NAVLE Endocrine

Feline Hypoadrenocorticism Study Guide

📅 March 28, 2026 ⏱ 25 min read

Overview and Clinical Importance

Feline hypoadrenocorticism (Addison's disease) is a rare but life-threatening endocrine disorder resulting from inadequate production of adrenocortical hormones, primarily glucocorticoids (cortisol) and mineralocorticoids (aldosterone). With only approximately 48 documented cases in the veterinary literature since 1983, this condition remains significantly rarer in cats than in dogs. However, its waxing and waning clinical signs often mimic more common feline diseases, earning it the nickname "the great pretender." Early recognition is crucial as untreated cases can progress to life-threatening Addisonian crisis.

Zone	Hormone Produced	Primary Function
Zona Glomerulosa	Aldosterone (mineralocorticoid)	Sodium retention, potassium excretion, fluid balance
Zona Fasciculata	Cortisol (glucocorticoid)	Glucose metabolism, stress response, immune modulation
Zona Reticularis	Androgens (DHEA, androstenedione)	Sex hormone precursors

Adrenal Gland Anatomy and Physiology

Adrenal Gland Structure

The feline adrenal glands are paired, small triangular organs located craniomedial to each kidney in the retroperitoneal space. Each gland consists of two distinct functional regions: the outer adrenal cortex (comprising approximately 80-90% of the gland) and the inner adrenal medulla. The cortex is further divided into three zones, each producing specific hormones.

Hypothalamic-Pituitary-Adrenal (HPA) Axis

Cortisol secretion is regulated by the HPA axis through a negative feedback loop. Corticotropin-releasing hormone (CRH) is released from the hypothalamus, stimulating the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH then acts on the adrenal cortex to stimulate cortisol production. Elevated cortisol levels provide negative feedback to both the hypothalamus and pituitary, completing the regulatory loop.

High-YieldRemember the mnemonic "GFR-Salt-Sugar-Sex" for the adrenal cortex zones: Glomerulosa-Fasciculata-Reticularis produce aldosterone (Salt), cortisol (Sugar), and androgens (Sex) respectively. Destruction of greater than 90% of both adrenal cortices is required before clinical signs of hypoadrenocorticism develop.

Type	Etiology	Hormones Affected
Primary (Typical)	Immune-mediated adrenal destruction (most common), lymphomatous infiltration, adrenal hemorrhage, infections	Both glucocorticoids and mineralocorticoids
Primary (Atypical)	Early-stage primary disease (selective zona fasciculata destruction)	Glucocorticoids only (may progress)
Secondary	Pituitary dysfunction, pituitary tumor, lymphocytic panhypophysitis	Glucocorticoids only (mineralocorticoids preserved)
Iatrogenic	Abrupt withdrawal of chronic glucocorticoid therapy	Glucocorticoids only (temporary)

Etiology and Pathophysiology

Classification of Hypoadrenocorticism

Pathophysiologic Consequences

Mineralocorticoid (Aldosterone) Deficiency

Hyponatremia: Impaired sodium reabsorption in renal collecting ducts leads to sodium wasting
Hyperkalemia: Reduced potassium excretion causes dangerous accumulation
Hypovolemia: Water follows sodium, causing dehydration and hypotension
Metabolic acidosis: Impaired hydrogen ion excretion

Glucocorticoid (Cortisol) Deficiency

Hypoglycemia: Impaired gluconeogenesis and glycogenolysis
GI dysfunction: Loss of GI mucosal integrity causing vomiting and anorexia
Impaired stress response: Inability to mount appropriate response to stress
Lack of stress leukogram: Absence of expected lymphopenia and eosinopenia in a sick cat

Clinical Sign	Frequency	Pathophysiology
Lethargy/depression	93-100%	Cortisol deficiency
Anorexia	100%	GI dysfunction, nausea
Weight loss	86%	Chronic illness
Dehydration	85-92%	Sodium/water loss
Weakness	85%	Hyperkalemia
Hypothermia	77%	Poor perfusion
Episodic vomiting	36-40%	GI mucosal compromise
Collapse/shock	23-40%	Hypovolemia
Bradycardia	15%	Hyperkalemia

Signalment and Clinical Presentation

Signalment

Based on the 48 documented feline cases in the literature:

Age: Range 7 months to 14 years; median 4 years (cats less than 6 years overrepresented)
Sex: No predisposition; neutered males and females equally affected
Breed: Domestic shorthair/longhair most common; British Shorthair overrepresented

Clinical Signs

Clinical signs are often vague, nonspecific, and characteristically wax and wane. Temporary improvement with fluid therapy or corticosteroid administration is a hallmark.

High-YieldUnlike dogs with Addison's disease, diarrhea is RARE in feline hypoadrenocorticism. Cats typically present with anorexia and episodic vomiting rather than diarrhea. This is a key species difference frequently tested on the NAVLE.

