

Definitive Diagnosis: ACTH Stimulation Test

The adrenocorticotropic hormone (ACTH) stimulation test (BOX 4) is the gold standard for confirming Addison’s disease. This test evaluates the adrenal glands’ ability to produce cortisol in response to stimulation by synthetic ACTH.

BOX 4: Procedure for Performing ACTH Stimulation Test

1. Collect a pre-stimulation blood sample into a red top tube to measure baseline cortisol.
2. Administer synthetic ACTH (cosyntropin) intravenously at a dose of 5 mcg/kg (up to a maximum of 250 mcg/dog). Avoid compounded formulations as their efficacy can be variable.
3. After 60 minutes, collect a second blood sample into a red top tube for post-stimulation cortisol measurement.
4. Submit both serum samples to a laboratory for cortisol analysis.

The diagnosis of Addison’s disease is confirmed when the post-ACTH cortisol level is less than or equal to 2 mcg/dL. Recent research has investigated dogs suspected of Addison’s disease but with slightly higher post-ACTH cortisol levels (up to 10 mcg/dL). In these cases, Addison’s disease was ruled out based on the diagnosis of an alternative condition (like inflammatory bowel disease), lack of response to glucocorticoid treatment, or the absence of recurring Addison’s signs after discontinuing glucocorticoids. In rare instances, dogs with confirmed Addison’s disease may have post-ACTH stimulation cortisol levels slightly above the cut-off, between 2 to 3 mcg/dL. Clinical judgment and consideration of the entire clinical picture are important in these borderline cases.

Treatment Strategies for Canine Addison’s Disease

Treatment approaches for Addison’s disease vary depending on the clinical presentation, ranging from managing chronic, stable cases to addressing life-threatening Addisonian crises.

Managing Chronic Addison’s Disease

For stable patients with chronic Addison’s disease, long-term management involves hormone replacement therapy with both mineralocorticoids and glucocorticoids.

Mineralocorticoid Replacement:

Two forms of mineralocorticoid supplementation are available: oral fludrocortisone and injectable desoxycorticosterone pivalate (DOCP).

• Fludrocortisone: Fludrocortisone acetate is administered orally, typically at a dose of 0.01 mg/kg every 12 hours. It has both mineralocorticoid and glucocorticoid activity. While this dual action might seem advantageous, it can complicate dosage adjustments. For example, increasing the fludrocortisone dose to manage electrolyte imbalances might lead to excessive glucocorticoid effects and potential side effects of hypercortisolemia.

• Desoxycorticosterone Pivalate (DOCP): DOCP, such as Percorten-V or Zycortal, is administered as a monthly injection. Because DOCP has only mineralocorticoid activity, it necessitates concurrent glucocorticoid supplementation (e.g., prednisone). Many veterinarians prefer DOCP due to its effectiveness and the ability to independently adjust glucocorticoid dosage. DOCP is also shown to be more effective in normalizing renin activity compared to fludrocortisone, suggesting it may be a more physiologically appropriate mineralocorticoid replacement. The standard starting dose is 2.2 mg/kg every 25 days, although some clinicians may start at a lower dose of 1.5 mg/kg. Zycortal is approved for subcutaneous administration, while Percorten-V is labeled for intramuscular use but can also be administered subcutaneously off-label.

  Electrolyte levels should be monitored 14 days and 25 days post-DOCP injection to adjust the dosage and interval. At 14 days, if hyponatremia or hyperkalemia is present, the subsequent dose should be increased by 10-15%. If hypernatremia or hypokalemia is noted, the dose should be decreased by 10-15%. At 25 days, electrolyte imbalances suggest shortening the dosing interval by 1-2 days. Stable electrolyte levels at 25 days may allow for extending the interval to 28 days, with electrolyte re-evaluation at this new interval. While some studies have explored extending the interval up to 90 days, this requires very frequent electrolyte monitoring, particularly initially. It’s generally preferred to adjust the DOCP dose rather than extend the dosing interval significantly beyond 28-30 days, and adjusting both simultaneously is not recommended. Once a stable dose and interval are established, many owners can be trained to administer DOCP injections at home.

Glucocorticoid Replacement:

Dogs receiving DOCP always require glucocorticoid supplementation. While some dogs on fludrocortisone might not need additional prednisone long-term, initial concurrent glucocorticoid administration followed by tapering after stabilization is often beneficial for quicker stabilization.

Oral prednisone is commonly used for glucocorticoid replacement, starting at 0.5 to 1.0 mg/kg daily. This dose is gradually reduced over several weeks to the lowest effective dose that controls Addison’s signs without causing side effects like increased thirst, urination, appetite, or panting. Smaller maintenance doses, sometimes as low as 0.03 mg/kg/day, may be sufficient in some dogs. Dosage adjustments should be based on clinical signs, not repeat ACTH stimulation tests in dogs with confirmed natural Addison’s disease.

Managing Atypical Addison’s Disease

Dogs with atypical Addison’s disease, exhibiting only glucocorticoid deficiency, require only glucocorticoid supplementation, managed as described above. However, it’s crucial to monitor these dogs for the potential development of mineralocorticoid deficiency. Electrolyte levels should be rechecked 2 weeks after diagnosis, then monthly for 3 months, and then every 3 months for the first year.

