Addison’s disease, or primary hypoadrenocorticism, is a condition that arises from the insufficient functioning of the adrenal cortices in dogs. These adrenal glands, situated in the abdomen near the kidneys, are vital endocrine organs composed of an outer cortex and an inner medulla. The adrenal cortex itself is further divided into three distinct layers, each responsible for producing different hormones crucial for bodily functions. From the outermost layer inwards, these are the zona glomerulosa, zona fasciculata, and zona reticularis, which produce aldosterone, cortisol, and adrenal androgens, respectively.
While Addison’s disease predominantly affects dogs, it is rarely seen in cats. This condition has a hereditary component and is notably more common in certain dog breeds, including Standard Poodles, Portuguese Water Dogs, Nova Scotia Duck Tolling Retrievers, and Bearded Collies. Breeds such as West Highland White Terriers, Great Pyrenees, and Wheaten Terriers are also frequently affected. The most widely accepted cause is immune-mediated adrenalitis, where the body’s immune system mistakenly attacks the adrenal glands. However, in many cases, a definitive cause isn’t identified, and it’s classified as idiopathic Addison’s disease. Secondary Addison’s can also occur due to other conditions that destroy the adrenal glands, such as amyloidosis, hemorrhage, or neoplasia. Intravascular lymphoma has also been documented as a secondary cause in younger dogs.
In most instances, Addison’s disease involves a deficiency in both glucocorticoids (mainly cortisol) and mineralocorticoids (primarily aldosterone). However, variations exist, such as atypical Addison’s disease, which presents with isolated glucocorticoid deficiency. Severely affected dogs may experience an Addisonian crisis, a life-threatening state. Beyond common gastrointestinal signs, dogs in crisis can exhibit hypovolemic shock and collapse. This article will delve into the diagnosis and management of various manifestations of hypoadrenocorticism in dogs.
Clinical Presentation of Addison’s Disease in Dogs
The clinical signs of hypoadrenocorticism in dogs can vary widely in severity and how long they have been present. Glucocorticoids like cortisol are essential for managing stress and maintaining the health and function of the gastrointestinal lining. Consequently, a deficiency often leads to initial, vague symptoms that come and go, such as intermittent vomiting, diarrhea, melena (dark, tarry stools indicative of digested blood), lethargy, and dehydration. These symptoms can be misleading because dogs may temporarily improve with basic supportive care, leading to delayed or missed diagnosis of Addison’s disease.
Classic and Potential Signs of Hypoadrenocorticism in Dogs:
- Reduced appetite or anorexia
- Vomiting, sometimes with blood (hematemesis)
- Diarrhea, melena (dark, tarry stools)
- Weakness, lethargy, or decreased stamina
Figure 1. Melena, characterized by dark, tarry stools, is a common finding in dogs with hypoadrenocorticism. It may not be immediately obvious due to ileus and can become apparent 2 to 3 days after hospitalization, particularly when packed cell volume drops unexpectedly without another clear cause.
When mineralocorticoid deficiency, specifically aldosterone, is also present alongside glucocorticoid deficiency, the clinical picture can become more critical. Aldosterone plays a crucial role in the kidneys by promoting sodium, chloride, and water retention while facilitating potassium excretion. A lack of aldosterone results in imbalances such as hypochloremia (low chloride), hypovolemia (decreased blood volume), metabolic acidosis, and hyperkalemia (elevated potassium).
In atypical Addison’s disease, where only cortisol is deficient, the clinical signs primarily stem from hypocortisolism.
It’s important to note that some dogs experiencing an Addisonian crisis may have a history of treatment for nonspecific symptoms, while others may not have shown any prior clinical signs, making diagnosis challenging without thorough investigation.
