Canine Hypoadrenocorticism Study Guide

Overview and Clinical Importance

Hypoadrenocorticism (Addison's disease) is an uncommon but potentially life-threatening endocrine disorder resulting from inadequate production of adrenocortical hormones, primarily glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Often called "The Great Pretender," this disease mimics many common conditions, making it a diagnostic challenge and a favorite NAVLE topic.

The disease has an estimated prevalence of 0.06% to 0.28% in the canine population. Early recognition and treatment are critical, as untreated Addisonian crisis can result in death from hypovolemic shock, cardiac arrhythmias, and severe electrolyte disturbances. With appropriate therapy, the long-term prognosis is excellent, with median survival times exceeding 4.7 years.

Anatomy and Physiology of the Adrenal Glands

The adrenal glands are paired endocrine organs located craniomedial to the kidneys in the retroperitoneal space. Each gland consists of two distinct regions: the outer cortex (80-90% of the gland) and the inner medulla (10-20%). In dogs, the left adrenal gland is typically larger and positioned more caudal than the right.

Adrenal Cortex Zones and Hormone Production

Etiology and Classification

Primary Hypoadrenocorticism (Most Common)

Primary hypoadrenocorticism results from destruction or dysfunction of the adrenal cortex itself. The most common cause is immune-mediated adrenalitis, leading to destruction of all three cortical zones. This results in deficiency of both mineralocorticoids and glucocorticoids ("typical" Addison's disease).

Causes of Primary Hypoadrenocorticism

• Immune-mediated destruction (most common - greater than 90% of cases)
• Iatrogenic: Mitotane (Lysodren) overdose, trilostane toxicity
• Granulomatous disease: Histoplasmosis, blastomycosis, cryptococcosis
• Neoplastic infiltration or metastatic disease
• Adrenal hemorrhage or infarction

Secondary Hypoadrenocorticism (Rare)

Secondary hypoadrenocorticism results from inadequate ACTH secretion from the pituitary gland. This causes atrophy of the zona fasciculata and zona reticularis, but the zona glomerulosa is spared because aldosterone production is primarily regulated by the renin-angiotensin-aldosterone system (RAAS), not ACTH.

Typical vs. Atypical Hypoadrenocorticism

Epidemiology and Breed Predisposition

Signalment

• Age: Young to middle-aged (median 3-4 years), range 2 months to 14 years
• Sex: Female predisposition (~70% of cases)
• Reproductive status: Spayed/neutered dogs at higher risk than intact

Breed Predisposition

Hypoadrenocorticism has a strong genetic component and is inherited as an autosomal recessive trait in several breeds.

Pathophysiology

Effects of Glucocorticoid Deficiency

• Impaired gluconeogenesis leading to hypoglycemia
• Reduced GI mucosal integrity causing vomiting, diarrhea, GI hemorrhage
• Impaired vascular tone contributing to hypotension
• Lack of stress response (no "stress leukogram")

Effects of Mineralocorticoid Deficiency

• Sodium and water loss leading to hyponatremia and hypovolemia
• Potassium retention causing hyperkalemia
• Metabolic acidosis from hydrogen ion retention
• Prerenal azotemia from decreased renal perfusion

Clinical Signs and Presentation

Chronic/Waxing-Waning Presentation

The majority of dogs present with vague, nonspecific signs that wax and wane over weeks to months. These signs often improve temporarily with supportive care (IV fluids), only to recur when the patient is discharged.

Addisonian Crisis (Acute Presentation)

Approximately 30% of dogs present in Addisonian crisis, a life-threatening emergency characterized by hypovolemic shock.

• Collapse, obtundation, or stupor
• Severe dehydration (greater than 10%)
• Weak/thready pulses, prolonged CRT
• Hypothermia
• PARADOXICAL BRADYCARDIA - bradycardia in a shocky patient (due to hyperkalemia)

Diagnostic Findings

Complete Blood Count (CBC)

Serum Biochemistry

Electrocardiographic (ECG) Findings

Definitive Diagnosis: ACTH Stimulation Test

The ACTH stimulation test is the gold standard for diagnosing hypoadrenocorticism.

Protocol

• Collect baseline serum cortisol sample
• Administer synthetic ACTH (cosyntropin) at 5 mcg/kg IV
• Collect post-ACTH serum cortisol sample at 1 hour

Interpretation

Treatment

Emergency Management of Addisonian Crisis

Treatment priorities: Correct hypovolemia, hyperkalemia, hypoglycemia, and acid-base abnormalities.

Step 1: Aggressive Fluid Resuscitation

• Fluid of choice: 0.9% NaCl (normal saline)
• Shock dose: 60-90 mL/kg/hr for dogs

Step 2: Treat Life-Threatening Hyperkalemia

Step 3: Glucocorticoid Replacement

• Dexamethasone SP: 0.1-0.5 mg/kg IV (does NOT interfere with ACTH stim test)

Long-Term Maintenance Therapy

Memory Aids and Board Tips

Cortical Zone Mnemonic

"GFR - Salt, Sugar, Sex" - Glomerulosa (mineralocorticoids/salt), Fasciculata (glucocorticoids/sugar), Reticularis (sex steroids)

ECG Changes of Hyperkalemia

"Potassium PEAKS the T, then FLATTENS the P, then WIDENS the QRS"

Treatment Priorities

"FLUIDS First, Fix Potassium, then add Steroids"

Prognosis

With appropriate treatment, the prognosis is excellent. Median survival time exceeds 4.7 years, with most dogs dying from causes other than Addison's disease.