Addressing Addisonian Crisis

Addisonian crisis is a life-threatening emergency requiring immediate and intensive treatment (BOX 5).

BOX 5: Treatment of Addisonian Crisis

Immediate Actions:

• Correct Hypovolemia and Hypotension: Administer balanced crystalloid intravenous fluids (e.g., Plasmalyte 148, lactated Ringer’s, or Normosol-R) in boluses of 20-30 mL/kg over 15-20 minutes, reassessing vital signs (heart rate, pulse quality, blood pressure) after each bolus. Continue until vital signs normalize. Monitor lactate levels as an objective measure of resuscitation. Avoid rapid sodium correction if hyponatremia is severe and chronic to prevent myelinolysis; sodium concentration should not be increased by more than 12 mEq/L in 24 hours.

• Correct Acidosis: Intravenous fluid therapy with balanced crystalloids is usually sufficient to correct metabolic acidosis.

• Manage Hyperkalemia:

  • Fluid therapy alone is often adequate for mild to moderate hyperkalemia.
  • Severe Hyperkalemia (>8.5-9.0 mEq/L) or ECG Derangements (bradycardia, spiked T waves, flattened P waves, widened QRS complexes):
    • Calcium Gluconate (10% solution): 0.5-1.5 mL/kg IV over 10-15 minutes. Monitor ECG for worsening bradycardia as a side effect. Calcium gluconate stabilizes the heart but does not directly lower potassium.
    • Dextrose: 1 mL/kg 50% dextrose diluted 1:3 with balanced crystalloids.
    • Regular Insulin: 0.2 U/kg IV, followed by a bolus of 1-2 g dextrose per unit of insulin, then dextrose added to IV fluids to maintain a 2.5-5.0% dextrose solution. Insulin is crucial for life-threatening arrhythmias. Dextrose alone can help lower potassium by stimulating endogenous insulin release but is slower.
    • Beta-2 Agonists: (e.g., inhaled albuterol or IV terbutaline at 0.01 mg/kg).

• Treat Hypoglycemia: 1 mL/kg 50% dextrose diluted 1:2 with balanced crystalloid if blood glucose is low. Avoid insulin for hyperkalemia treatment until normoglycemia is confirmed to prevent worsening hypoglycemia.

• Address Severe Anemia: Packed red blood cell transfusion if severe anemia from gastrointestinal blood loss is present.

• Glucocorticoid Replacement:

  • Dexamethasone: 0.2 mg/kg IV initially, then 0.1 mg/kg every 12 hours until oral prednisone is tolerated. Dexamethasone does not interfere with ACTH stimulation test results.
  • Hydrocortisone Sodium Succinate: 0.5-0.625 mg/kg/hour IV infusion. Hydrocortisone will interfere with ACTH stimulation test results, so use dexamethasone if ACTH stimulation testing is pending.

• Supportive Care:

  • Warming measures for hypothermia.
  • Antiemetics for vomiting.
  • Gastroprotectants to protect the gastrointestinal tract.
  • Pain management as needed.
  • Nutritional support; patients usually start eating within 24 hours of treatment.

Figure 2. Intravenous fluid administration is critical in managing an Addisonian crisis. Continuous ECG and blood pressure monitoring are essential to detect hyperkalemia and assess the patient’s response to therapy.

After initial fluid resuscitation, intravenous dexamethasone can be administered. Dexamethasone is preferred initially as it doesn’t interfere with subsequent ACTH stimulation testing, unlike prednisone, prednisolone, and methylprednisolone. The patient should remain hospitalized for continued IV fluids until electrolyte imbalances are corrected and clinical signs are controlled with oral medications. Oral prednisone is typically started in the acute recovery phase at 0.5-1.0 mg/kg/day and gradually tapered down for long-term home care. Mineralocorticoid supplementation with DOCP or fludrocortisone is generally initiated after Addison’s disease diagnosis is confirmed. Future dosing of both mineralocorticoids and glucocorticoids will be guided by electrolyte levels and clinical signs.

Prognosis for Dogs with Addison’s Disease

With accurate diagnosis and appropriate management, the prognosis for dogs with Addison’s disease is generally excellent (FIGURE 3). Most dogs can live long, healthy lives and succumb to causes unrelated to Addison’s disease. A study of 205 dogs with Addison’s disease reported a median survival time of 4.7 years, with no significant impact from age, breed, sex, or weight at diagnosis. However, successful long-term management requires diligent owners who are observant of subtle signs of illness, committed to daily medication, and compliant with regular veterinary recheck appointments for the dog’s lifetime. With consistent care and veterinary follow-up, dogs with Addison’s disease can enjoy a high quality of life.

Figure 3. Long-term management allows dogs with Addison’s disease to thrive. This golden retriever, diagnosed at 2 years old after presenting with lethargy and gastrointestinal upset, is thriving 8 years post-diagnosis on DOCP and prednisone.