Diagnosing Addison’s Disease in Dogs
For any dog suspected of having hypoadrenocorticism, measuring resting cortisol levels is an excellent initial screening test. This test is highly sensitive for ruling out Addison’s disease; a resting cortisol level above 2.0 mcg/dL effectively excludes the diagnosis in almost all dogs. However, a low resting cortisol level alone is not definitive, as it can be normal in some dogs. Therefore, further testing is required to confirm Addison’s disease. Typical bloodwork abnormalities that raise suspicion for Addison’s include hyperkalemia, hyponatremia, and the absence of a stress leukogram, which is usually expected in sick animals.
Serum Chemistry Analysis for Addison’s Diagnosis
In dogs with a relevant history and clinical signs, a sodium-to-potassium ratio (Na:K ratio) of less than 27 should strongly suggest the need for definitive testing for Addison’s disease. It’s crucial to remember that low Na:K ratios aren’t exclusive to Addison’s and can be observed in other conditions such as renal failure, whipworm infection (trichuriasis), pregnancy, and body cavity effusions.
Differential Diagnoses for Low Sodium:Potassium Ratio in Dogs:
Digestive System & Renal:
- Acute kidney injury (anuria or oliguria)
- Trichuriasis (whipworm infection)
- Cavitary effusions (e.g., chylothorax)
- Pregnancy and periparturient illness
- Use of angiotensin-converting enzyme (ACE) inhibitors
Additional abnormalities that may appear on serum biochemistry panels include azotemia (elevated waste products in blood), hypoalbuminemia (low albumin), hypocholesterolemia (low cholesterol), hypoglycemia (low blood sugar), hypercalcemia (high calcium), and elevated liver enzyme levels. Most dogs with Addison’s do not exhibit all these abnormalities but might have a few that are particularly pronounced, such as hypoglycemia or azotemia. The vague symptoms of Addison’s often lead to investigations into other organ systems, particularly the gastrointestinal tract and kidneys. The laboratory findings in Addison’s can mimic those of acute kidney injury (like azotemia, electrolyte imbalances, and isosthenuria – urine that is not concentrated); thus, Addison’s should always be a primary differential diagnosis in dogs presenting with these findings.
In dogs with atypical Addison’s disease, electrolyte imbalances are typically absent. In these cases, diagnosis relies more on recognizing signs of hypocortisolism, such as vomiting, diarrhea, melena, and lethargy, which should prompt further investigation. Some studies indicate that aldosterone levels might be low in atypical Addison’s, although the reason for the lack of electrolyte abnormalities is not fully understood.
Common Clinicopathologic Abnormalities in Dogs with Hypoadrenocorticism:
- Hyperkalemia (high potassium)
- Hyponatremia (low sodium)
- Hypochloremia (low chloride)
- Acidosis (increased acidity in blood)
- Azotemia (elevated waste products in blood)
- Hypoglycemia (low blood sugar)
- Elevated alanine and aspartate aminotransferase (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 (normal or increased lymphocytes)
Complete Blood Count (CBC) in Diagnosing Addison’s
Alongside serum biochemistry, a complete blood count (CBC) can provide further clues. A normal lymphocyte count in a sick dog is unusual because illness from other causes typically triggers cortisol release, leading to lymphopenia (decreased lymphocytes) as part of a stress leukogram. In Addison’s disease, the absence of this stress response can be a diagnostic hint. Studies have shown that lymphocyte counts are generally higher than 750/mcL in dogs with Addison’s. Therefore, in a dog with a lymphocyte count below 750/mcL (and not previously treated with glucocorticoids), Addison’s is less likely.
In addition to not showing a stress leukogram, dogs with Addison’s can exhibit mild to severe anemia. Severe anemia may be accompanied by 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, a dog’s packed cell volume (PCV) might initially be normal or slightly low but can drop significantly 1 to 2 days later after rehydration and ongoing blood loss. Ileus, a common complication in Addison’s, can delay the appearance of melena for 2 to 3 days.