Parameter	Finding	Clinical Significance
Sodium (Na+)	Decreased	100% of cases - hyponatremia
Potassium (K+)	Increased	90% of cases - can cause arrhythmias
Na:K Ratio	Less than 24	Highly suggestive (normal 27-40); most show 17.9-23.7
BUN/Creatinine	Increased	100% - prerenal azotemia
Phosphorus	Increased	100% - hyperphosphatemia

Diagnosis

Laboratory Findings

Serum Biochemistry - Classic Electrolyte Pattern

NAVLE TipThe classic electrolyte pattern is NOT pathognomonic - urinary obstruction (FLUTD), peritoneal effusion, and acute kidney injury can produce similar findings. ACTH stimulation test is required for definitive diagnosis.

CBC Findings

Absence of stress leukogram: Lack of lymphopenia/eosinopenia in a sick cat is a critical clue
Lymphocytosis/Eosinophilia: May be present (unusual in a sick cat)
Mild non-regenerative anemia: 23% of cases (may be masked by dehydration)

Electrocardiography (ECG)

ACTH Stimulation Test - Gold Standard

The ACTH stimulation test is the definitive diagnostic test. Protocol: (1) Baseline cortisol, (2) Administer synthetic ACTH 125 mcg IV, (3) Post-ACTH samples at 60 and 90 minutes.

Normal response: Post-ACTH cortisol 5-17 mcg/dL
Hypoadrenocorticism: Baseline AND post-ACTH cortisol both less than 2 mcg/dL (flat response)
Key: Lack of cortisol stimulation is diagnostic

High-YieldACTH stim test does NOT differentiate primary vs secondary hypoadrenocorticism. Measure endogenous ACTH: Primary = high ACTH (>100 pg/mL); Secondary = low ACTH (<20 pg/mL).

K+ Level	ECG Changes	Urgency
5.5-6.5 mEq/L	Tall, peaked T waves	Monitor
6.5-7.5 mEq/L	P wave flattening, PR prolongation	Initiate treatment
7.5-8.5 mEq/L	Loss of P waves, QRS widening	URGENT - Give calcium
Greater than 8.5 mEq/L	Sine wave, V-fib, asystole	CRITICAL

Differential Diagnosis

Condition	Electrolyte Pattern	Distinguishing Feature
Urinary obstruction (FLUTD)	Low Na:K, hyperkalemia	Distended bladder; most common differential in male cats
Acute kidney injury	Hyperkalemia, azotemia	Oliguria/anuria; ACTH stim normal
Peritoneal effusion	Hyponatremia, hyperkalemia	Abdominal fluid on imaging
Chylothorax	Hyponatremia, hyperkalemia	Pleural effusion; triglyceride-rich

Treatment

Emergency Management - Addisonian Crisis

High-YieldCats take longer to respond to treatment than dogs - expect 3-5 days for clinical improvement rather than 24-48 hours.

Long-Term Maintenance Therapy

NAVLE TipUse PREDNISOLONE (not prednisone) in cats! Cats cannot efficiently convert prednisone to prednisolone. This is a commonly tested species difference.

Priority	Treatment	Notes
1. IV Fluids	0.9% NaCl shock dose 45-60 mL/kg/hr	AVOID lactated Ringer's (contains K+)
2. Hyperkalemia	Calcium gluconate 10%: 0.5-1 mL/kg IV slowly; Regular insulin + dextrose	Ca is cardioprotective; monitor ECG
3. Glucocorticoid	Dexamethasone SP 0.5-2 mg/kg IV	Give after baseline cortisol if possible
4. Dextrose	50% dextrose 0.5-1 mL/kg IV if hypoglycemic	Monitor blood glucose

Prognosis

60% of diagnosed cats alive at median 2.75 years; longest survival 70 months
Cats that survive initial crisis and respond can have normal life expectancy
Poor prognostic indicators: Failure to respond in 2-5 days, underlying lymphoma, concurrent diabetes

Medication	Dose	Notes
Fludrocortisone (Florinef)	0.1 mg/cat PO daily	Mineralocorticoid + some glucocorticoid
DOCP (Percorten-V/Zycortal)	10-12.5 mg/cat IM q25-35 days	Pure mineralocorticoid; off-label
Prednisolone	0.1-0.2 mg/kg PO daily	NOT prednisone - cats cannot convert

Memory Aids and Board Tips

"ADDISON" Mnemonic

A - Anorexia is most common (100%)

D - Diarrhea is RARE (unlike dogs!)

D - Depression/lethargy in nearly all

I - Intermittent (waxing/waning) signs

S - Sodium low, K+ high (Na:K <27)

O - Only ACTH stim test is diagnostic

N - No stress leukogram in a sick cat!

Practice NAVLE Questions

Test your knowledge with 10,000+ exam-style questions, detailed explanations, and timed exams.

Start Your Free Trial →