Diagnostic Imaging for Addison’s Disease
Diagnostic imaging is not typically essential for diagnosing Addison’s disease. However, due to the nonspecific nature of the symptoms, thoracic and abdominal imaging are frequently part of the diagnostic process to rule out other conditions. Some findings on ultrasound and radiographs can be supportive. Ultrasonography may reveal smaller and thinner adrenal glands in affected dogs compared to healthy dogs. Radiographs might suggest hypovolemia, indicated by a small heart and liver, and reduced diameter of major blood vessels like the cranial lobar pulmonary artery and caudal vena cava.
Definitive Diagnosis: ACTH Stimulation Test
The adrenocorticotropic hormone (ACTH) stimulation test is crucial for confirming a diagnosis of Addison’s disease. This test involves measuring serum cortisol levels both before and one hour after administering synthetic ACTH. Using a lower dose of synthetic cosyntropin (5 mcg/kg) compared to the older standard dose (250 mcg/dog) helps reduce testing costs. Reconstituted cosyntropin is stable when stored in plastic (not glass) syringes and frozen for up to 6 months, making it more cost-effective for veterinary practices. A definitive diagnosis of Addison’s disease is made when post-ACTH cortisol levels are 2 mcg/dL or less. Interestingly, some dogs suspected of Addison’s but with slightly higher post-ACTH cortisol levels (up to 10 mcg/dL) might still be ruled out for Addison’s if other conditions are diagnosed, they don’t respond to glucocorticoid treatment, or Addison’s signs don’t recur after stopping glucocorticoids. In rare instances, dogs with confirmed Addison’s may have post-ACTH cortisol levels slightly above 2 mcg/dL, in the 2 to 3 mcg/dL range.
Procedure for Performing ACTH Stimulation Test in Dogs:
- Collect a pre-ACTH blood sample into a red top tube to measure baseline cortisol.
- Administer 5 mcg/kg of synthetic ACTH intravenously (maximum 250 mcg/dog). Avoid compounded formulations.
- Exactly 60 minutes post-ACTH administration, collect a second blood sample into a red top tube.
- Submit both serum samples to a laboratory for cortisol measurement and analysis.
Treatment Strategies for Addison’s Disease in Dogs
Treatment for Addison’s disease varies depending on the severity of the presentation. Some dogs have chronic, milder symptoms, while others experience a life-threatening Addisonian crisis requiring immediate and intensive care. Many fall somewhere in between, needing fluid therapy and supportive care alongside steroid supplementation.
Managing Chronic Addison’s Disease
For clinically stable dogs with chronic Addison’s, long-term treatment typically involves replacing both mineralocorticoids and glucocorticoids.
Mineralocorticoid Replacement
Mineralocorticoid supplementation is available in two primary forms: daily oral fludrocortisone and monthly injections of desoxycorticosterone pivalate (DOCP).
Fludrocortisone: Fludrocortisone acetate (given orally at 0.01 mg/kg every 12 hours) has both glucocorticoid and mineralocorticoid effects. While this dual action might seem advantageous, it can complicate dose adjustments. For example, increasing the fludrocortisone dose to normalize sodium and potassium levels might inadvertently lead to excessive glucocorticoid effects and potential hypercortisolemia side effects.
Desoxycorticosterone Pivalate (DOCP): DOCP, available under brand names like Percorten-V and Zycortal, exclusively provides mineralocorticoid activity. This necessitates concurrent glucocorticoid supplementation, typically with prednisone. Many veterinarians prefer DOCP because it allows for independent adjustment of glucocorticoid dosage and is considered highly effective. DOCP is also thought to be more effective at normalizing renin activity compared to fludrocortisone, suggesting it is a superior mineralocorticoid replacement. The standard initial DOCP dose is 2.2 mg/kg every 25 days, although some veterinarians start with 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 given subcutaneously off-label.
After initiating DOCP treatment, electrolyte levels should be checked at 14 days to assess the dose and again at 25 days to evaluate the dosing interval. At the 14-day check, if hyponatremia or hyperkalemia is present, the next DOCP dose (at 25-28 days) should be increased by 10% to 15%. If hypernatremia or hypokalemia is observed, the dose should be decreased by 10% to 15%. At the 25-day mark, if hyponatremia or hyperkalemia is still present, the dosing interval should be shortened by 1 to 2 days. If electrolytes are within normal ranges, the dosing interval can often be extended to 28 days for client convenience, with electrolyte levels reconfirmed at this interval. Some studies suggest dosing intervals can be extended up to 90 days, but this requires frequent electrolyte monitoring to optimize the interval. It’s generally preferred to adjust the DOCP dose rather than extending the interval beyond 28-30 days, and adjusting both dose and interval simultaneously is not recommended. Once an optimal dose and interval are established, many owners can be trained to administer DOCP injections at home.
Glucocorticoid Replacement Therapy
Dogs receiving DOCP must also receive glucocorticoid supplementation. While some dogs on fludrocortisone might not require additional prednisone long-term, starting with supplemental glucocorticoids initially and then tapering them off after stabilization often leads to quicker symptom control.
Prednisone is typically used for glucocorticoid replacement, starting at a dose of 0.5 to 1.0 mg/kg daily. This dose should be gradually reduced over several weeks to find the lowest effective maintenance dose that controls Addison’s symptoms while minimizing side effects like increased thirst and urination, increased appetite, and panting. Larger dogs may be more sensitive to glucocorticoid side effects. While published maintenance doses are usually 0.1 to 0.22 mg/kg/day, many dogs can be managed successfully on even lower doses (as low as 0.03 mg/kg/day). Dosage adjustments should be based on clinical signs, not on repeat ACTH stimulation tests, for dogs with confirmed naturally occurring Addison’s disease.
Treatment of Atypical Addison’s Disease
Dogs with atypical Addison’s disease, which primarily involves glucocorticoid deficiency, only require glucocorticoid supplementation, following the guidelines mentioned above for prednisone. However, it’s crucial to monitor these dogs for the potential development of electrolyte imbalances over time, which would necessitate the addition of mineralocorticoid therapy. Electrolyte levels should be rechecked 2 weeks after diagnosis, then monthly for 3 months, and then every 3 months for the first year.
Managing Addisonian Crisis
Addisonian crisis is a life-threatening emergency. Dogs in crisis may present with arrhythmias or bradycardia due to hyperkalemia and need immediate treatment to correct this electrolyte imbalance. Hypoglycemia is also common, reported in up to 38% of Addisonian crisis cases. Insulin therapy for hyperkalemia should be avoided until normal blood glucose is confirmed to prevent exacerbating hypoglycemia, which can lead to seizures. Prerenal azotemia is frequently observed in these patients.
Prompt recognition and treatment of Addisonian crisis are critical for a positive outcome. Fluid resuscitation is paramount to address hypovolemia, hypotension, metabolic acidosis, and hyperkalemia. Balanced crystalloid solutions like Plasmalyte 148, lactated Ringer’s, or Normosol-R are now recommended over 0.9% sodium chloride. While sodium chloride was previously recommended, concerns about neurologic signs due to rapid sodium correction (myelinolysis) are relevant if hyponatremia is chronic, particularly when sodium levels are below 120 mEq/L. In such cases, sodium levels should be corrected gradually, not exceeding an increase of 12 mEq/L every 24 hours, and fluids with lower sodium concentrations may be used. Balanced crystalloids are also more effective at correcting acidosis. Fluid resuscitation should be performed using boluses of 20 to 30 mL/kg given over 15 to 20 minutes, with vital signs reassessed after each bolus until they return to normal. Lactate levels can also be monitored as an objective measure of resuscitation.
Figure 2. Intravenous fluid administration is critical in managing a dog experiencing an Addisonian crisis. ECG and blood pressure monitoring are essential to detect hyperkalemia and assess response to therapy.
Following fluid resuscitation, intravenous dexamethasone can be administered. Dexamethasone is preferred as it does not interfere with subsequent ACTH stimulation test results because it is not detected by cortisol assays, unlike prednisone, prednisolone, and methylprednisolone. The dog should remain hospitalized and on IV fluids until electrolyte imbalances are stabilized and clinical signs are controlled with oral medications, including prednisone. In the acute phase, prednisone is typically given at 0.5 to 1.0 mg/kg/day and gradually tapered as the dog recovers and transitions to home care. Mineralocorticoid supplementation with DOCP or fludrocortisone is usually started after Addison’s diagnosis is confirmed. Ongoing dosing will be guided by laboratory results, especially electrolyte levels, and clinical signs.
Treatment of Addisonian Crisis in Dogs: Key Steps
Address Critical Imbalances:
- Hypovolemia and Hypotension: Administer balanced crystalloids (20-30 mL/kg boluses), reassess and repeat as needed.
- Acidosis: IV fluid therapy is usually sufficient to correct acidosis.
- Hyperkalemia:
- Fluid therapy is often adequate unless hyperkalemia is severe (>8.5-9.0 mEq/L) or ECG abnormalities are present (bradycardia, peaked T waves, flattened P waves, widened QRS complexes).
- For ECG changes or severe hyperkalemia:
- Calcium gluconate (10% solution): 0.5-1.5 mL/kg over 10-15 minutes (monitor ECG for bradycardia). Stabilizes the heart but does not directly lower potassium.
- Dextrose: 1 mL/kg of 50% dextrose, diluted 1:3 with balanced crystalloids.
- Regular insulin: 0.2 U/kg, followed by 1-2 g dextrose/unit of insulin, then dextrose added to IV fluids to create a 2.5%-5.0% dextrose solution. Insulin is preferred for life-threatening arrhythmias. Dextrose alone helps lower potassium but is slower.
- Alpha-2 agonists (e.g., inhaled albuterol or IV terbutaline at 0.01 mg/kg).
- Hypoglycemia: 1 mL/kg of 50% dextrose, diluted 1:2 with balanced crystalloid.
- Severe Anemia (from GI blood loss): Packed red blood cell transfusion may be needed.
- Glucocorticoid Deficiency:
- Dexamethasone: 0.2 mg/kg IV initially, then 0.1 mg/kg every 12 hours until oral prednisone is tolerated. Can be given before ACTH stimulation test.
- Hydrocortisone sodium succinate: 0.5-0.625 mg/kg/hr. Cannot be given before ACTH stimulation test.
- Supportive Care:
- Warming measures for hypothermia.
- Antiemetics for vomiting.
- Gastroprotectants for GI health.
- Pain management as needed.
- Nutritional support (patients usually start eating within 24 hours).
Prognosis for Dogs with Addison’s Disease
With proper diagnosis and management, the prognosis for dogs with Addison’s disease is generally excellent, and they can enjoy a good quality of life. Most dogs with Addison’s will live a normal lifespan and die from causes unrelated to their Addison’s disease. A study of 205 dogs with Addison’s reported a median survival time of 4.7 years, with no significant impact from factors like age, breed, sex, or weight. However, successful long-term management requires diligent owners who are attentive to subtle signs of illness, committed to daily medication, and compliant with regular veterinary check-ups for the dog’s lifetime. With consistent treatment and veterinary follow-up, dogs with Addison’s disease can lead long, healthy, and happy lives.
Figure 3. This Golden Retriever, diagnosed with hypoadrenocorticism at 2 years old after exhibiting nonspecific lethargy and gastrointestinal signs, is thriving 8 years post-diagnosis. He is maintained on DOCP (1.3 mg/kg every 30 days) and prednisone (0.03 mg/kg daily). Dogs with hypoadrenocorticism typically have an excellent quality of life with diligent client medication and monitoring.
